Mechanical torque measurement predicts load to implant cut-out: a biomechanical study investigating DHS anchorage in femoral heads.

PubMed

Suhm, Norbert; Hengg, Clemens; Schwyn, Ronald; Windolf, Markus; Quarz, Volker; Hänni, Markus

2007-08-01

Bone strength plays an important role in implant anchorage. Bone mineral density (BMD) is used as surrogate parameter to quantify bone strength and to predict implant anchorage. BMD can be measured by means of quantitative computer tomography (QCT) or dual energy X-ray absorptiometry (DXA). These noninvasive methods for BMD measurement are not available pre- or intra-operatively. Instead, the surgeon could determine bone strength by direct mechanical measurement. We have evaluated mechanical torque measurement for (A) its capability to quantify local bone strength and (B) its predictive value towards load at implant cut-out. Our experimental study was performed using sixteen paired human cadaver proximal femurs. BMD was determined for all specimens by QCT. The torque to breakaway of the cancellous bone structure (peak torque) was measured by means of a mechanical probe at the exact position of subsequent DHS placement. The fixation strength of the DHS achieved was assessed by cyclic loading in a stepwise protocol beginning with 1,500 N increasing 500 N every 5,000 cycles until 4,000 N. A highly significant correlation of peak torque with BMD (QCT) was found (r = 0.902, r (2) = 0.814, P < 0.001). Peak torque correlated highly significant with the load at implant cut-out (r = 0.795, P < 0.001). All specimens with a measured peak torque below 6.79 Nm failed at the first load level of 1,500 N. The specimens with a peak torque above 8.63 Nm survived until the last load level of 4,000 N. Mechanical peak torque measurement is able to quantify bone strength. In an experimental setup, peak torque identifies those specimens that are likely to fail at low load. In clinical routine, implant migration and cut-out depend on several parameters, which are difficult to control, such as fracture type, fracture reduction achieved, and implant position. The predictive value of peak torque towards cut-out in a clinical set-up therefore has to be carefully validated.

INCREASING DURATION OF TYPE 1 DIABETES PERTURBS THE STRENGTH-STRUCTURE RELATIONSHIP AND INCREASES BRITTLENESS OF BONE

PubMed Central

Nyman, Jeffry S.; Even, Jesse L.; Jo, Chan-Hee; Herbert, Erik G.; Murry, Matthew R.; Cockrell, Gael E.; Wahl, Elizabeth C.; Bunn, R. Clay; Lumpkin, Charles K.; Fowlkes, John L.; Thrailkill, Kathryn M.

2011-01-01

Type 1 diabetes (T1DM) increases the likelihood of a fracture. Despite serious complications in the healing of fractures among those with diabetes, the underlying causes are not delineated for the effect of diabetes on the fracture resistance of bone. Therefore, in a mouse model of T1DM, we have investigated the possibility that a prolonged state of diabetes perturbs the relationship between bone strength and structure (i.e., affects tissue properties). At 10, 15, and 18 weeks following injection of streptozotocin to induce diabetes, diabetic male mice and age-matched controls were examined for measures of skeletal integrity. We assessed 1) the moment of inertia (IMIN) of the cortical bone within diaphysis, trabecular bone architecture of the metaphysis, and mineralization density of the tissue (TMD) for each compartment of the femur by microcomputed tomography and 2) biomechanical properties by three point bending test (femur) and nanoindentation (tibia). In the metaphysis, a significant decrease in trabecular bone volume fraction and trabecular TMD was apparent after 10 weeks of diabetes. For cortical bone, type 1 diabetes was associated with decreased cortical TMD, IMIN, rigidity, and peak moment as well as a lack of normal age-related increases in the biomechanical properties. However, there were only modest differences in material properties between diabetic and normal mice at both whole bone and tissue-levels. As the duration of diabetes increased, bone toughness decreased relative to control. If the sole effect of diabetes on bone strength was due to a reduction in bone size, then IMIN would be the only significant variable explaining the variance in the maximum moment. However, general linear modeling found that the relationship between peak moment and IMIN depended on whether the bone was from a diabetic mouse and the duration of diabetes. Thus, these findings suggest that the elevated fracture risk among diabetics is impacted by complex changes in tissue properties that ultimately reduce the fracture resistance of bone. PMID:21185416

Non-destructive NIR spectral imaging assessment of bone water: Comparison to MRI measurements.

PubMed

Rajapakse, Chamith S; Padalkar, Mugdha V; Yang, Hee Jin; Ispiryan, Mikayel; Pleshko, Nancy

2017-10-01

Bone fracture risk increases with age, disease states, and with use of certain therapeutics, such as acid-suppressive drugs, steroids and high-dose bisphosphonates. Historically, investigations into factors that underlie bone fracture risk have focused on evaluation of bone mineral density (BMD). However, numerous studies have pointed to factors other than BMD that contribute to fragility, including changes in bone collagen and water. The goal of this study is to investigate the feasibility of using near infrared spectral imaging (NIRSI) to determine the spatial distribution and relative amount of water and organic components in whole cross-sections of bone, and to compare those results to those obtained using magnetic resonance imaging (MRI) methods. Cadaver human whole-section tibiae samples harvested from 18 donors of ages 27-97years underwent NIRSI and ultrashort echo time (UTE) MRI. As NIRSI data is comprised of broad absorbances, second derivative processing was evaluated as a means to narrow peaks and obtain compositional information. The (inverted) second derivative peak heights of the NIRSI absorbances correlated significantly with the mean peak integration of the water, collagen and fat NIR absorbances, respectively, indicating that either processing method could be used for compositional assessment. The 5797cm -1 absorbance was validated as arising from the fat present in bone marrow, as it completely disappeared after ultrasonication. The MRI UTE-determined bound water content in tibial cortical bone samples ranged from 62 to 91%. The NIRSI water peaks at 5152cm -1 and at 7008cm -1 correlated significantly with the UTE data, with r=0.735, p=0.016, and r=0.71, p=0.0096, respectively. There was also a strong correlation between the intensity of the NIRSI water peak at 7008cm -1 and the intensity of the collagen peak at 4608cm -1 (r=0.69, p=0.004). Since NIRSI requires minimal to no sample preparation, this approach has great potential to become a gold standard modality for the investigation of changes in water content, distribution, and environment in pre-clinical studies of bone pathology and therapeutics. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison of dental implant stabilities by impact response and resonance frequencies using artificial bone.

PubMed

Kim, Dae-Seung; Lee, Woo-Jin; Choi, Soon-Chul; Lee, Sam-Sun; Heo, Min-Suk; Huh, Kyung-Hoe; Kim, Tae-Il; Yi, Won-Jin

2014-06-01

We compared implant stability as determined by the peak frequency from the impact response with the implant stability quotient (ISQ) by resonance frequency analysis (RFA) in various artificial bone conditions. The clinical bone conditions were simulated using an artificial bone material with different cortical thicknesses and trabecular densities. The artificial bone material was solid, rigid polyurethane. The polyurethane foam of 0.8g/cm(3) density was used for the cortical bone layer, and that of 0.08, 0.16, 0.24, 0.32, and 0.48g/cm(3) densities for the trabecular bone layer. The cortical bone material of 4 different thicknesses (1.4, 1.6, 1.8, and 2.0mm) was attached to the trabecular bone with varying density. Two types of dental implants (10 and 13mm lengths of 4.0mm diameter) were placed into the artificial bone blocks. An inductive sensor was used to measure the vibration caused by tapping the adapter-implant assembly. The peak frequency of the power spectrum of the impact response was used as the criterion for implant stability. The ISQ value was also measured for the same conditions. The stability, as measured by peak frequency (SPF) and ISQ value, increased as the trabecular density and the cortical density increased in linear regression analysis. The SPF and ISQ values were highly correlated with each other when the trabecular bone density and cortical bone thickness changed (Pearson correlation=0.90, p<0.01). The linear regression of the SPF with the cortical bone thickness showed higher goodness of fit (R(2) measure) than the ISQ value with the cortical bone thickness. The SPF could differentiate implantation conditions as many as the ISQ value when the trabecular bone density and the cortical density changed. However, the ISQ value was not consistent with the general stability tendency in some conditions. The SPF showed better consistency and differentiability with implant stability than the ISQ value by resonance frequency analysis in the various implantation conditions. Copyright © 2013 IPEM. Published by Elsevier Ltd. All rights reserved.

N-acetyl cysteine (NAC)-mediated detoxification and functionalization of poly(methyl methacrylate) bone cement.

PubMed

Tsukimura, Naoki; Yamada, Masahiro; Aita, Hideki; Hori, Norio; Yoshino, Fumihiko; Chang-Il Lee, Masaichi; Kimoto, Katsuhiko; Jewett, Anahid; Ogawa, Takahiro

2009-07-01

Currently used poly(methyl methacrylate) (PMMA)-based bone cement lacks osteoconductivity and induces osteolysis and implant loosening due to its cellular and tissue-toxicity. A high percentage of revision surgery following the use of bone cement has become a significant universal problem. This study determined whether incorporation of the amino acid derivative N-acetyl cysteine (NAC) in bone cement reduces its cytotoxicity and adds osteoconductivity to the material. Biocompatibility and bioactivity of PMMA-based bone cement with or without 25mm NAC incorporation was examined using rat bone marrow-derived osteoblastic cells. Osteoconductive potential of NAC-incorporated bone cement was determined by microCT bone morphometry and implant biomechanical test in the rat model. Generation of free radicals within the polymerizing bone cement was examined using electron spin resonance spectroscopy. Severely compromised viability and completely suppressed phenotypes of osteoblasts on untreated bone cement were restored to the normal level by NAC incorporation. Bone volume formed around 25mm NAC-incorporated bone cement was threefold greater than that around control bone cement. The strength of bone-bone cement integration was 2.2 times greater for NAC-incorporated bone cement. For NAC-incorporated bone cement, the spike of free radical generation ended within 12h, whereas for control bone cement, a peak level lasted for 6 days and a level greater than half the level of the peak was sustained for 20 days. NAC also increased the level of antioxidant glutathione in osteoblasts. These results suggest that incorporation of NAC in PMMA bone cement detoxifies the material by immediate and effective in situ scavenging of free radicals and increasing intracellular antioxidant reserves, and consequently adds osteoconductivity to the material.

The wakefulness promoting drug Modafinil causes adenosine receptor-mediated upregulation of receptor activator of nuclear factor κB ligand in osteoblasts: Negative impact of the drug on peak bone accrual in rats.

PubMed

Pal China, Shyamsundar; Pal, Subhashis; Chattopadhyay, Sourav; Porwal, Konica; Mittal, Monika; Sanyal, Sabyasachi; Chattopadhyay, Naibedya

2018-06-01

Modafinil is primarily prescribed for treatment of narcolepsy and other sleep-associated disorders. However, its off-prescription use as a cognition enhancer increased considerably, specially among youths. Given its increasing use in young adults the effect of modafinil on peak bone accrual is an important issue but has never been investigated. Modafinil treatment to young male rats caused trabecular and cortical bone loss in tibia and femur, and reduction in biomechanical strength. Co-treatment of modafinil with alendronate (a drug that suppresses bone resorption) reversed the trabecular bone loss but failed to prevent cortical loss. Modafinil increased serum type 1 pro-collagen N-terminal protein (P1NP) and collagen type 1 cross-linked C-telopeptide (CTX-1) indicating a high turnover bone loss. The drug also increased receptor activator of nuclear factor κB ligand (RANKL) to osteoprotegerin (OPG) ratio in serum which likely resulted in increased osteoclast number per bone surface. Furthermore, conditioned medium from modafinil treated osteoblasts increased the expression of osteoclastogenic genes in bone marrow-derived macrophages and the effect was blocked by RANKL neutralizing antibody. In primary osteoblasts, modafinil stimulated cAMP production and using pharmacological approach, we showed that modafinil signalled via adenosine receptors (A 2A R and A 2B R) which resulted in increased RANKL expression. ZM-241,385 (an A 2A R inhibitor) and MRS 1754 (an A 2B R inhibitor) suppressed modafinil-induced upregulation of RANKL/OPG ratio in the calvarium of new born rat pups. Our data suggests that by activating osteoblast adenosine receptors modafinil increases the production of osteoclastogenic cytokine, RANKL that in turn results in high turnover bone loss in young rats. Copyright © 2018. Published by Elsevier Inc.

Effect of insulin-like growth factor-1 (IGF-1) plus alendronate on bone density during puberty in IGF-1-deficient MIDI mice.

PubMed

Stabnov, L; Kasukawa, Y; Guo, R; Amaar, Y; Wergedal, J E; Baylink, D J; Mohan, S

2002-06-01

Insulin-like growth factor-1 (IGF-1) increases both bone formation and bone resorption processes. To test the hypothesis that treatment with an antiresorber along with IGF-1, during the pubertal growth phase, would be more effective than IGF-1 alone to increase peak bone mass, we used an IGF-1 MIDI mouse model, which exhibits a >60% reduction in circulating IGF-1 levels. We first determined an optimal IGF-1 delivery by evaluating IGF-1 administration (2 mg/kg body weight/day) by either a single daily injection, three daily injections, or by continuous delivery via a minipump during puberty. Of the three regimens, the three daily IGF-1 injections and IGF-1 through a minipump produced a significant increase in total body bone mineral density (BMD) (6.0% and 4.4%, respectively) and in femoral BMD (4.3% and 6.2%, respectively) compared with the control group. Single subcutaneous (s.c.) administration did not increase BMD. We chose IGF-1 administration three times daily for testing the combined effects of IGF-1 and alendronate (100 microg/kg per day). The treatment of IGF-1 + alendronate for a period of 2 weeks increased total body BMD at 1 week and 3 weeks after treatment (21.1% and 20.5%, respectively) and femoral BMD by 29% at 3 weeks after treatment. These increases were significantly greater than those produced by IGF-1 alone. IGF-1, but not alendronate, increased bone length. IGF-1 and/or alendronate increased both periosteal and endosteal circumference. Combined treatment caused a greater increase in the total body bone mineral content (BMC) and periosteal circumference compared with individual treatment with IGF-1 or alendronate. Our data demonstrate that: (1) inhibition of bone turnover during puberty increases net bone density; and (2) combined treatment with IGF-1 and alendronate is more effective than IGF-1 or alendronate alone in increasing peak bone mass in an IGF-1-deficient MIDI mouse model.

Pharmacological activation of aldehyde dehydrogenase 2 promotes osteoblast differentiation via bone morphogenetic protein-2 and induces bone anabolic effect

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mittal, Monika; Pal, Subhashis; China, Shyamsundar

Aldehyde dehydrogenases (ALDHs) are a family of enzymes involved in detoxifying aldehydes. Previously, we reported that an ALDH inhibitor, disulfiram caused bone loss in rats and among ALDHs, osteoblast expressed only ALDH2. Loss-of-function mutation in ALDH2 gene is reported to cause bone loss in humans which suggested its importance in skeletal homeostasis. We thus studied whether activating ALDH2 by N-(1, 3-benzodioxol-5-ylmethyl)-2, 6-dichlorobenzamide (alda-1) had osteogenic effect. We found that alda-1 increased and acetaldehyde decreased the differentiation of rat primary osteoblasts and expressions of ALDH2 and bone morphogenetic protein-2 (BMP-2). Silencing ALDH2 in osteoblasts abolished the alda-1 effects. Further, alda-1 attenuatedmore » the acetaldehyde-induced lipid-peroxidation and oxidative stress. BMP-2 is essential for bone regeneration and alda-1 increased its expression in osteoblasts. We then showed that alda-1 (40 mg/kg dose) augmented bone regeneration at the fracture site with concomitant increase in BMP-2 protein compared with control. The osteogenic dose (40 mg/kg) of alda-1 attained a bone marrow concentration that was stimulatory for osteoblast differentiation, suggesting that the tissue concentration of alda-1 matched its pharmacologic effect. In addition, alda-1 promoted modeling-directed bone growth and peak bone mass achievement, and increased bone mass in adult rats which reiterated its osteogenic effect. In osteopenic ovariectomized (OVX) rats, alda-1 reversed trabecular osteopenia with attendant increase in serum osteogenic marker (procollagen type I N-terminal peptide) and decrease in oxidative stress. Alda-1 has no effect on liver and kidney function. We conclude that activating ALDH2 by alda-1 had an osteoanabolic effect involving increased osteoblastic BMP-2 production and decreased OVX-induced oxidative stress. - Highlights: • Alda-1 induced osteoblast differentiation that involved upregulation of ALDH2 and BMP-2 • Alda-1 attenuated acetaldehyde-induced inhibition of osteoblast differentiation • Alda-1 enhanced bone regeneration at the fracture site and peak bone mass achievement • Alda-1 reversed trabecular osteopenia in OVX rats via an osteoanabolic mechanism.« less

Positive effects of bisphosphonates on bone and muscle in a mouse model of Duchenne muscular dystrophy.

PubMed

Yoon, Sung-Hee; Sugamori, Kim S; Grynpas, Marc D; Mitchell, Jane

2016-01-01

Patients with Duchenne muscular dystrophy are at increased risk of decreased bone mineral density and bone fracture as a result of inactivity. To determine if antiresorptive bisphosphonates could improve bone quality and their effects on muscle we studied the Mdx mouse, treated with pamidronate during peak bone growth at 5 and 6 weeks of age, and examined the outcome at 13 weeks of age. Pamidronate increased cortical bone architecture and strength in femurs with increased resistance to fracture. While overall long bone growth was not affected by pamidronate, there was significant inhibition of remodeling in metaphyseal trabecular bone with evidence of residual calcified cartilage. Pamidronate treatment had positive effects on skeletal muscle in the Mdx mice with decreased serum and muscle creatine kinase and evidence of improved muscle histology and grip strength. Copyright © 2015 Elsevier B.V. All rights reserved.

Physical activity in the prevention and amelioration of osteoporosis in women : interaction of mechanical, hormonal and dietary factors.

PubMed

Borer, Katarina T

2005-01-01

Osteoporosis is a serious health problem that diminishes quality of life and levies a financial burden on those who fear and experience bone fractures. Physical activity as a way to prevent osteoporosis is based on evidence that it can regulate bone maintenance and stimulate bone formation including the accumulation of mineral, in addition to strengthening muscles, improving balance, and thus reducing the overall risk of falls and fractures. Currently, our understanding of how to use exercise effectively in the prevention of osteoporosis is incomplete. It is uncertain whether exercise will help accumulate more overall peak bone mass during childhood, adolescence and young adulthood. Also, the consistent effectiveness of exercise to increase bone mass, or at least arrest the loss of bone mass after menopause, is also in question. Within this framework, section 1 introduces mechanical characteristics of bones to assist the reader in understanding their responses to physical activity. Section 2 reviews hormonal, nutritional and mechanical factors necessary for the growth of bones in length, width and mineral content that produce peak bone mass in the course of childhood and adolescence using a large sample of healthy Caucasian girls and female adolescents for reference. Effectiveness of exercise is evaluated throughout using absolute changes in bone with the underlying assumption that useful exercise should produce changes that approximate or exceed the absolute magnitude of bone parameters in a healthy reference population. Physical activity increases growth in width and mineral content of bones in girls and adolescent females, particularly when it is initiated before puberty, carried out in volumes and at intensities seen in athletes, and accompanied by adequate caloric and calcium intakes. Similar increases are seen in young women following the termination of statural growth in response to athletic training, but not to more limited levels of physical activity characteristic of longitudinal training studies. After 9-12 months of regular exercise, young adult women often show very small benefits to bone health, possibly because of large subject attrition rates, inadequate exercise intensity, duration or frequency, or because at this stage of life accumulation of bone mass may be at its natural peak. The important influence of hormones as well as dietary and specific nutrient abundance on bone growth and health are emphasised, and premature bone loss associated with dietary restriction and estradiol withdrawal in exercise-induced amenorrhoea is described. In section 3, the same assessment is applied to the effects of physical activity in postmenopausal women. Studies of postmenopausal women are presented from the perspective of limitations of the capacity of the skeleton to adapt to mechanical stress of exercise due to altered hormonal status and inadequate intake of specific nutrients. After menopause, effectiveness of exercise to increase bone mineral depends heavily on adequate availability of dietary calcium. Relatively infrequent evidence that physical activity prevents bone loss or increases bone mineral after menopause may be a consequence of inadequate calcium availability or low intensity of exercise in training studies. Several studies with postmenopausal women show modest increases in bone mineral toward the norm seen in a healthy population in response to high-intensity training. Physical activities continue to stimulate increases in bone diameter throughout the lifespan. These exercise-stimulated increases in bone diameter diminish the risk of fractures by mechanically counteracting the thinning of bones and increases in bone porosity. Seven principles of bone adaptation to mechanical stress are reviewed in section 4 to suggest how exercise by human subjects could be made more effective. They posit that exercise should: (i) be dynamic, not static; (ii) exceed a threshold intensity; (iii) exceed a threshold strain frequency; (iv) be relatively brief but intermittent; (v) impose an unusual loading pattern on the bones; (vi) be supported by unlimited nutrient energy; and (vii) include adequate calcium and cholecalciferol (vitamin D3) availability.

Stimulation of liver IGF-1 expression promotes peak bone mass achievement in growing rats: a study with pomegranate seed oil.

PubMed

Bachagol, Deepa; Joseph, Gilbert Stanley; Ellur, Govindraj; Patel, Kalpana; Aruna, Pamisetty; Mittal, Monika; China, Shyamsundar Pal; Singh, Ravendra Pratap; Sharan, Kunal

2018-02-01

Peak bone mass (PBM) achieved at adulthood is a strong determinant of future onset of osteoporosis, and maximizing it is one of the strategies to combat the disease. Recently, pomegranate seed oil (PSO) has been shown to have bone-sparing effect in ovariectomized mice. However, its effect on growing skeleton and its molecular mechanism remain unclear. In the present study, we evaluated the effect of PSO on PBM in growing rats and associated mechanism of action. PSO was given at various doses to 21-day-old growing rats for 90 days by oral gavage. The changes in bone parameters were assessed by micro-computed tomography and histology. Enzyme-linked immunosorbent assay was performed to analyze the levels of serum insulin-like growth factor type 1 (IGF-1). Western blotting from bone and liver tissues was done. Chromatin immunoprecipitation assay was performed to study the histone acetylation levels at IGF-1 gene. The results of the study show that PSO treatment significantly increases bone length, bone formation rate, biomechanical parameters, bone mineral density and bone microarchitecture along with enhancing muscle and brown fat mass. This effect was due to the increased serum levels of IGF-1 and stimulation of its signaling in the bones. Studies focusing on acetylation of histones in the liver, the major site of IGF-1 synthesis, showed enrichment of acetylated H3K9 and H3K14 at IGF-1 gene promoter and body. Further, the increased acetylation at H3K9 and H3K14 was associated with a reduced HDAC1 protein level. Together, our data suggest that PSO promotes the PBM achievement via increased IGF-1 expression in liver and IGF-1 signaling in bone. Copyright © 2017 Elsevier Inc. All rights reserved.

Genetic effects on bone mass and turnover-relevance to black/white differences.

PubMed

Parfitt, A M

1997-08-01

The mass of a bone is given by its volume and its apparent density--mass per unit external volume. Most measurements of so-called density are of mass incompletely normalized by some index of bone size. Genes control about 60% to 75% of the variance of peak bone mass/density and a much smaller proportion of the variance in rate of loss. Genetic influence on bone mass/density are mediated in large part by body size, bone size, and muscle mass. Most of the fifty-fold increase in bone mass from birth to maturity is due to bone growth, which is linked to muscle growth and bodily growth. Three-D apparent bone density in the vertebrae increases about 15% during the pubertal growth spurt. The genetic potential for bone accumulation can be frustrated by insufficient calcium intake, disruption of the calendar of puberty and inadequate physical activity. The growing skeleton is much more responsive than the mature skeleton to the osteotrophic effect of exercise, which is mediated by the detection of deviations from a target value for strain, and orchestration of cellular responses that restore the target value, processes collectively termed the mechanostat. Production of metaphyseal cancellous bone and growth in length are both linked to endochondral ossification, which is driven by growth plate cartilage cell proliferation. Production of diaphyseal cortical bone and growth in width are both linked to periosteal apposition, which is driven by osteoblast precursor proliferation. During adolescence trabeculae and cortices become thicker by net endosteal apposition, which increases apparent density. Two lines of evidence support a genetic basis for black/white differences in bone mass. First, the magnitude (10% to 40%) is incommensurate with known nongenetic factors. Second, the difference is already evident in the fetus and increases progressively during growth, especially in adolescence; the difference in peak bone mass persists throughout life. The genetic determination of bone mass is mediated by two classes of gene. The first regulates growth of the body, including muscles and bones, under the control of a master gene or set of genes whose products function as the sizostat. The second regulates the increase in apparent bone density in response to load bearing, under the control of a master gene or set of genes whose products function as the mechanostat.

Insulin Resistance Is Associated With Smaller Cortical Bone Size in Nondiabetic Men at the Age of Peak Bone Mass.

PubMed

Verroken, Charlotte; Zmierczak, Hans-Georg; Goemaere, Stefan; Kaufman, Jean-Marc; Lapauw, Bruno

2017-06-01

In type 2 diabetes mellitus, fracture risk is increased despite preserved areal bone mineral density. Although this apparent paradox may in part be explained by insulin resistance affecting bone structure and/or material properties, few studies have investigated the association between insulin resistance and bone geometry. We aimed to explore this association in a cohort of nondiabetic men at the age of peak bone mass. Nine hundred ninety-six nondiabetic men aged 25 to 45 years were recruited in a cross-sectional, population-based sibling pair study at a university research center. Insulin resistance was evaluated using the homeostasis model assessment of insulin resistance (HOMA-IR), with insulin and glucose measured from fasting serum samples. Bone geometry was assessed using peripheral quantitative computed tomography at the distal radius and the radial and tibial shafts. In age-, height-, and weight-adjusted analyses, HOMA-IR was inversely associated with trabecular area at the distal radius and with cortical area, periosteal and endosteal circumference, and polar strength strain index at the radial and tibial shafts (β ≤ -0.13, P < 0.001). These associations remained essentially unchanged after additional adjustment for dual-energy X-ray absorptiometry-derived body composition, bone turnover markers, muscle size or function measurements, or adiponectin, leptin, insulin-like growth factor 1, or sex steroid levels. In this cohort of nondiabetic men at the age of peak bone mass, insulin resistance is inversely associated with trabecular and cortical bone size. These associations persist after adjustment for body composition, muscle size or function, or sex steroid levels, suggesting an independent effect of insulin resistance on bone geometry. Copyright © 2017 Endocrine Society

Skeletal site-specific effects of whole body vibration in mature rats: from deleterious to beneficial frequency-dependent effects.

PubMed

Pasqualini, Marion; Lavet, Cédric; Elbadaoui, Mohamed; Vanden-Bossche, Arnaud; Laroche, Norbert; Gnyubkin, Vasily; Vico, Laurence

2013-07-01

Whole body vibration (WBV) is receiving increasing interest as an anti-osteoporotic prevention strategy. In this context, selective effects of different frequency and acceleration magnitude modalities on musculoskeletal responses need to be better defined. Our aim was to investigate the bone effects of different vibration frequencies at constant g level. Vertical WBV was delivered at 0.7 g (peak acceleration) and 8, 52 or 90 Hz sinusoidal vibration to mature male rats 10 min daily for 5 days/week for 4 weeks. Peak accelerations measured by skin or bone-mounted accelerometers at L2 vertebral and tibia crest levels revealed similar values between adjacent skin and bone sites. Local accelerations were greater at 8 Hz compared with 52 and 90 Hz and were greater in vertebra than tibia for all the frequencies tested. At 52 Hz, bone responses were mainly seen in L2 vertebral body and were characterized by trabecular reorganization and stimulated mineral apposition rate (MAR) without any bone volume alteration. At 90 Hz, axial and appendicular skeletons were affected as were the cortical and trabecular compartments. Cortical thickness increased in femur diaphysis (17%) along with decreased porosity; trabecular bone volume increased at distal femur metaphysis (23%) and even more at L2 vertebral body (32%), along with decreased SMI and increased trabecular connectivity. Trabecular thickness increased at the tibia proximal metaphysis. Bone cellular activities indicated a greater bone formation rate, which was more pronounced at vertebra (300%) than at long bone (33%). Active bone resorption surfaces were unaffected. At 8 Hz, however, hyperosteoidosis with reduced MAR along with increased resorption surfaces occurred in the tibia; hyperosteoidosis and trend towards decreased MAR was also seen in L2 vertebra. Trabecular bone mineral density was decreased at femur and tibia. Thus the most favorable regimen is 90 Hz, while deleterious effects were seen at 8 Hz. We concluded that the skeleton is frequency-scalable, thus highlighting the importance of WBV regimen conditions and suggesting that cautions are required for frequencies less than 10 Hz, at least in rats. Copyright © 2013 Elsevier Inc. All rights reserved.

Improved bone metabolism in female elite athletes after vitamin K supplementation.

PubMed

Craciun, A M; Wolf, J; Knapen, M H; Brouns, F; Vermeer, C

1998-10-01

In female elite athletes strenuous exercise may result in hypoestrogenism and amenorrhoea. As a consequence a low peak bone mass and rapid bone loss are often seen in relatively young athletes. In postmenopausal women, increased intake of vitamin K may result in an increase of serum markers for bone formation, a decrease of urinary markers for bone resorption, and a decrease in urinary calcium loss. In the present paper we report an intervention study among eight female athletes, four of whom had been amenorrhoeic for more than one year, whereas the others had been using oral contraceptives. All participants received vitamin K supplementation (10 mg/day) during one month, and various bone markers were measured before and after treatment. At baseline the athletes not using oral contraceptives were biochemically vitamin K-deficient as deduced from the calcium binding capacity of the circulating bone protein osteocalcin. In all subjects increased vitamin K was associated with an increased calcium-binding capacity of osteocalcin. In the low-estrogen group vitamin K supplementation induced a 15-20% increase of bone formation markers and a parallel 20-25% decrease of bone resorption markers. This shift is suggestive for an improved balance between bone formation and resorption.

Primary stability, insertion torque and bone density of cylindric implant ad modum Branemark: is there a relationship? An in vitro study.

PubMed

Trisi, Paolo; De Benedittis, Simona; Perfetti, Giorgio; Berardi, Davide

2011-05-01

Protocols of immediate loading have been reported in several studies. It has also been demonstrated that the cause of failure of immediate loaded implants is due to the micromotion on the bone-implant interface induced by immediate loading. There should be a minimum gap between the implant and the peri-implant bone, without micromotions occurring above a definite threshold risk as they induce bone resorption and fibrosis around the implant. Measurement of the torque necessary to insert an implant in the bone is a parameter for measuring initial stability. The higher the implant insertion torque, the higher the initial stability attained. The aim of this study was to evaluate in vitro the correlation between the micromotion of cylindric screw implants ad modum Branemark and the insertion torque in bone of different densities. The test was carried out on 2 × 2 cm samples of fresh bovine bone of three different densities: hard (H), medium (M) and soft (S). One hundred and fifty hexa implants ad modum Branemark were used, 3.75 mm in diameter and 9 mm long. To screw in the implants, a customized manual key was used, controlled digitally to evaluate the peak insertion torques. Ten implants were prepared for each torque (20, 35, 45, 70 and 100 N/cm). The bone sample was then fixed on a loading device, which allowed evaluating the micromotion. On each sample, we applied a 25 N horizontal force. The results indicate that the peak insertion torque and the implant micromotion are statistically correlated, and statistically significant differences in H and M bone were found compared with S bone. In S bone, we noted a micromotion significantly higher than the risk threshold, and it was not possible to reach peak insertion torque above 35 N/cm. In H and M bone, the micromotion is below the threshold of all insertion torques. Increasing the peak insertion torque, we can reduce the extent of the micromotion between the implant and the bone when submitted to lateral forces in vitro. In soft bone, the micromotion was always high; hence, immediate loading of implants in low-density bone should be evaluated with care. © 2010 John Wiley & Sons A/S.

Bone density in the obese child - clinical considerations and diagnostic challenges

PubMed Central

Kelley, Jennifer; Crabtree, Nicola; Zemel, Babette S.

2017-01-01

The prevalence of obesity in children has reached epidemic proportions. Concern about bone health in obese children, in part, derives from the potentially increased fracture risk associated with obesity. Additional risk factors that affect bone mineral accretion, may also contribute to obesity, such as low physical activity and nutritional factors. Consequences of obesity, such as inflammation, insulin resistance and non-alcoholic fatty liver disease, may also affect bone mineral acquisition, especially during the adolescent years when rapid increases in bone contribute to attaining peak bone mass. Further, numerous pediatric health conditions are associated with excess adiposity, altered body composition or endocrine disturbances that can affect bone accretion. Thus, there is a multitude of reasons for considering clinical assessment of bone health in an obese child. Multiple diagnostic challenges affect the measurement of bone density and its interpretation. These include greater precision error, difficulty in positioning, and the effects of increased lean and fat tissue on bone health outcomes. Future research is required to address these issues to improve bone health assessment in obese children. PMID:28105511

Implant-bone interface stress distribution in immediately loaded implants of different diameters: a three-dimensional finite element analysis.

PubMed

Ding, Xi; Zhu, Xing-Hao; Liao, Sheng-Hui; Zhang, Xiu-Hua; Chen, Hong

2009-07-01

To establish a 3D finite element model of a mandible with dental implants for immediate loading and to analyze stress distribution in bone around implants of different diameters. Three mandible models, embedded with thread implants (ITI, Straumann, Switzerland) with diameters of 3.3, 4.1, and 4.8 mm, respectively, were developed using CT scanning and self-developed Universal Surgical Integration System software. The von Mises stress and strain of the implant-bone interface were calculated with the ANSYS software when implants were loaded with 150 N vertical or buccolingual forces. When the implants were loaded with vertical force, the von Mises stress concentrated on the mesial and distal surfaces of cortical bone around the neck of implants, with peak values of 25.0, 17.6 and 11.6 MPa for 3.3, 4.1, and 4.8 mm diameters, respectively, while the maximum strains (5854, 4903, 4344 muepsilon) were located on the buccal cancellous bone around the implant bottom and threads of implants. The stress and strain were significantly lower (p < 0.05) with the increased diameter of implant. When the implants were loaded with buccolingual force, the peak von Mises stress values occurred on the buccal surface of cortical bone around the implant neck, with values of 131.1, 78.7, and 68.1 MPa for 3.3, 4.1, and 4.8 mm diameters, respectively, while the maximum strains occurred on the buccal surface of cancellous bone adjacent to the implant neck, with peak values of 14,218, 12,706, and 11,504 microm, respectively. The stress of the 4.1-mm diameter implants was significantly lower (p < 0.05) than those of 3.3-mm diameter implants, but not statistically different from that of the 4.8 mm implant. With an increase of implant diameter, stress and strain on the implant-bone interfaces significantly decreased, especially when the diameter increased from 3.3 to 4.1 mm. It appears that dental implants of 10 mm in length for immediate loading should be at least 4.1 mm in diameter, and uniaxial loading to dental implants should be avoided or minimized.

Vitamin D status in young women and its relationship to body fat, final height and peak bone mass

USDA-ARS?s Scientific Manuscript database

Vitamin D insufficiency has now reached epidemic proportion and has been linked to low bone mineral density (BMD), increased risk of fracture and obesity in adults. However, this relationship has not been well characterized in adolescents and young adults. We examined the relationship between seru...

Vitamin D Status and Its Relationship to Body Fat, Final Height, and Peak Bone Mass in Young Women

USDA-ARS?s Scientific Manuscript database

Vitamin D insufficiency has now reached epidemic proportion and has been linked to low bone mineral density (BMD), increased risk of fracture and obesity in adults. However, this relationship has not been well characterized in adolescents and young adults. We examined the relationship between seru...

Strategies to reverse bone loss in women with functional hypothalamic amenorrhea: a systematic review of the literature.

PubMed

Vescovi, J D; Jamal, S A; De Souza, M J

2008-04-01

Functional hypothalamic amenorrhea (FHA) impairs the attainment of peak bone mass and as such can increase the risk of fractures later in life. To document available treatment strategies, we conducted a systematic review of the literature. We report that hormonal therapies have limited effectiveness in increasing bone mass, whereas increased caloric intake resulting in weight gain and/or resumption of menses is an essential strategy for restoring bone mass in women with FHA. Women with functional hypothalamic amenorrhea (FHA) may not achieve peak bone mass (PBM), which increases the risk of stress fractures, and may increase the risk of osteoporotic fractures in later life. To identify effective treatment strategies for women with FHA, we conducted a systematic review of the literature. We included randomized controlled trials (RCTs), cross-sectional studies, and case studies that reported on the effects of pharmacological and non-pharmacological interventions on bone mineral density (BMD) or bone turnover in women with FHA. Most published studies (n=26) were designed to treat the hormonal abnormalities observed in women with FHA (such as low estrogen, leptin, insulin-like growth factor-1, and DHEA); however none of these treatments demonstrated consistent improvements in BMD. Therapies containing an estrogen given for 8-24 months resulted in variable improvements (1.0-19.0%) in BMD, but failed to restore bone mass to that of age-matched controls. Three studies reported on the use of bisphosphonates (3-12 months) in anorexic women, which appear to have limited effectiveness to improve BMD compared to nutritional treatments. Another three investigations showed no improvements in BMD after androgen therapy (DHEA and testosterone) in anorexic women. In contrast, reports (n=9) describing an increase in caloric intake that results in weight gain and/or the resumption of menses reported a 1.1-16.9% increase in BMD concomitant with an improvement in bone formation and reduction in bone resorption markers. Our literature review indicates that the most successful, and indeed essential strategy for improving BMD in women with FHA is to increase caloric intake such that body mass is increased and there is a resumption of menses. Further long-term studies to determine the persistence of this effect and to determine the effects of this and other strategies on fracture risk are needed.

Better Bones Buddies: An Osteoporosis Prevention Program

ERIC Educational Resources Information Center

Schrader, Susan L.; Blue, Rebecca; Horner, Arlene

2005-01-01

Although osteoporosis typically surfaces in later life, peak bone mass attained before age 20 is a key factor in its prevention. However, most American children's diets lack sufficient calcium during the critical growth periods of preadolescence and adolescence to achieve peak bone mass. "Better Bones (BB) Buddies" is an educational…

The role of the collaborative functions of the composite structure of organic and inorganic constituents and their influence on the electrical properties of human bone.

PubMed

Kohata, Kazuhiro; Itoh, Soichiro; Horiuchi, Naohiro; Yoshioka, Taro; Yamashita, Kimihiro

2016-08-12

The electrical potential, which is generated in bone by collagen displacement, has been well documented. However, the role of mineral crystals in bone piezoelectricity has not yet been elucidated. We examined the mechanism that the composite structure of organic and inorganic constituents and their collaborative functions play an important role in the electrical properties of human bone. The electrical potential and bone structure were evaluated using thermally stimulated depolarized current (TSDC) and micro computed tomography, respectively. After electrical polarization of bone specimens, the stored electrical charge was calculated using TSDC measurements. The CO3/PO4 peak ratio was calculated using attenuated total reflection to compare the content of carbonate ion in the bone specimens. The TSDC curve contained 3 peaks at 100, 300 and 500°C, which were classified into 4 patterns. The CO3/PO4 peak ratio positively correlated with the stored charges at approximately 300°C in the polarized bone. There was a positive correlation between the stored bone charge and the bone mineral density only. It is suggested that the peak at 300°C is attributed to carbonate apatite and the total bone mass of human bone, not the three-dimensional structure, affects the stored charge.

In vivo cyclic compression causes cartilage degeneration and subchondral bone changes in mouse tibiae.

PubMed

Ko, Frank C; Dragomir, Cecilia; Plumb, Darren A; Goldring, Steven R; Wright, Timothy M; Goldring, Mary B; van der Meulen, Marjolein C H

2013-06-01

Alterations in the mechanical loading environment in joints may have both beneficial and detrimental effects on articular cartilage and subchondral bone, and may subsequently influence the development of osteoarthritis (OA). Using an in vivo tibial loading model, the aim of this study was to investigate the adaptive responses of cartilage and bone to mechanical loading and to assess the influence of load level and duration. Cyclic compression at peak loads of 4.5N and 9.0N was applied to the left tibial knee joint of adult (26-week-old) C57BL/6 male mice for 1, 2, and 6 weeks. Only 9.0N loading was utilized in young (10-week-old) mice. Changes in articular cartilage and subchondral bone were analyzed by histology and micro-computed tomography. Mechanical loading promoted cartilage damage in both age groups of mice, and the severity of joint damage increased with longer duration of loading. Metaphyseal bone mass increased with loading in young mice, but not in adult mice, whereas epiphyseal cancellous bone mass decreased with loading in both young and adult mice. In both age groups, articular cartilage thickness decreased, and subchondral cortical bone thickness increased in the posterior tibial plateau. Mice in both age groups developed periarticular osteophytes at the tibial plateau in response to the 9.0N load, but no osteophyte formation occurred in adult mice subjected to 4.5N peak loading. This noninvasive loading model permits dissection of temporal and topographic changes in cartilage and bone and will enable investigation of the efficacy of treatment interventions targeting joint biomechanics or biologic events that promote OA onset and progression. Copyright © 2013 by the American College of Rheumatology.

In vivo cyclic compression causes cartilage degeneration and subchondral bone changes in mouse tibiae

PubMed Central

Ko, Frank C.; Dragomir, Cecilia; Plumb, Darren A.; Goldring, Steven R.; Wright, Timothy M.; Goldring, Mary B.; van der Meulen, Marjolein C.H.

2013-01-01

Objectives Alterations in the mechanical loading environment in joints may have both beneficial and detrimental effects on articular cartilage and subchondral bone and subsequently influence the development of osteoarthritis (OA). We used an in vivo tibial loading model to investigate the adaptive responses of cartilage and bone to mechanical loading and to assess the influence of load level and duration. Methods We applied cyclic compression of 4.5 and 9.0N peak loads to the left tibia via the knee joint of adult (26-week-old) C57Bl/6 male mice for 1, 2, and 6 weeks. Only 9.0N loading was utilized in young (10-week-old) mice. The changes in articular cartilage and subchondral bone were analyzed by histology and microcomputed tomography. Results Loading promoted cartilage damage in both age groups, with increased damage severity dependent upon the duration of loading. Metaphyseal bone mass increased in the young mice, but not in the adult mice, whereas epiphyseal cancellous bone mass decreased with loading in both young and adult mice. Articular cartilage thickness decreased, and subchondral cortical bone thickness increased in the posterior tibial plateau in both age groups. Both age groups developed periarticular osteophytes at the tibial plateau in response to the 9.0N load, but no osteophyte formation occurred in adult mice subjected to 4.5N peak loading. Conclusion This non-invasive loading model permits dissection of temporal and topographical changes in cartilage and bone and will enable investigation of the efficacy of treatment interventions targeting joint biomechanics or biological events that promote OA onset and progression. PMID:23436303

Anorexia Nervosa and Bone

PubMed Central

Misra, Madhusmita; Klibanski, Anne

2014-01-01

Anorexia nervosa (AN) is a condition of severe low weight that is associated with low bone mass, impaired bone structure and reduced bone strength, all of which contribute to increased fracture risk., Adolescents with AN have decreased rates of bone accrual compared with normal-weight controls, raising addition concerns of suboptimal peak bone mass and future bone health in this age group. Changes in lean mass and compartmental fat depots, hormonal alterations secondary to nutritional factors contribute to impaired bone metabolism in AN. The best strategy to improve bone density is to regain weight and menstrual function. Oral estrogen-progesterone combinations are not effective in increasing bone density in adults or adolescents with AN, and transdermal testosterone replacement is not effective in increasing bone density in adult women with AN. However, physiologic estrogen replacement as transdermal estradiol with cyclic progesterone does increase bone accrual rates in adolescents with AN to approximate that in normal-weight controls, leading to a maintenance of bone density Z-scores. A recent study has shown that risedronate increases bone density at the spine and hip in adult women with AN. However, bisphosphonates should be used with great caution in women of reproductive age given their long half-life and potential for teratogenicity, and should be considered only in patients with low bone density and clinically significant fractures when non-pharmacological therapies for weight gain are ineffective. Further studies are necessary to determine the best therapeutic strategies for low bone density in AN. PMID:24898127

Parallels between Nutrition and Physical Activity: Research Questions in Development of Peak Bone Mass

ERIC Educational Resources Information Center

Weaver, Connie M.

2015-01-01

Lifestyle choices are attributed to 40% to 60% of adult peak bone mass. The National Osteoporosis Foundation (NOF) sought to update its 2000 consensus statement on peak bone mass and partnered with the American Society for Nutrition, which, in turn, charged a 9-member writing committee with using a systematic review approach to update the previous…

Bone health in anorexia nervosa

PubMed Central

Misra, Madhusmita; Klibanski, Anne

2013-01-01

Purpose of review Anorexia nervosa is associated with low bone mineral density (BMD), concerning for an increased risk of fractures, and decreased bone accrual in adolescents, concerning for suboptimal peak bone mass. This review discusses causes of impaired bone health in anorexia nervosa and potential therapeutic strategies. Recent findings Low BMD in anorexia nervosa is consequent to decreased lean mass, hypogonadism, low insulin-like growth factor-1 (IGF-1), relative hypercortisolemia and alterations in hormones impacted by energy availability. Weight gain causes some improvement in bone accrual, but not to the extent observed in controls, and vitamin D supplementation does not increase BMD. Oral estrogen is not effective in increasing BMD, likely from IGF-1 suppressive effects. In contrast, transdermal estrogen replacement is effective in increasing bone accrual in adolescents with anorexia nervosa, although not to the extent seen in controls. Recombinant human IGF-1 increases bone formation in adolescents, and with oral estrogen increases BMD in adults with anorexia nervosa. Bisphosphonates increase BMD in adults, but not in adolescents, and should be used cautiously given their long half-life. Summary Further investigation is necessary to explore therapies for low BMD in anorexia nervosa. Weight gain is to be encouraged. Transdermal estrogen in adolescents, and bisphosphonates in adults, have a potential therapeutic role. PMID:21897220

Peak-bone-mass development in young adults: effects of study program related levels of occupational and leisure time physical activity and exercise. A prospective 5-year study.

PubMed

Kemmler, W; Bebenek, M; von Stengel, S; Bauer, J

2015-02-01

Young adulthood is characterized by profound life-style changes. This study suggests that reduction of sport or exercise, induced by alteration of the occupational situation, negatively impacts generation/maintenance of peak bone mass. In order to compensate occupational-related reductions of physical activity, workplace exercise programs will be helpful. Only few studies have determined the effect of physical activity or physical exercise on bone mineral density (BMD) in the period of late skeletal maturation, i.e. around peak bone mass. The aim of this article was to determine the long-term effect of different levels of physical activity and exercise directly and indirectly derived by occupation during young adulthood. Sixty-one male and female dental students (DES) and 53 male and female sport students (SPS) 21±2 years old were accompanied over the course (4.8±0.5 years) of their study program. BMD at the lumbar spine (LS), hip, and whole body (WB) were determined using dual-energy X-ray absorptiometry. Parameters of physical activity increased non-significantly in both groups with no relevant differences between the groups. Indices of exercise, however, increased significantly in the SPS group while a significant decrease was assessed for the DES group. Independent of gender, BMD of the SPS increased significantly (p≤0.007) at all skeletal sites (LS, 2.4±3.9%; hip, 1.6±3.5%; WB, 1.8±2.8%) while BMD of the DES remained unchanged at LS (-0.6±4.4%, p=0.432) and WB (0.5±1.9%, p=0.092) but decreased significantly at the hip (-1.9±4.3%, p=0.010). BMD-changes at LS, hip, and WB differ significantly between SPS and DES (p≤0.017). Results remained unchanged after adjusting for baseline BMD-values that differed (p=0.030 to p=0.082) in favor of the SPS group. Changes of exercise levels directly or indirectly caused by occupational factors during young adulthood significantly affected generation and/or maintenance of peak bone mass. Compensatory exercise is thus highly relevant for bone health of young adults.

Bone mineral as an electrical energy reservoir.

PubMed

Nakamura, Miho; Hiratai, Rumi; Yamashita, Kimihiro

2012-05-01

Mechanical stress in bone induces an electrical potential generated by piezoelectricity arising from displacement of collagen fibrils. Where and for how long the potential is stored in bone; however, are still poorly understood. We investigated the electrical properties of collagen fibrils and apatite minerals and found that bone, when polarized electrically by applying an external voltage, depolarizes by two mechanisms. Plots of thermally stimulated depolarization current show two significant peaks: one at 100°C, attributed to collagen fibrils because decalcified bone exhibits depolarization peak at 100°C, and the other at 500°C, attributed to apatite minerals because calcined bone exhibits depolarization peak at 500°C and has activation energy similar to that for synthesized apatite. The crystallographic c-axis orientation of calcined bone depends on the direction in which the bone is cut, either transverse or longitudinal, and strongly affects the polarization efficacy. Copyright © 2012 Wiley Periodicals, Inc.

Mechanical torque measurement in the proximal femur correlates to failure load and bone mineral density ex vivo.

PubMed

Grote, Stefan; Noeldeke, Tatjana; Blauth, Michael; Mutschler, Wolf; Bürklein, Dominik

2013-06-07

Knowledge of local bone quality is essential for surgeons to determine operation techniques. A device for intraoperative measurement of local bone quality has been developed by the AO-Research Foundation (Densi - Probe®). We used this device to experimentally measure peak breakaway torque of trabecular bone in the proximal femur and correlated this with local bone mineral density (BMD) and failure load. Bone mineral density of 160 cadaver femurs was measured by ex situ dualenergy X-ray absorptiometry. The failure load of all femurs was analyzed by side-impact analysis. Femur fractures were fixed and mechanical peak torque was measured with the DensiProbe® device. Correlation was calculated whereas correlation coefficient and significance was calculated by Fisher's Ztransformation. Moreover, linear regression analysis was carried out. The unpaired Student's t-test was used to assess the significance of differences. The Ward triangle region had the lowest BMD with 0.511 g/cm(2) (±0.17 g/cm(2)), followed by the upper neck region with 0.546 g/cm(2) (±0.16 g/cm(2)), trochanteric region with 0.685 g/cm(2) (±0.19 g/cm(2)) and the femoral neck with 0.813 g/cm(2) (±0.2 g/cm(2)). Peak torque of DensiProbe® in the femoral head was 3.48 Nm (±2.34 Nm). Load to failure was 4050.2 N (±1586.7 N). The highest correlation of peak torque measured by Densi Probe® and load to failure was found in the femoral neck (r=0.64, P<0.001). The overall correlation of mechanical peak torque with T-score was r=0.60 (P<0.001). A correlation was found between mechanical peak torque, load to failure of bone and BMD in vitro. Trabecular strength of bone and bone mineral density are different aspects of bone strength, but a correlation was found between them. Mechanical peak torque as measured may contribute additional information about bone strength, especially in the perioperative testing.

Effects of Ankle Arthrodesis on Biomechanical Performance of the Entire Foot

PubMed Central

Wang, Yan; Li, Zengyong; Wong, Duo Wai-Chi; Zhang, Ming

2015-01-01

Background/Methodology Ankle arthrodesis is one popular surgical treatment for ankle arthritis, chronic instability, and degenerative deformity. However, complications such as foot pain, joint arthritis, and bone fracture may cause patients to suffer other problems. Understanding the internal biomechanics of the foot is critical for assessing the effectiveness of ankle arthrodesis and provides a baseline for the surgical plan. This study aimed to understand the biomechanical effects of ankle arthrodesis on the entire foot and ankle using finite element analyses. A three-dimensional finite element model of the foot and ankle, involving 28 bones, 103 ligaments, the plantar fascia, major muscle groups, and encapsulated soft tissue, was developed and validated. The biomechanical performances of a normal foot and a foot with ankle arthrodesis were compared at three gait instants, first-peak, mid-stance, and second-peak. Principal Findings/Conclusions Changes in plantar pressure distribution, joint contact pressure and forces, von Mises stress on bone and foot deformation were predicted. Compared with those in the normal foot, the peak plantar pressure was increased and the center of pressure moved anteriorly in the foot with ankle arthrodesis. The talonavicular joint and joints of the first to third rays in the hind- and mid-foot bore the majority of the loading and sustained substantially increased loading after ankle arthrodesis. An average contact pressure of 2.14 MPa was predicted at the talonavicular joint after surgery and the maximum variation was shown to be 80% in joints of the first ray. The contact force and pressure of the subtalar joint decreased after surgery, indicating that arthritis at this joint was not necessarily a consequence of ankle arthrodesis but rather a progression of pre-existing degenerative changes. Von Mises stress in the second and third metatarsal bones at the second-peak instant increased to 52 MPa and 34 MPa, respectively, after surgery. These variations can provide indications for outcome assessment of ankle arthrodesis surgery. PMID:26222188

Effects of Ankle Arthrodesis on Biomechanical Performance of the Entire Foot.

PubMed

Wang, Yan; Li, Zengyong; Wong, Duo Wai-Chi; Zhang, Ming

2015-01-01

Ankle arthrodesis is one popular surgical treatment for ankle arthritis, chronic instability, and degenerative deformity. However, complications such as foot pain, joint arthritis, and bone fracture may cause patients to suffer other problems. Understanding the internal biomechanics of the foot is critical for assessing the effectiveness of ankle arthrodesis and provides a baseline for the surgical plan. This study aimed to understand the biomechanical effects of ankle arthrodesis on the entire foot and ankle using finite element analyses. A three-dimensional finite element model of the foot and ankle, involving 28 bones, 103 ligaments, the plantar fascia, major muscle groups, and encapsulated soft tissue, was developed and validated. The biomechanical performances of a normal foot and a foot with ankle arthrodesis were compared at three gait instants, first-peak, mid-stance, and second-peak. Changes in plantar pressure distribution, joint contact pressure and forces, von Mises stress on bone and foot deformation were predicted. Compared with those in the normal foot, the peak plantar pressure was increased and the center of pressure moved anteriorly in the foot with ankle arthrodesis. The talonavicular joint and joints of the first to third rays in the hind- and mid-foot bore the majority of the loading and sustained substantially increased loading after ankle arthrodesis. An average contact pressure of 2.14 MPa was predicted at the talonavicular joint after surgery and the maximum variation was shown to be 80% in joints of the first ray. The contact force and pressure of the subtalar joint decreased after surgery, indicating that arthritis at this joint was not necessarily a consequence of ankle arthrodesis but rather a progression of pre-existing degenerative changes. Von Mises stress in the second and third metatarsal bones at the second-peak instant increased to 52 MPa and 34 MPa, respectively, after surgery. These variations can provide indications for outcome assessment of ankle arthrodesis surgery.

Effect of whole body vibration training on quadriceps strength, bone mineral density, and functional capacity in children with hemophilia: a randomized clinical trial.

PubMed

El-Shamy, S

2017-06-01

The objective was to evaluate the effects of whole body vibration training on quadriceps strength, bone mineral density, and functional capacity in children with hemophilia. Thirty children with hemophilia with age ranging from 9 to 13 years were selected and randomly assigned to either the study group that received whole body vibration training (30-40 Hz, 2-4 mm of peak-to-peak vertical plate displacement for 15 minutes/day, 3 days/week/ 12 weeks) plus the conventional physical therapy program or the control group that performed a conventional physical therapy program only. Outcomes included quadriceps strength, bone mineral density, and the functional capacity. Children in the study group showed a significant improvement in all outcomes compared with the control group. The quadriceps peak torque after treatment was 70.26 and 56.46 Nm for the study and control group, respectively (p⟨0.001). The lumbar spine bone mineral density after treatment was 0.85 and 0.72 g/cm 2 for the study and control group, respectively (p⟨0.001). The functional capacity after treatment was 325 and 290 m for the study and control group, respectively (p=0.006). Whole body vibration training is an effective modality in increasing quadriceps strength, bone mineral density, and functional capacity in children with hemophilia.

Effect of whole body vibration training on quadriceps strength, bone mineral density, and functional capacity in children with hemophilia: a randomized clinical trial

PubMed Central

El-Shamy, S.

2017-01-01

Objectives: The objective was to evaluate the effects of whole body vibration training on quadriceps strength, bone mineral density, and functional capacity in children with hemophilia. Methods: Thirty children with hemophilia with age ranging from 9 to 13 years were selected and randomly assigned to either the study group that received whole body vibration training (30-40 Hz, 2-4 mm of peak-to-peak vertical plate displacement for 15 minutes/day, 3 days/week/ 12 weeks) plus the conventional physical therapy program or the control group that performed a conventional physical therapy program only. Outcomes included quadriceps strength, bone mineral density, and the functional capacity. Results: Children in the study group showed a significant improvement in all outcomes compared with the control group. The quadriceps peak torque after treatment was 70.26 and 56.46 Nm for the study and control group, respectively (p<0.001). The lumbar spine bone mineral density after treatment was 0.85 and 0.72 g/cm2 for the study and control group, respectively (p<0.001). The functional capacity after treatment was 325 and 290 m for the study and control group, respectively (p=0.006). Conclusions: Whole body vibration training is an effective modality in increasing quadriceps strength, bone mineral density, and functional capacity in children with hemophilia. PMID:28574408

Gamma Radiation Induces Micronucleated Reticulocytes in 3-D Bone Marrow Bioreactors in Vitro

PubMed Central

Sun, Hongliang; Dertinger, Stephen D.; Hyrien, Ollivier; David Wu, J. H.; Chen, Yuhchyau

2009-01-01

Radiation injury to the bone marrow is potentially lethal due to the potent DNA-damaging effects on cells of the hematopoietic system, including bone marrow stem cell, progenitor, and the precursor cell populations. Investigation of radiation genotoxic effects on bone marrow progenitor/precursor cells has been challenged by the lack of optimal in vitro surrogate organ culture systems, and the overall difficulty to sustain lineage-specific proliferation and differentiation of hematopoiesis in vitro. We report the investigation of radiation genotoxic effects in bone marrow cultures of C57Bl/6 mice established in 3-D bioreactors, which sustain long-term bone marrow cultures. For these studies, genotoxicity is measured by the induction of micronucleated reticulocytes (MN-RET). The kinetics and dose-response relationship of MN-RET induction in response to gamma-radiation of bioreactor-maintained bone marrow cultures are presented. Our data showed that 3-D long-term bone marrow cultures had sustained erythropoiesis capable of generating reticulocytes up to 8 weeks. The peak time-interval of viable cell output and percentage of reticulocytes increased steadily and reached the initial peak between the 14th to 21st days after inoculations. This was followed by a rebound or staying relatively constant until week 8. The percentage of MN-RET reached the maximum between 24 and 32 hours post 1 Gy gamma-ray. There was a near linear MN-RET induction by gamma radiation from 0 Gy to 1.0 Gy, followed by an attenuated increase to 1.5 – 2.0 Gy. The MN-RET response showed a downtrend beyond 2 Gy. Our data suggest that bone marrow culture in the 3-D bioreactor may be a useful organ culture system for the investigation of radiation genotoxic effect in vitro. PMID:19786117

[Fetal programming and the etiology of osteoporosis].

PubMed

Pieńkowski, Wojciech; Wolski, Hubert; Drews, Krzysztof; Seremak-Mrozikiewicz, Agnieszka

2015-08-01

Osteoporosis is a multifactorial skeletal disorder characterized by low bone mass and microarchitectural deterioration of bone tissue, resulting in increased risk of fracture. Peak bone mass is an important predictor of later risk of osteoporosis. Epidemiological studies revealed that the risk of osteoporosis might be modified by exposure to environmental factors during intrauterine life and early postnatal period. This review summarizes the influence of fetal programming on the development of osteoporosis based on the epidemiological studies and potential mechanisms of epigenetic regulation of gene expression.

The ever-expanding conundrum of primary osteoporosis: aetiopathogenesis, diagnosis, and treatment.

PubMed

Stagi, Stefano; Cavalli, Loredana; Seminara, Salvatore; de Martino, Maurizio; Brandi, Maria Luisa

2014-06-07

In recent years, as knowledge regarding the etiopathogenetic mechanisms of bone involvement characterizing many diseases has increased and diagnostic techniques evaluating bone health have progressively improved, the problem of low bone mass/quality in children and adolescents has attracted more and more attention, and the body evidence that there are groups of children who may be at risk of osteoporosis has grown. This interest is linked to an increased understanding that a higher peak bone mass (PBM) may be one of the most important determinants affecting the age of onset of osteoporosis in adulthood. This review provides an updated picture of bone pathophysiology and characteristics in children and adolescents with paediatric osteoporosis, taking into account the major causes of primary osteoporosis (PO) and evaluating the major aspects of bone densitometry in these patients. Finally, some options for the treatment of PO will be briefly discussed.

The ever-expanding conundrum of primary osteoporosis: aetiopathogenesis, diagnosis, and treatment

PubMed Central

2014-01-01

In recent years, as knowledge regarding the etiopathogenetic mechanisms of bone involvement characterizing many diseases has increased and diagnostic techniques evaluating bone health have progressively improved, the problem of low bone mass/quality in children and adolescents has attracted more and more attention, and the body evidence that there are groups of children who may be at risk of osteoporosis has grown. This interest is linked to an increased understanding that a higher peak bone mass (PBM) may be one of the most important determinants affecting the age of onset of osteoporosis in adulthood. This review provides an updated picture of bone pathophysiology and characteristics in children and adolescents with paediatric osteoporosis, taking into account the major causes of primary osteoporosis (PO) and evaluating the major aspects of bone densitometry in these patients. Finally, some options for the treatment of PO will be briefly discussed. PMID:24906390

Early diet and peak bone mass: 20 year follow-up of a randomized trial of early diet in infants born preterm.

PubMed

Fewtrell, Mary S; Williams, Jane E; Singhal, Atul; Murgatroyd, Peter R; Fuller, Nigel; Lucas, Alan

2009-07-01

Preterm infants are at risk of metabolic bone disease due to inadequate mineral intake with unknown consequences for later bone health. To test the hypotheses that (1) early diet programs peak bone mass and bone turnover; (2) human milk has a beneficial effect on these outcomes; (3) preterm subjects have reduced peak bone mass compared to population reference data. 20 year follow-up of 202 subjects (43% male; 24% of survivors) who were born preterm and randomized to: (i) preterm formula versus banked breast milk or (ii) preterm versus term formula; as sole diet or supplement to maternal milk. Outcome measures were (i) anthropometry; (ii) hip, lumbar spine (LS) and whole body (WB) bone mineral content (BMC) and bone area (BA) measured using DXA; (iii) bone turnover markers. Infant dietary randomization group did not influence peak bone mass or turnover. The proportion of human milk in the diet was significantly positively associated with WBBA and BMC. Subjects receiving >90% human milk had significantly higher WBBA (by 3.5%, p=0.01) and BMC (by 4.8%, p=0.03) than those receiving <10%. Compared to population data, subjects had significantly lower height SDS (-0.41 (SD 1.05)), higher BMI SDS (0.31 (1.33)) and lower LSBMD SDS (-0.29 (1.16)); height and bone mass deficits were greatest in those born SGA with birthweight <1250 g (height SDS -0.81 (0.95), LSBMD SDS -0.61 (1.3)). Infant dietary randomization group did not affect peak bone mass or turnover suggesting the observed reduced final height and LS bone mass, most marked in growth restricted subjects with the lowest birthweight, may not be related to sub-optimal early nutrition. The higher WB bone mass associated with human milk intake, despite its low nutrient content, may reflect non-nutritive factors in breast milk. These findings may have implications for later osteoporosis risk and require further investigation.

Peak bone strength is influenced by calcium intake in growing rats.

PubMed

Viguet-Carrin, S; Hoppler, M; Membrez Scalfo, F; Vuichoud, J; Vigo, M; Offord, E A; Ammann, P

2014-11-01

In this study we investigated the effect of supplementing the diet of the growing male rat with different levels of calcium (from low to higher than recommended intakes at constant Ca/P ratio), on multiple factors (bone mass, strength, size, geometry, material properties, turnover) influencing bone strength during the bone accrual period. Rats, age 28days were supplemented for 4weeks with high Ca (1.2%), adequate Ca (0.5%) or low Ca level (0.2%). Bone metabolism and structural parameters were measured. No changes in body weight or food intake were observed among the groups. As anticipated, compared to the adequate Ca intake, low-Ca intake had a detrimental impact on bone growth (33.63 vs. 33.68mm), bone strength (-19.7% for failure load), bone architecture (-58% for BV/TV) and peak bone mass accrual (-29% for BMD) due to the hormonal disruption implied in Ca metabolism. In contrast, novel, surprising results were observed in that higher than adequate Ca intake resulted in improved peak bone strength (106 vs. 184N/mm for the stiffness and 61 vs. 89N for the failure load) and bone material properties (467 vs. 514mPa for tissue hardness) but these effects were not accompanied by changes in bone mass, size, microarchitecture or bone turnover. Hormonal factors, IGF-I and bone modeling were also evaluated. Compared to the adequate level of Ca, IGF-I level was significantly lower in the low-Ca intake group and significantly higher in the high-Ca intake group. No detrimental effects of high Ca were observed on bone modeling (assessed by histomorphometry and bone markers), at least in this short-term intervention. In conclusion, the decrease in failure load in the low calcium group can be explained by the change in bone geometry and bone mass parameters. Thus, improvements in mechanical properties can be explained by the improved quality of intrinsic bone tissue as shown by nanoindentation. These results suggest that supplemental Ca may be beneficial for the attainment of peak bone strength and that multiple factors linked to bone mass and strength should be taken into account when setting dietary levels of adequate mineral intake to support optimal peak bone mass acquisition. Copyright © 2014 Elsevier Inc. All rights reserved.

Modifying landing mat material properties may decrease peak contact forces but increase forefoot forces in gymnastics landings.

PubMed

Mills, Chris; Yeadon, Maurice R; Pain, Matthew T G

2010-09-01

This study investigated how changes in the material properties of a landing mat could minimise ground reaction forces (GRF) and internal loading on a gymnast during landing. A multi-layer model of a gymnastics competition landing mat and a subject-specific seven-link wobbling mass model of a gymnast were developed to address this aim. Landing mat properties (stiffness and damping) were optimised using a Simplex algorithm to minimise GRF and internal loading. The optimisation of the landing mat parameters was characterised by minimal changes to the mat's stiffness (<0.5%) but increased damping (272%) compared to the competition landing mat. Changes to the landing mat resulted in reduced peak vertical and horizontal GRF and reduced bone bending moments in the shank and thigh compared to a matching simulation. Peak bone bending moments within the thigh and shank were reduced by 6% from 321.5 Nm to 302.5Nm and GRF by 12% from 8626 N to 7552 N when compared to a matching simulation. The reduction in these forces may help to reduce the risk of bone fracture injury associated with a single landing and reduce the risk of a chronic injury such as a stress fracture.

The Biomechanical Properties of Pedicle Screw Fixation Combined With Trajectory Bone Cement Augmentation in Osteoporotic Vertebrae.

PubMed

Fan, Haitao T; Zhang, Renjie J; Shen, Cailiang L; Dong, Fulong L; Li, Yong; Song, Peiwen W; Gong, Chen; Wang, Yijin J

2016-03-01

The biomechanics of pedicle screw fixation combined with trajectory cement augmentation with various filling volumes were measured by pull-out, periodic antibending, and compression fatigue tests. To investigate the biomechanical properties of the pedicle screw fixation combined with trajectory bone cement (polymethylmethacrylate) augmentation in osteoporotic vertebrae and to explore the optimum filling volume of the bone cement. Pedicle screw fixation is considered to be the most effective posterior fixation method. The decrease of the bone mineral density apparently increases the fixation failure risk caused by screw loosening and displacement. Trajectory bone cement augmentation has been confirmed to be an effective method to increase the bone intensity and could markedly increase the stability of the fixation interface. Sixteen elderly cadaveric 1-5 lumbar vertebral specimens were diagnosed with osteoporosis. The left and right vertebral pedicles were alternatively randomized for treatment in all groups, with the contralateral pedicles as control. The study groups included: group A (pedicle screw fixation with full trajectory bone cement augmentation), group B (75% filling), group C (50% filling), and group D (25% filling). Finally, the bone cement leakage and dispersion were assessed and the mechanical testing was conducted. The bone cement was well dispersed around the pedicle screw. The augmented bone intensity, pull-out strength, periodic loading times, and compression fatigue performance were markedly higher than those of the control groups. With the increase in trajectory bone cement, the leakage was also increased (P<0.05). The pull-out strength of the pedicle screw was increased with an increase in bone mineral density and trajectory bone cement. It peaked at 75% filling, with the largest power consumption. The optimal filling volume of the bone cement was 75% of the trajectory volume (about 1.03 mL). The use of excessive bone cement did not increase the fixation intensity but increased the risk of leakage.

[Alterations of bone metabolism in children and adolescents with diabetes mellitus type 1].

PubMed

Pater, Agnieszka; Odrowąż-Sypniewska, Grażyna

2011-01-01

Diabetes mellitus type 1 is one of the most common chronic diseases in children and adolescents. The incidence of diabetes mellitus type 1 is increasing rapidly worldwide. Recently, the largest rate of increase is observed in children aged 0-4 years. Chronic hyperglycemia leads to microvascular and macrovascular complications including retinopathy, nephropathy, neuropathy and cardiomyopathy. Pathological changes occur in the bone structure. The lack of diagnosis and treatment of alterations of the bone tIssue metabolism may lead to osteoporosis, which is characterized by much reduced bone mineral density and changes in the microarchitecture of the bone tIssue, which in consequence results in increased susceptibility to fractures. Diabetes mellitus type 1 most often starts before achieving peak bone mass, which constitutes a point of reference for predicting risk of fractures in a later period of life. Mechanisms responsible for loss of the bone tIssue in diabetes of type 1 still remain unexplained. Many research findings indicate the anabolic role of insulin and insulin-like growth factors, mainly IGF-1. The aim of this manuscript is to review recent papers about alterations of bone metabolism in children and adolescents with diabetes mellitus type 1.

The Effects of GATA-1 and NF-E2 Deficiency on Bone Biomechanical, Biochemical, and Mineral Properties

PubMed Central

Kacena, Melissa A.; Gundberg, Caren M.; Kacena, William J.; Landis, William J.; Boskey, Adele L.; Bouxsein, Mary L.; Horowitz, Mark C.

2014-01-01

Mice deficient in GATA-1 or NF-E2, transcription factors required for normal megakaryocyte (MK) development, have increased numbers of MKs, reduced numbers of platelets, and a striking high bone mass phenotype. Here, we show the bone geometry, microarchitecture, biomechanical, biochemical, and mineral properties from these mutant mice. We found that the outer geometry of the mutant bones was similar to controls, but that both mutants had a striking increase in total bone area (up to a 35% increase) and trabecular bone area (up to a 19% increase). Interestingly, only the NF-E2 deficient mice had a significant increase in cortical bone area (21%) and cortical thickness (27%), which is consistent with the increase in bone mineral density (BMD) seen only in the NF-E2 deficient femurs. Both mutant femurs exhibited significant increases in several biomechanical properties including peak load (up to a 32% increase) and stiffness (up to a 13% increase). Importantly, the data also demonstrate differences between the two mutant mice. GATA-1 deficient femurs break in a ductile manner, whereas NF-E2 deficient femurs are brittle in nature. To better understand these differences, we examined the mineral properties of these bones. Although none of the parameters measured were different between the NF-E2 deficient and control mice, an increase in calcium (21%) and an increase in the mineral/matrix ratio (32%) was observed in GATA-1 deficient mice. These findings appear to contradict biomechanical findings, suggesting the need for further research into the mechanisms by which GATA-1 and NF-E2 deficiency alter the material properties of bone. PMID:23359245

Distinct frequency dependent effects of whole-body vibration on non-fractured bone and fracture healing in mice.

PubMed

Wehrle, Esther; Wehner, Tim; Heilmann, Aline; Bindl, Ronny; Claes, Lutz; Jakob, Franz; Amling, Michael; Ignatius, Anita

2014-08-01

Low-magnitude high-frequency vibration (LMHFV) provokes anabolic effects in non-fractured bone; however, in fracture healing, inconsistent results were reported and optimum vibration conditions remain unidentified. Here, we investigated frequency dependent effects of LMHFV on fracture healing. Twelve-week-old, female C57BL/6 mice received a femur osteotomy stabilized using an external fixator. The mice received whole-body vibrations (20 min/day) with 0.3g peak-to-peak acceleration and a frequency of either 35 or 45 Hz. After 10 and 21 days, the osteotomized femurs and intact bones (contra-lateral femurs, lumbar spine) were evaluated using bending-testing, µ-computed tomography, and histomorphometry. In non-fractured trabecular bone, vibration with 35 Hz significantly increased the relative amount of bone (+28%) and the trabecular number (+29%), whereas cortical bone was not influenced. LMHFV with 45 Hz failed to provoke anabolic effects in trabecular or cortical bone. Fracture healing was not significantly influenced by whole-body vibration with 35 Hz, whereas 45 Hz significantly reduced bone formation (-64%) and flexural rigidity (-34%) of the callus. Although the exact mechanisms remain open, our results suggest that small vibration setting changes could considerably influence LMHFV effects on bone formation in remodeling and repair, and even disrupt fracture healing, implicating caution when treating patients with impaired fracture healing. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Role of Collagen and Inorganic Components in Electrical Polarizability of Bone

PubMed Central

HIRATAI, Rumi; NAKAMURA, Miho; YAMASHITA, Kimihiro

2013-01-01

ABSTRACT Hydroxyapatite (HA) has polarization capability and is able to accumulate electrical storage in bone. Experiments were conducted to measure the polarization capability of rabbit femurs. After preparing and polarizing bone samples using 2% KOH treatment (denoted 2% koh), 2% KOH and baking (2% koh+bake) and decalcification (decalcification) as well as untreated bone (untreated), stored charges were quantitatively determined using thermally stimulated depolarization current (TSDC) measurements. In TSDC spectra, untreated and 2% koh samples showed peaks at 100 and 500°C, while 2% koh+bake showed one peak at 580°C and decalcification one peak around 100°C. These evidences indicated that collagen and inorganic components play a major role in polarization of the bone at different temperature conditions. PMID:24141277

Manganese Supplementation in Deer under Balanced Diet Increases Impact Energy and Contents in Minerals of Antler Bone Tissue.

PubMed

Cappelli, Jamil; Garcia, Andrés; Ceacero, Francisco; Gomez, Santiago; Luna, Salvador; Gallego, Laureano; Gambin, Pablo; Landete-Castillejos, Tomás

2015-01-01

Bone ash, collagen, Ca and P composition, are considered the main factors affecting mechanical properties in bones. However, a series of studies in bone and antler have shown that some trace minerals, such as manganese, may play a role whose importance exceeds what may be expected considering their low content. A previous study showed that a reduction in manganese in antlers during a year of late winter frosts led to generalized antler breakage in Spain, which included a reduction of 30% of cortical thickness, 27% reduction in impact energy, and 10% reduction in work to peak force. Starting for this observation, we experimentally studied the effects of manganese supplementation in adults and yearling (yearlings) red deer under a balanced diet. Subjects were 29 deer of different age classes (adult n = 19, yearlings n = 10) that were divided in a manganese injected group (n = 14) and a control group (n = 15). Antler content in ashes and minerals, intrinsic mechanical properties and cross section structure were examined at 4 points along the antler beam. A one way ANOVA (mean per antler) showed that in yearlings, manganese supplementation only increased its content and that of Fe. However, in adults, Mn supplementation increased the mean content per antler of Ca, Na, P, B, Co, Cu, K, Mn, Ni, Se (while Si content was reduced), and impact work but not Young's modulus of elasticity, bending strength or work to peak force. A GLM series on characteristics in the uppermost part examined in the antler, often showing physiological exhaustion and depletion of body stores, showed also a 16% increase in work to peak force in the antlers of the treated group. Thus, manganese supplementation altered mineral composition of antler and improved structure and some mechanical properties despite animals having a balanced diet.

Manganese Supplementation in Deer under Balanced Diet Increases Impact Energy and Contents in Minerals of Antler Bone Tissue

PubMed Central

Cappelli, Jamil; Garcia, Andrés; Ceacero, Francisco; Gomez, Santiago; Luna, Salvador; Gallego, Laureano; Gambin, Pablo; Landete-Castillejos, Tomás

2015-01-01

Bone ash, collagen, Ca and P composition, are considered the main factors affecting mechanical properties in bones. However, a series of studies in bone and antler have shown that some trace minerals, such as manganese, may play a role whose importance exceeds what may be expected considering their low content. A previous study showed that a reduction in manganese in antlers during a year of late winter frosts led to generalized antler breakage in Spain, which included a reduction of 30% of cortical thickness, 27% reduction in impact energy, and 10% reduction in work to peak force. Starting for this observation, we experimentally studied the effects of manganese supplementation in adults and yearling (yearlings) red deer under a balanced diet. Subjects were 29 deer of different age classes (adult n = 19, yearlings n = 10) that were divided in a manganese injected group (n = 14) and a control group (n = 15). Antler content in ashes and minerals, intrinsic mechanical properties and cross section structure were examined at 4 points along the antler beam. A one way ANOVA (mean per antler) showed that in yearlings, manganese supplementation only increased its content and that of Fe. However, in adults, Mn supplementation increased the mean content per antler of Ca, Na, P, B, Co, Cu, K, Mn, Ni, Se (while Si content was reduced), and impact work but not Young’s modulus of elasticity, bending strength or work to peak force. A GLM series on characteristics in the uppermost part examined in the antler, often showing physiological exhaustion and depletion of body stores, showed also a 16% increase in work to peak force in the antlers of the treated group. Thus, manganese supplementation altered mineral composition of antler and improved structure and some mechanical properties despite animals having a balanced diet. PMID:26177083

Pharmacologic Calcitriol Inhibits Osteoclast Lineage Commitment via the BMP-Smad1 and IκB-NF-κB Pathways.

PubMed

Li, Anna; Cong, Qian; Xia, Xuechun; Leong, Wai Fook; Yeh, James; Miao, Dengshun; Mishina, Yuji; Liu, Huijuan; Li, Baojie

2017-07-01

Vitamin D is involved in a range of physiological processes and its active form and analogs have been used to treat diseases such as osteoporosis. Yet how vitamin D executes its function remains unsolved. Here we show that the active form of vitamin D calcitriol increases the peak bone mass in mice by inhibiting osteoclastogenesis and bone resorption. Although calcitriol modestly promoted osteoclast maturation, it strongly inhibited osteoclast lineage commitment from its progenitor monocyte by increasing Smad1 transcription via the vitamin D receptor and enhancing BMP-Smad1 activation, which in turn led to increased IκBα expression and decreased NF-κB activation and NFATc1 expression, with IκBα being a Smad1 target gene. Inhibition of BMP type I receptor or ablation of Bmpr1a in monocytes alleviated the inhibitory effects of calcitriol on osteoclast commitment, bone resorption, and bone mass augmentation. These findings uncover crosstalk between the BMP-Smad1 and RANKL-NF-κB pathways during osteoclastogenesis that underlies the action of active vitamin D on bone health. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

Invited review: Dairy intake and bone health: a viewpoint from the state of the art.

PubMed

Caroli, A; Poli, A; Ricotta, D; Banfi, G; Cocchi, D

2011-11-01

The aim of this review was to focus on the complex relationships between milk and dairy products intake and bone health, with particular emphasis on osteoporosis. The literature was extensively examined to provide an objective overview of the most significant achievements on the subject. Osteoporosis can be defined as a disease characterized by low bone mass and microarchitectural deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk. Although the major determinants of peak bone mass and strength are genetic, major factors during childhood and adolescence may affect the ability to achieve peak bone mass. These include nutrition, particularly calcium and protein intake, physical activity, endocrine status, as well as exposure to a wide variety of risk factors. The role of calcium intake in determining bone mineral mass is well recognized to be the most critical nutritional factor to achieve optimal peak bone mass. The greatest amount of dietary calcium is obtained from milk and dairy foods, which also provide the human diet with vitamin D (particularly for products fortified with vitamin D), potassium, and other macro- and micronutrients. Although studies supporting the beneficial effects of milk or calcium on bone health are predominant in the literature, perplexity or discordance on this subject was expressed by some authors. Discordant data, mainly on the risk of fractures, provided limited proof of the unfavorable effect of dairy intake. More often, discordant works indicate no effect of dairy consumption on bone safety. Some considerations can be drawn from this viewpoint. Milk and dairy products are an optimal source of calcium as well as of other limiting nutrients (e.g., potassium and magnesium), with important effects on bone health. Bioactive components occurring in milk and dairy products may play an essential role on bone metabolism, as shown by in vivo and in vitro studies on colostrum acidic proteins and milk basic proteins. Calcium intake positively affects bone mass and is crucial in childhood and youth for correct bone development. In elderly people, calcium intake as well as vitamin D availability should be carefully checked. As a general conclusion, calcium is essential for bone health, although it will not prevent bone loss due to other factors; in this context, milk and dairy foods are bioavailable, relatively inexpensive sources of calcium for the human diet. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Effect of low-intensity whole-body vibration on bone defect repair and associated vascularization in mice.

PubMed

Matsumoto, Takeshi; Goto, Daichi

2017-12-01

Low-intensity whole-body vibration (LIWBV) may stimulate bone healing, but the involvement of vascular ingrowth, which is essential for bone regeneration, has not been well examined. We thus investigated the LIWBV effect on vascularization during early-stage bone healing. Mice aged 13 weeks were subjected to cortical drilling on tibial bone. Two days after surgery (day 0), mice were exposed daily to sine-wave LIWBV at 30 Hz and 0.1 g peak-to-peak acceleration for 20 min/day (Vib) or were sham-treated (sham). Following vascular casting with a zirconium-based contrast agent on days 6, 9, or 12 and sacrifice, vascular and bone images were obtained by K-edge subtraction micro-CT using synchrotron lights. Bone regeneration advanced more in the Vib group from days 9 to 12. The vascular volume fraction decreased from days 6 to 9 in both groups; however, from days 9 to 12, it was increased in shams, while it stabilized in the Vib group. The vascular volume fraction tended to be or was smaller in the Vib group on days 6 and 12. The vessel number density was higher on day 9 but lower on day 12 in the Vib group. These results suggest that the LIWBV-promoted bone repair is associated with the modulation of vascularization, but additional studies are needed to determine the causality of this association.

Evaluation of bone quality in osteoporosis model mice by Raman spectroscopy

NASA Astrophysics Data System (ADS)

Ishimaru, Yasumitsu; Oshima, Yusuke; Imai, Yuuki; Iimura, Tadahiro; Takanezawa, Sota; Hino, Kazunori; Miura, Hiromasa

2017-04-01

To evaluate the bone quality in the osteoporosis, we generated sciatic nerve resection (NX) mice as an osteoporosis model and analyzed by Raman spectroscopy. Raman spectra were measured in anterior cortical surface of the proximal tibia at 5 points in each bone. After that, the samples were fixed with 70% ethanol. We then performed DXA and μCT measurement. Raman peak intensity ratios were significantly different between NX and Control. Those changes in the Raman peak intensity ratios may reflect loss of bone quality in the osteoporosis model. Raman spectroscopy is a promising technique for measuring the bone quality and bone strength.

Does bone cement in percutaneous vertebroplasty act as a stress riser?

PubMed

Aquarius, René; van der Zijden, Astrid Maria; Homminga, Jasper; Verdonschot, Nico; Tanck, Esther

2013-11-15

An in vitro cadaveric study. To determine whether percutaneous vertebroplasty (PVP) with a clinically relevant amount of bone cement is capable of causing stress peaks in adjacent-level vertebrae. It is often suggested that PVP of a primary spinal fracture causes stress peaks in adjacent vertebrae, thereby leading to additional fractures. The in vitro studies that demonstrated this relationship, however, use bigger volumes of bone cement used clinically. Ten fresh-frozen vertebrae were loaded until failure, while registering force and displacement as well as the pressure under the lower endplate. After failure, the vertebrae were augmented with clinically relevant amounts of bone cement and then again loaded until failure. The force, displacement, and pressure under the lower endplate were again registered. Stress peaks were not related to the location of the injected bone cement. Both failure load and stiffness were significantly lower after augmentation. On the basis of our findings, we conclude that vertebral augmentation with clinically relevant amounts of bone cement does not lead to stress peaks under the endplate. It is therefore unlikely that PVP, in itself, causes detrimental stresses in the adjacent vertebrae, leading to new vertebral fractures. N/A.

The Effect of Prepubertal Calcium Carbonate Supplementation on Skeletal Development in Gambian Boys—A 12-Year Follow-Up Study

PubMed Central

Cole, T. J.; Laskey, M. A.; Ceesay, M.; Mendy, M. B.; Sawo, Y.; Prentice, A.

2014-01-01

Context: Calcium intake during growth is essential for future bone health but varies widely between individuals and populations. The impact on bone of increasing calcium intake is unknown in a population where low calcium intake, stunting, and delayed puberty are common. Objective: To determine the effect of prepubertal calcium supplementation on mean age at peak velocity for bone growth and mineral accrual. Design and Setting: Prospective follow-up of boys in rural Gambia, West Africa, who had participated in a double-blind, randomized, placebo-controlled trial of calcium supplementation. Participants: Eighty boys, initially aged 8.0–11.9 years, were followed up for 12 years. Interventions: Subjects received 1 year of calcium carbonate supplementation (1000 mg daily, 5 d/wk). Main Outcome Measures: Dual-energy x-ray absorptiometry measurements were carried out for whole body (WB), lumbar spine, and total hip bone mineral content, bone area (BA), and WB lean mass. Super imposition by translation and rotation models was made to assess bone growth. Results: Age at peak velocity was consistently earlier in the calcium group compared to the placebo group, for WB bone mineral content (mean, −6.2 [SE, 3.1]; P = .05), WB BA (mean, −7.0 [SE, 3.2] mo; P = .03), lumbar spine and total hip BA. By young adulthood, supplementation did not change the amount of bone accrued (mineral or size) or the rate of bone growth. Conclusions: Twelve months of prepubertal calcium carbonate supplementation in boys with a low calcium diet advanced the adolescent growth spurt but had no lasting effect on bone mineral or bone size. There is a need for caution when applying international recommendations to different populations. PMID:24762110

Shock wave treatment shows dose-dependent enhancement of bone mass and bone strength after fracture of the femur.

PubMed

Wang, Ching-Jen; Yang, Kuender D; Wang, Feng-Sheng; Hsu, Chia-Chen; Chen, Hsiang-Ho

2004-01-01

Shock wave treatment is believed to improve bone healing after fracture. The purpose of this study was to evaluate the effect of shock wave treatment on bone mass and bone strength after fracture of the femur in a rabbit model. A standardized closed fracture of the right femur was created with a three-point bending method in 24 New Zealand white rabbits. Animals were randomly divided into three groups: (1) control (no shock wave treatment), (2) low-energy (shock wave treatment at 0.18 mJ/mm2 energy flux density with 2000 impulses), and (3) high-energy (shock wave treatment at 0.47 mJ/mm2 energy flux density with 4000 impulses). Bone mass (bone mineral density (BMD), callus formation, ash and calcium contents) and bone strength (peak load, peak stress and modulus of elasticity) were assessed at 12 and 24 weeks after shock wave treatment. While the BMD values of the high-energy group were significantly higher than the control group (P = 0.021), the BMD values between the low-energy and control groups were not statistically significant (P = 0.358). The high-energy group showed significantly more callus formation (P < 0.001), higher ash content (P < 0.001) and calcium content (P = 0.003) than the control and low-energy groups. With regard to bone strength, the high-energy group showed significantly higher peak load (P = 0.012), peak stress (P = 0.015) and modulus of elasticity (P = 0.011) than the low-energy and control groups. Overall, the effect of shock wave treatment on bone mass and bone strength appears to be dose dependent in acute fracture healing in rabbits.

Molecular spectroscopic identification of the water compartments in bone.

PubMed

Unal, Mustafa; Yang, Shan; Akkus, Ozan

2014-10-01

Matrix bound water is a correlate of bone's fracture resistance and assessment of bound water is emerging as a novel measure of bone's mechanical integrity. Raman spectroscopy is one of the few nondestructive modalities to assess the hydration status in bone; however, it has not been used to study the OH-band in bone. A sequential dehydration protocol was developed to replace unbound (heat drying) and bound (ethanol or deuterium) water in bone. Raman spectra were collected serially to track the OH-band during dehydration. Spectra of synthetic hydroxyapatite, demineralized bone and bulk water were collected to identify mineral and collagen contributions to the OH-band. Band assignments were supported by computational simulations of the molecular vibrations of Gly-Pro-Hyp amino acid sequence. Experimentally and theoretically obtained spectra were interpreted for band-assignments. Water loss was measured gravimetrically and correlated to Raman intensities. Four peaks were identified to be sensitive to dehydration: 3220cm(-1) (water), 3325cm(-1) (NH and water), 3453cm(-1) (hydroxyproline and water), and 3584cm(-1) (mineral and water). These peaks were differentially sensitive to deuterium treatment such that some water peaks were replaced with deuterium oxide faster than the rest. Specifically, the peaks at 3325 and 3584cm(-1) were more tightly bound to the matrix than the remaining bands. Comparison of dehydration in mineralized and demineralized bone revealed a volume of water that may be locked in the matrix by mineral crystals. The OH-range of bone was dominated by collagen and the water since the spectral profile of dehydrated demineralized bone was similar to that of the mineralized bone. Furthermore, water associates to bone mainly by collagen as findings of experimentally and theoretically spectra. The current work is among the first thorough analysis of the Raman OH stretch band in bone and such spectral information may be used to understand the involvement of water in the fragility of aging and in diseased bone. Published by Elsevier Inc.

Epidemiology of Osteoporosis in Women with Cognitive Impairment

ERIC Educational Resources Information Center

Schrager, Sarina

2006-01-01

Osteoporosis is increasing due to the aging of the population. Women with cognitive impairment from childhood are at disproportionally high risk for osteoporosis and fractures. Suggested explanations for this increased risk include high use of anticonvulsant medications, lower peak bone densities, and higher rates of nonambulation. Down syndrome…

Stress distributions of a bracket type orthodontic miniscrew and the surrounding bone under moment loadings: Three-dimensional finite element analysis

PubMed Central

Ajami, Shabnam; Mina, Ahmad; Nabavizadeh, Seyed Amin

2016-01-01

Objectives: To evaluate the effect of moments and the combination of forces and moments on the mechanical properties of a bracket type miniscrew, resembling engagement of a rectangular wire by three-dimensional (3D) finite element study. Materials and Methods: By solid work software (Dassaunlt systems solid works, concord, Mass), a 3D miniscrew model of 6, 8, 10 mm lengths was designed and inserted in the osseous block, consisted of the cortical, and cancellous bones. The stress distributions, maximum stresses, and deflections of the miniscrew were evaluated for all parts using ANSYS (Work Bench, 2014). Results: As the magnitudes of the load increased from 100 to 200, 400 and 800 grf-mm, the peak of stresses in the 6 mm long miniscrew were increased from 7.7 to 61.5 Mpa. The maximum values of Von Mises in the cancellous bone were tremendously lower in comparison to the cortical bone by one hundredth. As the length of the miniscrew in contact with the bone was increased, the amounts and patterns of stress distribution in the cortical bone and the miniscrew did not change significantly. Conclusions: As the moment magnitude increased, the pick stresses increased linearly. The existence of cancellous bone was not significantly responsible for the stress distribution. The pattern of stress distribution did not change by the length of the miniscrew. PMID:27127753

Age-related differences in volumetric bone mineral density, microarchitecture, and bone strength of distal radius and tibia in Chinese women: a high-resolution pQCT reference database study.

PubMed

Hung, V W Y; Zhu, T Y; Cheung, W-H; Fong, T-N; Yu, F W P; Hung, L-K; Leung, K-S; Cheng, J C Y; Lam, T-P; Qin, L

2015-06-01

In a cohort of 393 Chinese women, by using high-resolution peripheral quantitative computed tomography (HR-pQCT), we found that significant cortical bone loss occurred after midlife. Prominent increase in cortical porosity began at the fifth decade but reached a plateau before the sixth decade. Trabecular bone loss was already evident in young adulthood and continued throughout life. This study aimed to investigate age-related differences in volumetric bone mineral density (vBMD), microarchitecture, and estimated bone strength at peripheral skeleton in Chinese female population. In a cross-sectional cohort of 393 Chinese women aged 20-90 years, we obtained vBMD, microarchtecture, and micro-finite element-derived bone strength at distal radius and tibia using HR-pQCT. The largest predictive age-related difference was found for cortical porosity (Ct.Po) which showed over four-fold and two-fold differences at distal radius and tibia, respectively, over the adulthood. At both sites, cortical bone area, vBMD, and thickness showed significant quadratic association with age with significant decrease beginning after midlife. Change of Ct.Po became more prominent between age of 50 and 57 (0.26 %/year at distal radius, 0.54 %/year at distal tibia, both p ≤ 0.001) but thereafter, reached a plateau (0.015 and 0.028 %/year, both p > 0.05). In contrast, trabecular vBMD and microarchitecture showed linear association with age with significant deterioration observed throughout adulthood. Estimated age of peak was around age of 20 for trabecular vBMD and microarchitecture and Ct.Po and age of 40 for cortical vBMD and microarchitecture. Estimated stiffness and failure load peaked at mid-30s at the distal radius and at age 20 at distal tibia. Age-related differences in vBMD and microarchitecture in Chinese women differed by bone compartments. Significant cortical bone loss occurred after midlife. Prominent increase in Ct.Po began at the fifth decade but appeared to be arrested before the sixth decade. Loss of trabecular bone was already evident in young adulthood and continued throughout life.

Bone density and anisotropy affect periprosthetic cement and bone stresses after anatomical glenoid replacement: A micro finite element analysis.

PubMed

Chevalier, Yan; Santos, Inês; Müller, Peter E; Pietschmann, Matthias F

2016-06-14

Glenoid loosening is still a main complication for shoulder arthroplasty. We hypothesize that cement and bone stresses potentially leading to fixation failure are related not only to glenohumeral conformity, fixation design or eccentric loading, but also to bone volume fraction, cortical thickness and degree of anisotropy in the glenoid. In this study, periprosthetic bone and cement stresses were computed with micro finite element models of the replaced glenoid depicting realistic bone microstructure. These models were used to quantify potential effects of bone microstructural parameters under loading conditions simulating different levels of glenohumeral conformity and eccentric loading simulating glenohumeral instability. Results show that peak cement stresses were achieved near the cement-bone interface in all loading schemes. Higher stresses within trabecular bone tissue and cement mantle were obtained within specimens of lower bone volume fraction and in regions of low anisotropy, increasing with decreasing glenohumeral conformity and reaching their maxima below the keeled design when the load is shifted superiorly. Our analyses confirm the combined influences of eccentric load shifts with reduced bone volume fraction and anisotropy on increasing periprosthetic stresses. They finally suggest that improving fixation of glenoid replacements must reduce internal cement and bone tissue stresses, in particular in glenoids of low bone density and heterogeneity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of orthopedic implants with a polycaprolactone polymer coating containing bone morphogenetic protein-2 on osseointegration in bones of sheep.

PubMed

Niehaus, Andrew J; Anderson, David E; Samii, Valerie F; Weisbrode, Steven E; Johnson, Jed K; Noon, Mike S; Tomasko, David L; Lannutti, John J

2009-11-01

To determine elution characteristics of bone morphogenetic protein (BMP)-2 from a polycaprolactone coating applied to orthopedic implants and determine effects of this coating on osseointegration. 6 sheep. An in vitro study was conducted to determine BMP-2 elution from polycaprolactone-coated implants. An in vivo study was conducted to determine the effects on osseointegration when the polycaprolactone with BMP-2 coating was applied to bone screws. Osseointegration was assessed via radiography, measurement of peak removal torque and bone mineral density, and histomorphometric analysis. Physiologic response was assessed by measuring serum bone-specific alkaline phosphatase activity and uptake of bone markers. Mean +/- SD elution on day 1 of the in vitro study was 263 +/- 152 pg/d, which then maintained a plateau at 59.8 +/- 29.1 pg/d. Mean peak removal torque for screws coated with polycalprolactone and BMP-2 (0.91 +/- 0.65 dN x m) and screws coated with polycaprolactone alone (0.97 +/- 1.30 dN.m) did not differ significantly from that for the control screws (2.34 +/- 1.62 dN x m). Mean bone mineral densities were 0.535 +/- 0.060 g/cm(2), 0.596 +/- 0.093 g/cm(2), and 0.524 +/- 0.142 g/cm(2) for the polycaprolactone-BMP-2-coated, polycaprolactone-coated, and control screws, respectively, and did not differ significantly among groups. Histologically, bone was in closer apposition to the implant with the control screws than with either of the coated screws. BMP-2 within the polycaprolactone coating did not stimulate osteogenesis. The polycaprolactone coating appeared to cause a barrier effect that prevented formation of new bone. A longer period or use of another carrier polymer may result in increased osseointegration.

Synthesis of nitric oxide in human osteoblasts in response to physiologic stimulation of electrotherapy.

PubMed

Hamed, Ayman; Kim, Paul; Cho, Michael

2006-12-01

Electrotherapy for bone healing, remodeling and wound healing may be mediated by modulation of nitric oxide (NO). Using NO-specific fluorophore (DAF-2), we report here that application of non-invasive, physiologic electrical stimulation induces NO synthesis in human osteoblasts, and that such NO generation is comparable to that induced by estrogen treatment. For example, application of a sinusoidal 1 Hz, 2 V/cm (peak to peak) electrical stimulation (ES) increases NO-bound DAF-2 fluorescence intensity by a 2-fold within 60 min exposure by activating nitric oxide synthase (NOS). Increase in the NO level is found to depend critically on the frequency and strength of ES. While the frequency of 1 Hz ES seems optimal, the ES strength >0.5 V/cm is required to induce significant NO increase, however. Nitric oxide synthesis in response to ES is completely prevented by blocking estrogen receptors using a competitive inhibitor, suggesting that NO generation is likely initiated by activation of estrogen receptors at the cell surface. Based on these findings, physiologic stimulation of electrotherapy appears to represent a potential non-invasive, non-genomic, and novel physical technique that could be used to regulate NO-mediated bone density and facilitate bone remodeling without adverse effects associated with hormone therapy.

Transgenic Expression of Osteoactivin/gpnmb Enhances Bone Formation In Vivo and Osteoprogenitor Differentiation Ex Vivo.

PubMed

Frara, Nagat; Abdelmagid, Samir M; Sondag, Gregory R; Moussa, Fouad M; Yingling, Vanessa R; Owen, Thomas A; Popoff, Steven N; Barbe, Mary F; Safadi, Fayez F

2016-01-01

Initial identification of osteoactivin (OA)/glycoprotein non-melanoma clone B (gpnmb) was demonstrated in an osteopetrotic rat model, where OA expression was increased threefold in mutant bones, compared to normal. OA mRNA and protein expression increase during active bone regeneration post-fracture, and primary rat osteoblasts show increased OA expression during differentiation in vitro. To further examine OA/gpnmb as an osteoinductive agent, we characterized the skeletal phenotype of transgenic mouse overexpressing OA/gpnmb under the CMV-promoter (OA-Tg). Western blot analysis showed increased OA/gpnmb in OA-Tg osteoblasts, compared to wild-type (WT). In OA-Tg mouse femurs versus WT littermates, micro-CT analysis showed increased trabecular bone volume and thickness, and cortical bone thickness; histomorphometry showed increased osteoblast numbers, bone formation and mineral apposition rates in OA-Tg mice; and biomechanical testing showed higher peak moment and stiffness. Given that OA/gpnmb is also over-expressed in osteoclasts in OA-Tg mice, we evaluated bone resorption by ELISA and histomorphometry, and observed decreased serum CTX-1 and RANK-L, and decreased osteoclast numbers in OA-Tg, compared to WT mice, indicating decreased bone remodeling in OA-Tg mice. The proliferation rate of OA-Tg osteoblasts in vitro was higher, compared to WT, as was alkaline phosphatase staining and activity, the latter indicating enhanced differentiation of OA-Tg osteoprogenitors. Quantitative RT-PCR analysis showed increased TGF-β1 and TGF-β receptors I and II expression in OA-Tg osteoblasts, compared to WT. Together, these data suggest that OA overexpression has an osteoinductive effect on bone mass in vivo and stimulates osteoprogenitor differentiation ex vivo. © 2015 Wiley Periodicals, Inc.

The effect of surface demineralization of cortical bone allograft on the properties of recombinant adeno-associated virus coatings.

PubMed

Yazici, Cemal; Yanoso, Laura; Xie, Chao; Reynolds, David G; Samulski, R Jude; Samulski, Jade; Yannariello-Brown, Judith; Gertzman, Arthur A; Zhang, Xinping; Awad, Hani A; Schwarz, Edward M

2008-10-01

Freeze-dried recombinant adeno-associated virus (rAAV) coated structural allografts have emerged as an approach to engender necrotic cortical bone with host factors that will persist for weeks following surgery to facilitate revascularization, osteointegration, and remodeling. However, one major limitation is the nonporous cortical surface that prohibits uniform distribution of the rAAV coating prior to freeze-drying. To overcome this we have developed a demineralization method to increase surface absorbance while retaining the structural integrity of the allograft. Demineralized bone wafers (DBW) made from human femoral allograft rings demonstrated a significant 21.1% (73.6+/-3.9% versus 52.5+/-2.6%; p<0.001) increase in percent surface area coating versus mineralized controls. Co-incubation of rAAV-luciferase (rAAV-Luc) coated DBW with a monolayer of C3H10T1/2 cells in culture led to peak luciferase levels that were not significantly different from soluble rAAV-Luc controls (p>0.05), although the peaks occurred at 60h and 12h, respectively. To assess the transduction efficiency of rAAV-Luc coated DBW in vivo, we first performed a dose response with allografts containing 10(7), 10(9) or 10(10) particles that were surgically implanted into the quadriceps of mice, and assayed by in vivo bioluminescence imaging (BLI) on days 1, 3, 5, 7, 10, 14, and 21. The results demonstrated a dose response in which the DBW coated with 10(10) rAAV-Luc particles achieved peak gene expression levels on day 3, which persisted until day 21, and was significantly greater than the 10(7) dose throughout this time period (p<0.01). A direct comparison of mineralized versus DBW coated with 10(10) rAAV-Luc particles failed to demonstrate any significant differences in transduction kinetics or efficiency in vivo. Thus, surface demineralization of human cortical bone allograft increases its absorbance for uniform rAAV coating, without affecting vector transduction efficiency.

Replacement of segmental bone defects using porous bioceramic cylinders: a biomechanical and X-ray diffraction study.

PubMed

Zhang, C; Wang, J; Feng, H; Lu, B; Song, Z; Zhang, X

2001-03-05

A porous ceramic material [hydroxyapatitetricalcium phosphate (HA-TCP)] was implanted in the femora of 30 dogs to investigate the possibility of using this material to repair segmental bone defects. A bone segment, 1.5 cm in length, was removed from the diaphysis of one femur in each dog to create the defect. Cylinders of corresponding size were inserted into the defects. The animals were divided into three groups with recovery times of 2 months, 4 months, and 6 months, respectively. The implants were harvested and subjected to biomechanic tests (bending strength) and X-ray diffraction analysis. The bending strengths of the implant construct increased gradually over time postoperatively. The values of strength for the three different time groups had significant variations (p < 0.05). The X-ray diffraction analysis indicated that the peaks of the TCP included in the cylinders decreased in intensity after implantation and tended to be similar to those of natural bone by 6 months after operation. Conversely, the peaks for the HA had fewer changes compared with preimplantation values. Based on the results of this experiment it was concluded that the porous HA-TCP ceramic cylinders have potential for repair of segmental bone defects if assisted by adequate stabilizing fixtures during the early postoperative period.

Surface Damage on Dental Implants with Release of Loose Particles after Insertion into Bone.

PubMed

Senna, Plinio; Antoninha Del Bel Cury, Altair; Kates, Stephen; Meirelles, Luiz

2015-08-01

Modern dental implants present surface features of distinct dimensions that can be damaged during the insertion procedure into bone. The aims of this study were (1) to quantify by means of roughness parameters the surface damage caused by the insertion procedure of dental implants and (2) to investigate the presence of loose particles at the interface. Three groups of dental implants representing different surface topographies were inserted in fresh cow rib bone blocks. The surface roughness was characterized by interferometry on the same area before and after the insertion. Scanning electron microscopy (SEM)-back-scattered electron detector (BSD) analysis was used to identify loose particles at the interface. The amplitude and hybrid roughness parameters of all three groups were lower after insertion. The surface presenting predominance of peaks (Ssk [skewness] > 0) associated to higher structures (height parameters) presented higher damage associated to more pronounced reduction of material volume. SEM-BSD images revealed loose titanium and aluminum particles at the interface mainly at the crestal cortical bone level. Shearing forces during the insertion procedure alters the surface of dental implants. Loose metal particles can be generated at bone-implant interface especially around surfaces composed mainly by peaks and with increased height parameters. © 2013 Wiley Periodicals, Inc.

Surface Damage on Dental Implants with Release of Loose Particles after Insertion into Bone

PubMed Central

Senna, Plinio; Del Bel Cury, Altair Antoninha; Kates, Stephen; Meirelles, Luiz

2015-01-01

Background Modern dental implants present surface features of distinct dimensions that can be damaged during the insertion procedure into bone. Purpose The aims of this study were (1) to quantify by means of roughness parameters the surface damage caused by the insertion procedure of dental implants and (2) to investigate the presence of loose particles at the interface. Materials and Methods Three groups of dental implants representing different surface topographies were inserted in fresh cow rib bone blocks. The surface roughness was characterized by interferometry on the same area before and after the insertion. SEM-BSD analysis was used to identify loose particles at the interface. Results The amplitude and hybrid roughness parameters of all three groups were lower after insertion. The surface presenting predominance of peaks (Ssk>0) associated to higher structures (height parameters) presented higher damage associated to more pronounced reduction of material volume. SEM-BSD images revealed loose titanium and aluminum particles at the interface mainly at the crestal cortical bone level. Conclusions Shearing forces during the insertion procedure alters the surface of dental implants. Loose metal particles can be generated at bone-implant interface especially around surfaces composed mainly by peaks and with increased height parameters. PMID:24283455

Quantification of bone strength by intraoperative torque measurement: a technical note.

PubMed

Suhm, Norbert; Haenni, Markus; Schwyn, Ronald; Hirschmann, Michael; Müller, Andreas Marc

2008-06-01

Bone strength describes the resistance of bone against mechanical failure. Bone strength depends on both the amount of bone and the bone's quality, and the bone strength may be looked upon as a relevant parameter to judge an osteosynthesis' stability. Information about bone strength was barely available intraoperatively in the past. The previous work of our group reported on development and laboratory evaluation of mechanical torque measurement as a method for the intraoperative quantification of bone strength. With the clinical series presented here we intend to verify that the im gesamten Text DensiProbe instrumentation for intraoperative torque measurement and the related measurement method are eligible for intraoperative use based on the following criteria: application of the method may not create complications, the measurement can be performed by the surgeon himself and may only cause a limited increase in the procedure time. From December 2006 until May 2007 ten patients with a pertrochanteric femoral fracture or a lateral femoral neck fracture eligible for stabilization with DHS were included in the study after having received informed consent. Any medication and comorbidity that might have influenced bone quality or bone mineral density (BMD) in these patients was documented. Bone strength was intraoperatively measured with DensiProbe. Complications that were obviously related with torque measurement were documented as well as any deviation from the suggested procedure; 6 and 12 weeks postoperative follow-up included clinical and radiological examination. The time required for torque measurement, the overall operating time and the number of persons present in the operating room were protocolled. BMD values of the contralateral femoral neck were postoperatively assessed by dual energy X-ray absorptiometry (DEXA) and compared to intraoperative peak torque values measured by DensiProbe. No major complication was observed during intraoperative application of DensiProbe by trained surgeons. The unintended extraction of the guide wire together with the torque measurement probe was reported only once and is looked upon as a minor complication. Fracture healing was uneventful in all patients. The mean time for torque measurement was 2.35 +/- 0.9 min accounting for 2.2 +/- 1.1% of total surgery time. The presence of an additional person was not required to perform torque measurement but to protocol the data. There was a tendency towards correlation between BMD values of the femoral neck and intraoperative peak torque values. The data presented clearly indicate that the DensiProbe instrumentation and measurement principle are eligible for routine intraoperative use by trained surgeons. Interpretation of possible correlations between BMD values measured by means of DEXA and the Peak Torque values assessed by DensiProbe has to be considered very carefully, because BMD and Peak Torque analyse bone at a different scale. Only within the framework of a multicenter study it will be possible to include a sufficient number of patients for calculation of the methods' predictive value towards implant failure and to verify acceptance of the method by the surgeons.

Far-field brainstem responses evoked by vestibular and auditory stimuli exhibit increases in interpeak latency as brain temperature is decreased

NASA Technical Reports Server (NTRS)

Hoffman, L. F.; Horowitz, J. M.

1984-01-01

The effect of decreasing of brain temperature on the brainstem auditory evoked response (BAER) in rats was investigated. Voltage pulses, applied to a piezoelectric crystal attached to the skull, were used to evoke stimuli in the auditory system by means of bone-conducted vibrations. The responses were recorded at 37 C and 34 C brain temperatures. The peaks of the BAER recorded at 34 C were delayed in comparison with the peaks from the 37 C wave, and the later peaks were more delayed than the earlier peaks. These results indicate that an increase in the interpeak latency occurs as the brain temperature is decreased. Preliminary experiments, in which responses to brief angular acceleration were used to measure the brainstem vestibular evoked response (BVER), have also indicated increases in the interpeak latency in response to the lowering of brain temperature.

EDTA-insoluble, calcium-binding proteoglycan in bovine bone

NASA Technical Reports Server (NTRS)

Hashimoto, Y.; Lester, G. E.; Caterson, B.; Yamauchi, M.

1995-01-01

A calcium ion precipitable, trypsin-generated proteoglycan fragment has been isolated from the demineralized, EDTA-insoluble matrices of bone. The demineralized matrix was completely digested with trypsin, increasing concentrations of CaCl2 were added to the supernatant, and the resulting precipitates were analyzed. The amount of precipitate gradually increased with higher concentrations of calcium and was reversibly solubilized by EDTA. After molecular sieve and anion exchange chromatography, a proteoglycan-containing peak was obtained. Immunochemical analysis showed that this peak contained chondroitin 4-sulfate and possibly keratan sulfate. Amino acid analysis showed that this proteoglycan contained high amounts of aspartic acid/asparagine (Asx), serine (Ser), glutamic acid/glutamine (Glx), proline (Pro), and glycine (Gly); however, it contained little leucine (Leu) which suggests that it is not a member of the leucine-rich small proteoglycan family. In addition, significant amounts of phosphoserine (P-Ser) and hydroxyproline (Hyp) were identified in hydrolysates of this fraction. A single band (M(r) 59 kDa) was obtained on SDS-PAGE that stained with Stains-all but not with Coomassie Brilliant Blue R-250. If bone powder was trypsinized prior to demineralization, this proteoglycan-containing fraction was not liberated. Collectively, these results indicate that a proteoglycan occurs in the demineralized matrix that is precipitated with CaCl2 and is closely associated with both mineral and collagen matrices. Such a molecule might facilitate the structural network for the induction of mineralization in bone.

Hydroxyapatite synthesis using EDTA

PubMed Central

Kang, Nak Heon; Kim, Soon Je; Song, Seung Han; Choi, Sang mun; Choi, Sik Young; Kim, Youn Jung

2013-01-01

Bone comprises structure of body and is consisted of inorganic substances. It exists in an organic structure in the body. Even though it is firm and has self healing mechanism, it can be damaged by trauma, cancer, or bone diseases. Allograft can be an alternative solution for autologous bone graft. Hydroxyapatite(Ca10(PO4)6(OH)2), an excellent candidate for allograft, can be applied to bone defect area. There are several methods to produce hydroxyapatite, however economical cost and time consuming make the production difficult. In this study we synthesized the hydroxyapatite with Ethyenediamine tetraacetic acid. Freeze Dried Bone Allograft(Hans Biomed) was used to be a control group. Synthesized hydroxyapatite was a rod shape, white powdery type substance with 2 ~ 5 μm length and 0.5 ~ 1 μm width. X-ray diffraction showed the highest sharp peak at 32° and high peaks at 25.8°, 39.8°, 46.8°, 49.5°, and 64.0° indicating a similar substance to the freeze Dried Bone Allograft. 3 days after the cell growth of synthesized hydroxyapatite showed 1.5 fold more than the Bone Allograft. Cellular and media alkaline phosphate activity increased similar to the bone alloagraft. In this study we came up with a new method to produce the hydroxyapatite. It is a convenient method that can be held in room temperature and low pressure. Also the the product can be manufactured in large quantity. It can be also transformed into scaffold structure which will perform a stronger configuration. The manufacturing method will help the bony defect patients and make future medical products. PMID:23714942

Whole Body Vibration Training is Osteogenic at the Spine in College-Age Men and Women.

PubMed

Ligouri, Gianna C; Shoepe, Todd C; Almstedt, Hawley C

2012-03-01

Osteoporosis is a chronic skeletal disease characterized by low bone mass which is currently challenging the American health care system. Maximizing peak bone mass early in life is a cost-effective method for preventing osteoporosis. Whole body vibration (WBV) is a novel exercise method with the potential to increase bone mass, therefore optimizing peak bone and decreasing the risk for osteoporotic fracture. The aim of this investigation was to evaluate changes in bone mineral density at the hip, spine, and whole body in college-age men and women who underwent a WBV training protocol. Active men (n=6) and women (n=4), ages 18-22 participated in the WBV training; while an additional 14 volunteers (1 male, 13 female) served as controls. All participants completed baseline and follow-up questionnaires to assess health history, physical activity, dietary intake, and menstrual history. The WBV training program, using a Vibraflex 550, incorporated squats, stiff-leg dead lifts, stationary lunges, push-up holds, bent-over rows, and jumps performed on the platform, and occurred 3 times a week, for 12 weeks. Dual energy x-ray absorptiometry (Hologic Explorer, Waltham, MA, USA) was used to assess bone mineral density (BMD, g/cm(2)). A two-tailed, t-test identified significantly different changes in BMD between the WBV and control groups at the lateral spine (average change of 0.022 vs. -0.015 g/cm(2)). The WBV group experienced a 2.7% and 1.0% increase in BMD in the lateral spine and posterior-anterior spine while the control group decreased 1.9% and 0.9%, respectively. Results indicate that 12 weeks of WBV training was osteogenic at the spine in college-age men and women.

Decreased Bone Mineral Density in Adults Born with Very Low Birth Weight: A Cohort Study

PubMed Central

Hovi, Petteri; Andersson, Sture; Järvenpää, Anna-Liisa; Eriksson, Johan G.; Strang-Karlsson, Sonja; Kajantie, Eero; Mäkitie, Outi

2009-01-01

Background Very-low-birth-weight (VLBW, <1,500 g) infants have compromised bone mass accrual during childhood, but it is unclear whether this results in subnormal peak bone mass and increased risk of impaired skeletal health in adulthood. We hypothesized that VLBW is associated with reduced bone mineral density (BMD) in adulthood. Methods and Findings The Helsinki Study of Very Low Birth Weight Adults is a multidisciplinary cohort study representative of all VLBW births within the larger Helsinki area from 1978 to 1985. This study evaluated skeletal health in 144 such participants (all born preterm, mean gestational age 29.3 wk, birth weight 1,127 g, birth weight Z score 1.3), and in 139 comparison participants born at term, matched for sex, age, and birth hospital. BMD was measured by dual energy X-ray absorptiometry at age 18.5 to 27.1 y. Adults born with VLBW had, in comparison to participants born at term, a 0.51-unit (95% confidence interval [CI] 0.28–0.75) lower lumbar spine Z score and a 0.56-unit (95% CI 0.34–0.78) lower femoral neck Z score for areal BMD. These differences remained statistically significant after adjustment for the VLBW adults' shorter height and lower self-reported exercise intensity. Conclusions Young adults born with VLBW, when studied close to the age of peak bone mass, have significantly lower BMD than do their term-born peers. This suggests that compromised childhood bone mass accrual in preterm VLBW children translates into increased risk for osteoporosis in adulthood, warranting vigilance in osteoporosis prevention. Please see later in the article for the Editors' Summary PMID:19707270

Growth hormone and bone health.

PubMed

Bex, Marie; Bouillon, Roger

2003-01-01

Growth hormone (GH) and insulin-like growth factor-I have major effects on growth plate chondrocytes and all bone cells. Untreated childhood-onset GH deficiency (GHD) markedly impairs linear growth as well as three-dimensional bone size. Adult peak bone mass is therefore about 50% that of adults with normal height. This is mainly an effect on bone volume, whereas true bone mineral density (BMD; g/cm(3)) is virtually normal, as demonstrated in a large cohort of untreated Russian adults with childhood-onset GHD. The prevalence of fractures in these untreated childhood-onset GHD adults was, however, markedly and significantly increased in comparison with normal Russian adults. This clearly indicates that bone mass and bone size matter more than true bone density. Adequate treatment with GH can largely correct bone size and in several studies also bone mass, but it usually requires more than 5 years of continuous treatment. Adult-onset GHD decreases bone turnover and results in a mild deficit, generally between -0.5 and -1.0 z-score, in bone mineral content and BMD of the lumbar spine, radius and femoral neck. Cross-sectional surveys and the KIMS data suggest an increased incidence of fractures. GH replacement therapy increases bone turnover. The three controlled studies with follow-up periods of 18 and 24 months demonstrated a modest increase in BMD of the lumbar spine and femoral neck in male adults with adult-onset GHD, whereas no significant changes in BMD were observed in women. GHD, whether childhood- or adult-onset, impairs bone mass and strength. Appropriate substitution therapy can largely correct these deficiencies if given over a prolonged period. GH therapy for other bone disorders not associated with primary GHD needs further study but may well be beneficial because of its positive effects on the bone remodelling cycle. Copyright 2003 S. Karger AG, Basel

Effects of age-related differences in femoral loading and bone mineral density on strains in the proximal femur during controlled walking.

PubMed

Anderson, Dennis E; Madigan, Michael L

2013-10-01

Maintenance of healthy bone mineral density (BMD) is important for preventing fractures in older adults. Strains experienced by bone in vivo stimulate remodeling processes, which can increase or decrease BMD. However, there has been little study of age differences in bone strains. This study examined the relative contributions of age-related differences in femoral loading and BMD to age-related differences in femoral strains during walking using gait analysis, static optimization, and finite element modeling. Strains in older adult models were similar or larger than in young adult models. Reduced BMD increased strains in a fairly uniform manner, whereas older adult loading increased strains in early stance but decreased strains in late stance. Peak ground reaction forces, hip joint contact forces, and hip flexor forces were lower in older adults in late stance phase, and this helped older adults maintain strains similar to those of young adults despite lower BMD. Because walking likely represents a "baseline" level of stimulus for bone remodeling processes, increased strains during walking in older adults might indicate the extent of age-related impairment in bone remodeling processes. Such a measure might be clinically useful if it could be accurately determined with age-appropriate patient-specific loading, geometry, and BMD.

Skeletal unloading induces resistance to insulin-like growth factor I

NASA Technical Reports Server (NTRS)

Bikle, D. D.; Harris, J.; Halloran, B. P.; Morey-Holton, E. R.

1994-01-01

In previous studies with a hindlimb elevation model, we demonstrated that skeletal unloading transiently inhibits bone formation. This effect is limited to the unloaded bones (the normally loaded humerus does not cease growing), suggesting that local factors are of prime importance. IGF-I is one such factor; it is produced in bone and stimulates bone formation. To determine the impact of skeletal unloading on IGF-I production and function, we assessed the mRNA levels of IGF-I and its receptor (IGF-IR) in the proximal tibia and distal femur of growing rats during 2 weeks of hindlimb elevation. The mRNA levels for IGF-I and IGF-IR rose during hindlimb elevation, returning toward control values during recovery. This was accompanied by a 77% increase in IGF-I levels in the bone, peaking at day 10 of unloading. Changes in IGF binding protein levels were not observed. Infusion of IGF-I (200 micrograms/day) during 1 week of hindlimb elevation doubled the increase in bone mass of the control animals but failed to reverse the cessation of bone growth in the hindlimb-elevated animals. We conclude that skeletal unloading induces resistance to IGF-I, which may result secondarily in increased local production of IGF-I.

Progesterone as a bone-trophic hormone.

PubMed

Prior, J C

1990-05-01

Experimental, epidemiological, and clinical data indicate that progesterone is active in bone metabolism. Progesterone appears to act directly on bone by engaging an osteoblast receptor or indirectly through competition for a glucocorticoid osteoblast receptor. Progesterone seems to promote bone formation and/or increase bone turnover. It is possible, through estrogen-stimulated increased progesterone binding to the osteoblast receptor, that progesterone plays a role in the coupling of bone resorption with bone formation. A model of the interdependent actions of progesterone and estrogen on appropriately-"ready" cells in each bone multicellular unit can be tied into the integrated secretions of these hormones within the ovulatory cycle. Figure 5 is an illustration of this concept. It shows the phases of the bone remodeling cycle in parallel with temporal changes in gonadal steroids across a stylized ovulatory cycle. Increasing estrogen production before ovulation may reverse the resorption occurring in a "sensitive" bone multicellular unit while gonadal steroid levels are low at the time of menstrual flow. The bone remodeling unit would then be ready to begin a phase of formation as progesterone levels peaked in the midluteal phase. From this perspective, the normal ovulatory cycle looks like a natural bone-activating, coherence cycle. Critical analysis of the reviewed data indicate that progesterone meets the necessary criteria to play a causal role in mineral metabolism. This review provides the preliminary basis for further molecular, genetic, experimental, and clinical investigation of the role(s) of progesterone in bone remodeling. Much further data are needed about the interrelationships between gonadal steroids and the "life cycle" of bone. Feldman et al., however, may have been prophetic when he commented; "If this anti-glucocorticoid effect of progesterone also holds true in bone, then postmenopausal osteoporosis may be, in part, a progesterone deficiency disease."

Bone modeling and remodeling: potential as therapeutic targets for the treatment of osteoporosis.

PubMed

Langdahl, Bente; Ferrari, Serge; Dempster, David W

2016-12-01

The adult skeleton is renewed by remodeling throughout life. Bone remodeling is a process where osteoclasts and osteoblasts work sequentially in the same bone remodeling unit. After the attainment of peak bone mass, bone remodeling is balanced and bone mass is stable for one or two decades until age-related bone loss begins. Age-related bone loss is caused by increases in resorptive activity and reduced bone formation. The relative importance of cortical remodeling increases with age as cancellous bone is lost and remodeling activity in both compartments increases. Bone modeling describes the process whereby bones are shaped or reshaped by the independent action of osteoblast and osteoclasts. The activities of osteoblasts and osteoclasts are not necessarily coupled anatomically or temporally. Bone modeling defines skeletal development and growth but continues throughout life. Modeling-based bone formation contributes to the periosteal expansion, just as remodeling-based resorption is responsible for the medullary expansion seen at the long bones with aging. Existing and upcoming treatments affect remodeling as well as modeling. Teriparatide stimulates bone formation, 70% of which is remodeling based and 20-30% is modeling based. The vast majority of modeling represents overflow from remodeling units rather than de novo modeling. Denosumab inhibits bone remodeling but is permissive for modeling at cortex. Odanacatib inhibits bone resorption by inhibiting cathepsin K activity, whereas modeling-based bone formation is stimulated at periosteal surfaces. Inhibition of sclerostin stimulates bone formation and histomorphometric analysis demonstrated that bone formation is predominantly modeling based. The bone-mass response to some osteoporosis treatments in humans certainly suggests that nonremodeling mechanisms contribute to this response and bone modeling may be such a mechanism. To date, this has only been demonstrated for teriparatide, however, it is clear that rediscovering a phenomenon that was first observed more half a century ago will have an important impact on our understanding of how new antifracture treatments work.

Effect of metabolic and respiratory acidosis on intracellular calcium in osteoblasts

PubMed Central

Bushinsky, David A.

2010-01-01

In vivo, metabolic acidosis {decreased pH from decreased bicarbonate concentration ([HCO3−])} increases urine calcium (Ca) without increased intestinal Ca absorption, resulting in a loss of bone Ca. Conversely, respiratory acidosis [decreased pH from increased partial pressure of carbon dioxide (Pco2)] does not appreciably alter Ca homeostasis. In cultured bone, chronic metabolic acidosis (Met) significantly increases cell-mediated net Ca efflux while isohydric respiratory acidosis (Resp) does not. The proton receptor, OGR1, appears critical for cell-mediated, metabolic acid-induced bone resorption. Perfusion of primary bone cells or OGR1-transfected Chinese hamster ovary (CHO) cells with Met induces transient peaks of intracellular Ca (Cai). To determine whether Resp increases Cai, as does Met, we imaged Cai in primary cultures of bone cells. pH for Met = 7.07 ([HCO3−] = 11.8 mM) and for Resp = 7.13 (Pco2 = 88.4 mmHg) were similar and lower than neutral (7.41). Both Met and Resp induced a marked, transient increase in Cai in individual bone cells; however, Met stimulated Cai to a greater extent than Resp. We used OGR1-transfected CHO cells to determine whether OGR1 was responsible for the greater increase in Cai in Met than Resp. Both Met and Resp induced a marked, transient increase in Cai in OGR1-transfected CHO cells; however, in these cells Met was not different than Resp. Thus, the greater induction of Cai by Met in primary bone cells is not a function of OGR1 alone, but must involve H+ receptors other than OGR1, or pathways sensitive to Pco2, HCO3−, or total CO2 that modify the effect of H+ in primary bone cells. PMID:20504884

Effect of metabolic and respiratory acidosis on intracellular calcium in osteoblasts.

PubMed

Frick, Kevin K; Bushinsky, David A

2010-08-01

In vivo, metabolic acidosis {decreased pH from decreased bicarbonate concentration ([HCO(3)(-)])} increases urine calcium (Ca) without increased intestinal Ca absorption, resulting in a loss of bone Ca. Conversely, respiratory acidosis [decreased pH from increased partial pressure of carbon dioxide (Pco(2))] does not appreciably alter Ca homeostasis. In cultured bone, chronic metabolic acidosis (Met) significantly increases cell-mediated net Ca efflux while isohydric respiratory acidosis (Resp) does not. The proton receptor, OGR1, appears critical for cell-mediated, metabolic acid-induced bone resorption. Perfusion of primary bone cells or OGR1-transfected Chinese hamster ovary (CHO) cells with Met induces transient peaks of intracellular Ca (Ca(i)). To determine whether Resp increases Ca(i), as does Met, we imaged Ca(i) in primary cultures of bone cells. pH for Met = 7.07 ([HCO(3)(-)] = 11.8 mM) and for Resp = 7.13 (Pco(2) = 88.4 mmHg) were similar and lower than neutral (7.41). Both Met and Resp induced a marked, transient increase in Ca(i) in individual bone cells; however, Met stimulated Ca(i) to a greater extent than Resp. We used OGR1-transfected CHO cells to determine whether OGR1 was responsible for the greater increase in Ca(i) in Met than Resp. Both Met and Resp induced a marked, transient increase in Ca(i) in OGR1-transfected CHO cells; however, in these cells Met was not different than Resp. Thus, the greater induction of Ca(i) by Met in primary bone cells is not a function of OGR1 alone, but must involve H(+) receptors other than OGR1, or pathways sensitive to Pco(2), HCO(3)(-), or total CO(2) that modify the effect of H(+) in primary bone cells.

Ionizing Radiation Stimulates Expression of Pro-Osteoclastogenic Genes in Marrow and Skeletal Tissue

NASA Technical Reports Server (NTRS)

Alwood, J. S.; Shahnazari, M.; Chicana, B.; Schreurs, A. S.; Kumar, A.; Bartolini, A.; Shirazi-Fard, Y.; Globus, R. K.

2015-01-01

Exposure to ionizing radiation can cause rapid mineral loss and increase bone-resorbing osteoclasts within metabolically-active, cancellous-bone tissue leading to structural deficits. To better understand mechanisms involved in rapid, radiation-induced bone loss, we determined the influence of total-body irradiation on expression of select cytokines known both to stimulate osteoclastogenesis and contribute to inflammatory bone disease. Adult (16wk), male C57BL/6J mice were exposed to either 2Gy gamma rays (137Cs, 0.8Gy/min) or heavy ions (56Fe, 600MeV, 0.50-1.1Gy/min); this dose corresponds to either a single fraction of radiotherapy (typical total dose is =10Gy) or accumulates over long-duration, interplanetary missions. Serum, marrow, and mineralized tissue were harvested 4hrs-7d later. Gamma irradiation caused a prompt (2.6-fold within 4hrs) and persistent (peaking at 4.1-fold within 1d) rise in the expression of the obligate osteoclastogenic cytokine, receptor activator of nuclear factor kappaB-ligand (Rankl) within marrow cells over controls. Similarly, Rankl expression peaked in marrow cells within 3d of iron exposure (9.2-fold). Changes in Rankl expression induced by gamma irradiation preceded and overlapped with a rise in expression of other pro-osteoclastic cytokines in marrow (e.g., monocyte chemotactic protein-1 increased 11.9-fold, tumor necrosis factor-alpha increased 1.7- fold over controls). Marrow expression of the RANKL decoy receptor, osteoprotegerin (Opg), also rose after irradiation (11.3-fold). The ratio Rankl/Opg in marrow was increased 1.8-fold, a net pro-resorption balance. As expected, radiation increased a serum marker of resorption (tartrate resistant acid phosphatase) and led to cancellous bone loss (16% decrease in bone volume/total volume) through reduced trabecular struts. We conclude that total-body irradiation (gamma or heavy-ion) caused temporal, concerted regulation of gene expression within marrow and mineralized tissue for select cytokines which are responsible for osteoclastogenesis and elevated resorption; this is likely to account for rapid and progressive 52 deterioration of cancellous microarchitecture following exposure to ionizing radiation.

One year of abaloparatide, a selective peptide activator of the PTH1 receptor, increased bone mass and strength in ovariectomized rats.

PubMed

Varela, Aurore; Chouinard, Luc; Lesage, Elisabeth; Guldberg, Robert; Smith, Susan Y; Kostenuik, Paul J; Hattersley, Gary

2017-02-01

Abaloparatide is a novel 34 amino acid peptide selected to be a potent and selective activator of the parathyroid hormone receptor 1 (PTHR1) signaling pathway. The effects of 12months of abaloparatide treatment on bone mass, bone strength and bone quality was assessed in osteopenic ovariectomized (OVX) rats. SD rats were subjected to OVX or sham surgery at 6months of age and left untreated for 3months to allow OVX-induced bone loss. Eighteen OVX rats were sacrificed after this bone depletion period, and the remaining OVX rats received daily s.c. injections of vehicle (n=18) or abaloparatide at 1, 5 or 25μg/kg/d (n=18/dose level) for 12months. Sham controls (n=18) received vehicle daily. Bone changes were assessed by DXA and pQCT after 0, 3, 6 or 12months of treatment, and destructive biomechanical testing was conducted at month 12 to assess bone strength and bone quality. Abaloparatide dose-dependently increased bone mass at the lumbar spine and at the proximal and diaphyseal regions of the tibia and femur. pQCT revealed that increased cortical bone volume at the tibia was a result of periosteal expansion and endocortical bone apposition. Abaloparatide dose-dependently increased structural strength of L4-L5 vertebral bodies, the femur diaphysis, and the femur neck. Increments in peak load for lumbar spine and the femur diaphysis of abaloparatide-treated rats persisted even after adjusting for treatment-related increments in BMC, and estimated material properties were maintained or increased at the femur diaphysis with abaloparatide. The abaloparatide groups also exhibited significant and positive correlations between bone mass and bone strength at these sites. These data indicate that gains in cortical and trabecular bone mass with abaloparatide are accompanied by and correlated with improvements in bone strength, resulting in maintenance or improvement in bone quality. Thus, this study demonstrated that long-term daily administration of abaloparatide to osteopenic OVX rats led to dose-dependent improvements in bone mass, geometry and strength. Copyright © 2016. Published by Elsevier Inc.

Evaluation of laser photobiomodulation on bone defect in the femur of osteoporotic rats: a Raman spectral study

NASA Astrophysics Data System (ADS)

Soares, Luiz Guilherme P.; Aciole, Jouber Mateus d. S.; Neves, Bruno Luiz R. C.; Silveira, Landulfo; Pinheiro, Antônio L. B.

2015-03-01

Phototherapies have shown positive effects on the bone repair process, increasing the blood supply to the injured area. The aim of this study was to assess through Raman spectroscopy, the efficacy of laser phototherapy (λ = 780 nm, P = 70 mW, CW, 20.4 J/cm2 per session, 163.2 J/cm2 per treatment) on the bone repair process of osteoporotic rats. The osteoporosis induction was achieved by ovariectomy surgery. Thirty Wistar rats were divided into 4 groups (Basal; OVX, OVX + Clot and OVX + Clot + Laser), then subdivided into 2 subgroups according to the experimental time (15 and 30 days). After the osteoporosis induction time (60 days), a bone defect with 2 mm was created with a trephine drill in the right femur in the animals of groups OVX, Clot and Clot + Laser. After surgery, the irradiation protocol was applied in the same groups on repeated sessions every 48 hours during 15 days. The samples were analyzed by Raman Spectroscopy to assess the inorganic content of phosphate and carbonated hydroxyapatite (~960 and 1070 cm-1, respectively) and organic lipids and proteins (~1454 cm-1). Statistical analysis (ANOVA, Student-T test) showed significant difference between groups Basal, OVX + Clot, and OVX + Clot + Laser for the inorganic content peaks at ~960 (p≤0.001), and ~1070 cm-1 (p≤0.001) in both periods of 15 and 30 days, however on peak at ~1450 cm-1 no differences were detected. It was concluded that the Laser phototherapy increased deposition of HA on bone repair process of osteoporotic rats.

Differential effects of formononetin and cladrin on osteoblast function, peak bone mass achievement and bioavailability in rats.

PubMed

Gautam, Abnish K; Bhargavan, Biju; Tyagi, Abdul M; Srivastava, Kamini; Yadav, Dinesh K; Kumar, Manmeet; Singh, Akanksha; Mishra, Jay S; Singh, Amar Bahadur; Sanyal, Sabyasachi; Maurya, Rakesh; Manickavasagam, Lakshmi; Singh, Sheelendra P; Wahajuddin, Wahajuddin; Jain, Girish K; Chattopadhyay, Naibedya; Singh, Divya

2011-04-01

Dietary soy isoflavones including genistein and daidzein have been shown to have favorable effects during estrogen deficiency in experimental animals and humans. We have evaluated osteogenic effect of cladrin and formononetin, two structurally related methoxydaidzeins found in soy food and other natural sources. Cladrin, at as low as 10 nM, maximally stimulated both osteoblast proliferation and differentiation by activating MEK-Erk pathway. On the other hand, formononetin maximally stimulated osteoblast differentiation at 100 nM that involved p38 MAPK pathway but had no effect on osteoblast proliferation. Unlike daidzein, these two compounds neither activated estrogen receptor in osteoblast nor had any effect on osteoclast differentiation. Daily oral administration of each of these compounds at 10.0 mg kg(-1) day(-1) dose to recently weaned female Sprague-Dawley rats for 30 consecutive days, increased bone mineral density at various anatomic positions studied. By dynamic histomorphometry of bone, we observed that rats treated with cladrin exhibited increased mineral apposition and bone formation rates compared with control, while formononetin had no effect. Cladrin had much better plasma bioavailability compared with formononetin. None of these compounds exhibited estrogen agonistic effect in uteri. Our data suggest that cladrin is more potent among the two in promoting parameters of peak bone mass achievement, which could be attributed to its stimulatory effect on osteoblast proliferation and better bioavailability. To the best of our knowledge, this is the first attempt to elucidate structure-activity relationship between the methoxylated forms of daidzein and their osteogenic effects. Copyright © 2011 Elsevier Inc. All rights reserved.

Oxandrolone treatment of constitutional short stature in boys during adolescence: effect on linear growth, bone age, pubic hair, and testicular development.

PubMed

Marti-Henneberg, C; Niirianen, A K; Rappaport, R

1975-05-01

Seventeen constitutionally short boys were studied throughout puberty. Nine received oxandrolone (0.1 mg/kg/day). Treatment was started before onset of puberty. Eight boys served as control subjects. No significant increase in linear growth or skeletal maturation was observed in the treated group. Likewise the peak height velocity was unchanged. Pubic hair developed similarly in both groups in relation to chronologic and skeletal age. The only significant difference was a diminution in testicular volume index during treatment after bone age of 12 years and until bone age of 14 6/12 years.

Ionizing radiation stimulates expression of pro-osteoclastogenic genes in marrow and skeletal tissue

DOE PAGES

Alwood, Joshua S.; Shahnazari, Mohammad; Chicana, Betsabel; ...

2015-03-03

Exposure to ionizing radiation can cause rapid mineral loss and increase bone-resorbing osteoclasts within metabolically active, cancellous bone tissue leading to structural deficits. To better understand mechanisms involved in rapid, radiation-induced bone loss, we determined the influence of total body irradiation on expression of select cytokines known both to stimulate osteoclastogenesis and contribute to inflammatory bone disease. Adult (16 week), male C57BL/6J mice were exposed to either 2 Gy gamma rays ( 137Cs, 0.8 Gy/min) or heavy ions ( 56Fe, 600MeV, 0.50–1.1 Gy/min); this dose corresponds to either a single fraction of radiotherapy (typical total dose is ≥10 Gy) ormore » accumulates over long-duration interplanetary missions. Serum, marrow, and mineralized tissue were harvested 4 h—7 days later. Gamma irradiation caused a prompt (2.6-fold within 4 h) and persistent (peaking at 4.1-fold within 1 day) rise in the expression of the obligate osteoclastogenic cytokine, receptor activator of nuclear factor kappa-B ligand ( Rankl), within marrow cells over controls. Similarly, Rankl expression peaked in marrow cells within 3 days of iron exposure (9.2-fold). Changes in Rankl expression induced by gamma irradiation preceded and overlapped with a rise in expression of other pro-osteoclastic cytokines in marrow (eg, monocyte chemotactic protein-1 increased by 11.9-fold, and tumor necrosis factor-alpha increased by 1.7-fold over controls). The ratio, Rankl/ Opg, in marrow increased by 1.8-fold, a net pro-resorption balance. In the marrow, expression of the antioxidant transcription factor, Nfe2l2, strongly correlated with expression levels of Nfatc1, Csf1, Tnf, and Rankl. Radiation exposure increased a serum marker of bone resorption (tartrate-resistant acid phosphatase) and led to cancellous bone loss (16% decrement after 1 week). Finally, we conclude that total body irradiation (gamma or heavy-ion) caused temporal elevations in the concentrations of specific genes expressed within marrow and mineralized tissue related to bone resorption, including select cytokines that lead to osteoclastogenesis and elevated resorption; this is likely to account for rapid and progressive deterioration of cancellous microarchitecture following exposure to ionizing radiation.« less

Ionizing radiation stimulates expression of pro-osteoclastogenic genes in marrow and skeletal tissue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alwood, Joshua S.; Shahnazari, Mohammad; Chicana, Betsabel

Exposure to ionizing radiation can cause rapid mineral loss and increase bone-resorbing osteoclasts within metabolically active, cancellous bone tissue leading to structural deficits. To better understand mechanisms involved in rapid, radiation-induced bone loss, we determined the influence of total body irradiation on expression of select cytokines known both to stimulate osteoclastogenesis and contribute to inflammatory bone disease. Adult (16 week), male C57BL/6J mice were exposed to either 2 Gy gamma rays ( 137Cs, 0.8 Gy/min) or heavy ions ( 56Fe, 600MeV, 0.50–1.1 Gy/min); this dose corresponds to either a single fraction of radiotherapy (typical total dose is ≥10 Gy) ormore » accumulates over long-duration interplanetary missions. Serum, marrow, and mineralized tissue were harvested 4 h—7 days later. Gamma irradiation caused a prompt (2.6-fold within 4 h) and persistent (peaking at 4.1-fold within 1 day) rise in the expression of the obligate osteoclastogenic cytokine, receptor activator of nuclear factor kappa-B ligand ( Rankl), within marrow cells over controls. Similarly, Rankl expression peaked in marrow cells within 3 days of iron exposure (9.2-fold). Changes in Rankl expression induced by gamma irradiation preceded and overlapped with a rise in expression of other pro-osteoclastic cytokines in marrow (eg, monocyte chemotactic protein-1 increased by 11.9-fold, and tumor necrosis factor-alpha increased by 1.7-fold over controls). The ratio, Rankl/ Opg, in marrow increased by 1.8-fold, a net pro-resorption balance. In the marrow, expression of the antioxidant transcription factor, Nfe2l2, strongly correlated with expression levels of Nfatc1, Csf1, Tnf, and Rankl. Radiation exposure increased a serum marker of bone resorption (tartrate-resistant acid phosphatase) and led to cancellous bone loss (16% decrement after 1 week). Finally, we conclude that total body irradiation (gamma or heavy-ion) caused temporal elevations in the concentrations of specific genes expressed within marrow and mineralized tissue related to bone resorption, including select cytokines that lead to osteoclastogenesis and elevated resorption; this is likely to account for rapid and progressive deterioration of cancellous microarchitecture following exposure to ionizing radiation.« less

Intraoperative mechanical bone strength determination in tibiotalocalcaneal fusion: a biomechanical investigation.

PubMed

Klos, Kajetan; Windolf, Markus; Schwieger, Karsten; Kuhn, Philipp; Hänni, Markus; Gueorguiev, Boyko; Hofmann, Gunther O; Mückley, Thomas

2009-12-01

Bone strength is currently measured with indirect techniques. We investigated the use of an intraoperative mechanical measurement for local bone strength determination and prediction of intramedullary-nail fusion failure. We investigated whether intraoperative local bone strength determination may be useful to the surgeon in predicting intramedullary nail hindfoot fusion performance. In seven human specimens, bone mineral density (BMD) was determined with qCT. A device (DensiProbe) specially devised for nailed tibiotalocalcaneal arthrodesis (TTCA) was inserted at the intended calcaneal screw sites of an intramedullary nail, and the cancellous break-away torque was measured. The constructs were then cyclically loaded to failure in dorsiflexion-plantarfexion. The BMD range was wide (42.8 to 185.9 mg HA/cm(3)). The proximal-screw site peak torque was 0.47 to 1.61 Nm; distal-screw site peak torque was 0.24 to 1.06 Nm. The number of cycles to failure correlated with peak torque both proximally (p = 0.021; r(2) = 0.69) and distally (p = 0.001; r(2) = 0.92). Proximally, peak torque did not correlate with BMD (p = 0.060; r(2) = 0.54); distally, it correlated significantly (p = 0.003; r(2) = 0.86). DensiProbe measurements can be used in the hindfoot to assess bone strength. In this study, specimens that failed early could be identified. However, in clinical practice fusion failure is multifactorial in origin, and failure prediction cannot be based upon peak torque measurements alone. The technique described here may be of use to give an intraoperative decision aid to predict intramedullary nail hindfoot fusion performance.

Glucocorticoid-induced bone loss can be reversed by the actions of PTH and Risedronate on different pathways for bone formation and mineralization

PubMed Central

Yao, Wei; Cheng, Zhiqiang; Pham, Aaron; Busse, Cheryl; Zimmermann, Elizabeth A.; Ritchie, Robert O.; Lane, Nancy E.

2008-01-01

Glucocorticoid (GC) excess decreases bone mineralization and microarchitecture and lead to reduced bone strength. Both anabolic (PTH) and anti-resorptive agents are used to prevent and treat GC-induced bone loss, yet these bone active agents alter bone turnover by very different mechanisms. Our study objective was to determine how PTH and risedronate (Ris) alter bone quality following GC excess. Five-month-old Swiss-Webster male mice were treated with the glucocorticoid (GC) prednisolone (5 mg/kg 60-day slow-release pellet) or placebo (PL)]. At day 28−56, two groups of GC-treated animals had either PTH (5μg/kg, 5x/wk) or Ris (5μg/kg, 5x/wk) intervention. Bone quality and quantity measurements include x-ray tomography microscopy (XTM) for the degree of bone mineralization (DBM), microCT for bone microarchitecture, compression testing for trabecular bone strength, biochemistry and histomorphometry for bone turnover. In addition, real-time PCR and immunohistochemistry were performed to monitor the expression of several key genes regulating Wnt signaling (bone formation) and mineralization. Results Compared to the placebo treated mice, GC treatment decreased trabecular bone volume (BV/TV) and serum osteocalcin, but increased serum CTX and osteoclast surface with a peak at day 28. GC+PTH increased and GC+Ris restored BV/TV to the PL levels after a 28 day treatment period. Average DBM was lowered after GC treatment (−27%), and it was restored to PL level with GC+Ris and GC+PTH. At day 56, RT-PCR revealed that continuous exposure to GC and GC+PTH increased, while GC+Ris decreased the expression of genes that inhibit bone mineralization (Dmp1 and Phex), compared to the PL group. Wnt signaling antagonists Dkk1, Sost and Wif1 were up-regulated by GC treatment but were down-regulated after GC+PTH treatment. Immunohistochemistry of bone sections found GC increased N terminal dmp-1 while PTH treatment increased both N and C terminal dmp-1 staining around osteocytes. Summary GC excess reduced expression of genes that regulate mineralization and increased expression of genes that inhibit Wnt signaling which were associated with reduced bone formation and bone volume over a 60 day treatment period. The addition of both PTH and Ris improved bone mass, DBM and bone strength during concurrent GC treatment, with PTH lowering expression of Wnt inhibitors and increasing bone formation; while Ris lowered the expression of mineralization inhibitors and reversed the deterioration of bone mineralization induced by GC excess. PMID:18975341

Greater association of peak neuromuscular performance with cortical bone geometry, bone mass and bone strength than bone density: A study in 417 older women.

PubMed

Belavý, Daniel L; Armbrecht, Gabriele; Blenk, Tilo; Bock, Oliver; Börst, Hendrikje; Kocakaya, Emine; Luhn, Franziska; Rantalainen, Timo; Rawer, Rainer; Tomasius, Frederike; Willnecker, Johannes; Felsenberg, Dieter

2016-02-01

We evaluated which aspects of neuromuscular performance are associated with bone mass, density, strength and geometry. 417 women aged 60-94years were examined. Countermovement jump, sit-to-stand test, grip strength, forearm and calf muscle cross-sectional area, areal bone mineral content and density (aBMC and aBMD) at the hip and lumbar spine via dual X-ray absorptiometry, and measures of volumetric vBMC and vBMD, bone geometry and section modulus at 4% and 66% of radius length and 4%, 38% and 66% of tibia length via peripheral quantitative computed tomography were performed. The first principal component of the neuromuscular variables was calculated to generate a summary neuromuscular variable. Percentage of total variance in bone parameters explained by the neuromuscular parameters was calculated. Step-wise regression was also performed. At all pQCT bone sites (radius, ulna, tibia, fibula), a greater percentage of total variance in measures of bone mass, cortical geometry and/or bone strength was explained by peak neuromuscular performance than for vBMD. Sit-to-stand performance did not relate strongly to bone parameters. No obvious differential in the explanatory power of neuromuscular performance was seen for DXA aBMC versus aBMD. In step-wise regression, bone mass, cortical morphology, and/or strength remained significant in relation to the first principal component of the neuromuscular variables. In no case was vBMD positively related to neuromuscular performance in the final step-wise regression models. Peak neuromuscular performance has a stronger relationship with leg and forearm bone mass and cortical geometry as well as proximal forearm section modulus than with vBMD. Copyright © 2015 Elsevier Inc. All rights reserved.

Drinking water fluoridation and bone.

PubMed

Allolio, B; Lehmann, R

1999-01-01

Drinking water fluoridation has an established role in the prevention of dental caries, but may also positively or negatively affect bone. In bone fluoride is incorporated into hydroxylapatite to form the less soluble fluoroapatite. In higher concentrations fluoride stimulates osteoblast activity leading to an increase in cancellous bone mass. As optimal drinking water fluoridation (1 mg/l) is widely used, it is of great interest, whether long-term exposition to artificial water fluoridation has any impact on bone strength, bone mass, and -- most importantly -- fracture rate. Animal studies suggest a biphasic pattern of the effect of drinking water fluoridation on bone strength with a peak strength at a bone fluoride content of 1200 ppm followed by a decline at higher concentrations eventually leading to impaired bone quality. These changes are not paralleled by changes in bone mass suggesting that fluoride concentrations remain below the threshold level required for activation of osteoblast activity. Accordingly, in most epidemiological studies in humans bone mass was not altered by optimal drinking water fluoridation. In contrast, studies on the effect on hip fracture rate gave conflicting results ranging from an increased fracture incidence to no effect, and to a decreased fracture rate. As only ecological studies have been performed, they may be biased by unknown confounding factors -- the so-called ecological fallacy. However, the combined results of these studies indicate that any increase or decrease in fracture rate is likely to be small. It has been calculated that appropriately designed cohort studies to solve the problem require a sample size of >400,000 subjects. Such studies will not be performed in the foreseeable future. Future investigations in humans should, therefore, concentrate on the effect of long-term drinking water fluoridation on bone fluoride content and bone strength.

ANABOLIC BONE WINDOW WITH WEEKLY TERIPARATIDE THERAPY IN POSTMENOPAUSAL OSTEOPOROSIS: A PILOT STUDY.

PubMed

Gopalaswamy, Vinaya; Dhibar, Deba Prasad; Gupta, Vipin; Arya, Ashutosh Kumar; Khandelwal, Niranjan; Bhansali, Anil; Garg, Sudhir Kumar; Agarwal, Neelam; Rao, Sudhaker D; Bhadada, Sanjay Kumar

2017-06-01

Osteoporosis is a major public health problem that reduces bone strength and increases fracture risk. Teriparatide is an established and the only currently available anabolic therapy for the treatment of postmenopausal osteoporosis (PMO) with a recommended daily dose of 20 μg given subcutaneously. However, there are limited data regarding the long-term effect of once-weekly teriparatide therapy on bone mineral density (BMD), bone turnover markers (BTMs), and anabolic bone window. In this prospective observational study, 26 patients with PMO were treated with weekly teriparatide therapy (60 μg) for 2 years. BMD was measured at baseline, 12 months, and 24 months. The bone formation marker type 1 collagen C-terminal propeptide (P1NP) and the bone resorption marker C-terminal telopeptide of type 1 collagen (CTx) were measured at baseline; 6 weeks; and 6, 12, 18, and 24 months. BMDs at the lumbar spine increased by 3.1% and 10.8% after 1 and 2 years of weekly teriparatide therapy, respectively. The T-score increased significantly at the lumbar spine compared to baseline after 2 years of therapy (P = .015). Serum P1NP levels increased significantly at 6 months (P = .024), peaked at 1 year, and remained above the baseline even after 2 years. Serum CTx levels decreased significantly at 6 months (P = .025) and remained below baseline after 2 years of teriparatide therapy. Weekly teriparatide therapy (60 μg) appears to be as effective as daily teriparatide for the treatment of PMO by extending the anabolic bone window. AE = adverse event; BMD = bone mineral density; BTM = bone turnover marker; CTx = C-terminal telopeptide of type 1 collagen; DXA = dual-energy X-ray absorptiometry; iPTH = intact parathyroid hormone; P1NP = type 1 collagen C-terminal propeptide; PMO = postmenopausal osteoporosis.

Changes in bone resorption across the menopause transition: effects of reproductive hormones, body size, and ethnicity.

PubMed

Sowers, MaryFran R; Zheng, Huiyong; Greendale, Gail A; Neer, Robert M; Cauley, Jane A; Ellis, Jayne; Johnson, Sarah; Finkelstein, Joel S

2013-07-01

Our objective was to characterize changes in bone resorption in relation to the final menstrual period (FMP), reproductive hormones, body mass index (BMI), and ethnicity. Urinary type I collagen N-telopeptide (NTX), estradiol, and FSH levels were measured annually for up to 8 years spanning the menopause transition in 918 African American, Chinese, Japanese, or Caucasian women. Urinary NTX began to increase sharply about 2 years before the FMP, reaching its peak level about 1 to 1.5 years after the FMP. NTX levels declined modestly from 2 to 6 years after the FMP but remained about 20% higher than before the menopause transition. The sharp rise in FSH occurred in conjunction with a sharp decline in estradiol and shortly after FSH levels began increasing rapidly. The mean increase in urinary NTX across the menopause transition was greatest in women with BMI <25 kg/m² and smallest in women with BMI >30 kg/m². Increases in NTX were greatest in Japanese women and smallest in African Americans. These differences were attenuated, but not eliminated, when analyses were adjusted for covariates, particularly BMI. During the menopause transition, a decline in ovarian function beginning about 2 years before the FMP is followed by an increase in bone resorption and subsequently by bone loss. The magnitude of the increase in bone resorption is inversely associated with BMI. Ethnic differences in changes in bone resorption are attenuated, but not eliminated, by adjustment for BMI. Ethnic differences in BMI, and corresponding ethnic differences in bone resorption, appear to account for much of the ethnic variation in perimenopausal bone loss.

Peak bone mass and patterns of change in total bone mineral density and bone mineral contents from childhood into young adulthood

PubMed Central

Lu, Juan; Shin, Yongyun; Yen, Miao-Shan; Sun, Shumei S.

2014-01-01

The literature has not reached a consensus on the age when peak bone mass is achieved. This study examines growth patterns of TBMC and TBMD, peak bone mass, effect of concurrent anthropometry measures and physical activity on growth patterns in a sample of 312 white males and 343 females aged eight to 30 years. We analyzed data from participants enrolled in Fels Longitudinal Study. Descriptive analysis was used to ascertain characteristics of participants and growth patterns of TBMC and TBMD. Mixed effects models were applied to predict ages at attainment of peak TBMC and TBMD and assess effects of height, weight, BMI and habitual physical activity on the attainment. Significant differences between sexes were observed for measures of TBMC and TBMD, and differences varied with age. For females, predicted median ages at peak TBMC and TBMD attainments are 21.96 (IQR: 21.81–22.21) and 22.31 (IQR: 21.95–22.59) years, respectively. For males, predicted median ages are 23.34 (IQR: 24.34–26.19) and 26.86 (IQR: 25.14–27.98) respectively. For females, height, weight and BMI, but not physical activity, had significant influences on attainment of TBMC and TBMD (P <0.01). For males, weight and BMI, but not height and physical activity, exerted significant influence on attainment of TBMC and TBMD (P<0.01), and also modified correlations between age and peak TBMC and TBMD. Our results suggest that (1) for both sexes, trajectories of TBMC and TBMD follow a curvilinear pattern between ages eight and 30 years; (2) predicted ages at peak TBMC and TBMD are from early to late 20s for both white males and females, with females reaching their peaks significantly earlier than males; and (3) concurrent height, weight and BMI, but not habitual physical activity, exert significant effects on trajectories of TBMC and TBMD. PMID:25440183

Biomechanics of a Bone-Periodontal Ligament-Tooth Fibrous Joint

PubMed Central

Lin, Jeremy D.; Özcoban, Hüseyin; Greene, Janelle; Jang, Andrew T.; Djomehri, Sabra; Fahey, Kevin; Hunter, Luke; Schneider, Gerold A; Ho, Sunita P.

2013-01-01

This study investigates bone-tooth association under compression to identify strain amplified sites within the bone-periodontal ligament (PDL)-tooth fibrous joint. Our results indicate that the biomechanical response of the joint is due to a combinatorial response of constitutive properties of organic, inorganic, and fluid components. Second maxillary molars within intact maxillae (N=8) of 5-month-old rats were loaded with a μ-XCT-compatible in situ loading device at various permutations of displacement rates (0.2, 0.5, 1.0, 1.5, 2.0 mm/min) and peak reactionary load responses (5, 10, 15, 20 N). Results indicated a nonlinear biomechanical response of the joint, in which the observed reactionary load rates were directly proportional to displacement rates (velocities). No significant differences in peak reactionary load rates at a displacement rate of 0.2 mm/min were observed. However, for displacement rates greater than 0.2 mm/min, an increasing trend in reactionary rate was observed for every peak reactionary load with significant increases at 2.0 mm/min. Regardless of displacement rates, two distinct behaviors were identified with stiffness (S) and reactionary load rate (LR) values at a peak load of 5 N (S5 N=290–523 N/mm) being significantly lower than those at 10 N (LR5 N=1–10 N/s) and higher (S10N–20 N=380–684 N/mm; LR10N–20 N=1–19 N/s). Digital image correlation revealed the possibility of a screw-like motion of the tooth into the PDL-space, i.e., predominant vertical displacement of 35 μm at 5 N, followed by a slight increase to 40 μm at 10 N and 50 μm at 20 N of the tooth and potential tooth rotation at loads above 10 N. Narrowed and widened PDL spaces as a result of tooth displacement indicated areas of increased apparent strain within the complex. We propose that such highly strained regions are “hot spots” that can potentiate local tissue adaptation under physiological loading and adverse tissue adaptation under pathological loading conditions. PMID:23219279

Hydroxyapatite synthesis using EDTA.

PubMed

Kang, Nak Heon; Kim, Soon Je; Song, Seung Han; Choi, Sang mun; Choi, Sik Young; Kim, Youn Jung

2013-05-01

Bone comprises structure of the body and consisted of inorganic substances. It exists in an organic structure in the body. Even though it is firm and has self-healing mechanism, it can be damaged by trauma, cancer, or bone diseases. Allograft can be an alternative solution for autologous bone graft. Hydroxyapatite (Ca10(PO4)6(OH)2), an excellent candidate for allograft, can be applied to bone defect area. There are several methods to produce hydroxyapatite; however, economical cost and being time consuming make the production difficult. In this study, we synthesized hydroxyapatite with EDTA. Freeze-dried bone allograft (Hans Biomed) was used as the control group. Synthesized hydroxyapatite was a rod-shaped, white powdery substance with 2- to 5-μm length and 0.5- to 1-μm width. X-ray diffraction showed the highest sharp peak at 32°C and high peaks at 25.8°C, 39.8°C, 46.8°C, 49.5°C, and 64.0°C, indicating a similar substance to the freeze-dried bone allograft. After 3 days, the cell growth of synthesized hydroxyapatite showed 1.5-fold more than did the bone allograft. Cellular and media alkaline phosphate activity increased similar to the bone allograft. In this study, we came up with a new method to produce the hydroxyapatite. It is a convenient method that can be held in room temperature and low pressure. Also, the product can be manufactured in large quantity. It can be also transformed into scaffold structure, which will perform a stronger configuration. The manufacturing method will help the bony defect patients and make future medical products.

Modelling dental implant extraction by pullout and torque procedures.

PubMed

Rittel, D; Dorogoy, A; Shemtov-Yona, K

2017-07-01

Dental implants extraction, achieved either by applying torque or pullout force, is used to estimate the bone-implant interfacial strength. A detailed description of the mechanical and physical aspects of the extraction process in the literature is still missing. This paper presents 3D nonlinear dynamic finite element simulations of a commercial implant extraction process from the mandible bone. Emphasis is put on the typical load-displacement and torque-angle relationships for various types of cortical and trabecular bone strengths. The simulations also study of the influence of the osseointegration level on those relationships. This is done by simulating implant extraction right after insertion when interfacial frictional contact exists between the implant and bone, and long after insertion, assuming that the implant is fully bonded to the bone. The model does not include a separate representation and model of the interfacial layer for which available data is limited. The obtained relationships show that the higher the strength of the trabecular bone the higher the peak extraction force, while for application of torque, it is the cortical bone which might dictate the peak torque value. Information on the relative strength contrast of the cortical and trabecular components, as well as the progressive nature of the damage evolution, can be revealed from the obtained relations. It is shown that full osseointegration might multiply the peak and average load values by a factor 3-12 although the calculated work of extraction varies only by a factor of 1.5. From a quantitative point of view, it is suggested that, as an alternative to reporting peak load or torque values, an average value derived from the extraction work be used to better characterize the bone-implant interfacial strength. Copyright © 2017 Elsevier Ltd. All rights reserved.

Weight-bearing exercise and bone mineral accrual in children and adolescents: a review of controlled trials.

PubMed

Hind, K; Burrows, M

2007-01-01

Osteoporosis is a serious skeletal disease and as there is currently no cure, there is a large emphasis on its prevention, including the optimisation of peak bone mass. There is increasing evidence that regular weight-bearing exercise is an effective strategy for enhancing bone status during growth. This systematic review evaluates randomised and non-randomised controlled trials to date, on the effects of exercise on bone mineral accrual in children and adolescents. An online search of Medline and the Cochrane database enabled the identification of studies. Those that met the inclusion criteria were included in the review and graded according to risk for bias. Twenty-two trials were reviewed. Nine were conducted in prepubertal children (Tanner I), 8 in early pubertal (Tanner II-III) and 5 in pubertal (Tanner IV-V). Sample sizes ranged from n=10 to 65 per group. Exercise interventions included games, dance, resistance training and jumping exercises, ranging in duration from 3 to 48 months. Approximately half of the trials (n=10) included ground reaction force (GRF) data (2 to 9 times body weight). All trials in early pubertal children, 6 in pre pubertal and 2 in pubertal children, reported positive effects of exercise on bone (P<0.05). Mean increases in bone parameters over 6 months were 0.9-4.9% in prepubertal, 1.1-5.5% in early pubertal and 0.3-1.9% in pubertal exercisers compared to controls (P<0.05). Although weight-bearing exercise appears to enhance bone mineral accrual in children, particularly during early puberty; it remains unclear as to what constitutes the optimal exercise programme. Many studies to date have a high risk for bias and only a few have a low risk. Major limitations concerned selection procedures, compliance rates and control of variables. More well designed and controlled investigations are needed. Furthermore, the specific exercise intervention that will provide the optimal stimulus for peak bone mineral accretion is unclear. Future quantitative, dose-response studies using larger sample sizes and interventions that vary in GRF and frequency may characterise the most and least effective exercise programmes for bone mineral accrual in this population. In addition, the measurement of bone quality parameters and volumetric BMD would provide a greater insight into the mechanisms implicated in the adaptation of bone to exercise.

Mechanical torque measurement for in vivo quantification of bone strength in the proximal femur.

PubMed

Mueller, Marc Andreas; Hengg, Clemens; Hirschmann, Michael; Schmid, Denise; Sprecher, Christoph; Audigé, Laurent; Suhm, Norbert

2012-10-01

Bone strength determines fracture risk and fixation strength of osteosynthesis implants. In vivo, bone strength is currently measured indirectly by quantifying bone mineral density (BMD) which is however only one determinant of the bone's biomechanical competence besides the bone's macro- and micro-architecture and tissue related parameters. We have developed a measurement principle (DensiProbe™ Hip) for direct, mechanical quantification of bone strength within the proximal femur upon hip fracture fixation. Previous cadaver tests indicated a close correlation between DensiProbe™ Hip measurements, 3D micro-CT analysis and biomechanical indicators of bone strength. The goal of this study was to correlate DensiProbe™ Hip measurements with areal bone mineral density (BMD). Forty-three hip fracture patients were included in this study. Intraoperatively, DensiProbe™ Hip was inserted to the subsequent hip screw tip position within the femoral head. Peak torque to breakaway of local cancellous bone was registered. Thirty-seven patients underwent areal BMD measurements of the contralateral proximal femur. Failure of fixation was assessed radio graphically 6 and 12 weeks postoperatively. Peak torque and femoral neck BMD showed significant correlations (R=0.60, P=0.0001). In regression analysis, areal BMD explained 46% of femoral neck BMD variance in a quadratic relationship. Throughout the 12-week follow-up period, no failure of fixation was observed. DensiProbe™ Hip may capture variations of bone strength beyond areal BMD which are currently difficult to measure in vivo. A multicenter study will clarify if peak torque predicts fixation failure. Copyright © 2012 Elsevier Ltd. All rights reserved.

Different effects on bone strength and cell differentiation in pre pubertal caloric restriction versus hypothalamic suppression✩,✩✩

PubMed Central

Joshi, R.N.; Safadi, F.F.; Barbe, M.F.; Carpio-Cano, Fe Del; Popoff, S.N.; Yingling, V.R.

2013-01-01

Hypothalamic amenorrhea and energy restriction during puberty affect peak bone mass accrual. One hypothesis suggests energy restriction alters hypothalamic function resulting in suppressed estradiol levels leading to bone loss. However, both positive and negative results have been reported regarding energy restriction and bone strength. Therefore, the purpose of this study was to investigate energy restriction and hypothalamic suppression during pubertal onset on bone mechanical strength and the osteogenic capacity of bone marrow-derived cells in two models: female rats treated with gonadotropin releasing hormone antagonists (GnRH-a) or 30% energy restriction. At 23 days of age, female Sprague Dawley rats were assigned to three groups: control group (C, n=10), GnRH-a group (n=10), and Energy Restriction (ER, n=12) group. GnRH-a animals received daily injections for 27 days. The animals in the ER group received 70% of the control animals’ intake. After sacrifice (50 days of age), body weight, uterine and muscle weights were measured. Bone marrow-derived stromal cells were cultured and assayed for proliferation and differentiation into osteoblasts. Outcome measures included bone strength, bone histomorphometry and architecture, serum IGF-1 and osteocalcin. GnRH-a suppressed uterine weight, decreased osteoblast proliferation, bone strength, trabecular bone volume and architecture compared to control. Elevated serum IGF-1 and osteocalcin levels and body weight were found. The ER model had an increase in osteoblast proliferation compared to the GnRH-a group, similar bone strength relative to body weight and increased trabecular bone volume in the lumbar spine compared to control. The ER animals were smaller but had developed bone strength sufficient for their size. In contrast, suppressed estradiol via hypothalamic suppression resulted in bone strength deficits and trabecular bone volume loss. In summary, our results support the hypothesis that during periods of nutritional stress the increased vertebral bone volume may be an adaptive mechanism to store mineral which differs from suppressed estradiol resulting from hypothalamic suppression. PMID:21807131

Prematurity and bone health.

PubMed

Pieltain, C; de Halleux, V; Senterre, Th; Rigo, J

2013-01-01

Recent advances in neonatal care significantly increases survival rate in preterm and particularly in extremely low birth weight infants (ELBW infants) and nutrition is becoming one of the most challenging issue to improve short and long term health and developmental outcomes. Nutrition is also relevant for bone development and mineralization reducing the risk of osteopenia and metabolic bone disease (MBD). Osteopenia of prematurity is a multifactorial disease including predominantly nutritional but also biomechanical and environmental factors. At birth, the fetal active mineral transfer is interrupted and the preterm becomes related to the parenteral and enteral mineral supplies. On the other hand, physiological adaptation of bone to extra uterine life leads to an increase in bone resorption. This process occurring earlier in preterm than in term infants can be accompanied by an increased risk of bone fragility and fractures. Early provision of highly bioavailable mineral supplies, correction of vitamin D deficiency and the screening of serum phosphorus concentration combined to urinary mineral excretion appears to be helpful for the prevention of MBD. When available, DEXA is more sensitive than ultrasound for quantifying osteopenia in VLBW infants at the time of discharge. Catch-up of mineralization is rapidly observed during the post term period and osteopenia of prematurity seems to be a self-resolving disease although the potential long-term consequences on the attainment of peak bone mass remains uncertain. Copyright © 2013 S. Karger AG, Basel.

Genetically engineered flavonol enriched tomato fruit modulates chondrogenesis to increase bone length in growing animals.

PubMed

Choudhary, Dharmendra; Pandey, Ashutosh; Adhikary, Sulekha; Ahmad, Naseer; Bhatia, Chitra; Bhambhani, Sweta; Trivedi, Prabodh Kumar; Trivedi, Ritu

2016-02-26

Externally visible body and longitudinal bone growth is a result of proliferation of chondrocytes. In growth disorder, there is delay in the age associated increase in height. The present study evaluates the effect of extract from transgenic tomato fruit expressing AtMYB12 transcription factor on bone health including longitudinal growth. Constitutive expression of AtMYB12 in tomato led to a significantly enhanced biosynthesis of flavonoids in general and the flavonol biosynthesis in particular. Pre-pubertal ovary intact BALB/c mice received daily oral administration of vehicle and ethanolic extract of wild type (WT-TOM) and transgenic AtMYB12-tomato (MYB12-TOM) fruits for six weeks. Animal fed with MYB12-TOM showed no inflammation in hepatic tissues and normal sinusoidal Kupffer cell morphology. MYB12-TOM extract significantly increased tibial and femoral growth and subsequently improved the bone length as compared to vehicle and WT-TOM. Histomorphometry exhibited significantly wider distal femoral and proximal tibial growth plate, increased number and size of hypertrophic chondrocytes in MYB12-TOM which corroborated with micro-CT and expression of BMP-2 and COL-10, marker genes for hypertrophic cells. We conclude that metabolic reprogramming of tomato by AtMYB12 has the potential to improve longitudinal bone growth thus helping in achievement of greater peak bone mass during adolescence.

Elevated fasting and postprandial C-terminal telopeptide after Roux-en-Y gastric bypass.

PubMed

Maghsoodi, Negar; Alaghband-Zadeh, Jamshid; Cross, Gemma F; Werling, Malin; Fändriks, Lars; Docherty, Neil G; Olbers, Torsten; Dew, Tracy; Sherwood, Roy A; Vincent, Royce P; le Roux, Carel W

2017-07-01

Background Roux-en-Y gastric bypass increases circulating bile acid concentrations, known mediators of postprandial suppression of markers of bone resorption. Long-term data, however, indicate that Roux-en-Y gastric bypass confers an increased risk of bone loss on recipients. Methods Thirty-six obese individuals, median age 44 (26-64) with median body mass index at baseline of 42.5 (40.4-46) were studied before and 15 months after Roux-en-Y gastric bypass. After an overnight fast, patients received a 400 kcal mixed meal. Blood samples were collected premeal then at 30-min periods for 120 min. Pre and postmeal samples were analysed for total bile acids, parathyroid hormone and C-terminal telopeptide. Results Body weight loss post Roux-en-Y gastric bypass was associated with a median 4.9-fold increase in peak postprandial total bile acid concentration, and a median 2.4-fold increase in cumulative food evoked bile acid response. Median fasting parathyroid hormone, postprandial reduction in parathyroid hormone and total parathyroid hormone release over 120 min remained unchanged after surgery. After surgery, median fasting C-terminal telopeptide increased 2.3-fold, peak postprandial concentrations increased 3.8-fold and total release was increased 1.9-fold. Conclusions Fasting and postprandial total bile acids and C-terminal telopeptide are increased above reference range after Roux-en-Y gastric bypass. These changes occur in spite of improved vitamin D status with supplementation. These results suggest that post-Roux-en-Y gastric bypass increases in total bile acids do not effectively oppose an ongoing resorptive signal operative along the gut-bone axis. Serial measurement of C-terminal telopeptide may be of value as a risk marker for long-term skeletal pathology in patients post Roux-en-Y gastric bypass.

Delayed Expression of Circulating TGF-β1 and BMP-2 Levels in Human Nonunion Long Bone Fracture Healing.

PubMed

Hara, Yoshiaki; Ghazizadeh, Mohammad; Shimizu, Hajime; Matsumoto, Hisashi; Saito, Nobuyuki; Yagi, Takanori; Mashiko, Kazuki; Mashiko, Kunihiro; Kawai, Makoto; Yokota, Hiroyuki

2017-01-01

The healing process of bone fracture requires a well-controlled multistage and sequential order beginning immediately after the injury. However, complications leading to nonunion exist, creating serious problems and costs for patients. Transforming growth factor-beta 1 (TGF-β1) and bone morphogenic protein 2 (BMP-2) are two major growth factors involved in human bone fracture healing by promoting various stages of bone ossification. In this study, we aimed to determine the role of these factors during the fracture healing of human long bones and assess their impacts on nonunion condition. We performed a comprehensive analysis of plasma TGF-β1 and BMP-2 levels in blood samples from 10 patients with proved nonunion and 10 matched patients with normal union following a predetermined time schedule. The concentrations of TGF-β1 and BMP-2 were measured at each time point using a solid-phase ELISA. TGF-β1 and BMP-2 levels were detectable in all patients. For all patients, a maximal peak for TGF-β1 was found at 3-week. In normal union group, TGF-β1 showed a maximal peak at 2-week while nonunion group had a delayed maximal peak at 3-week. Plasma levels of BMP-2 for all patients and for normal union group reached a maximal peak at 1-week, but nonunion group showed a delayed maximal peak at 2-week. In general, plasma TGF-β1 or BMP-2 level was not significantly different between normal union and nonunion groups. The expression levels of TGF-β1 and BMP-2 appeared to be delayed in nonunion patients which could play an important role in developing an early marker of fracture union condition and facilitate improved patient's management.

Varying whole body vibration amplitude differentially affects tendon and ligament structural and material properties

PubMed Central

Keller, Benjamin V.; Davis, Matthew L.; Thompson, William R.; Dahners, Laurence E.; Weinhold, Paul S.

2014-01-01

Whole Body Vibration (WBV) is becoming increasingly popular for helping to maintain bone mass and strengthening muscle. Vibration regimens optimized for bone maintenance often operate at hypogravity levels (<1 G) and regimens for muscle strengthening often employ hypergravity (>1 G) vibrations. The effect of vibratory loads on tendon and ligament properties is unclear though excessive vibrations may be injurious. Our objective was to evaluate how tendon gene expression and the mechanical/histological properties of tendon and ligament were affected in response to WBV in the following groups: no vibration, low vibration (0.3 G peak-to-peak), and high vibration (2 G peak-to-peak). Rats were vibrated for 20 min a day, 5 days a week, for 5 weeks. Upon sacrifice, the medial collateral ligament (MCL), patellar tendon (PT), and the Achilles Tendon (AT) were isolated with insertion sites intact. All tissues were tensile tested to determine structural and material properties or used for histology. Patellar tendon was also subjected to quantitative RT-PCR to evaluate expression of anabolic and catabolic genes. No differences in biomechanical data between the control and the low vibration groups were found. There was evidence of significant weakness in the MCL with high vibration, but no significant effect on the PT or AT. Histology of the MCL and PT showed a hypercellular tissue response and some fiber disorganization with high vibration. High vibration caused an increase in collagen expression and a trend for an increase in IGF-1 expression suggesting a potential anabolic response to prevent tendon overuse injury. PMID:23623311

Biomechanical study of tarsometatarsal joint fusion using finite element analysis.

PubMed

Wang, Yan; Li, Zengyong; Zhang, Ming

2014-11-01

Complications of surgeries in foot and ankle bring patients with severe sufferings. Sufficient understanding of the internal biomechanical information such as stress distribution, contact pressure, and deformation is critical to estimate the effectiveness of surgical treatments and avoid complications. Foot and ankle is an intricate and synergetic system, and localized intervention may alter the functions to the adjacent components. The aim of this study was to estimate biomechanical effects of the TMT joint fusion using comprehensive finite element (FE) analysis. A foot and ankle model consists of 28 bones, 72 ligaments, and plantar fascia with soft tissues embracing all the segments. Kinematic information and ground reaction force during gait were obtained from motion analysis. Three gait instants namely the first peak, second peak and mid-stance were simulated in a normal foot and a foot with TMT joint fusion. It was found that contact pressure on plantar foot increased by 0.42%, 19% and 37%, respectively after TMT fusion compared with normal foot walking. Navico-cuneiform and fifth meta-cuboid joints sustained 27% and 40% increase in contact pressure at second peak, implying potential risk of joint problems such as arthritis. Von Mises stress in the second metatarsal bone increased by 22% at midstance, making it susceptible to stress fracture. This study provides biomechanical information for understanding the possible consequences of TMT joint fusion. Copyright © 2014 IPEM. Published by Elsevier Ltd. All rights reserved.

Comparison of the Pullout Strength of Different Pedicle Screw Designs and Augmentation Techniques in an Osteoporotic Bone Model.

PubMed

Kiyak, Gorkem; Balikci, Tevfik; Heydar, Ahmed Majid; Bezer, Murat

2018-02-01

Mechanical study. To compare the pullout strength of different screw designs and augmentation techniques in an osteoporotic bone model. Adequate bone screw pullout strength is a common problem among osteoporotic patients. Various screw designs and augmentation techniques have been developed to improve the biomechanical characteristics of the bone-screw interface. Polyurethane blocks were used to mimic human osteoporotic cancellous bone, and six different screw designs were tested. Five standard and expandable screws without augmentation, eight expandable screws with polymethylmethacrylate (PMMA) or calcium phosphate augmentation, and distal cannulated screws with PMMA and calcium phosphate augmentation were tested. Mechanical tests were performed on 10 unused new screws of each group. Screws with or without augmentation were inserted in a block that was held in a fixture frame, and a longitudinal extraction force was applied to the screw head at a loading rate of 5 mm/min. Maximum load was recorded in a load displacement curve. The peak pullout force of all tested screws with or without augmentation was significantly greater than that of the standard pedicle screw. The greatest pullout force was observed with 40-mm expandable pedicle screws with four fins and PMMA augmentation. Augmented distal cannulated screws did not have a greater peak pullout force than nonaugmented expandable screws. PMMA augmentation provided a greater peak pullout force than calcium phosphate augmentation. Expandable pedicle screws had greater peak pullout forces than standard pedicle screws and had the advantage of augmentation with either PMMA or calcium phosphate cement. Although calcium phosphate cement is biodegradable, osteoconductive, and nonexothermic, PMMA provided a significantly greater peak pullout force. PMMA-augmented expandable 40-mm four-fin pedicle screws had the greatest peak pullout force.

Age-related changes in the fracture resistance of male Fischer F344 rat bone.

PubMed

Uppuganti, Sasidhar; Granke, Mathilde; Makowski, Alexander J; Does, Mark D; Nyman, Jeffry S

2016-02-01

In addition to the loss in bone volume that occurs with age, there is a decline in material properties. To test new therapies or diagnostic tools that target such properties as material strength and toughness, a pre-clinical model of aging would be useful in which changes in bone are similar to those that occur with aging in humans. Toward that end, we hypothesized that similar to human bone, the estimated toughness and material strength of cortical bone at the apparent-level decreases with age in the male Fischer F344 rat. In addition, we tested whether the known decline in trabecular architecture in rats translated to an age-related decrease in vertebra (VB) strength and whether non-X-ray techniques could quantify tissue changes at micron and sub-micron length scales. Bones were harvested from 6-, 12-, and 24-month (mo.) old rats (n=12 per age). Despite a loss in trabecular bone with age, VB compressive strength was similar among the age groups. Similarly, whole-bone strength (peak force) in bending was maintained (femur) or increased (radius) with aging. There was though an age-related decrease in post-yield toughness (radius) and bending strength (femur). The ability to resist crack initiation was actually higher for the 12-mo. and 24-mo. than for 6-mo. rats (notch femur), but the estimated work to propagate the crack was less for the aged bone. For the femur diaphysis region, porosity increased while bound water decreased with age. For the radius diaphysis, there was an age-related increase in non-enzymatic and mature enzymatic collagen crosslinks. Raman spectroscopy analysis of embedded cross-sections of the tibia mid-shaft detected an increase in carbonate subsitution with advanced aging for both inner and outer tissue. Published by Elsevier Inc.

Spatial relationship between bone formation and mechanical stimulus within cortical bone: Combining 3D fluorochrome mapping and poroelastic finite element modelling.

PubMed

Carrieroa, A; Pereirab, A F; Wilson, A J; Castagno, S; Javaheri, B; Pitsillides, A A; Marenzana, M; Shefelbine, S J

2018-06-01

Bone is a dynamic tissue and adapts its architecture in response to biological and mechanical factors. Here we investigate how cortical bone formation is spatially controlled by the local mechanical environment in the murine tibia axial loading model (C57BL/6). We obtained 3D locations of new bone formation by performing 'slice and view' 3D fluorochrome mapping of the entire bone and compared these sites with the regions of high fluid velocity or strain energy density estimated using a finite element model, validated with ex-vivo bone surface strain map acquired ex-vivo using digital image correlation. For the comparison, 2D maps of the average bone formation and peak mechanical stimulus on the tibial endosteal and periosteal surface across the entire cortical surface were created. Results showed that bone formed on the periosteal and endosteal surface in regions of high fluid flow. Peak strain energy density predicted only the formation of bone periosteally. Understanding how the mechanical stimuli spatially relates with regions of cortical bone formation in response to loading will eventually guide loading regime therapies to maintain or restore bone mass in specific sites in skeletal pathologies.

G-CSF Analogue Treatment Increases Peripheral Neutrophil Numbers in Pigs - a Potential Alternative for In-Feed Antibiotics

USDA-ARS?s Scientific Manuscript database

Immunomodulators is a promising area for therapeutic, prophylactic, and metaphylactic use to prevent and combat infectious disease during periods of peak disease incidence. Granulocyte colony-stimulating factor (G-CSF) enhances neutrophil production and release from the bone marrow and is already li...

Evaluation of the effects of implant materials and designs on thermal necrosis of bone in cemented hip arthroplasty.

PubMed

Li, Chaodi; Kotha, Shiva; Mason, James

2003-01-01

The exothermic polymerization of bone cement may induce thermal necrosis of bone in cemented hip arthroplasty. A finite element formulation was developed to predict the evolution of the temperature with time in the cemented hip replacement system. The developed method is capable of taking into account both the chemical reaction that generates heat during bone cement polymerization (through a kinetic model) and the physical process of heat conduction (with an energy balance equation). The possibility of thermal necrosis of bone was then evaluated based on the temperature history in the bone and an appropriate damage criterion. Specifically, we evaluate the role of implant materials and designs on the thermal response of the system. Results indicated that the peak temperature at the bone/cement interface with a metal prosthesis was lower than that with a polymer or a composite prosthesis in hip replacement systems. Necrosis of bone was predicted to occur with a polymer or a composite prosthesis while no necrosis was predicted with a metal prosthesis in the simulated conditions. When reinforcing osteoporotic hips with injected bone cement in the cancellous core of the femur, the volume of bone cement implanted is increased which may increase the risk of thermal necrosis of bone. We evaluate whether this risk can be decreased through the use of an insulator to contain the bone cement. No thermal necrosis of bone was predicted with a 3 mm thick polyurethane insulator while more damage is predicted for the use of bone cement without the insulator. This method provides a numerical tool for the quantitative simulation of the thermal behavior of bone-cement-prosthesis designs and for examining and refining new designs computationally.

Sex Steroid Actions in Male Bone

PubMed Central

Laurent, Michaël R.; Claessens, Frank; Gielen, Evelien; Lagerquist, Marie K.; Vandenput, Liesbeth; Börjesson, Anna E.; Ohlsson, Claes

2014-01-01

Sex steroids are chief regulators of gender differences in the skeleton, and male gender is one of the strongest protective factors against osteoporotic fractures. This advantage in bone strength relies mainly on greater cortical bone expansion during pubertal peak bone mass acquisition and superior skeletal maintenance during aging. During both these phases, estrogens acting via estrogen receptor-α in osteoblast lineage cells are crucial for male cortical and trabecular bone, as evident from conditional genetic mouse models, epidemiological studies, rare genetic conditions, genome-wide meta-analyses, and recent interventional trials. Genetic mouse models have also demonstrated a direct role for androgens independent of aromatization on trabecular bone via the androgen receptor in osteoblasts and osteocytes, although the target cell for their key effects on periosteal bone formation remains elusive. Low serum estradiol predicts incident fractures, but the highest risk occurs in men with additionally low T and high SHBG. Still, the possible clinical utility of serum sex steroids for fracture prediction is unknown. It is likely that sex steroid actions on male bone metabolism rely also on extraskeletal mechanisms and cross talk with other signaling pathways. We propose that estrogens influence fracture risk in aging men via direct effects on bone, whereas androgens exert an additional antifracture effect mainly via extraskeletal parameters such as muscle mass and propensity to fall. Given the demographic trends of increased longevity and consequent rise of osteoporosis, an increased understanding of how sex steroids influence male bone health remains a high research priority. PMID:25202834

Fast decomposition of two ultrasound longitudinal waves in cancellous bone using a phase rotation parameter for bone quality assessment: Simulation study.

PubMed

Taki, Hirofumi; Nagatani, Yoshiki; Matsukawa, Mami; Kanai, Hiroshi; Izumi, Shin-Ichi

2017-10-01

Ultrasound signals that pass through cancellous bone may be considered to consist of two longitudinal waves, which are called fast and slow waves. Accurate decomposition of these fast and slow waves is considered to be highly beneficial in determination of the characteristics of cancellous bone. In the present study, a fast decomposition method using a wave transfer function with a phase rotation parameter was applied to received signals that have passed through bovine bone specimens with various bone volume to total volume (BV/TV) ratios in a simulation study, where the elastic finite-difference time-domain method is used and the ultrasound wave propagated parallel to the bone axes. The proposed method succeeded to decompose both fast and slow waves accurately; the normalized residual intensity was less than -19.5 dB when the specimen thickness ranged from 4 to 7 mm and the BV/TV value ranged from 0.144 to 0.226. There was a strong relationship between the phase rotation value and the BV/TV value. The ratio of the peak envelope amplitude of the decomposed fast wave to that of the slow wave increased monotonically with increasing BV/TV ratio, indicating the high performance of the proposed method in estimation of the BV/TV value in cancellous bone.

The impact of zoledronic acid on regenerate and native bone after consolidation and removal of the external fixator: an animal model study.

PubMed

Saghieh, Said; Khoury, Nabil J; Tawil, Ayman; Masrouha, Karim Z; Musallam, Khaled M; Khalaf, Kinda; Dosh, Laura; Jaouhari, Rosemarie Reich; Birjawi, Ghina; El-Hajj-Fuleihan, Ghada

2010-02-01

We investigated the role of zoledronic acid on the regenerate and native bone after consolidation and removal of the external fixator in a rabbit model of distraction osteogenesis using 28 New Zealand white rabbits. The rabbits were randomly distributed into two groups. The first group received three doses of zoledronic acid (ZA) 0.1 mg/kg subcutaneously at weekly intervals while the second group received injections of sterile saline. Distraction started on day 7 at a rate of 0.8 mm/day for 12 days. At week 3 the average lengthening, regenerate density, and regenerate continuity were comparable between the two groups. At week 11 the regenerate in the treated group had a significant increase in Bone Mineral Density (BMD) and Bone Mineral Content (BMC) compared to the placebo group. On axial compression, the regenerate showed an increase in the peak load and a higher modulus of elasticity in the treated group. At 6 months, radiographs demonstrated signs of osteopenia of the proximal metaphysis in the control group, and failure of new bone formation around the pin sites in the treated group. BMC and BMD value differences between the two groups were not statistically significant. Histologically, there was persistence of more bone trabeculae in the medullary canal of the regenerate with the persistence of the pin-holes in the treated group. Mechanically, the regenerates in the treated group remain stronger in resisting the axial compression. The proximal fragment in the treated group exhibited a statistically significant decrease in the peak load, toughness and efail %. In conclusion, bisphosphonate-treated rabbits have a stronger regenerate during distraction, and directly after removal of the fixator. They do not develop disuse osteopenia in their lengthened tibia. This treatment may shorten the time in the external fixator and prevent fragility fractures in the treated extremity. However, its long-term safety has not yet been established. (c) 2009 Elsevier Inc. All rights reserved.

Effects of nano-scaled fish bone on the gelation properties of Alaska pollock surimi.

PubMed

Yin, Tao; Park, Jae W

2014-05-01

Gelation properties of Alaska pollock surimi as affected by addition of nano-scaled fish bone (NFB) at different levels (0%, 0.1%, 0.25%, 0.5%, 1% and 2%) were investigated. Breaking force and penetration distance of surimi gels after setting increased significantly as NFB concentration increased up to 1%. The first peak temperature and value of storage modulus (G'), which is known to relate to the unfolding and aggregation of light meromyosin, increased as NFB concentration increased. In addition, 1% NFB treatment demonstrated the highest G' after gelation was completed. The activity of endogenous transglutaminase (TGase) in Alaska pollock surimi increased as NFB calcium concentration increased. The intensity of myosin heavy chain cross-links also increased as NFB concentration increased indicating the formation of more ε-(γ-glutamyl) lysine covalent bond by endogenous TGase and calcium ions from NFB. Copyright © 2013 Elsevier Ltd. All rights reserved.

A comparison of skeletal maturity and growth.

PubMed

Molinari, Luciano; Gasser, Theo; Largo, Remo

2013-07-01

Somatic and bone development have each been studied in detail, but rarely in conjunction. The aim of this study was to determine what somatic and bone development have in common and how they differ. A second aim was to check for a pubertal spurt in bone age (BA) and to quantify it in a similar way as has been done for height. The Preece-Baines model is used to fit longitudinal data for BA. The data analysed are from the 1st Zurich Longitudinal Growth Study comprising 120 boys and 112 girls with almost complete data from birth to adulthood. Variability of somatic milestones was reduced in terms of BA and there was an aftergrowth after reaching adult RUS score 1000. A strong increase in the RUS score was seen at a late stage of the pubertal spurt (PS). Somatic milestones correlated with the RUS score attained at these ages and more so at an early stage of the PS. A PS for BA was clearly identified with a location at 14.2 years for boys and 12.2 years for girls. Age of peak bone development correlated highly with age of peak velocity of somatic variables. BA can be successfully modelled as a semi-quantitative entity. Bone development shows marked associations with somatic development, despite the fact that the latter reflects changes in size, while the former is essentially a maturity index and reflects changes in biochemical composition of tissues.

Effects of LED phototherapy on bone defects grafted with MTA, bone morphogenetic proteins and guided bone regeneration: a Raman spectroscopic study.

PubMed

Pinheiro, Antonio L B; Soares, Luiz G P; Cangussú, Maria Cristina T; Santos, Nicole R S; Barbosa, Artur Felipe S; Silveira Júnior, Landulfo

2012-09-01

We studied peaks of calcium hydroxyapatite (CHA) and protein and lipid CH groups in defects grafted with mineral trioxide aggregate (MTA) treated or not with LED irradiation, bone morphogenetic proteins and guided bone regeneration. A total of 90 rats were divided into ten groups each of which was subdivided into three subgroups (evaluated at 15, 21 and 30 days after surgery). Defects were irradiated with LED light (wavelength 850 ± 10 nm) at 48-h intervals for 15 days. Raman readings were taken at the surface of the defects. There were no statistically significant differences in the CHA peaks among the nonirradiated defects at any of the experimental time-points. On the other hand, there were significant differences between the defects filled with blood clot and the irradiated defects at all time-points (p < 0.001, p = 0.02, p < 0.001). There were significant differences between the mean peak CHA in nonirradiated defects at all the experimental time-points (p < 0.01). The mean peak of the defects filled with blood clot was significantly different from that of the defects filled with MTA (p < 0.001). There were significant differences between the defects filled with blood clot and the irradiated defects (p < 0.001). The results of this study using Raman spectral analysis indicate that infrared LED light irradiation improves the deposition of CHA in healing bone grafted or not with MTA.

Bone disease in cystic fibrosis: new pathogenic insights opening novel therapies.

PubMed

Jacquot, J; Delion, M; Gangloff, S; Braux, J; Velard, F

2016-04-01

Mutations within the gene encoding for the chloride ion channel cystic fibrosis transmembrane conductance regulator (CFTR) results in cystic fibrosis (CF), the most common lethal autosomal recessive genetic disease that causes a number of long-term health problems, as the bone disease. Osteoporosis and increased vertebral fracture risk associated with CF disease are becoming more important as the life expectancy of patients continues to improve. The etiology of low bone density is multifactorial, most probably a combination of inadequate peak bone mass during puberty and increased bone losses in adults. Body mass index, male sex, advanced pulmonary disease, malnutrition and chronic therapies are established additional risk factors for CF-related bone disease (CFBD). Consistently, recent evidence has confirmed that CFTR plays a major role in the osteoprotegerin (OPG) and COX-2 metabolite prostaglandin E2 (PGE2) production, two key regulators in the bone formation and regeneration. Several others mechanisms were also recognized from animal and cell models contributing to malfunctions of osteoblast (cell that form bone) and indirectly of bone-resorpting osteoclasts. Understanding such mechanisms is crucial for the development of therapies in CFBD. Innovative therapeutic approaches using CFTR modulators such as C18 have recently shown in vitro capacity to enhance PGE2 production and normalized the RANKL-to-OPG ratio in human osteoblasts bearing the mutation F508del-CFTR and therefore potential clinical utility in CFBD. This review focuses on the recently identified pathogenic mechanisms leading to CFBD and potential future therapies for treating CFBD.

The influence of uncemented femoral stem length and design on its primary stability: a finite element analysis.

PubMed

Reimeringer, M; Nuño, N; Desmarais-Trépanier, C; Lavigne, M; Vendittoli, P A

2013-01-01

One of the crucial factors for short- and long-term clinical success of total hip arthroplasty cementless implants is primary stability. Indeed, motion at the bone-implant interface above 40 μm leads to partial bone ingrowth, while motion exceeding 150 μm completely inhibits bone ingrowth. The aim of this study was to investigate the effect of two cementless femoral stem designs with different lengths on the primary stability. A finite element model of a composite Sawbones(®) fourth generation, implanted with five lengths of the straight prosthesis design and four lengths of the curved prosthesis design, was loaded with hip joint and abductor forces representing two physiological activities: fast walking and stair climbing. We found that reducing the straight stem length from 146 to 54 mm increased the average micromotion from 17 to 52 μm during fast walking, while the peak value increased from 42 to 104 μm. With the curved stem, reducing length from 105 to 54 mm increased the average micromotion from 10 to 29 μm, while the peak value increased from 37 to 101 μm. Similar findings are obtained for stair climbing for both stems. Although the present study showed that femoral stem length as well as stem design directly influences its primary stability, for the two femoral stems tested, length could be reduced substantially without compromising the primary stability. With the aim of minimising surgical invasiveness, newer femoral stem design and currently well performing stems might be used with a reduced length without compromising primary stability and hence, long-term survivorship.

Effects of Loading Duration and Short Rest Insertion on Cancellous and Cortical Bone Adaptation in the Mouse Tibia

PubMed Central

Yang, Haisheng; Embry, Rachel E.; Main, Russell P.

2017-01-01

The skeleton’s osteogenic response to mechanical loading can be affected by loading duration and rest insertion during a series of loading events. Prior animal loading studies have shown that the cortical bone response saturates quickly and short rest insertions between load cycles can enhance cortical bone formation. However, it remains unknown how loading duration and short rest insertion affect load-induced osteogenesis in the mouse tibial compressive loading model, and particularly in cancellous bone. To address this issue, we applied cyclic loading (-9 N peak load; 4 Hz) to the tibiae of three groups of 16 week-old female C57BL/6 mice for two weeks, with a different number of continuous load cycles applied daily to each group (36, 216 and 1200). A fourth group was loaded under 216 daily load cycles with a 10 s rest insertion after every fourth cycle. We found that as few as 36 load cycles per day were able to induce osteogenic responses in both cancellous and cortical bone. Furthermore, while cortical bone area and thickness continued to increase through 1200 cycles, the incremental increase in the osteogenic response decreased as load number increased, indicating a reduced benefit of the increasing number of load cycles. In the proximal metaphyseal cancellous bone, trabecular thickness increased with load up to 216 cycles. We also found that insertion of a 10 s rest between load cycles did not improve the osteogenic response of the cortical or cancellous tissues compared to continuous loading in this model given the age and sex of the mice and the loading parameters used here. These results suggest that relatively few load cycles (e.g. 36) are sufficient to induce osteogenic responses in both cortical and cancellous bone in the mouse tibial loading model. Mechanistic studies using the mouse tibial loading model to examine bone formation and skeletal mechanobiology could be accomplished with relatively few load cycles. PMID:28076363

Age-related Changes in the Fracture Resistance of Male Fischer F344 Rat Bone

PubMed Central

Uppuganti, Sasidhar; Granke, Mathilde; Makowski, Alexander J.; Does, Mark D.; Nyman, Jeffry S.

2015-01-01

In addition to the loss in bone volume that occurs with age, there is a decline in material properties. To test new therapies or diagnostic tools that target such properties as material strength and toughness, a pre-clinical model of aging would be useful in which changes in bone are similar to those that occur with aging in humans. Toward that end, we hypothesized that similar to human bone, the estimated toughness and material strength of cortical bone at the apparent-level decreases with age in the male Fischer F344 rat. In addition, we tested whether the known decline in trabecular architecture in rats translated to an age-related decrease in vertebra (VB) strength and whether non-X-ray techniques could quantify tissue changes at micron and sub-micron length scales. Bones were harvested from 6-, 12-, and 24-month (mo.) old rats (n=12 per age). Despite a loss in trabecular bone with age, VB compressive strength was similar among the age groups. Similarly, whole-bone strength (peak force) in bending was maintained (femur) or increased (radius) with aging. There was though an age-related decrease in post-yield toughness (radius) and bending strength (femur). The ability to resist crack initiation was actually higher for the 12-mo. and 24-mo. than for 6-mo. rats (notch femur), but the estimated work to propagate the crack was less for the aged bone. For the femur diaphysis region, porosity increased while bound water decreased with age. For the radius diaphysis, there was an age-related increase in non-enzymatic and mature enzymatic collagen crosslinks. Both Raman spectroscopy and reference point indentation detected differences in tissue properties with age, though the trends did not necessarily match observations from human tissue. PMID:26610688

Bone health in HIV-infected children and adolescents.

PubMed

Eckard, Allison R; Mora, Stefano

2016-05-01

Chronic HIV infection and exposure to antiretroviral therapy compromises bone health in children and adolescents, potentially impacting their long-term quality of life. Thus, the purpose of this article is to review the most recent literature on this topic in HIV-infected children and adolescents. Recent studies continue to demonstrate bone abnormalities in HIV-infected children and adolescents, whether HIV is acquired perinatally or during adolescence. Researchers have employed new modalities, both high tech and those that can be utilized in resource-limited settings, to better assess bone health. New data suggest that this population may also be experiencing an increase incidence of fractures, and they may not acquire the same peak bone mass as their HIV-uninfected counterparts. Reassuringly, however, in-utero tenofovir exposure does not appear to have a significant impact on bone health in HIV-exposed, uninfected infants. HIV-infected children and adolescents are exposed to HIV and antiretroviral therapy for many decades starting early in life and during the most critical time for skeletal growth and bone mass accrual. Recent findings underscore the need for further research on bone in this population. Longitudinal studies are especially needed to evaluate long-term risk of osteoporosis and fracture.

Influence of Screw Length and Bone Thickness on the Stability of Temporary Implants

PubMed Central

Fernandes, Daniel Jogaib; Elias, Carlos Nelson; Ruellas, Antônio Carlos de Oliveira

2015-01-01

The purpose of this work was to study the influence of screw length and bone thickness on the stability of temporary implants. A total of 96 self-drilling temporary screws with two different lengths were inserted into polyurethane blocks (n = 66), bovine femurs (n = 18) and rabbit tibia (n = 12) with different cortical thicknesses (1 to 8 mm). Screws insertion in polyurethane blocks was assisted by a universal testing machine, torque peaks were collected by a digital torquemeter and bone thickness was monitored by micro-CT. The results showed that the insertion torque was significantly increased with the thickness of cortical bone from polyurethane (p < 0.0001), bovine (p = 0.0035) and rabbit (p < 0.05) sources. Cancellous bone improved significantly the mechanical implant stability. Insertion torque and insertion strength was successfully moduled by equations, based on the cortical/cancellous bone behavior. Based on the results, insertion torque and bone strength can be estimate in order to prevent failure of the cortical layer during temporary screw placement. The stability provided by a cortical thickness of 2 or 1 mm coupled to cancellous bone was deemed sufficient for temporary implants stability. PMID:28793582

An integrative modeling approach for the efficient estimation of cross sectional tibial stresses during locomotion.

PubMed

Derrick, Timothy R; Edwards, W Brent; Fellin, Rebecca E; Seay, Joseph F

2016-02-08

The purpose of this research was to utilize a series of models to estimate the stress in a cross section of the tibia, located 62% from the proximal end, during walking. Twenty-eight male, active duty soldiers walked on an instrumented treadmill while external force data and kinematics were recorded. A rigid body model was used to estimate joint moments and reaction forces. A musculoskeletal model was used to gather muscle length, muscle velocity, moment arm and orientation information. Optimization procedures were used to estimate muscle forces and finally internal bone forces and moments were applied to an inhomogeneous, subject specific bone model obtained from CT scans to estimate stress in the bone cross section. Validity was assessed by comparison to stresses calculated from strain gage data in the literature and sensitivity was investigated using two simplified versions of the bone model-a homogeneous model and an ellipse approximation. Peak compressive stress occurred on the posterior aspect of the cross section (-47.5 ± 14.9 MPa). Peak tensile stress occurred on the anterior aspect (27.0 ± 11.7 MPa) while the location of peak shear was variable between subjects (7.2 ± 2.4 MPa). Peak compressive, tensile and shear stresses were within 0.52 MPa, 0.36 MPa and 3.02 MPa respectively of those calculated from the converted strain gage data. Peak values from a inhomogeneous model of the bone correlated well with homogeneous model (normal: 0.99; shear: 0.94) as did the normal ellipse model (r=0.89-0.96). However, the relationship between shear stress in the inhomogeneous model and ellipse model was less accurate (r=0.64). The procedures detailed in this paper provide a non-invasive and relatively quick method of estimating cross sectional stress that holds promise for assessing injury and osteogenic stimulus in bone during normal physical activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

A New Insight to Bone Turnover: Role of ω-3 Polyunsaturated Fatty Acids

PubMed Central

López-Frías, Magdalena; López-Aliaga, Inmaculada; Ochoa, Julio J.

2013-01-01

Background. Evidence has shown that long-chain polyunsaturated fatty acids (LCPUFA), especially the ω-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are beneficial for bone health and turnover. Objectives. This review summarizes findings from both in vivo and in vitro studies and the effects of LC PUFA on bone metabolism, as well as the relationship with the oxidative stress, the inflammatory process, and obesity. Results. Some studies in humans indicate that LCPUFA can increase bone formation, affect peak bone mass in adolescents, and reduce bone loss. However, the cellular mechanisms of action of the LCPUFA are complex and involve modulation of fatty acid metabolites such as prostaglandins, resolvins and protectins, several signaling pathways, cytokines, and growth factors, although in certain aspects there is still some controversy. LCPUFA affect receptor activator of nuclear factor κ β (RANK), a receptor found on the osteoclast, causing bone resorption, which controls osteoclast formation. Conclusions. Since fatty acids are an endogenous source of reactive oxygen species, free radicals alter the process of bone turnover; however, although there are clinical evidences linking bone metabolism and dietary lipids, more clinical trials are necessary to prove whether ω-3 PUFA supplementation plays a major role in bone health. PMID:24302863

Influence of implant collar design on stress and strain distribution in the crestal compact bone: a three-dimensional finite element analysis.

PubMed

Shen, Wan-Ling; Chen, Chen-Sheng; Hsu, Ming-Lun

2010-01-01

To evaluate the influence of implant collar geometry on the distribution of stress and strain in the crestal compact bone contiguous to an implant collar for four types of bone under axial and oblique loads. Finite element models of threaded implants with three kinds of implant collar designs (divergent, straight, and convergent) with their corresponding suprastructures embedded in the posterior mandible were created with ANSYS software. Eight different test conditions incorporating four types of bone (orthotropic and effectively isotropic in part 1 and high and low densities in part 2) under separate 100-N axial and 35.6-degree oblique forces were created to investigate the stress and strain distributions in the crestal compact bone around the implant collars. In all eight conditions, the divergent collar demonstrated the lowest maximum von Mises and principal stresses and strains in the crestal compact bone contiguous to the implant collar, followed by the straight and convergent collars. The oblique load induced higher peak values than the axial load. The orthotropic design amplified and increased the pathologic microstrains and tensile stresses in the crestal compact bone compared to the effectively isotropic design, especially in models with a convergent collar design. In part 2 of the study, the maximum von Mises stresses and strains increased with a decrease in the cancellous bone density. Under oblique loading, the convergent and straight collars showed pathologic microstrain values as well as excessive ultimate tensile stresses in the orthotropic bone model with low-density cancellous bone. Within the limitations, it was concluded that stress and strain distributions in the adjacent compact bone are influenced by the implant collar design. The divergent implant collar design was associated with the lowest stress and strain concentrations in the crestal compact bone.

[Effect of 50 Hz 1.8 mT sinusoidal electromagnetic fields on bone mineral density in growing rats].

PubMed

Gao, Yu-Hai; Zhou, Yan-Feng; Li, Shao-Feng; Li, Wen-Yuan; Xi, Hui-Rong; Yang, Fang-Fang; Chen, Ke-Ming

2017-12-25

To study effects of 50 Hz 1.8 mT sinusoidal electromagnetic fields (SEMFs) on bone mineral density (BMD) in SD rats. Thirty SD rats weighted(110±10) and aged 1 month were randomly divided into control group and electromagnetic field group, 15 in each group. Normal control group of 50 Hz 0 mT density and sinusoidal electromagnetic field group of 50 Hz 1.8 mT were performed respectively with 1.5 h/d and weighted weight once a week, and observed food-intake. Rats were anesthesia by intraperitoneal injection and dual energy X-ray absorptiometry were used to detect bone density of whole body, and detected bone density of femur and vertebral body. Osteocalcin and tartrate-resistant acid phosphatase 5b were detected by ELSA; weighted liver, kidney and uterus to calculate purtenance index, then detected pathologic results by HE. Compared with control group, there was no significant change in weight every week, food-intake every day; no obvious change of bone density of whole body at 2 and 4 weeks, however bone density of whole body, bone density of excised femur and vertebra were increased at 6 weeks. Expression of OC was increased, and TRACP 5b expression was decreased. No change of HE has been observed in liver, kidney and uterus and organic index. 50 Hz 1.8 mT sinusoidal electromagnetic fields could improve bone formation to decrease relevant factors of bone absorbs, to improve peak bone density of young rats, in further provide a basis for clinical research electromagnetic fields preventing osteoporosis foundation.

[Synthesis and characterization of CO-3(2-) doping nano-hydroxyapatite].

PubMed

Liao, Jian-Guo; Li, Yan-Qun; Duan, Xing-Ze; Liu, Qiong

2014-11-01

CO3(2-) doping is an effective method to increase the biological activity of nano-hydroxyapatite (n-HA). In the present study, calcium nitrate and trisodium phosphate were chosen as raw materials, with a certain amount of Na2CO3 as a source of CO-3(2-) ions, to synthesize nano-carbonate hydroxyapatite (n-CHA) slurry by solution precipitation method. The structure and micro-morphology of n-CHA were characterized by transmission electron microscope (TEM), X-ray diffraction (XRD), Fourier transform-infrared spectroscopy (FTIR) and Raman spectroscopy (RS). The results revealed that the synthetic n-HA crystals are acicular in nanometer scale and have a crystal size of 20-30 nm in diameter and 60-80 nm in length, which are similar to natural bone apatite. And the crystallinity of n-CHA crystals decreases to the increment of CO3(2-). Samples with more CO3(2) have composition and structure more similar to the bone apatite. The value of lattice parameters a decreases, value of c increases, and c/a value increases with the increase in the amount of CO3(2-), in accordance with crystal cell parameters change rule of type B replacement. In the AB mixed type (substitution OH- and PO4(3-)) CHA, IR characteristic peak of CO3(2-) out-of-plane bending vibration appears at 872 cm(-1), meanwhile, the asymmetry flexible vibration band is split into band at 1 454 cm(-1) and band at 1 420 cm(-1), while weak CO3(2)-peak appears at 1 540 cm(-1). CO3(2-) Raman peak of symmetric stretching vibration appears at 1 122 cm(-1). CO3(2-) B-type (substitution PO4(3-)) peak appeared at 1 071 cm(-1). Through the calculation of integral area ratio of PO4(3-)/ CO3(2-), OH-/CO3(2-), and PO4(3-)/OH-, low quantity CO3(2-) is B-type and high quantity CO3(2-) is A-type (substitution OH-). The results show that the synthesized apatite crystals are AB hybrid substitued nano-carbonate hydroxyapatite, however B-type replacement is the main substitute mode. Due to similarity inthe shape, size, crystal structure and growth mode, the synthesized apatite crystals can be called a kind of bone-like apatite.

Preservation and promotion of bone formation in the mandible as a response to a novel calcium-phosphate based biomaterial in mineral deficiency induced low bone mass male versus female rats

PubMed Central

Srinivasan, Kritika; Naula, Diana P.; Mijares, Dindo Q.; Janal, Malvin N.; LeGeros, Raquel Z.; Zhang, Yu

2016-01-01

Calcium and other trace mineral supplements have previously demonstrated to safely improve bone quality. We hypothesize that our novel calcium-phosphate based biomaterial (SBM) preserves and promotes mandibular bone formation in male and female rats on mineral deficient diet (MD). Sixty Sprague-Dawley rats were randomly assigned to receive one of three diets (n = 10): basic diet (BD), MD or mineral deficient diet with 2% SBM. Rats were sacrificed after 6 months. Micro-Computed Tomography (μCT) was used to evaluate bone volume and 3D-microarchitecture while microradiography (Faxitron) was used to measure bone mineral density from different sections of the mandible. Results showed that bone quality varied with region, gender and diet. MD reduced bone mineral density (BMD) and volume and increased porosity. SBM preserved BMD and bone mineral content (BMC) in the alveolar bone and condyle in both genders. In the alveolar crest and mandibular body, while preserving more bone in males, SBM also significantly supplemented female bone. Results indicate that mineral deficiency leads to low bone mass in skeletally immature rats, comparatively more in males. Furthermore, SBM administered as a dietary supplement was effective in preventing mandibular bone loss in all subjects. This study suggests that the SBM preparation has potential use in minimizing low peak bone mass induced by mineral deficiency and related bone loss irrespective of gender. PMID:26914814

Epidemiology and treatment of osteoporosis in women: an Indian perspective

PubMed Central

Khadilkar, Anuradha V; Mandlik, Rubina M

2015-01-01

The number of women with osteoporosis, ie, with reduced bone mass and the disruption of bone architecture, is increasing in India. While data on prevalence of osteoporosis among women in India come from studies conducted in small groups spread across the country, estimates suggest that of the 230 million Indians expected to be over the age of 50 years in 2015, 20%, ie, ~46 million, are women with osteoporosis. Thus, osteoporosis is a major public health problem in Indian women. Low calcium intakes with extensive prevalence of vitamin D deficiency, increasing longevity, sex inequality, early menopause, genetic predisposition, lack of diagnostic facilities, and poor knowledge of bone health have contributed toward the high prevalence of osteoporosis. Bone health may be optimized by creating an environment to achieve peak bone mass during adolescence, maintenance of healthy bone throughout the life cycle, and prevention of bone loss postmenopausal. In Indian women, calcium, vitamin D, and bisphosphonates are the commonest first-line therapies used. The use of other drugs such as hormone replacement therapy, estrogen agonists, calcitonin, parathyroid hormone, and denosumab is decided as per the affordability and availability of treatment options. Major gaps still remain in the diagnosis and management of osteoporosis, thus highlighting the need for more structured research in this area. This review focuses on the epidemiology of osteoporosis in Indian women and available treatments. PMID:26527900

Epidemiology and treatment of osteoporosis in women: an Indian perspective.

PubMed

Khadilkar, Anuradha V; Mandlik, Rubina M

2015-01-01

The number of women with osteoporosis, ie, with reduced bone mass and the disruption of bone architecture, is increasing in India. While data on prevalence of osteoporosis among women in India come from studies conducted in small groups spread across the country, estimates suggest that of the 230 million Indians expected to be over the age of 50 years in 2015, 20%, ie, ~46 million, are women with osteoporosis. Thus, osteoporosis is a major public health problem in Indian women. Low calcium intakes with extensive prevalence of vitamin D deficiency, increasing longevity, sex inequality, early menopause, genetic predisposition, lack of diagnostic facilities, and poor knowledge of bone health have contributed toward the high prevalence of osteoporosis. Bone health may be optimized by creating an environment to achieve peak bone mass during adolescence, maintenance of healthy bone throughout the life cycle, and prevention of bone loss postmenopausal. In Indian women, calcium, vitamin D, and bisphosphonates are the commonest first-line therapies used. The use of other drugs such as hormone replacement therapy, estrogen agonists, calcitonin, parathyroid hormone, and denosumab is decided as per the affordability and availability of treatment options. Major gaps still remain in the diagnosis and management of osteoporosis, thus highlighting the need for more structured research in this area. This review focuses on the epidemiology of osteoporosis in Indian women and available treatments.

Fat, Sugar, and Bone Health: A Complex Relationship

PubMed Central

Tian, Li; Yu, Xijie

2017-01-01

With people aging, osteoporosis is expected to increase notably. Nutritional status is a relatively easily-modified risk factor, associated with many chronic diseases, and is involved in obesity, diabetes, and coronary heart disease (CHD), along with osteoporosis. Nutrients, such as fats, sugars, and proteins, play a primary function in bone metabolism and maintaining bone health. In Western nations, diets are generally high in saturated fats, however, currently, the nutritional patterns dominating in China continue to be high in carbohydrates from starch, cereals, and sugars. Moreover, high fat or high sugar (fructose, glucose, or sucrose) impart a significant impact on bone structural integrity. Due to diet being modifiable, demonstrating the effects of nutrition on bone health can provide an approach for osteoporosis prevention. Most researchers have reported that a high-fat diet consumption is associated with bone mineral density (BMD) and, as bone strength diminishes, adverse microstructure changes occur in the cancellous bone compartment, which is involved with lipid metabolism modulation disorder and the alteration of the bone marrow environment, along with an increased inflammatory environment. Some studies, however, demonstrated that a high-fat diet contributes to achieving peak bone mass, along with microstructure, at a younger age. Contrary to these results, others have shown that a high-fructose diet consumption leads to stronger bones with a superior microarchitecture than those with the intake of a high-glucose diet and, at the same time, research indicated that a high-fat diet usually deteriorates cancellous bone parameters, and that the incorporation of fructose into a high-fat diet did not aggravate bone mass loss. High-fat/high-sucrose diets have shown both beneficial and detrimental influences on bone metabolism. Combined, these studies showed that nutrition exerts different effects on bone health. Thus, a better understanding of the regulation between dietary nutrition and bone health might provide a basis for the development of strategies to improve bone health by modifying nutritional components. PMID:28513571

Fat, Sugar, and Bone Health: A Complex Relationship.

PubMed

Tian, Li; Yu, Xijie

2017-05-17

With people aging, osteoporosis is expected to increase notably. Nutritional status is a relatively easily-modified risk factor, associated with many chronic diseases, and is involved in obesity, diabetes, and coronary heart disease (CHD), along with osteoporosis. Nutrients, such as fats, sugars, and proteins, play a primary function in bone metabolism and maintaining bone health. In Western nations, diets are generally high in saturated fats, however, currently, the nutritional patterns dominating in China continue to be high in carbohydrates from starch, cereals, and sugars. Moreover, high fat or high sugar (fructose, glucose, or sucrose) impart a significant impact on bone structural integrity. Due to diet being modifiable, demonstrating the effects of nutrition on bone health can provide an approach for osteoporosis prevention. Most researchers have reported that a high-fat diet consumption is associated with bone mineral density (BMD) and, as bone strength diminishes, adverse microstructure changes occur in the cancellous bone compartment, which is involved with lipid metabolism modulation disorder and the alteration of the bone marrow environment, along with an increased inflammatory environment. Some studies, however, demonstrated that a high-fat diet contributes to achieving peak bone mass, along with microstructure, at a younger age. Contrary to these results, others have shown that a high-fructose diet consumption leads to stronger bones with a superior microarchitecture than those with the intake of a high-glucose diet and, at the same time, research indicated that a high-fat diet usually deteriorates cancellous bone parameters, and that the incorporation of fructose into a high-fat diet did not aggravate bone mass loss. High-fat/high-sucrose diets have shown both beneficial and detrimental influences on bone metabolism. Combined, these studies showed that nutrition exerts different effects on bone health. Thus, a better understanding of the regulation between dietary nutrition and bone health might provide a basis for the development of strategies to improve bone health by modifying nutritional components.

Polarization Raman spectroscopy to explain rodent models of brittle bone

NASA Astrophysics Data System (ADS)

Makowski, Alexander J.; Nyman, Jeffry S.; Mahadevan-Jansen, Anita

2013-03-01

Activation Transcription Factor 4 (Atf-4) is essential for osteoblast maturation and proper collagen synthesis. We recently found that these bones demonstrate a rare brittleness phenotype, which is independent of bone strength. We utilized a confocal Renishaw Raman microscope (50x objective; NA=.75) to evaluate embedded, polished cross-sections of mouse tibia from both wild-type and knockout mice at 8 weeks of age (24 mice, n<=8 per group). Analysis of peak ratios indicated statistically significant changes in both mineral and collagen; however, compositional changes did not fully encompass biomechanical differences. To investigate the impact of material organization, we acquired colocalized spectra aligning the polarization angle parallel and perpendicular to the long bone axis from wet intact femurs. To validate our results, we used MMP9-/- mice, which have a brittleness phenotype that is not explained by compositional Raman measures. Polarization angle difference spectra show marked significant changes in orientation of these compositional differences when comparing wild type to knockout bones. Relative to wild-type, Atf4 -/- and MMP9 -/- bones show significant differences (t-test; p<0.05) in prominent collagen peaks. Further investigation of known peak ratios illustrates that this physical anisotropy of molecular organization is tightly clustered in brittle knockout bones. Such findings could have alternate interpretations about net collagen orientation or the angular distribution of collagen molecules. Use of polarization specific Raman measurements has implicated a structural profile that furthers our understanding of models of bone brittleness. Polarization content of Raman spectra may prove significant in future studies of brittle fracture and human fracture risk.

Real-Time Measurement of Solute Transport Within the Lacunar-Canalicular System of Mechanically Loaded Bone: Direct Evidence for Load-Induced Fluid Flow

PubMed Central

Price, Christopher; Zhou, Xiaozhou; Li, Wen; Wang, Liyun

2011-01-01

Since proposed by Piekarski and Munro in 1977, load-induced fluid flow through the bone lacunar-canalicular system (LCS) has been accepted as critical for bone metabolism, mechanotransduction, and adaptation. However, direct unequivocal observation and quantification of load-induced fluid and solute convection through the LCS have been lacking due to technical difficulties. Using a novel experimental approach based on fluorescence recovery after photobleaching (FRAP) and synchronized mechanical loading and imaging, we successfully quantified the diffusive and convective transport of a small fluorescent tracer (sodium fluorescein, 376 Da) in the bone LCS of adult male C57BL/6J mice. We demonstrated that cyclic end-compression of the mouse tibia with a moderate loading magnitude (–3 N peak load or 400 µɛ surface strain at 0.5 Hz) and a 4-second rest/imaging window inserted between adjacent load cycles significantly enhanced (+31%) the transport of sodium fluorescein through the LCS compared with diffusion alone. Using an anatomically based three-compartment transport model, the peak canalicular fluid velocity in the loaded bone was predicted (60 µm/s), and the resulting peak shear stress at the osteocyte process membrane was estimated (∼5 Pa). This study convincingly demonstrated the presence of load-induced convection in mechanically loaded bone. The combined experimental and mathematical approach presented herein represents an important advance in quantifying the microfluidic environment experienced by osteocytes in situ and provides a foundation for further studying the mechanisms by which mechanical stimulation modulates osteocytic cellular responses, which will inform basic bone biology, clinical understanding of osteoporosis and bone loss, and the rational engineering of their treatments. © 2011 American Society for Bone and Mineral Research. PMID:20715178

Bone quality assessment for total hip arthroplasty with intraoperative trabecular torque measurements.

PubMed

Klotz, Matthias C M; Beckmann, Nicholas A; Bitsch, Rudi G; Seebach, Elisabeth; Reiner, Tobias; Jäger, Sebastian

2014-11-13

In cases of poor bone quality, intraoperative torque measurement might be an alternative to preoperative dual-energy X-ray absorptiometry (DXA) to assess bone quality in total hip arthroplasty (THA). Trabecular peak torque measurement was applied in 14 paired fresh frozen human femurs. Here, a 6.5 × 23 mm wingblade was inserted into the proximal femur without harming the lateral cortical bone. Further tests of the proximal femur also evaluated bone strength (DXA, micro-computed tomography (μCT), monoaxial compression test), and the results were compared to the trabecular torque measurement. Student's t-test was used to compare the values of the groups. Pearson product-moment was applied to correlate the values of the peak torque measurement with the bone strength measured by DXA, μCT, and monoaxial compression test. In the femoral head, the mean trabecular peak torque was 4.38 ± 1.86 Nm. These values showed a strong correlation with the values of the DXA, the μCT, and the biomechanical load test (Pearson's product-moment: DXA: 0.86, μCT-BMD: 0.80, load test: 0.85). Furthermore, the torque measurement showed a more pronounced correlation with the biomechanical load test compared to the DXA. The use of this method provides highly diagnostic information about bone quality. Since the approach was adjusted for THA, no harm of the lateral bone stock will result from this measurement during surgery. The results of this initial study employing small sample sizes indicate that this new method is as sensitive as DXA in predicting bone quality and may function as an intraoperative alternative to DXA in THA. Nevertheless, before this method will turn into clinical use, more research and clinical trials are necessary.

Decreasing maternal myostatin programs adult offspring bone strength in a mouse model of osteogenesis imperfecta

PubMed Central

Oestreich, Arin K.; Kamp, William M.; McCray, Marcus G.; Carleton, Stephanie M.; Karasseva, Natalia; Lenz, Kristin L.; Jeong, Youngjae; Daghlas, Salah A.; Yao, Xiaomei; Wang, Yong; Pfeiffer, Ferris M.; Ellersieck, Mark R.; Schulz, Laura C.; Phillips, Charlotte L.

2016-01-01

During fetal development, the uterine environment can have effects on offspring bone architecture and integrity that persist into adulthood; however, the biochemical and molecular mechanisms remain unknown. Myostatin is a negative regulator of muscle mass. Parental myostatin deficiency (Mstntm1Sjl/+) increases muscle mass in wild-type offspring, suggesting an intrauterine programming effect. Here, we hypothesized that Mstntm1Sjl/+ dams would also confer increased bone strength. In wild-type offspring, maternal myostatin deficiency altered fetal growth and calvarial collagen content of newborn mice and conferred a lasting impact on bone geometry and biomechanical integrity of offspring at 4 mo of age, the age of peak bone mass. Second, we sought to apply maternal myostatin deficiency to a mouse model with osteogenesis imperfecta (Col1a2oim), a heritable connective tissue disorder caused by abnormalities in the structure and/or synthesis of type I collagen. Femora of male Col1a2oim/+ offspring from natural mating of Mstntm1Sjl/+ dams to Col1a2oim/+sires had a 15% increase in torsional ultimate strength, a 29% increase in tensile strength, and a 24% increase in energy to failure compared with age, sex, and genotype-matched offspring from natural mating of Col1a2oim/+ dams to Col1a2oim/+ sires. Finally, increased bone biomechanical strength of Col1a2oim/+ offspring that had been transferred into Mstntm1Sjl/+ dams as blastocysts demonstrated that the effects of maternal myostatin deficiency were conferred by the postimplantation environment. Thus, targeting the gestational environment, and specifically prenatal myostatin pathways, provides a potential therapeutic window and an approach for treating osteogenesis imperfecta. PMID:27821779

Decreasing maternal myostatin programs adult offspring bone strength in a mouse model of osteogenesis imperfecta.

PubMed

Oestreich, Arin K; Kamp, William M; McCray, Marcus G; Carleton, Stephanie M; Karasseva, Natalia; Lenz, Kristin L; Jeong, Youngjae; Daghlas, Salah A; Yao, Xiaomei; Wang, Yong; Pfeiffer, Ferris M; Ellersieck, Mark R; Schulz, Laura C; Phillips, Charlotte L

2016-11-22

During fetal development, the uterine environment can have effects on offspring bone architecture and integrity that persist into adulthood; however, the biochemical and molecular mechanisms remain unknown. Myostatin is a negative regulator of muscle mass. Parental myostatin deficiency (Mstn tm1Sjl/+ ) increases muscle mass in wild-type offspring, suggesting an intrauterine programming effect. Here, we hypothesized that Mstn tm1Sjl/+ dams would also confer increased bone strength. In wild-type offspring, maternal myostatin deficiency altered fetal growth and calvarial collagen content of newborn mice and conferred a lasting impact on bone geometry and biomechanical integrity of offspring at 4 mo of age, the age of peak bone mass. Second, we sought to apply maternal myostatin deficiency to a mouse model with osteogenesis imperfecta (Col1a2 oim ), a heritable connective tissue disorder caused by abnormalities in the structure and/or synthesis of type I collagen. Femora of male Col1a2 oim/+ offspring from natural mating of Mstn tm1Sjl/+ dams to Col1a2 oim/+ sires had a 15% increase in torsional ultimate strength, a 29% increase in tensile strength, and a 24% increase in energy to failure compared with age, sex, and genotype-matched offspring from natural mating of Col1a2 oim/+ dams to Col1a2 oim/+ sires. Finally, increased bone biomechanical strength of Col1a2 oim/+ offspring that had been transferred into Mstn tm1Sjl/+ dams as blastocysts demonstrated that the effects of maternal myostatin deficiency were conferred by the postimplantation environment. Thus, targeting the gestational environment, and specifically prenatal myostatin pathways, provides a potential therapeutic window and an approach for treating osteogenesis imperfecta.

21 CFR 101.72 - Health claims: calcium, vitamin D, and osteoporosis.

Code of Federal Regulations, 2012 CFR

2012-04-01

... bone mass, which has been identified as one of many risk factors in the development of osteoporosis. Peak bone mass is the total quantity of bone present at maturity, and experts believe that it has the greatest bearing on whether a person will be at risk of developing osteoporosis and related bone fractures...

21 CFR 101.72 - Health claims: calcium, vitamin D, and osteoporosis.

Code of Federal Regulations, 2010 CFR

2010-04-01

... bone mass, which has been identified as one of many risk factors in the development of osteoporosis. Peak bone mass is the total quantity of bone present at maturity, and experts believe that it has the greatest bearing on whether a person will be at risk of developing osteoporosis and related bone fractures...

21 CFR 101.72 - Health claims: calcium, vitamin D, and osteoporosis.

Code of Federal Regulations, 2011 CFR

2011-04-01

... bone mass, which has been identified as one of many risk factors in the development of osteoporosis. Peak bone mass is the total quantity of bone present at maturity, and experts believe that it has the greatest bearing on whether a person will be at risk of developing osteoporosis and related bone fractures...

21 CFR 101.72 - Health claims: calcium, vitamin D, and osteoporosis.

Code of Federal Regulations, 2014 CFR

2014-04-01

... bone mass, which has been identified as one of many risk factors in the development of osteoporosis. Peak bone mass is the total quantity of bone present at maturity, and experts believe that it has the greatest bearing on whether a person will be at risk of developing osteoporosis and related bone fractures...

21 CFR 101.72 - Health claims: calcium, vitamin D, and osteoporosis.

Code of Federal Regulations, 2013 CFR

2013-04-01

... bone mass, which has been identified as one of many risk factors in the development of osteoporosis. Peak bone mass is the total quantity of bone present at maturity, and experts believe that it has the greatest bearing on whether a person will be at risk of developing osteoporosis and related bone fractures...

Body Mass, Training, Menses, and Bone in Adolescent Runners: A 3-y Follow-Up

USDA-ARS?s Scientific Manuscript database

Abstract: Endurance runners with low bone mass during adolescence may be at risk of developing a low peak bone mineral density (BMD) as a young adult. However, it is possible that they mature late and undergo delayed bone mass accumulation. PURPOSE: We evaluated 40 adolescent runners (age 15.9 ± 0....

[Diagnostic value of baseline serum luteinizing hormone level for central precocious puberty in girls].

PubMed

Ou-Yang, Li-Xue; Yang, Fan

2017-07-01

To evaluate the diagnostic value of baseline serum luteinizing hormone (LH) level for central precocious puberty (CPP) in girls. A total of 279 girls with precocious puberty were subjected to assessment of growth and development, bone age determination, baseline LH test, and follicle-stimulating hormone (FSH) test, gonadotropin-releasing hormone stimulation test, and other related examinations. Of the 279 patients, 175 were diagnosed with CPP and 104 with premature thelarche (PT). The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of baseline LH and FSH levels and their peak levels for CPP, and the correlation between the baseline LH level and the peak LH level was analyzed. The CPP group had significantly higher bone age, baseline LH and FSH levels, peak LH and FSH levels, and ratio of peak LH level to peak FSH level than the PT group (P<0.01). The ROC curve proved that baseline LH level and peak LH level had good diagnostic values for CPP. Among the three bone age subgroups in the CPP group (7.0-9.0 years, 9.0-11.0 years, and >11.0 years), baseline LH level showed the best diagnostic value in the >11.0 years subgroup, with the largest area under the ROC curve. At a baseline LH level of 0.45 IU/L, the Youden index reached the peak value, and the sensitivity and specificity were 66.7% and 80% respectively, for the diagnosis of CPP. At a peak LH level of 9.935 IU/L, the Youden index reached the peak value, and the sensitivity and specificity were 74.8% and 100% respectively, for the diagnosis of CPP. The baseline LH level was positively correlated with the peak LH level (r=0.440, P<0.01). Baseline LH level can be used as an primary screening index for the diagnosis of CPP. It has a certain diagnostic value for CPP at different bone ages, and may be used as a monitoring index during the treatment and follow-uP.

Effect of whole body vibration training on bone mineral density and bone quality in adolescents with Down syndrome: a randomized controlled trial.

PubMed

Matute-Llorente, A; González-Agüero, A; Gómez-Cabello, A; Olmedillas, H; Vicente-Rodríguez, G; Casajús, J A

2015-10-01

Adolescents with Down syndrome (DS) have poorer bone health than their peers without DS. Twenty-five adolescents with DS were randomly assigned to whole-body vibration training (WBV) or control groups. The results indicate that a 20-week WBV might be useful to improve subtotal bone mineral content and density in adolescents with DS. This study aims to determine the effects of 20 weeks of whole body vibration training (WBV) on bone mineral content (BMC), density (BMD), and structure variables in adolescents with Down syndrome (DS). This randomized controlled trial of 25 adolescents (12-18 years) with DS (8 females) generated 2 non-equal groups, WBV group (n = 11) and CON group (n = 14). Using an efficacy analysis, the primary outcomes were BMC and BMD by dual-energy X-ray absorptiometry and the secondary were bone structure variables by peripheral quantitative computed tomography. A synchronous vibration platform (PowerPlate®) was used (3/week, 10 repetitions (30-60 s) 1-min rest, frequency of 25-30 Hz, and peak-to-peak displacement of 2 mm (peak acceleration 2.5-3.6 g)). WBV group improved whole body BMC 2.8%, 95% CI [3.5, 2.1], subtotal area, BMC, and BMD by 2.8, 4.8, and 2%, respectively, 95% confidence intervals (CIs) [3.4, 2.1], [6.5, 3.1], and [2.8, 1.1], respectively (all, p < 0.05), showing group by time interactions in BMC and BMD (both p < 0.05). Lumbar spine BMC and BMD also increased in the WBV group by 6.6 and 3.3% both p < 0.05, 95 % CIs [8.6, 4.7], and [4.9, 1.7], respectively. Regarding bone structure, WBV group showed improvements in tibial BMC at 4 % (2.9 %, 95 % CI [3.0, 2.8]) and in volumetric BMD (vBMD), cortical vBMD, and cortical thickness at 66% of the radius (by 7.0, 2.4, and 10.9%; 95% CIs [7.4, 6.7], [2.6, 2.3], and [12.4, 9.3], respectively) (all, p < 0.05). A 20-week WBV, with this protocol, might be useful to improve subtotal BMC and BMD in adolescents with DS.

Fructus ligustri lucidi ethanol extract improves bone mineral density and properties through modulating calcium absorption-related gene expression in kidney and duodenum of growing rats.

PubMed

Feng, Xin; Lyu, Ying; Wu, Zhenghao; Fang, Yuehui; Xu, Hao; Zhao, Pengling; Xu, Yajun; Feng, Haotian

2014-04-01

Optimizing peak bone mass in early life is one of key preventive strategies against osteoporosis. Fructus ligustri lucidi (FLL), the fruit of Ligustrum lucidum Ait., is a commonly prescribed herb in many kidney-tonifying traditional Chinese medicinal formulas to alleviate osteoporosis. Previously, FLL extracts have been shown to have osteoprotective effect in aged or ovariectomized rats. In the present study, we investigated the effects of FLL ethanol extract on bone mineral density (BMD) and mechanical properties in growing male rats and explored the underlying mechanisms. Male weaning Sprague-Dawley rats were randomized into four groups and orally administrated for 4 months an AIN-93G formula-based diet supplementing with different doses of FLL ethanol extract (0.40, 0.65, and 0.90 %) or vehicle control, respectively. Then calcium balance, serum level of Ca, P, 25(OH)2D3, 1,25(OH)2D3, osteocalcin (OCN), C-terminal telopeptide of type I collagen (CTX-I), and parathyroid hormone, bone microarchitecture, and calcium absorption-related genes expression in duodenum and kidney were analyzed. The results demonstrated that FLL ethanol extract increased BMD of growing rats and improved their bone microarchitecture and mechanical properties. FLL ethanol extract altered bone turnover, as evidenced by increasing a bone formation maker, OCN, and decreasing a bone resorption maker, CTX-I. Intriguingly, both Ca absorption and Ca retention rate were elevated by FLL ethanol extract treatment, possibly through the mechanisms of up-regulating the transcriptions of calcitropic genes in kidney (1α-hydroxylase) and duodenum (vitamin D receptor, calcium transporter calbindin-D9k, and transient receptor potential vanilloid 6). In conclusion, FLL ethanol extract increased bone mass gain and improved bone properties via modulating bone turnover and up-regulating calcium absorption-related gene expression in kidney and duodenum, which could then activate 1,25(OH)2D3-dependent calcium transport in male growing rats.

Differential Effects of Teriparatide and Denosumab on Intact PTH and Bone Formation Indices: AVA Osteoporosis Study

PubMed Central

Zhou, Hua; Recker, Robert R.; Brown, Jacques P.; Recknor, Christopher P.; Lewiecki, E. Michael; Miller, Paul D.; Rao, Sudhaker D.; Kendler, David L.; Lindsay, Robert; Krege, John H.; Alam, Jahangir; Taylor, Kathleen A.; Janos, Boris; Ruff, Valerie A.

2016-01-01

Context: Denosumab-induced PTH elevation may stimulate early bone formation. Objective: Our objective was to evaluate whether denosumab-induced changes of intact PTH (iPTH) result in early anabolic effects according to histomorphometry and bone turnover markers (BTMs) compared with teriparatide, an established anabolic agent. Design: This open-label, randomized study used quadruple labeling to label bone before/after treatment, with a transiliac bone biopsy at 3 months. Setting: This study took both in both US and Canadian sites. Participants: Sixty-nine postmenopausal women with osteoporosis were included. Interventions: Teriparatide (20 μg/day) for 6 months and denosumab (60 mg once) were used in this study. Main Outcome Measure: Between-treatment comparison of change from baseline to month 3 in cancellous mineralizing surface/bone surface, histomorphometric indices in four bone envelopes, and BTM and iPTH at baseline, 1, 3, and 6 months was undertaken. Results: After denosumab, iPTH peaked at month 1 (P < .001), then declined, remaining above baseline through month 6 (P ≤ .01); after teriparatide, iPTH declined at all time points (P < .001). From baseline to month 3, cancellous mineralizing surface/bone surface increased with teriparatide and decreased with denosumab and at month 3, was higher with teriparatide. Similar results were observed in other bone envelopes. BTMs increased from baseline in teriparatide-treated subjects (procollagen type 1 N-terminal propeptide at month 1 and carboxyterminal cross-linking telopeptide of type 1 collagen at month 3); procollagen type 1 N-terminal propeptide and carboxyterminal cross-linking telopeptide of type 1 collagen decreased from baseline at all time points in denosumab-treated subjects. Conclusions: Denosumab treatment increased iPTH but inhibited bone formation indices. In contrast, teriparatide treatment decreased iPTH but stimulated bone formation indices. These findings are not consistent with the hypothesis of early indirect anabolic effect with denosumab. PMID:26859106

Bone marrow fat quantification in the presence of trabecular bone: initial comparison between water-fat imaging and single-voxel MRS

PubMed Central

Karampinos, Dimitrios C.; Melkus, Gerd; Baum, Thomas; Bauer, Jan S.; Rummeny, Ernst J.; Krug, Roland

2013-01-01

Purpose The purpose of the present study was to test the relative performance of chemical shift-based water-fat imaging in measuring bone marrow fat fraction in the presence of trabecular bone, having as reference standard the single-voxel magnetic resonance spectroscopy (MRS). Methods Six-echo gradient echo imaging and single-voxel MRS measurements were performed on the proximal femur of seven healthy volunteers. The bone marrow fat spectrum was characterized based on the magnitude of measurable fat peaks and an a priori knowledge of the chemical structure of triglycerides, in order to accurately extract the water peak from the overlapping broad fat peaks in MRS. The imaging-based fat fraction results were then compared to the MRS-based results both without and with taking into consideration the presence of short T2* water components in MRS. Results There was a significant underestimation of the fat fraction using the MRS model not accounting for short T2* species with respect to the imaging-based water fraction. A good equivalency was observed between the fat fraction using the MRS model accounting for short T2* species and the imaging-based fat fraction (R2=0.87). Conclusion The consideration of the short T2* water species effect on bone marrow fat quantification is essential when comparing MRS-based and imaging-based fat fraction results. PMID:23657998

The relationship between dental implant stability and trabecular bone structure using cone-beam computed tomography

PubMed Central

2016-01-01

Purpose The objective of this study was to investigate the relationships between primary implant stability as measured by impact response frequency and the structural parameters of trabecular bone using cone-beam computed tomography(CBCT), excluding the effect of cortical bone thickness. Methods We measured the impact response of a dental implant placed into swine bone specimens composed of only trabecular bone without the cortical bone layer using an inductive sensor. The peak frequency of the impact response spectrum was determined as an implant stability criterion (SPF). The 3D microstructural parameters were calculated from CT images of the bone specimens obtained using both micro-CT and CBCT. Results SPF had significant positive correlations with trabecular bone structural parameters (BV/TV, BV, BS, BSD, Tb.Th, Tb.N, FD, and BS/BV) (P<0.01) while SPF demonstrated significant negative correlations with other microstructural parameters (Tb.Sp, Tb.Pf, and SMI) using micro-CT and CBCT (P<0.01). Conclusions There was an increase in implant stability prediction by combining BV/TV and SMI in the stepwise forward regression analysis. Bone with high volume density and low surface density shows high implant stability. Well-connected thick bone with small marrow spaces also shows high implant stability. The combination of bone density and architectural parameters measured using CBCT can predict the implant stability more accurately than the density alone in clinical diagnoses. PMID:27127692

Optical assessment of bone bioimplants

NASA Astrophysics Data System (ADS)

Timchenko, P. E.; Timchenko, E. V.; Volova, L. T.; Dolgushkin, D. A.; Boltovskaya, V. V.; Frolov, O. O.; Fedorova, Ya. V.

2017-08-01

The results of application of the Raman spectroscopy method for the estimation of alternative sources for the production of bone spongy implants using the "Lioplast" technology, namely, the femoral heads resected in the operation of hip replacement surgery, are presented. It is shown that Raman spectroscopy can be used to estimate the component composition of the surface of bone implants during their processing. Comparing different sources of sponge bone production, no significant differences were found, but there are differences in the ratio of the intensities of the Raman peaks at wave numbers 1555 cm-1 and 1665 cm-1 corresponding to amide II and amide I, and also in the intensity of Raman peaks at wave numbers of 959 cm-1 (PO4 3- (ν1)) and 1068 cm-1 (CO3 2- (ν1) B-type substitution).

Numerical Simulation of Shock Wave Propagation in Fractured Cortical Bone

NASA Astrophysics Data System (ADS)

Padilla, Frédéric; Cleveland, Robin

2009-04-01

Shock waves (SW) are considered a promising method to treat bone non unions, but the associated mechanisms of action are not well understood. In this study, numerical simulations are used to quantify the stresses induced by SWs in cortical bone tissue. We use a 3D FDTD code to solve the linear lossless equations that describe wave propagation in solids and fluids. A 3D model of a fractured rat femur was obtained from micro-CT data with a resolution of 32 μm. The bone was subject to a plane SW pulse with a peak positive pressure of 40 MPa and peak negative pressure of -8 MPa. During the simulations the principal tensile stress and maximum shear stress were tracked throughout the bone. It was found that the simulated stresses in a transverse plane relative to the bone axis may reach values higher than the tensile and shear strength of the bone tissue (around 50 MPa). These results suggest that the stresses induced by the SW may be large enough to initiate local micro-fractures, which may in turn trigger the start of bone healing for the case of a non union.

Sarcopenia Is Negatively Related to High Gravitational Impacts Achieved From Day-to-day Physical Activity.

PubMed

Hartley, April; Gregson, Celia L; Hannam, Kimberly; Deere, Kevin C; Clark, Emma M; Tobias, Jon H

2018-04-17

Sarcopenia has been associated with reduced physical activity (PA). We aimed to determine if sarcopenia, and specific components of muscle size, function, and physical performance, are associated with high impacts achieved during habitual PA, as these are related to bone strength in community-dwelling older women. Participants were older women from the Cohort of Skeletal Health in Bristol and Avon. We defined sarcopenia using the EWGSOP criteria. Lower limb peak muscle power and force were assessed using Jumping Mechanography (JM). High vertical impacts were assessed by tri-axial accelerometry (at least 1.5g above gravity). Cross-sectional associations were analyzed by linear regression, adjusting for age, height and weight (or fat mass for models including appendicular lean mass index), comorbidities, smoking, alcohol, and Index of Multiple Deprivation. Our analyses included 380 participants, with mean age 76.7 (SD 3.0) years; 242 (64%) also completed JM. In age-adjusted analysis, a negative relationship was observed between severity of sarcopenia and high, but not medium or low, impacts (p = .03 for trend). Regarding components of sarcopenia underlying this relationship, multivariable analyses revealed that gait speed (β 1.47 [95% CI 1.14, 1.89], [β-1] reflects the proportionate increase in high impacts per SD increase in exposure) and peak force (1.40 [1.07, 1.84]) were independently associated with high impacts. Older women with sarcopenia experienced fewer bone-strengthening high impacts than those with presarcopenia or without sarcopenia. To increase bone strengthening activity in older women, interventions need to improve both lower limb muscle force and walking speed.

Growing Strong and Healthy with Mister Bone: An Educational Program to Have Strong Bones Later in Life

PubMed Central

Pampaloni, Barbara; Cianferotti, Luisella; Gronchi, Giorgio; Bartolini, Elisa; Fabbri, Sergio; Tanini, Annalisa; Brandi, Maria Luisa

2015-01-01

Optimal peak bone mass and bone health later in life are favored by a sufficient calcium intake in infancy, childhood and adolescence. The purpose of this study was to test a new educational program created to monitor and to improve calcium and vitamin D intake in children. Nutritional habits in children were evaluated through a food frequency questionnaire (FFQ) to assess the intake of calcium, vitamin D, dairy products, and total caloric energy at baseline and after seven months of exposure to a unique educational program applied between November 2013 and May 2014 in 176 schoolchildren (48% male, 52% female) attending the fourth and fifth grades of two selected primary schools in Florence, Italy. A significant increase of calcium (from 870 ± 190 to 1100 ± 200 mg/day, p < 0.05), and vitamin D (from 3.6 ± 1.53 to 4.1 ± 2 µg/day) intake in children was documented after the educational program. The amount of specific foods important for bone health consumed, such as milk and vegetables, increased significantly, both in male and female children (p < 0.05). The proposed educational program appears to be effective in modifying calcium intake in children, with a significant increase in the consumption of dairy products and vegetables, but without a significant change in the total caloric intake. PMID:26633485

The Effects of Partial Mechanical Loading and Ibandronate on Skeletal Tissues in the Adult Rat Hindquarter Suspension Model for Microgravity

NASA Technical Reports Server (NTRS)

Schultheis, Lester W.

1999-01-01

We report initial data from a suspended rat model that quantitatively relates chronic partial weightbearing to bone loss. Chronic partial weightbearing is our simulation of the effect of limited artificial gravity aboard spacecraft or reduced planetary gravity. Preliminary analysis of bone by PQCT, histomorphometry, mechanical testing and biochemistry suggest that chronic exposure to half of Earth gravity is insufficient to prevent severe bone loss. The effect of episodic full weightbearing activity (Earth Gravity) on rats otherwise at 50% weightbearing was also explored. This has similarity to treatment by an Earth G-rated centrifuge on a spacecraft that normally maintained artificial gravity at half of Earth G. Our preliminary evidence, using the above techniques to analyze bone, indicate that 2 hours daily of full weightbearing was insufficient to prevent the bone loss observed in 50% weightbearing animals. The effectiveness of partial weightbearing and episodic full weightbearing as potential countermeasures to bone loss in spaceflight was compared with treatment by ibandronate. Ibandronate, a long-acting potent bisphosphonate proved more effective in preventing bone loss and associated functionality based upon structure than our first efforts at mechanical countermeasures. The effectiveness of ibandronate was notable by each of the testing methods we used to study bone from gross structure and strength to tissue and biochemistry. These results appear to be independent of generalized systemic stress imposed by the suspension paradigm. Preliminary evidence does not suggest that blood levels of vitamin D were affected by our countermeasures. Despite the modest theraputic benefit of mechanical countermeasures of partial weightbearing and episodic full weightbearing, we know that some appropriate mechanical signal maintains bone mass in Earth gravity. Moreover, the only mechanism that correctly assigns bone mass and strength to oppose regionally specific force applied to bone is mechanical, a process based upon bone strain. Substantial evidence indicates that the specifics of dynamic loading i.e. time-varying forces are critical. Bone strain history is a predictor of the effect that mechanical conditions have on bone structure mass and strength. Using servo-controlled force plates on suspended rats with implanted strain gauges we manipulated impact forces of ambulation in the frequency (Fourier) domain. Our results indicate that high frequency components of impact forces are particularly potent in producing bone strain independent of the magnitude of the peak force or peak energy applied to the leg. Because a servo-system responds to forces produced by the rat's own muscle activity during ambulation, the direction of ground-reaction loads act on bone through the rat's own musculature. This is in distinction to passive vibration of the floor where forces reach bone through the natural filters of soft tissue and joints. Passive vibration may also be effective, but it may or may not increase bone in the appropriate architectural pattern to oppose the forces of normal ambulatory activity. Effectiveness of high frequency mechanical stimulation in producing regional (muscle directed) bone response will be limited by 1. the sensitivity of bone to a particular range of frequencies and 2. the inertia of the muscles, limiting their response to external forces by increasing tension along insertions. We have begun mathematical modeling of normal ambulatory activity. Effectiveness of high frequency mechanical stimulation in producing regional (muscle directed) bone response will be limited by 1. the sensitivity of bone to a particular range of frequencies and 2. the inertia of the muscles, limiting their response to external forces by increasing tension along insertions. We have begun mathematical modeling of the rat forelimb as a transfer function between impact force and bone strain to predict optimal dynamic loading conditions for this system. We plan additional studies of mechanical counter-measures that incorporate improved dynamic loading, features relevant to anticipated evaluation of artificial gravity, exercise regimens and exposure to Martian gravity, The combination of mechanical countermeasures with ibandronate will also be investigated for signs of synergy.

Insulin-Like Growth Factor Regulates Peak Bone Mineral Density in Mice by Both Growth Hormone-Dependent and -Independent Mechanisms

PubMed Central

Mohan, Subburaman; Richman, Charmaine; Guo, Rongqing; Amaar, Yousef; Donahue, Leah Rea; Wergedal, Jon; Baylink, David J.

2010-01-01

To evaluate the relative contribution of the GH/IGF axis to the development of peak bone mineral density (BMD), we measured skeletal changes in IGF-I knockout (KO), IGF-II KO, and GH-deficient lit/lit mice and their corresponding control mice at d 23 (prepubertal), 31 (pubertal), and 56 (postpubertal) in the entire femur by dual energy x-ray absorptiometry and in the mid-diaphysis by peripheral quantitative computed tomography. Lack of growth factors resulted in different degrees of failure of skeletal growth depending on the growth period and the growth factor involved. At d 23, femoral length, size, and BMD were reduced by 25–40%, 15–17%, and 8–10%, respectively, in mice deficient in IGF-I, IGF-II, and GH compared with the control mice. During puberty, BMD increased by 40% in control mice and by 15% in IGF-II KO and GH-deficient mice, whereas it did not increase in the IGF-I KO mice. Disruption of IGF-I, but not IGF-II, completely prevented the periosteal expansion that occurs during puberty, whereas it was reduced by 50% in GH-deficient mice. At d 56, femoral length, size, and BMD were reduced by 40–55%, 11–18%, and 25–32%, respectively, in mice deficient in IGF-I, IGF-II, and GH compared with the control mice. Our data demonstrate that: 1) mice deficient in IGF-I exhibit a greater impairment in bone accretion than mice deficient in IGF-II or GH; 2) GH/IGF-I, but not IGF-II, is critical for puberty-induced bone growth; and 3) IGF-I effects on bone accretion during prepuberty are mediated predominantly via mechanisms independent of GH, whereas during puberty they are mediated via both GH-dependent and GH-independent mechanisms. PMID:12586770

The effects of first gestation and lactation on bone metabolism in dairy goats and milk sheep.

PubMed

Liesegang, A; Risteli, J; Wanner, M

2006-06-01

The goal of the present study was to compare mobilization rate of calcium (Ca) from bone in pregnant and lactating goats and sheep. Blood samples were collected from goats and sheep monthly during pregnancy and at 1, 2, and 4 weeks postpartum (pp) and monthly during lactation until 6 months after parturition. Total bone mineral content (BMC) and total bone mineral density (BMD) were quantified using peripheral quantitative computed tomography at the same intervals as the blood was taken. Bone resorption was assessed by immunoassays quantitating two epitopes of the carboxyterminal telopeptide of type I collagen (ICTP, CTX). Bone formation was estimated by quantifying serum osteocalcin (OC) and bone-specific alkaline phosphatase (bAP). In addition, Ca and 1,25-dihydroxy vitamin D (1,25-VITD) concentrations were determined in serum. Mean ICTP and CTX concentrations of both animal species increased the first week after parturition. By the second week pp, the concentrations of both markers had decreased toward early gestation levels. In contrast, mean OC concentrations continually decreased until the 1st week pp. By the 2nd week pp, the mean concentrations of OC started to increase again. Mean bAP activities decreased during gestation and reached a nadir in the first week pp in goats and 4 weeks pp in sheep. Afterwards, mean bAP activities increased again in goats and sheep. 1,25-VITD concentrations peaked the first week pp and returned to early gestation values thereafter. Total BMC and BMD decreased from the 4th month of pregnancy until the 1st week pp in both species. Afterwards, BMC increased throughout the first month pp in goats and the first 3 months pp in sheep. BMD levels of sheep and goats returned to prepartum levels during lactation. The resorptive phase of bone remodeling is accelerated at parturition and in early lactation and is uncoupled from the process of bone formation. This allows the animal to achieve Ca homeostasis at the expense of bone. Increased bone remodeling during lactation may represent physiological mechanisms to help replace the maternal skeleton lost as the animal adapted to enormously increased Ca losses to the fetus and milk in late gestation and early lactation.

Non-Invasive Investigation of Bone Adaptation in Humans to Mechanical Loading

NASA Technical Reports Server (NTRS)

Whalen, R.

1999-01-01

Experimental studies have identified peak cyclic forces, number of loading cycles, and loading rate as contributors to the regulation of bone metabolism. We have proposed a theoretical model that relates bone density to a mechanical stimulus derived from average daily cumulative peak cyclic 'effective' tissue stresses. In order to develop a non-invasive experimental model to test the theoretical model we need to: (1) monitor daily cumulative loading on a bone, (2) compute the internal stress state(s) resulting from the imposed loading, and (3) image volumetric bone density accurately, precisely, and reproducibly within small contiguous volumes throughout the bone. We have chosen the calcaneus (heel) as an experimental model bone site because it is loaded by ligament, tendon and joint contact forces in equilibrium with daily ground reaction forces that we can measure; it is a peripheral bone site and therefore more easily and accurately imaged with computed tomography; it is composed primarily of cancellous bone; and it is a relevant site for monitoring bone loss and adaptation in astronauts and the general population. This paper presents an overview of our recent advances in the areas of monitoring daily ground reaction forces, biomechanical modeling of the forces on the calcaneus during gait, mathematical modeling of calcaneal bone adaptation in response to cumulative daily activity, accurate and precise imaging of the calcaneus with quantitative computed tomography (QCT), and application to long duration space flight.

Quantifying Leisure Physical Activity and Its Relation to Bone Density and Strength

PubMed Central

SHEDD, KRISTINE M.; HANSON, KATHY B.; ALEKEL, D. LEE; SCHIFERL, DANIEL J.; HANSON, LAURA N.; VAN LOAN, MARTA D.

2010-01-01

Purpose Compare three published methods of quantifying physical activity (total activity, peak strain, and bone-loading exposure (BLE) scores) and identify their associations with areal bone mineral density (aBMD), volumetric BMD (vBMD), and bone strength. Methods Postmenopausal women (N = 239; mean age: 53.8 yr) from Iowa (ISU) and California (UCD) completed the Paffenbarger Physical Activity Questionnaire, which was scored with each method. Dual energy x-ray absorptiometry assessed aBMD at the spine, hip, and femoral neck, and peripheral quantitative computed tomography (pQCT) measured vBMD and bone strength properties at the distal tibia and midshaft femur. Results UCD women had higher total activity scores and hours per week of leisure activity. All scoring methods were correlated with each other. No method was associated with aBMD. Peak strain score was negatively associated with polar moment of inertia and strength–strain index at the tibia, and total activity score was positively associated with cortical area and thickness at the femur. Separating by geographic site, the peak strain and hip BLE scores were negatively associated with pQCT measures at the tibia and femur among ISU subjects. Among UCD women, no method was significantly associated with any tibia measure, but total activity score was positively associated with measures at the femur (P < 0.05 for all associations). Conclusion Given the significantly greater hours per week of leisure activity done by UCD subjects, duration may be an important determinant of the effect physical activity has on bone. The positive association between leisure physical activity (assessed by the total activity score) and cortical bone measures in postmenopausal women may indicate a lifestyle factor that can help offset age-related bone loss. PMID:18046190

Quantifying leisure physical activity and its relation to bone density and strength.

PubMed

Shedd, Kristine M; Hanson, Kathy B; Alekel, D Lee; Schiferl, Daniel J; Hanson, Laura N; Van Loan, Marta D

2007-12-01

Compare three published methods of quantifying physical activity (total activity, peak strain, and bone-loading exposure (BLE) scores) and identify their associations with areal bone mineral density (aBMD), volumetric BMD (vBMD), and bone strength. Postmenopausal women (N = 239; mean age: 53.8 yr) from Iowa (ISU) and California (UCD) completed the Paffenbarger Physical Activity Questionnaire, which was scored with each method. Dual energy x-ray absorptiometry assessed aBMD at the spine, hip, and femoral neck, and peripheral quantitative computed tomography (pQCT) measured vBMD and bone strength properties at the distal tibia and midshaft femur. UCD women had higher total activity scores and hours per week of leisure activity. All scoring methods were correlated with each other. No method was associated with aBMD. Peak strain score was negatively associated with polar moment of inertia and strength-strain index at the tibia, and total activity score was positively associated with cortical area and thickness at the femur. Separating by geographic site, the peak strain and hip BLE scores were negatively associated with pQCT measures at the tibia and femur among ISU subjects. Among UCD women, no method was significantly associated with any tibia measure, but total activity score was positively associated with measures at the femur (P < 0.05 for all associations). Given the significantly greater hours per week of leisure activity done by UCD subjects, duration may be an important determinant of the effect physical activity has on bone. The positive association between leisure physical activity (assessed by the total activity score) and cortical bone measures in postmenopausal women may indicate a lifestyle factor that can help offset age-related bone loss.

Bone Metabolism in Adolescent Athletes With Amenorrhea, Athletes With Eumenorrhea, and Control Subjects

PubMed Central

Christo, Karla; Prabhakaran, Rajani; Lamparello, Brooke; Cord, Jennalee; Miller, Karen K.; Goldstein, Mark A.; Gupta, Nupur; Herzog, David B.; Klibanski, Anne; Misra, Madhusmita

2011-01-01

OBJECTIVE We hypothesized that, despite increased activity, bone density would be low in athletes with amenorrhea, compared with athletes with eumenorrhea and control subjects, because of associated hypogonadism and would be associated with a decrease in bone formation and increases in bone-resorption markers. METHODS In a cross-sectional study, we examined bone-density measures (spine, hip, and whole body) and body composition by using dual-energy radiograph absorptiometry and assessed fasting levels of insulin-like growth factor I and bone-turnover markers (N-terminal propeptied of type 1 procollagen and N-telopeptide) in 21 athletes with amenorrhea, 18 athletes with eumenorrhea, and 18 control subjects. Subjects were 12 to 18 years of age and of comparable chronologic and bone age. RESULTS Athletes with amenorrhea had lower bone-density z scores at the spine and whole body, compared with athletes with eumenorrhea and control subjects, and lower hip z scores, compared with athletes with eumenorrhea. Lean mass did not differ between groups. However, athletes with amenorrhea had lower BMI z scores than did athletes with eumenorrhea and lower insulin-like growth factor I levels than did control subjects. Levels of both markers of bone turnover were lower in athletes with amenorrhea than in control subjects. BMI z scores, lean mass, insulin-like growth factor I levels, and diagnostic category were important independent predictors of bone mineral density z scores. CONCLUSIONS Although they showed no significant differences in lean mass, compared with athletes with eumenorrhea and control subjects, athletes with amenorrhea had lower bone density at the spine and whole body. Insulin-like growth factor I levels, body-composition parameters, and menstrual status were important predictors of bone density. Follow-up studies are necessary to determine whether amenorrhea in athletes adversely affects the rate of bone mass accrual and therefore peak bone mass. PMID:18519482

Exercise does not enhance aged bone's impaired response to artificial loading in C57Bl/6 mice.

PubMed

Meakin, Lee B; Udeh, Chinedu; Galea, Gabriel L; Lanyon, Lance E; Price, Joanna S

2015-12-01

Bones adapt their structure to their loading environment and so ensure that they become, and are maintained, sufficiently strong to withstand the loads to which they are habituated. The effectiveness of this process declines with age and bones become fragile fracturing with less force. This effect in humans also occurs in mice which experience age-related bone loss and reduced adaptation to loading. Exercise engenders many systemic and local muscular physiological responses as well as engendering local bone strain. To investigate whether these physiological responses influence bones' adaptive responses to mechanical strain we examined whether a period of treadmill exercise influenced the adaptive response to an associated period of artificial loading in young adult (17-week) and old (19-month) mice. After treadmill acclimatization, mice were exercised for 30 min three times per week for two weeks. Three hours after each exercise period, right tibiae were subjected to 40 cycles of non-invasive axial loading engendering peak strain of 2250 με. In both young and aged mice exercise increased cross-sectional muscle area and serum sclerostin concentration. In young mice it also increased serum IGF1. Exercise did not affect bone's adaptation to loading in any measured parameter in young or aged bone. These data demonstrate that a level of exercise sufficient to cause systemic changes in serum, and adaptive changes in local musculature, has no effect on bone's response to loading 3h later. This study provides no support for the beneficial effects of exercise on bone in the elderly being mediated by systemic or local muscle-derived effects rather than local adaptation to altered mechanical strain. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Effects of Exercise on Bone Status in Female Subjects, from Young Girls to Postmenopausal Women: An Overview of Systematic Reviews and Meta-Analyses.

PubMed

Xu, Jincheng; Lombardi, Giovanni; Jiao, Wei; Banfi, Giuseppe

2016-08-01

Osteoporosis and postmenopausal bone loss pose a huge social and economic burden worldwide. Regular exercise and physical activity are effective interventions for maximizing or maintaining peak bone mass and preventing bone loss in the elderly; however, most recommendations are addressed to the general public and lack specific indications for girls and women, the segment of the population most at risk for developing osteoporosis. The aim of this overview of systematic reviews and meta-analyses was to summarize current evidence for the effects of exercise and physical activity interventions on bone status in girls and women, and to explore whether specific exercise programs exist for improving or maintaining bone mass or bone strength in females. The PubMed, EMBASE, PEDro, and Cochrane Library databases were searched from January 2009, updated to 22 June 2015, using the following groups of search terms: (i) 'physical activity' and 'exercise'; and (ii) 'bone', 'bone health', 'bone strength', 'bone structure', 'bone metabolism', 'bone turnover', and 'bone biomarkers'. Searches and screening were limited to systematic reviews or meta-analyses of studies in females and published in English. Our final analysis included 12 articles that met the inclusion criteria. Combined-impact exercise protocols (impact exercise with resistance training) are the best choice to preserve/improve bone mineral density in pre- and postmenopausal women. Peak bone mass in young girls can be improved with short bouts of school-based high-impact plyometric exercise programs. Whole-body vibration exercises have no beneficial effects on bone in postmenopausal or elderly women. Lifelong exercise, specific for age, is an effective way to sustain bone health in girls and women.

Raman spectroscopic study of the repair of surgical bone defects grafted or not with biphasic synthetic micro-granular HA + β-calcium triphosphate irradiated or not with λ850 nm LED light.

PubMed

Soares, Luiz Guilherme P; Marques, Aparecida Maria C; Guarda, Milena G; Aciole, Jouber Mateus S; Andrade, Aline S; Pinheiro, Antonio Luiz B; Silveira, Landulfo

2014-11-01

The handling of bone losses due to different etiologic factors is difficult and many techniques are aim to improve repair, including a wide range of biomaterials and, recently, photobioengineering. This work aimed to assess, through Raman spectroscopy, the level of bone mineralization using the intensities of the Raman peaks of both inorganic (~960, ~1,070, and 1,077 cm(-1)) and organic (~1,454 and ~1,666 cm(-1)) contents of bone tissue. Forty rats were divided into four groups each subdivided into two subgroups according to the time of sacrifice (15 and 30 days). Surgical bone defects were made on the femur of each animal with a trephine drill. On animals of group clot, the defect was filled only by blood clot, on group LED, the defect filled with the clot was further irradiated. On animals of groups biomaterial and LED + biomaterial, the defect was filled by biomaterial and the last one was further irradiated (λ850 ± 10 nm, 150 mW, Φ ~ 0.5 cm(2), 20 J/cm(2)-session, 140 J/cm(2)-treatment) at 48-h intervals and repeated for 2 weeks. At both 15th and 30th days following sacrifice, samples were taken and analyzed by Raman spectroscopy. At the end of the experimental time, the intensity of hydroxyapatite (HA) (~960 cm(-1)) were higher on group LED + biomaterial and the peaks of both organic content (~1,454 and ~1,666 cm(-1)) and transitional HA (~1,070 and ~1,077 cm(-1)) were lower on the same group. It is concluded that the use of LED phototherapy associated to biomaterial was effective in improving bone healing on bone defects as a result of the increasing deposition of HA measured by Raman spectroscopy.

Influence of prosthesis design and implantation technique on implant stresses after cementless revision THR

PubMed Central

2011-01-01

Background Femoral offset influences the forces at the hip and the implant stresses after revision THR. For extended bone defects, these forces may cause considerable bending moments within the implant, possibly leading to implant failure. This study investigates the influences of femoral anteversion and offset on stresses in the Wagner SL revision stem implant under varying extents of bone defect conditions. Methods Wagner SL revision stems with standard (34 mm) and increased offset (44 mm) were virtually implanted in a model femur with bone defects of variable extent (Paprosky I to IIIb). Variations in surgical technique were simulated by implanting the stems each at 4° or 14° of anteversion. Muscle and joint contact forces were applied to the reconstruction and implant stresses were determined using finite element analyses. Results Whilst increasing the implant's offset by 10 mm led to increased implant stresses (16.7% in peak tensile stresses), altering anteversion played a lesser role (5%). Generally, larger stresses were observed with reduced bone support: implant stresses increased by as much as 59% for a type IIIb defect. With increased offset, the maximum tensile stress was 225 MPa. Conclusion Although increased stresses were observed within the stem with larger offset and increased anteversion, these findings indicate that restoration of offset, key to restoring joint function, is unlikely to result in excessive implant stresses under routine activities if appropriate fixation can be achieved. PMID:21569522

The effects of vibration loading on adipose stem cell number, viability and differentiation towards bone-forming cells

PubMed Central

Tirkkonen, Laura; Halonen, Heidi; Hyttinen, Jari; Kuokkanen, Hannu; Sievänen, Harri; Koivisto, Anna-Maija; Mannerström, Bettina; Sándor, George K. B.; Suuronen, Riitta; Miettinen, Susanna; Haimi, Suvi

2011-01-01

Mechanical stimulation is an essential factor affecting the metabolism of bone cells and their precursors. We hypothesized that vibration loading would stimulate differentiation of human adipose stem cells (hASCs) towards bone-forming cells and simultaneously inhibit differentiation towards fat tissue. We developed a vibration-loading device that produces 3g peak acceleration at frequencies of 50 and 100 Hz to cells cultured on well plates. hASCs were cultured using either basal medium (BM), osteogenic medium (OM) or adipogenic medium (AM), and subjected to vibration loading for 3 h d–1 for 1, 7 and 14 day. Osteogenesis, i.e. differentiation of hASCs towards bone-forming cells, was analysed using markers such as alkaline phosphatase (ALP) activity, collagen production and mineralization. Both 50 and 100 Hz vibration frequencies induced significantly increased ALP activity and collagen production of hASCs compared with the static control at 14 day in OM. A similar trend was detected for mineralization, but the increase was not statistically significant. Furthermore, vibration loading inhibited adipocyte differentiation of hASCs. Vibration did not affect cell number or viability. These findings suggest that osteogenic culture conditions amplify the stimulatory effect of vibration loading on differentiation of hASCs towards bone-forming cells. PMID:21613288

Bone density and young athletic women. An update.

PubMed

Nichols, David L; Sanborn, Charlotte F; Essery, Eve V

2007-01-01

High-school girls and collegiate women have tremendous opportunities to participate in athletic teams. Young girls are also playing in club and select teams at an early age and often, year-round. There are many benefits for participating in sport and physical activity on both the physical and mental health of girls and women. Decreased risk for heart disease and diabetes mellitus, along with improved self-esteem and body-image, were among the first reported benefits of regular physical activity. In addition, sport participation and physical activity is also associated with bone health. Athletes have a greater bone mineral density compared with non-active and physically active females. The increase in bone mass should reduce the risk of fragility fractures in later life. There appears to be a window of opportunity during the development of peak bone mass in which the bone is especially responsive to weight-bearing physical activity. Impact loading sports such as gymnastics, rugby or volleyball tend to produce a better overall osteogenic response than sports without impact loading such as cycling, rowing and swimming. Relatively little is known about the impact of retiring from athletics on bone density. It appears that former athletes continue to have a higher bone density than non-athletes; however, the rate of bone loss appears to be similar in the femoral neck. The positive impact of sports participation on bone mass can be tempered by nutritional and hormonal status. It is not known whether female athletes need additional calcium compared with the general female population. Due to the increased energy expenditure of exercise and/or the pressure to obtain an optimal training bodyweight, some female athletes may develop low energy availability or an eating disorder and subsequently amenorrhoea and a loss of bone mineral density. The three inter-related clinical disorders are referred to as the 'female athlete triad'. This article presents a review of the relationship between sports training and bone health, specifically bone mineral density, in young athletic women.

Resistance of equine tibiae and radii to side impact loads.

PubMed

Piskoty, G; Jäggin, S; Michel, S A; Weisse, B; Terrasi, G P; Fürst, A

2012-11-01

There are no detailed studies describing the resistance of equine tibiae and radii to side impact loads, such as a horse kick and a better understanding of the general long bone impact behavioural model is required. To quantify the typical impact energy required to fracture or fissure an equine long bone, as well as to determine the range and time course of the impact force under conditions similar to that of a horse kick. Seventy-two equine tibiae and radii were investigated using a drop impact tester. The prepared bones were preloaded with an axial force of 2.5 kN and were then hit in the middle of the medial side. The impact velocity of the metal impactor, weighting 2 kg, was varied within the range of 6-11 m/s. The impact process was captured with a high-speed camera from the craniomedial side of the bone. The videos were used both for slow-motion observation of the process and for quantifying physical parameters, such as peak force via offline video tracking and subsequent numerical derivation of the 'position vs. time' function for the impactor. The macroscopic appearance of the resultant bone injuries was found to be similar to those produced by authentic horse kicks, indicating a successful simulation of the real load case. The impact behaviours of tibiae and radii do not differ considerably in terms of the investigated general characteristics. Peak force occurred between 0.15-0.30 ms after the start of the impact. The maximum contact force correlated with the 1.45-power of the impact velocity if no fracture occurred (F(max) ≈ 0.926 · v(i) (1.45) ). Peak force scatter was considerably larger within the fractured sub-group compared with fissured bones. The peak force for fracture tended to lie below the aforementioned function, within the range of F(max) = 11-23 kN ('fracture load'). The impact energy required to fracture a bone varied from 40-90 J. The video-based measuring method allowed quantifying of the most relevant physical parameters, such as contact force and energy balance. The results obtained should help with the development of bone implants and guards, supporting theoretical studies, and in the evaluation of bone injuries. © 2012 EVJ Ltd.

Bioapatite Recrystallization During Burning and its Effects on Phosphate Stable Oxygen Isotope Composition

NASA Astrophysics Data System (ADS)

Munro, L. E.; Longstaffe, F. J.; White, C. D.

2003-04-01

Stable oxygen isotopic compositions of phosphate from mammal bones are commonly used in palaeoenvironmental reconstructions. However, preservation of the primary bone oxygen isotopic composition is of concern during post-mortem alteration. Particularly in studies of archaeological interest, bone samples are often obtained from contexts where they have been heated, either in middens, or near hearths. Hence, in addition to alteration resulting from natural diagenetic processes, burning may also have contributed to modification of the primary oxygen isotopic signal. Various techniques can be employed to evaluate the degree of preservation of bone during burning. Anthropologists commonly use colour comparisons (Munsell Colour Chart) to assess the temperature of burning. Recrystallization of the carbonated hydroxyapatite, i.e., bioapatite, in bone is more rigorously assessed using X-ray diffraction and infra-red spectroscopy. In this study, freshly deceased (6<8 months) white-tailed deer leg bones (Odocoileus virginianus) were collected from Pinery Provincial Park, Ontario, Canada. Each long bone was sectioned, incrementally burned, colour-typed, ground to a standardized grain-size (45<63mm), and analysed using differential thermal analysis (DTA), thermogravimetric analysis (TGA), rotating anode X-ray diffraction (XRD), and Fourier transform infra-red spectroscopy (FTIR). Heating temperatures ranged from 25 to 900^oC, increasing in intervals of 25^oC. Two major stages of weight loss were recorded in the DTA/TGA data, 25-260^oC representing dehydration, and 270-600^oC reflecting incineration of organic matter. The end-product (900^oC) resembled pure hydroxyapatite. XRD patterns of the bioapatite remained virtually unchanged from 25-250^oC, after which peak intensity, sharpness and the XRD crystallinity index (XRD CI) increased from 0.80 at 250^oC to 1.26 at 900^oC. FTIR patterns showed analogous behaviour, demonstrating minimal fluctuations in the FTIR crystallinity index (FTIR CI) from 2.86 at 25^oC to 2.56 at 250^oC, and then an overall increasing trend from 2.54 at 275^oC to a maximum of 4.72 at 825^oC as v4PO4 peak splitting intensified. Initial results show that the δ18O (VSMOW) values of bioapatite phosphate decreased from 15.0 ppm at 300^oC to 10.6 ppm at 750^oC. These data suggest that primary phosphate oxygen isotopic compositions can be significantly altered during burning, even when only modest changes in crystallinity are indicated by XRD or FTIR.

Mechanics of limb bone loading during terrestrial locomotion in the green iguana (Iguana iguana) and American alligator (Alligator mississippiensis).

PubMed

Blob, R W; Biewener, A A

2001-03-01

In vivo measurements of strain in the femur and tibia of Iguana iguana (Linnaeus) and Alligator mississippiensis (Daudin) have indicated three ways in which limb bone loading in these species differs from patterns observed in most birds and mammals: (i) the limb bones of I. iguana and A. mississippiensis experience substantial torsion, (ii) the limb bones of I. iguana and A. mississippiensis have higher safety factors than those of birds or mammals, and (iii) load magnitudes in the limb bones of A. mississippiensis do not decrease uniformly with the use of a more upright posture. To verify these patterns, and to evaluate the ground and muscle forces that produce them, we collected three-dimensional kinematic and ground reaction force data from subadult I. iguana and A. mississippiensis using a force platform and high-speed video. The results of these force/kinematic studies generally confirm the loading regimes inferred from in vivo strain measurements. The ground reaction force applies a torsional moment to the femur and tibia in both species; for the femur, this moment augments the moment applied by the caudofemoralis muscle, suggesting large torsional stresses. In most cases, safety factors in bending calculated from force/video data are lower than those determined from strain data, but are as high or higher than the safety factors of bird and mammal limb bones in bending. Finally, correlations between limb posture and calculated stress magnitudes in the femur of I. iguana confirm patterns observed during direct bone strain recordings from A. mississippiensis: in more upright steps, tensile stresses on the anterior cortex decrease, but peak compressive stresses on the dorsal cortex increase. Equilibrium analyses indicate that bone stress increases as posture becomes more upright in saurians because the ankle and knee extensor muscles exert greater forces during upright locomotion. If this pattern of increased bone stress with the use of a more upright posture is typical of taxa using non-parasagittal kinematics, then similar increases in load magnitudes were probably experienced by lineages that underwent evolutionary shifts to a non-sprawling posture. High limb bone safety factors and small body size in these lineages could have helped to accommodate such increases in limb bone stress.

Monocyte recruitment and expression of monocyte chemoattractant protein-1 are developmentally regulated in remodeling bone in the mouse.

PubMed Central

Volejnikova, S.; Laskari, M.; Marks, S. C.; Graves, D. T.

1997-01-01

Tooth eruption is defined as the movement of a tooth from its site of development within the alveolar bone to its position of function in the oral cavity. It represents an excellent model to examine osseous metabolism as bone resorption and bone formation occur simultaneously and are spatially separated. Bone resorption occurs in the coronal (occlusal) area, whereas bone formation occurs in the basal area. Monocytes are thought to have a significant role in the regulation of osseous metabolism. The goal of this study was to examine the recruitment of monocytes to bone in C57BL/6J mice that are undergoing developmentally regulated bone remodeling. Monocytes were detected by immunohistochemistry and osteoclasts were counted as bone-associated multi-nucleated, tartrate-resistant acid phosphatase (TRAP)-positive cells. Cell numbers were obtained from histological sections of animals sacrificed daily for 14 days after birth; an image analysis system was used for quantification. The results demonstrated that, immediately after birth, there were relatively few monocytic cells. In the area of bone resorption, the number of monocytes increased with time, reaching peaks at 5 and 9 days, and decreased thereafter. A similar pattern was observed for osteoclasts. In the area of bone formation, there was a time-dependent increase in the number of monocytes. In contrast, the number of osteoclasts in this area was highest at the earliest time points and decreased after day 3. To investigate potential mechanisms for the recruitment of monocytes, expression of monocyte chemoattractant protein (MCP)-1 was assessed. The number of MCP-1-positive cells increased with time and was generally proportional to the recruitment of mononuclear phagocytes. Osteoblasts were the principal bone cell type expressing MCP-1. The results demonstrate that the recruitment of mononuclear cells in the occlusal area is associated with bone resorption. In contrast, recruitment of monocytes in the basal area is associated with bone formation and a decrease in the number of osteoclasts. These results suggest that monocytes have different functional roles in areas of bone formation compared with bone resorption. Furthermore, the expression of MCP-1 is developmentally regulated and may provide a mechanistic basis to explain the recruitment of monocytic cells. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:9137095

Bone mineral density in developing children with osteogenesis imperfecta

PubMed Central

Sakkers, Ralph J B; Pruijs, Hans E H; Joosse, Pieter; Castelein, René M

2013-01-01

Background and purpose — Osteogenesis imperfecta (OI) is a heritable disorder of connective tissue caused by a defect in collagen type I synthesis. For bone, this includes fragility, low bone mass, and progressive skeletal deformities, which can result in various degrees of short stature. The purpose of this study was to investigate development of bone mineral density in children with OI. Patients and methods — Development of lumbar bone mineral density was studied retrospectively in a cohort of 74 children with OI. Mean age was 16.3 years (SD 4.3). In 52 children, repeated measurements were available. Mean age at the start of measurement was 8.8 years (SD 4.1), and mean follow-up was 9 years (SD 2.7). A longitudinal data analysis was performed. In the total cohort (74 children), a cross-sectional analysis was performed with the latest-measured BMD. Age at the latest BMD measurement was almost equal for girls and boys: 17.4 and 17.7 years respectively. Result — Mean annual increase in BMD in the 52 children was 0.038 g/cm2/year (SD 0.024). Annual increase in BMD was statistically significantly higher in girls, in both the unadjusted and adjusted analysis. In cross-sectional analysis, in the whole cohort the latest-measured lumbar BMD was significantly higher in girls, in the children with OI of type I, in walkers, and in those who were older, in both unadjusted and adjusted analysis. Interpretation — During 9 years of follow-up, there appeared to be an increase in bone mineral density, which was most pronounced in girls. One possible explanation might be a later growth spurt and older age at peak bone mass in boys. PMID:23992144

Proteoglycan 4: A Dynamic Regulator of Skeletogenesis and Parathyroid Hormone Skeletal Anabolism

PubMed Central

Novince, Chad M; Michalski, Megan N; Koh, Amy J; Sinder, Benjamin P; Entezami, Payam; Eber, Matthew R; Pettway, Glenda J; Rosol, Thomas J; Wronski, Thomas J; Kozloff, Ken M; McCauley, Laurie K

2014-01-01

Proteoglycan 4 (Prg4), known for its lubricating and protective actions in joints, is a strong candidate regulator of skeletal homeostasis and parathyroid hormone (PTH) anabolism. Prg4 is a PTH-responsive gene in bone and liver. Prg4 null mutant mice were used to investigate the impact of proteoglycan 4 on skeletal development, remodeling, and PTH anabolic actions. Young Prg4 mutant and wild-type mice were administered intermittent PTH(1–34) or vehicle daily from 4 to 21 days. Young Prg4 mutant mice had decreased growth plate hypertrophic zones, trabecular bone, and serum bone formation markers versus wild-type mice, but responded with a similar anabolic response to PTH. Adult Prg4 mutant and wild-type mice were administered intermittent PTH(1–34) or vehicle daily from 16 to 22 weeks. Adult Prg4 mutant mice had decreased trabecular and cortical bone, and blunted PTH-mediated increases in bone mass. Joint range of motion and animal mobility were lower in adult Prg4 mutant versus wild-type mice. Adult Prg4 mutant mice had decreased marrow and liver fibroblast growth factor 2 (FGF-2) mRNA and reduced serum FGF-2, which were normalized by PTH. A single dose of PTH decreased the PTH/PTHrP receptor (PPR), and increased Prg4 and FGF-2 to a similar extent in liver and bone. Proteoglycan 4 supports endochondral bone formation and the attainment of peak trabecular bone mass, and appears to support skeletal homeostasis indirectly by protecting joint function. Bone- and liver-derived FGF-2 likely regulate proteoglycan 4 actions supporting trabeculae formation. Blunted PTH anabolic responses in adult Prg4 mutant mice are associated with altered biomechanical impact secondary to joint failure. PMID:21932346

Understanding leptin-dependent regulation of skeletal homeostasis

PubMed Central

Motyl, Katherine J.; Rosen, Clifford J.

2012-01-01

Despite growing evidence for adipose tissue regulation of bone mass, the role of the adipokine leptin in bone remodeling remains controversial. The majority of in vitro studies suggest leptin enhances osteoblastic proliferation and differentiation while inhibiting adipogenic differentiation from marrow stromal cells. Alternatively, some evidence demonstrates either no effect or a pro-apoptotic action of leptin on stromal cells. Similarly, in vivo work has demonstrated both positive and negative effects of leptin on bone mass. Most of the literature supports the idea that leptin suppresses bone mass by acting in the brainstem to reduce serotonin-dependent sympathetic signaling from the ventromedial hypothalamus to bone. However, other studies have found partly or entirely contrasting actions of leptin. Recently one study found a significant effect of surgery alone with intracerebroventricular administration of leptin, a technique crucial for understanding centrally-mediated leptin regulation of bone. Thus, two mainstream hypotheses for the role of leptin on bone emerge: 1) direct regulation through increased osteoblast proliferation and differentiation and 2) indirect suppression of bone formation through a hypothalamic relay. At the present time, it remains unclear whether these effects are relevant in only extreme circumstances (i.e. models with complete deficiency) or play an important homeostatic role in the regulation of peak bone acquisition and skeletal remodeling. Ultimately, determining the actions of leptin on the skeleton will be critical for understanding how the obesity epidemic may be impacting the prevalence of osteoporosis. PMID:22534195

Deficiency of retinaldehyde dehydrogenase 1 induces BMP2 and increases bone mass in vivo.

PubMed

Nallamshetty, Shriram; Wang, Hong; Rhee, Eun-Jung; Kiefer, Florian W; Brown, Jonathan D; Lotinun, Sutada; Le, Phuong; Baron, Roland; Rosen, Clifford J; Plutzky, Jorge

2013-01-01

The effects of retinoids, the structural derivatives of vitamin A (retinol), on post-natal peak bone density acquisition and skeletal remodeling are complex and compartment specific. Emerging data indicates that retinoids, such as all trans retinoic acid (ATRA) and its precursor all trans retinaldehyde (Rald), exhibit distinct and divergent transcriptional effects in metabolism. Despite these observations, the role of enzymes that control retinoid metabolism in bone remains undefined. In this study, we examined the skeletal phenotype of mice deficient in retinaldehyde dehydrogenase 1 (Aldh1a1), the enzyme responsible for converting Rald to ATRA in adult animals. Bone densitometry and micro-computed tomography (µCT) demonstrated that Aldh1a1-deficient (Aldh1a1(-/-) ) female mice had higher trabecular and cortical bone mass compared to age and sex-matched control C57Bl/6 wild type (WT) mice at multiple time points. Histomorphometry confirmed increased cortical bone thickness and demonstrated significantly higher bone marrow adiposity in Aldh1a1(-/-) mice. In serum assays, Aldh1a1(-/-) mice also had higher serum IGF-1 levels. In vitro, primary Aldh1a1(-/-) mesenchymal stem cells (MSCs) expressed significantly higher levels of bone morphogenetic protein 2 (BMP2) and demonstrated enhanced osteoblastogenesis and adipogenesis versus WT MSCs. BMP2 was also expressed at higher levels in the femurs and tibias of Aldh1a1(-/-) mice with accompanying induction of BMP2-regulated responses, including expression of Runx2 and alkaline phosphatase, and Smad phosphorylation. In vitro, Rald, which accumulates in Aldh1a1(-/-) mice, potently induced BMP2 in WT MSCs in a retinoic acid receptor (RAR)-dependent manner, suggesting that Rald is involved in the BMP2 increases seen in Aldh1a1 deficiency in vivo. Collectively, these data implicate Aldh1a1 as a novel determinant of cortical bone density and marrow adiposity in the skeleton in vivo through modulation of BMP signaling.

Loading and Skeletal Development and Maintenance

PubMed Central

Bergmann, P.; Body, J. J.; Boonen, S.; Boutsen, Y.; Devogelaer, J. P.; Goemaere, S.; Kaufman, J.; Reginster, J. Y.; Rozenberg, S.

2011-01-01

Mechanical loading is a major regulator of bone mass and geometry. The osteocytes network is considered the main sensor of loads, through the shear stress generated by strain induced fluid flow in the lacuno-canalicular system. Intracellular transduction implies several kinases and phosphorylation of the estrogen receptor. Several extra-cellular mediators, among which NO and prostaglandins are transducing the signal to the effector cells. Disuse results in osteocytes apoptosis and rapid imbalanced bone resorption, leading to severe osteoporosis. Exercising during growth increases peak bone mass, and could be beneficial with regards to osteoporosis later in life, but the gain could be lost if training is abandoned. Exercise programs in adults and seniors have barely significant effects on bone mass and geometry at least at short term. There are few data on a possible additive effect of exercise and drugs in osteoporosis treatment, but disuse could decrease drugs action. Exercise programs proposed for bone health are tedious and compliance is usually low. The most practical advice for patients is to walk a minimum of 30 to 60 minutes per day. Other exercises like swimming or cycling have less effect on bone, but could reduce fracture risk indirectly by maintaining muscle mass and force. PMID:21209784

The potential of materials analysis by electron rutherford backscattering as illustrated by a case study of mouse bones and related compounds.

PubMed

Vos, Maarten; Tökési, Károly; Benkö, Ilona

2013-06-01

Electron Rutherford backscattering (ERBS) is a new technique that could be developed into a tool for materials analysis. Here we try to establish a methodology for the use of ERBS for materials analysis of more complex samples using bone minerals as a test case. For this purpose, we also studied several reference samples containing Ca: calcium carbonate (CaCO(3)) and hydroxyapatite and mouse bone powder. A very good understanding of the spectra of CaCO(3) and hydroxyapatite was obtained. Quantitative interpretation of the bone spectrum is more challenging. A good fit of these spectra is only obtained with the same peak widths as used for the hydroxyapatite sample, if one allows for the presence of impurity atoms with a mass close to that of Na and Mg. Our conclusion is that a meaningful interpretation of spectra of more complex samples in terms of composition is indeed possible, but only if widths of the peaks contributing to the spectra are known. Knowledge of the peak widths can either be developed by the study of reference samples (as was done here) or potentially be derived from theory.

Associations between socioeconomic factors and proinflammatory cytokines in children, adolescents and young adults: a systematic review protocol

PubMed Central

Fredman, Nick John; Duque, Gustavo; Duckham, Rachel Louise; Green, Darci

2018-01-01

Introduction There is now substantial evidence of a social gradient in bone health. Social stressors, related to socioeconomic status, are suggested to produce an inflammatory response marked by increased levels of proinflammatory cytokines. Here we focus on the particular role in the years before the achievement of peak bone mass, encompassing childhood, adolescence and young adulthood. An examination of such associations will help explain how social factors such as occupation, level of education and income may affect later-life bone disorders. This paper presents the protocol for a systematic review of existing literature regarding associations between socioeconomic factors and proinflammatory cytokines in those aged 6–30 years. Methods and analysis We will conduct a systematic search of PubMed, OVID and CINAHL databases to identify articles that examine associations between socioeconomic factors and levels of proinflammatory cytokines, known to influence bone health, during childhood, adolescence or young adulthood. The findings of this review have implications for the equitable development of peak bone mass regardless of socioeconomic factors. Two independent reviewers will determine the eligibility of studies according to predetermined criteria, and studies will be assessed for methodological quality using a published scoring system. Should statistical heterogeneity be non-significant, we will conduct a meta-analysis; however, if heterogeneity prevent numerical syntheses, we will undertake a best-evidence analysis to determine whether socioeconomic differences exist in the levels of proinflammatory cytokines from childhood through to young adulthood. Ethics and dissemination This study will be a systematic review of published data, and thus ethics approval is not required. In addition to peer-reviewed publication, these findings will be presented at professional conferences in national and international arenas. PMID:29490962

[Finite element analysis on the effect of lateral wedge insole intervention on the contact characteristics of the subtalar joint].

PubMed

Zhou, En-Chang; Tang, Ping; Zhu, Chuan-Ying; Liu, Shi-Ming

2017-01-25

To establish a three-dimensional finite element model of the lower limb bones, and investigate the changes of the contact characteristics of the subtalar joint after using laterally wedge insole intervention. Using the reverse modeling technology, the lower limb bones of normal adult volunteers was scanned by CT. Mimics 10.0 and Geomagic Studio 6.0 software were used to reconstruct the 3D morphology of bones and external soft tissue of the feet. The laterally wedge insole was designed in ProE 5.0. And then all the models were imported into Hyperwork 10.0 and meshed, and given the material properties. The finite element analysis was carried out in ABAQUS 6.9. A three-dimensional finite element model of the lower extremity was established, which was consisted of 95 365 nodes and 246 238 elements. The contact area of the standing state of the lower joint was larger than that of the anterior middle joint surface. The peak stress was concentrated in the anterior lateral part of the posterior articular surface, and the average stress value was(3.85±1.03) MPa. Compared with the model of 0°, the contact area of the subtalar joint was reduced accordingly. There was a significant correlation between anterior middle joint | r |=0.964, P =0.008, and posterior articular | r |=0.978, P =0.002. The equivalent stress of 0° model distributed from(3.07±1.14) MPa to(3.85± 1.03) MPa, which had no statistically difference. Compared with the 0° model, the equivalent stress of the anterior and middle joint surfaces of the 8° model was significantly reduced( P <0.05), but the peak stress of the posterior articular surface was significantly increased( P <0.05). In the 12° model, the peak stress was sharply increased to(10.51±3.53) MPa. Compared with 8° model, there was no statistically difference( P <0.05). Although the peak stress was slightly increased in 16° model, but compared with 12° model, there was no statistically differences( P >0.05). Although a certain valgus can be obtained in subtalar by wearing LWI, the result comes at the cost of the stress concentration on posterior surface. Through this study, we can find that LWI with 8° tilt angle could provide appropriate valgus moment without causing excessive concentration. Therefore, in order to avoid secondary ankle complications, we should not increase the tilt angle blindly.

The mechanical consequences of load bearing in the equine third metacarpal across speed and gait: the nonuniform distributions of normal strain, shear strain, and strain energy density

PubMed Central

Rubin, Clinton T.; Seeherman, Howard; Qin, Yi-Xian; Gross, Ted S.

2013-01-01

Distributions of normal strain, shear strain, and strain energy density (SED) were determined across the midshaft of the third metacarpal (MCIII, or cannon bone) of 3 adult thoroughbred horses as a function of speed and gait. A complete characterization of the mechanical demands of the bone made through the stride and from mild through the extremes of locomotion was possible by using three 3-element rosette strain gauges bonded at the diaphyseal midshaft of the MCIII and evaluating the strain output with beam theory and finite element analysis. Mean ± sd values of normal strain, shear strain, and SED increased with speed and peaked during a canter (−3560±380 microstrain, 1760±470 microstrain, and 119±23 kPa, respectively). While the location of these peaks was similar across animals and gaits, the resulting strain distributions across the cortex were consistently nonuniform, establishing between a 73-fold (slow trot) to a 330-fold (canter) disparity between the sites of maximum and minimum SED for each gait cycle. Using strain power density as an estimate of strain history across the bone revealed a 154-fold disparity between peak and minimum at the walk but fell to ∼32-fold at the canter. The nonuniform, minimally varying, strain environment suggests either that bone homeostasis is mediated by magnitude-independent mechanical signals or that the duration of stimuli necessary to establish and maintain tissue integrity is relatively brief, and thus the vast majority of strain information is disregarded.—Rubin, C. T., Seeherman, H., Qin, Y.-X., Gross, T. S., The mechanical consequences of load bearing in the equine third metacarpal across speed and gait: the nonuniform distributions of normal strain, shear strain, and strain energy density. PMID:23355269

Comparison between infrared and Raman spectroscopic analysis of maturing rabbit cortical bone.

PubMed

Turunen, Mikael J; Saarakkala, Simo; Rieppo, Lassi; Helminen, Heikki J; Jurvelin, Jukka S; Isaksson, Hanna

2011-06-01

The molecular composition of the organic and inorganic matrices of bone undergoes alterations during maturation. The aim of this study was to compare Fourier transform infrared (FT-IR) and near-infrared (NIR) Raman microspectroscopy techniques for characterization of the composition of growing and developing bone from young to skeletally mature rabbits. Moreover, the specificity and differences of the techniques for determining bone composition were clarified. The humeri of female New Zealand White rabbits, with age range from young to skeletally mature animals (four age groups, n = 7 per group), were studied. Spectral peak areas, intensities, and ratios related to organic and inorganic matrices of bone were analyzed and compared between the age groups and between FT-IR and Raman microspectroscopic techniques. Specifically, the degree of mineralization, type-B carbonate substitution, crystallinity of hydroxyapatite (HA), mineral content, and collagen maturity were examined. Significant changes during maturation were observed in various compositional parameters with one or both techniques. Overall, the compositional parameters calculated from the Raman spectra correlated with analogous parameters calculated from the IR spectra. Collagen cross-linking (XLR), as determined through peak fitting and directly from the IR spectra, were highly correlated. The mineral/matrix ratio in the Raman spectra was evaluated with multiple different peaks representing the organic matrix. The results showed high correlation with each other. After comparison with the bone mineral density (BMD) values from micro-computed tomography (micro-CT) imaging measurements and crystal size from XRD measurements, it is suggested that Raman microspectroscopy is more sensitive than FT-IR microspectroscopy for the inorganic matrix of the bone. In the literature, similar spectroscopic parameters obtained with FT-IR and NIR Raman microspectroscopic techniques are often compared. According to the present results, however, caution is required when performing this kind of comparison.

Maternal Consumption of Hesperidin and Naringin Flavanones Exerts Transient Effects to Tibia Bone Structure in Female CD-1 Offspring

PubMed Central

Sacco, Sandra M.; Saint, Caitlin; LeBlanc, Paul J.; Ward, Wendy E.

2017-01-01

Hesperidin (HSP) and naringin (NAR), flavanones rich in citrus fruits, support skeletal integrity in adult and aging rodent models. This study determined whether maternal consumption of HSP and NAR favorably programs bone development, resulting in higher bone mineral density (BMD) and greater structure and biomechanical strength (i.e., peak load) in female offspring. Female CD-1 mice were fed a control diet or a HSP + NAR diet five weeks before pregnancy and throughout pregnancy and lactation. At weaning, female offspring were fed a control diet until six months of age. The structure and BMD of the proximal tibia were measured longitudinally using in vivo micro-computed tomography at 2, 4, and 6 months of age. The trabecular bone structure at two and four months and the trabecular BMD at four months were compromised at the proximal tibia in mice exposed to HSP and NAR compared to the control diet (p < 0.001). At six months of age, these differences in trabecular structure and BMD at the proximal tibia had disappeared. At 6 months of age, the tibia midpoint peak load, BMD, structure, and the peak load of lumbar vertebrae and femurs were similar (p > 0.05) between the HSP + NAR and control groups. In conclusion, maternal consumption of HSP and NAR does not enhance bone development in female CD-1 offspring. PMID:28282882

On the relationship between tibia torsional deformation and regional muscle contractions in habitual human exercises in vivo.

PubMed

Yang, Peng-Fei; Kriechbaumer, Andreas; Albracht, Kirsten; Sanno, Maximilian; Ganse, Bergita; Koy, Timmo; Shang, Peng; Brüggemann, Gert-Peter; Müller, Lars Peter; Rittweger, Jörn

2015-02-05

The mechanical relationship between bone and muscle has been long recognized. However, it still remains unclear how muscles exactly load on bone. In this study, utilizing an optical segment tracking technique, the in vivo tibia loading regimes in terms of tibia segment deformation in humans were investigated during walking, forefoot and rear foot stair ascent and running and isometric plantar flexion. Results suggested that the proximal tibia primarily bends to the posterior aspect and twists to the external aspect with respect to the distal tibia. During walking, peak posterior bending and peak torsion occurred in the first half (22%) and second half (76%) of the stance phase, respectively. During stair ascent, two noticeable peaks of torsion were found with forefoot strike (38% and 82% of stance phase), but only one peak of torsion was found with rear foot strike (78% of stance phase). The torsional deformation angle during both stair ascent and running was larger with forefoot strike than rear foot strike. During isometric plantar flexion, the tibia deformation regimes were characterized more by torsion (maximum 1.35°) than bending (maximum 0.52°). To conclude, bending and torsion predominated the tibia loading regimes during the investigated activities. Tibia torsional deformation is closely related to calf muscle contractions, which further confirm the notion of the muscle-bone mechanical link and shift the focus from loading magnitude to loading regimes in bone mechanobiology. It thus is speculated that torsion is another, yet under-rated factor, besides the compression and tension, to drive long bone mechano-adaptation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Childhood fractures are associated with decreased bone mass gain during puberty: an early marker of persistent bone fragility?

PubMed

Ferrari, Serge L; Chevalley, Thierry; Bonjour, Jean-Philippe; Rizzoli, René

2006-04-01

Whether peak bone mass is low among children with fractures remains uncertain. In a cohort of 125 girls followed over 8.5 years, 42 subjects reported 58 fractures. Among those, BMC gain at multiple sites and vertebral bone size at pubertal maturity were significantly decreased. Hence, childhood fractures may be markers of low peak bone mass acquisition and persistent skeletal fragility. Fractures in childhood may result from a deficit in bone mass accrual during rapid longitudinal growth. Whether low bone mass persists beyond this period however remains unknown. BMC at the spine, radius, hip, and femur diaphysis was prospectively measured over 8.5 years in 125 girls using DXA. Differences in bone mass and size between girls with and without fractures were analyzed using nonparametric tests. The contribution of genetic factors was evaluated by mother-daughter correlations and that of calcium intake by Cox proportional hazard models. Fifty-eight fractures occurred in 42 among 125 girls (cumulative incidence, 46.4%), one-half of all fractures affecting the forearm and wrist. Girls with and without fractures had similar age, height, weight. and calcium intake at all time-points. Before and during early puberty, BMC and width of the radius diaphysis was lower in the fracture compared with no-fracture group (p < 0.05), whereas aBMD and BMAD were similar in the two groups. At pubertal maturity (Tanner's stage 5, mean age +/- SD, 16.4 +/- 0.5 years), BMC at the ultradistal radius (UD Rad.), femur trochanter, and lumbar spine (LS), and LS projected bone area were all significantly lower in girls with fractures. Throughout puberty, BMC gain at these sites was also decreased in the fracture group (LS, -8.0%, p = 0.015; UD Rad., -12.0%, p = 0.004; trochanter, -8.4%, p = 0.05 versus no fractures). BMC was highly correlated between prepuberty and pubertal maturity (R = 0.54-0.81) and between mature daughters and their mothers (R = 0.32-0.46). Calcium intake was not related to fracture risk. Girls with fractures have decreased bone mass gain in the axial and appendicular skeleton and reduced vertebral bone size when reaching pubertal maturity. Taken together with the evidence of tracking and heritability for BMC, these observations indicate that childhood fractures may be markers for low peak bone mass and persistent bone fragility.

Androgens and estrogens in skeletal sexual dimorphism

PubMed Central

Laurent, Michaël; Antonio, Leen; Sinnesael, Mieke; Dubois, Vanessa; Gielen, Evelien; Classens, Frank; Vanderschueren, Dirk

2014-01-01

Bone is an endocrine tissue expressing androgen and estrogen receptors as well as steroid metabolizing enzymes. The bioactivity of circulating sex steroids is modulated by sex hormone-binding globulin and local conversion in bone tissue, for example, from testosterone (T) to estradiol (E2) by aromatase, or to dihydrotestosterone by 5α-reductase enzymes. Our understanding of the structural basis for gender differences in bone strength has advanced considerably over recent years due to increasing use of (high resolution) peripheral computed tomography. These microarchitectural insights form the basis to understand sex steroid influences on male peak bone mass and turnover in cortical vs trabecular bone. Recent studies using Cre/LoxP technology have further refined our mechanistic insights from global knockout mice into the direct contributions of sex steroids and their respective nuclear receptors in osteoblasts, osteoclasts, osteocytes, and other cells to male osteoporosis. At the same time, these studies have reinforced the notion that androgen and estrogen deficiency have both direct and pleiotropic effects via interaction with, for example, insulin-like growth factor 1, inflammation, oxidative stress, central nervous system control of bone metabolism, adaptation to mechanical loading, etc., This review will summarize recent advances on these issues in the field of sex steroid actions in male bone homeostasis. PMID:24385015

Sarcopenia Is Negatively Related to High Gravitational Impacts Achieved From Day-to-day Physical Activity

PubMed Central

Hartley, April; Gregson, Celia L; Hannam, Kimberly; Deere, Kevin C; Clark, Emma M; Tobias, Jon H

2018-01-01

Abstract Background Sarcopenia has been associated with reduced physical activity (PA). We aimed to determine if sarcopenia, and specific components of muscle size, function, and physical performance, are associated with high impacts achieved during habitual PA, as these are related to bone strength in community-dwelling older women. Methods Participants were older women from the Cohort of Skeletal Health in Bristol and Avon. We defined sarcopenia using the EWGSOP criteria. Lower limb peak muscle power and force were assessed using Jumping Mechanography (JM). High vertical impacts were assessed by tri-axial accelerometry (at least 1.5g above gravity). Cross-sectional associations were analyzed by linear regression, adjusting for age, height and weight (or fat mass for models including appendicular lean mass index), comorbidities, smoking, alcohol, and Index of Multiple Deprivation. Results Our analyses included 380 participants, with mean age 76.7 (SD 3.0) years; 242 (64%) also completed JM. In age-adjusted analysis, a negative relationship was observed between severity of sarcopenia and high, but not medium or low, impacts (p = .03 for trend). Regarding components of sarcopenia underlying this relationship, multivariable analyses revealed that gait speed (β 1.47 [95% CI 1.14, 1.89], [β-1] reflects the proportionate increase in high impacts per SD increase in exposure) and peak force (1.40 [1.07, 1.84]) were independently associated with high impacts. Conclusions Older women with sarcopenia experienced fewer bone-strengthening high impacts than those with presarcopenia or without sarcopenia. To increase bone strengthening activity in older women, interventions need to improve both lower limb muscle force and walking speed. PMID:29182712

The female athlete triad.

PubMed

Kazis, Keren; Iglesias, Elba

2003-02-01

The female athlete triad is a syndrome consisting of disordered eating, amenorrhea, and osteoporosis. The syndrome is increasing in prevalence as more women are participating in sports at a competitive level. Behaviors such as intense exercise or disordered eating patterns can lead to dysregulation of the hypothalamic-pituitarian-ovarian (HPO) axis, resulting in amenorrhea. Hypothalamic amenorrhea can lead to osteoporosis and increased fracture risk. Adolescents may particularly be at risk because it is during this crucial time that females attain their peak bone mass. Prevention of the female athlete triad through education and identification of athletes at risk may decrease the incidence of long-term deleterious consequences. Treatment of the female athlete triad is initially aimed at increasing caloric intake and decreasing physical activity until there is resumption of normal menses. Treatment of decreased bone mineral density and osteoporosis in the adolescent population, however, is controversial, with new treatment modalities currently being investigated in order to aid in the management of this disorder.

Somatic maturation and the relationship between bone mineral variables and types of sports among adolescents: cross-sectional study.

PubMed

Agostinete, Ricardo Ribeiro; Ito, Igor Hideki; Kemper, Han; Pastre, Carlos Marcelo; Rodrigues-Júnior, Mário Antônio; Luiz-de-Marco, Rafael; Fernandes, Rômulo Araújo

2017-01-01

Peak height velocity (PHV) is an important maturational event during adolescence that affects skeleton size. The objective here was to compare bone variables in adolescents who practiced different types of sports, and to identify whether differences in bone variables attributed to sports practice were dependent on somatic maturation status. Cross-sectional study, São Paulo State University (UNESP). The study was composed of 93 adolescents (12 to 16.5 years old), divided into three groups: no-sport group (n = 42), soccer/basketball group (n = 26) and swimming group (n = 25). Bone mineral density and content were measured using dual-energy x-ray absorptiometry and somatic maturation was estimated through using peak height velocity. Data on training load were provided by the coaches. Adolescents whose PHV occurred at an older age presented higher bone mineral density in their upper limbs (P = 0.018). After adjustments for confounders, such as somatic maturation, the swimmers presented lower values for bone mineral density in their lower limbs, spine and whole body. Only the bone mineral density in the upper limbs was similar between the groups. There was a negative relationship between whole-body bone mineral content and the weekly training hours (β: -1563.967; 95% confidence interval, CI: -2916.484 to -211.450). The differences in bone variables attributed to sport practice occurred independently of maturation, while high training load in situations of hypogravity seemed to be related to lower bone mass in swimmers.

Heat generation during removal of an abutment screw fragment from dental implants.

PubMed

Arias, Sergio R; Rueggeberg, Frederick A; Mettenburg, Donald; Sharawy, Mohamed; Looney, Stephen; Elsayed, Ranya; Elsalanty, Mohammed E

2018-04-01

Little information is available on the effect of drilling speed on surrounding bone during the removal of an abutment screw fragment. The purpose of this in vitro study was to compare, in vitro, the peak temperature increase during the removal of fractured abutment screws from implants placed in a porcine mandible, using drilling speeds of 600 or 2000 rpm. Twenty 4.3×13-mm dental implants were placed in 10 dissected porcine mandibles: 2 implants per mandible, 1 on each side. Localized defects were created in 20 surface-treated abutment screws, which were then tightened into each implant until a reproducible fracture occurred in each screw. The fractured screws were removed with a handpiece removal kit and irrigated with room-temperature water at either 600 or 2000 rpm. The temperature rise at the implant surface was measured at 3 levels with 3 type-K thermocouples. Repeated measure ANOVA was performed with the Tukey-Kramer post hoc test for mean pair-wise comparisons (α=.05 for all tests). Mean peak temperatures were significantly higher at 2000 rpm than at 600 rpm in the mid-body (P<.001) and crestal (P=.003) regions but not in the apical (P=.225) implant locations. No significant differences in mean peak temperatures were found among the 3 locations using 600 rpm (P=.179). In the 2000-rpm group, mean peak temperature in the mid-body area was consistently higher than that in the apical (P<.001) area, and more instances of temperature rise above 56°C and 60°C were observed. In 1 implant from this group, the estimated peak temperature exceeded the bone damage threshold value (50°C for 30 seconds). A drilling speed of 2000 rpm during the removal of abutment screw fragments caused overheating of the outer surface of the implant which may damage the surrounding bone; a speed of 600 rpm appears to be safe. Copyright © 2017 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Do laser/LED phototherapies influence the outcome of the repair of surgical bone defects grafted with biphasic synthetic microgranular HA + β-tricalcium phosphate? A Raman spectroscopy study.

PubMed

Soares, Luiz Guilherme Pinheiro; Marques, Aparecida Maria Cordeiro; Aciole, Jouber Mateus Santos; da Guarda, Milena Góes; Cangussú, Maria Cristina Teixeira; Silveira, Landulfo; Pinheiro, Antonio Luiz Barbosa

2014-09-01

The treatment of bone loss is difficult. Many techniques are proposed to improve repair, including biomaterials and, recently, phototherapies. This work studied bone mineralization by Raman spectroscopy assessing intensities of Raman peaks of both inorganic (∼ 960, ∼ 1,070 cm(-1)) and organic (∼ 1,454 cm(-1)) contents in animal model. Six groups were studied: clot, laser, light-emitting diode (LED), biomaterial (HA + β-tricalcium phosphate), laser + biomaterial, and LED + biomaterial. Defects at right tibia were performed with a drill. When indicated, defects were further irradiated at a 48-h interval during 2 weeks. At the 15th and 30th days, the tibias were withdrawn and analyzed. The ∼ 960-cm(-1) peak was significantly affected by phototherapy on both clot- and biomaterial-filled defects. The ∼ 1,070-cm(-1) peak was affected by both time and the use of the LED light on clot-filled defects. On biomaterial-filled defects, only the use of the laser light significantly influenced the outcome. No significant influence of either the time or the use of the light was detected on clot-filled defects as regards the ∼ 1,454-cm(-1) peak. Raman intensities of both mineral and matrix components indicated that the use of laser and LED phototherapies improved the repair of bone defects grafted or not with biphasic synthetic microgranular HA + β-tricalcium phosphate.

Biomechanical analysis of iliac crest loading following cortico-cancellous bone harvesting.

PubMed

Schmitz, Paul; Cornelius Neumann, Christoph; Neumann, Carsten; Nerlich, Michael; Dendorfer, Sebastian

2018-05-09

Iliac crest bone harvesting is a frequently performed surgical procedure widely used to treat bone defects. The objective of this study is to assess the biomechanical quantities related to risk for pelvic fracture after harvesting an autologous bone graft at the anterior iliac crest. Finite element models with a simulated harvest site (sized 15 × 20 mm, 15 × 35 mm, 30 × 20 mm and 30 × 35 mm) in the iliac wing are created. The relevant loading case is when the ipsilateral leg is lifted off the ground. Musculoskeletal analysis is utilized to compute the muscle and joint forces involved in this motion. These forces are used as boundary conditions for the finite element analyses. Bone tissue stress is analyzed. Critical stress peaks are located between the anterior superior iliac spine (ASIS) and the anterior edge of the harvest site. Irrespective of the graft size, the iliac wing does not show any significant stress peaks with the harvest site being 20 to 25 mm posterior to the ASIS. The harvest area itself inhibits the distribution of the forces applied on the ASIS to extend to the posterior iliac wing. This leads to a lack of stress posterior to the harvest site. A balanced stress distribution with no stress peaks appears when the bone graft is taken below the iliac crest. A harvest site located at least 20 to 25 mm posterior to the ASIS should be preferred to minimize the risk of iliac fatigue fracture.

Biomechanical evaluation of one-piece and two-piece small-diameter dental implants: In-vitro experimental and three-dimensional finite element analyses.

PubMed

Wu, Aaron Yu-Jen; Hsu, Jui-Ting; Chee, Winston; Lin, Yun-Te; Fuh, Lih-Jyh; Huang, Heng-Li

2016-09-01

Small-diameter dental implants are associated with a higher risk of implant failure. This study used both three-dimensional finite-element (FE) simulations and in-vitro experimental tests to analyze the stresses and strains in both the implant and the surrounding bone when using one-piece (NobelDirect) and two-piece (NobelReplace) small-diameter implants, with the aim of understanding the underlying biomechanical mechanisms. Six experimental artificial jawbone models and two FE models were prepared for one-piece and two-piece 3.5-mm diameter implants. Rosette strain gauges were used for in-vitro tests, with peak values of the principal bone strain recorded with a data acquisition system. Implant stability as quantified by Periotest values (PTV) were also recorded for both types of implants. Experimental data were analyzed statistically using Wilcoxon's rank-sum test. In FE simulations, the peak value and distribution of von-Mises stresses in the implant and bone were selected for evaluation. In in-vitro tests, the peak bone strain was 42% lower for two-piece implants than for one-piece implants. The PTV was slightly lower for one-piece implants (PTV = -6) than for two-piece implants (PTV = -5). In FE simulations, the stresses in the bone and implant were about 23% higher and 12% lower, respectively, for one-piece implants than those for two-piece implants. Due to the higher peri-implant bone stresses and strains, one-piece implants (NobelDirect) might be not suitable for use as small-diameter implants. Copyright © 2016. Published by Elsevier B.V.

β-Ecdysone Augments Peak Bone Mass in Mice of Both Sexes.

PubMed

Dai, Weiwei; Zhang, HongLiang; Zhong, Zhendong A; Jiang, Li; Chen, Haiyan; Lay, Yu-An Evan; Kot, Alexander; Ritchie, Robert O; Lane, Nancy E; Yao, Wei

2015-08-01

One of the strongest predictors for osteoporosis is peak bone mass. Interventions to augment peak bone mass have yet to be developed. β-Ecdysone (βEcd), a natural steroid-like compound produced by arthropods to initiate metamorphosis, is believed to have androgenic effects and so may be used to augment bone mass. The purpose of this study was to use both male and female (1) gonadal-sufficient; and (2) -insufficient mice to investigate sex differences in terms of bone development and structure after βEcd administration. Two-month-old male and female Swiss-Webster mice were randomized to receive either vehicle or βEcd (0.5 mg/kg) for 3 weeks. In a separate experiment to evaluate the effects of βEcd on sex hormone-deficient mice, gonadectomy was performed in male (orchiectomy [ORX]) and female mice (ovariectomy [OVX]). Sham-operated and the ORX/OVX mice were then treated for 3 weeks with βEcd. Primary endpoints for the study were trabecular bone structure and bone strength. In male mice, the trabecular bone volume was 0.18±0.02 in the placebo-treated (PL) and 0.23±0.02 in the βEcd-treated group (p<0.05 versus PL); and 0.09±0.01 in the ORX group (p<0.05 versus PL) and 0.12±0.01 in the ORX+βEcd group. Vertebral bone strength (maximum load) was 43±2 in PL and 51±1 in the βEcd-treated group (p<0.05 versus PL); and 30±4 in the ORX group (p<0.05 versus PL) and 37±3 in the ORX+βEcd group. In female mice, trabecular bone volume was 0.23±0.02 in PL and 0.26±0.02 in the βEcd-treated group (p<0.05 versus PL); and 0.15±0.01 in the OVX group (p<0.05 versus PL) and 0.14±0.01 in the OVX+βEcd group. Maximum load of the vertebrae was 45±2 in PL and 48±4 in the βEcd-treated group; and 39±4 in the OVX group (p<0.05 versus PL) and 44±4 in the OVX+βEcd group. These findings suggest the potential use of βEcd in the augmentation of bone mass in growing male and female mice. It may also partially prevent the detrimental effects of gonadectomy on trabecular bone. Our results support the potential use of βEcd or nature products that are rich in βEcd to augment peak bone mass. βEcd may differ from the other anabolic hormone treatments that may have severe side effects such as serious cardiac complications. However, its effects on humans remain to be determined.

Relationship of blood and bone lead to menopause and bone mineral density among middle-age women in Mexico City.

PubMed

Garrido Latorre, Francisco; Hernández-Avila, Mauricio; Tamayo Orozco, Juan; Albores Medina, Carlos A; Aro, Antonio; Palazuelos, Eduardo; Hu, Howard

2003-04-01

To describe the relationship of blood lead levels to menopause and bone lead levels, we conducted a cross-sectional study on 232 pre- or perimenopausal (PreM) and postmenopausal (PosM) women who participated in an osteoporosis-screening program in Mexico City during the first quarter of 1995. Information regarding reproductive characteristics and known risk factors for blood lead was obtained using a standard questionnaire by direct interview. The mean age of the population was 54.7 years (SD = 9.8), with a mean blood lead level of 9.2 microg/dL (SD = 4.7/dL) and a range from 2.1 to 32.1 microg/dL. After adjusting for age and bone lead levels, the mean blood lead level was 1.98 microg/dL higher in PosM women than in PreM women (p = 0.024). The increase in mean blood lead levels peaked during the second year of amenorrhea with a level (10.35 microg/dL) that was 3.51 microg/dL higher than that of PreM women. Other important predictors of blood lead levels were use of lead-glazed ceramics, schooling, trabecular bone lead, body mass index, time of living in Mexico City, and use of hormone replacement therapy. Bone density was not associated with blood lead levels. These results support the hypothesis that release of bone lead stores increases during menopause and constitutes an internal source of exposure possibly associated with health effects in women in menopause transition.

Comparison of Suture-Based Anchors and Traditional Bioabsorbable Anchors in Foot and Ankle Surgery.

PubMed

Hembree, W Chad; Tsai, Michael A; Parks, Brent G; Miller, Stuart D

We compared the pullout strength of a suture-based anchor versus a bioabsorbable anchor in the distal fibula and calcaneus and evaluated the relationship between bone mineral density and peak load to failure. Eight paired cadaveric specimens underwent a modified Broström procedure and Achilles tendon reattachment. The fibula and calcaneus in the paired specimens received either a suture-based anchor or a bioabsorbable suture anchor. The fibular and calcaneal specimens were loaded to failure, defined as a substantial decrease in the applied load or pullout from the bone. In the fibula, the peak load to failure was significantly greater with the suture-based versus the bioabsorbable anchors (133.3 ± 41.8 N versus 76.8 ± 35.3 N; p = .002). No significant difference in load with 5 mm of displacement was found between the 2 groups. In the calcaneus, no difference in the peak load to failure was found between the 2 groups, and the peak load to failure with 5 mm of displacement was significantly lower with the suture-based than with the bioabsorbable anchors (52.2 ± 9.8 N versus 75.9 ± 12.4 N; p = .003). Bone mineral density and peak load to failure were significantly correlated in the fibula with the suture-based anchor. An innovative suture-based anchor had a greater peak load to failure compared with a bioabsorbable anchor in the fibula. In the calcaneus, the load at 5 mm of displacement was significantly lower in the suture-based than in the bioabsorbable group. The correlation findings might indicate the need for a cortical bone shelf with the suture-based anchor. Suture-based anchors could be a viable alternative to bioabsorbable anchors for certain foot and ankle procedures. Copyright © 2016 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Calcium and bone health in children: a review.

PubMed

Stallings, V A

1997-01-01

The recent national survey shows that dietary calcium intake is variable in children and adolescents, with about half consuming less than the intake recommended by the Recommended Dietary Allowances or the National Institutes of Health Consensus Panel on Optimal Calcium Intake. Osteoporosis is a major disease in adults, resulting in 1.5 million fractures and over $10 billion in medical expenditures annually. Osteoporosis is of growing interest in the research, public health, and health consumer-lay communities and to the many primary care and specialty physicians and other health care professionals who work directly with patients with osteoporosis. Treatment of osteoporosis to prevent fracture is improving with newly introduced medications and approaches, but it is not as effective as needed. Effective prevention strategies are critical to decreasing the morbidity and mortality of the disease. Peak bone mass, obtained during childhood and adolescent growth, is one of the major determinants for the risk of developing osteoporosis and fracture. Genetic potential, gender, ethnic origins, nutritional factors such as calcium and vitamin D intake, growth patterns, and physical activity influence the accretion of bone mineral during childhood and determine the peak bone mass. Randomized, placebo-controlled intervention trials conducted in healthy children who are consuming amounts of dietary calcium in accordance with the US recommendations show that bone mass can be increased by calcium supplementation. Retrospective studies in adults suggest that childhood calcium intake is associated with risk of later osteoporosis and fracture. In addition, common childhood clinical conditions, such as low calcium intake related to lactose intolerance or the use of glucocorticoid medications for chronic illness, are risk factors for the development of osteoporosis in childhood, not just in adulthood. An approach for physicians and other pediatric care providers for screening children for low dietary calcium intake, low bone density, and other osteoporosis risk factors using dual-energy X-ray absorptiometry and the use of calcium supplementation in clinical care are presented.

Engraftment and bone mass are enhanced by PTHrP 1-34 in ectopically transplanted vertebrae (vossicle model) and can be non-invasively monitored with bioluminescence and fluorescence imaging.

PubMed

Hildreth, Blake Eason; Williams, Michelle M; Dembek, Katarzyna A; Hernon, Krista M; Rosol, Thomas J; Toribio, Ramiro E

2015-12-01

Evidence exists that parathyroid hormone-related protein (PTHrP) 1-34 may be more anabolic in bone than parathyroid hormone 1-34. While optical imaging is growing in popularity, scant information exists on the relationships between traditional bone imaging and histology and bioluminescence (BLI) and fluorescence (FLI) imaging. We aimed to evaluate the effects of PTHrP 1-34 on bone mass and determine if relationships existed between radiographic and histologic findings in bone and BLI and FLI indices. Vertebrae (vossicles) from mice coexpressing luciferase and green fluorescent protein were implanted subcutaneously into allogenic nude mice. Transplant recipients were treated daily with saline or PTHrP 1-34 for 4 weeks. BLI, FLI, radiography, histology, and µCT of the vossicles were performed over time. PTHrP 1-34 increased bioluminescence the most after 2 weeks, fluorescence at all time points, and decreased the time to peak bioluminescence at 4 weeks (P ≤ 0.027), the latter of which suggesting enhanced engraftment. PTHrP 1-34 maximized vertebral body volume at 4 weeks (P < 0.0001). The total amount of bone observed histologically increased in both groups at 2 and 4 weeks (P ≤ 0.002); however, PTHrP 1-34 exceeded time-matched controls (P ≤ 0.044). A positive linear relationship existed between the percentage of trabecular bone and (1) total bioluminescence (r = 0.595; P = 0.019); (2) total fluorescence (r = 0.474; P = 0.074); and (3) max fluorescence (r = 0.587; P = 0.021). In conclusion, PTHrP 1-34 enhances engraftment and bone mass, which can be monitored non-invasively by BLI and FLI.

Reversing sex steroid deficiency and optimizing skeletal development in the adolescent with gonadal failure.

PubMed

Vanderschueren, Dirk; Vandenput, Liesbeth; Boonen, Steven

2005-01-01

During puberty, the acquisition of skeletal mass and areal bone mineral density (BMD) mainly reflects an increase in bone size (length and perimeters) and not true volumetric BMD. Sexual dimorphism in bone mass and areal BMD is also explained by differences in bone size (longer and wider bones in males) and not by differences in volumetric BMD. Androgens stimulate skeletal growth by activation of the androgen receptor, whereas estrogens (following aromatization of androgens and stimulation of estrogen receptors) have a biphasic effect on skeletal growth during puberty. Recent evidence from clinical cases has shown that many of the growth-promoting effects of the sex steroids are mediated through estrogens rather than androgens. In addition, skeletal maturation and epiphyseal fusion are also estrogen-dependent in both sexes. Nevertheless, independent actions of androgens in these processes also occur. Both sex steroids maintain volumetric BMD during puberty. Androgens interact with the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis neonatally, resulting in a sexual dimorphic GH pattern during puberty, whereas estrogens stimulate GH and hereby IGF-I in both sexes. Hypogonadism in adolescents impairs not only bone size but also maintenance of volumetric BMD, hereby severely reducing peak areal BMD. Delayed puberty in boys and Turner's syndrome in women impair both bone length and size, reducing areal BMD. Whether volumetric BMD is also reduced and whether fracture risk is increased in these conditions remains controversial. Replacing sex steroids according to a biphasic pattern (starting at low doses and ending at high-normal doses) seems the safest approach to reach targeted height and to optimize bone development.

The effect of tamoxifen on pubertal bone development in adolescents with pubertal gynecomastia.

PubMed

Akgül, Sinem; Derman, Orhan; Kanbur, Nuray

2016-01-01

During puberty, estrogen has a biphasic effect on epiphyses; at low levels, it leads to an increase in height and bone mass, whereas at high levels, it leads to closure of the epiphysis. Tamoxifen is a selective estrogen receptor modulator that has been used in the treatment of pubertal gynecomastia. Although it has not been approved for this indication, studies have shown it to be both successful and safe. In males, the peak of pubertal bone development occurs during Tanner stage 3-4, which is also when pubertal gynecomastia reaches its highest prevalence. Thus tamoxifen treatment could potentially effect pubertal bone development. The aim of this study was to assess the effects of tamoxifen on bone mineral density (BMD) and skeletal maturation when used for pubertal gynecomastia. We evaluated 20 boys with pubertal gynecomastia receiving tamoxifen for at least 4 months. BMD was measured with dual-energy X-ray absorptiometry. Z-score and absolute BMD (g/cm(2)) was determined at baseline and 2 months after completing tamoxifen treatment. Bone age and height was evaluated before treatment and again one year later. Using absolute BMD (g/cm(2)), the mean difference from baseline was significant between the two groups both at spine (p=0.002) and femur (p=0.001), but not with the Z-score. This result was attributed to the expected increase during puberty according to sex and age. No significant effect on skeletal maturation was found (p=1.112). We conclude that when pubertal bone development is concerned, tamoxifen is safe for the treatment of pubertal gynecomastia as neither bone mineralization nor growth potential was affected.

Hand grip strength and maximum peak expiratory flow: determinants of bone mineral density of adolescent students.

PubMed

Cossio-Bolaños, Marco; Lee-Andruske, Cynthia; de Arruda, Miguel; Luarte-Rocha, Cristian; Almonacid-Fierro, Alejandro; Gómez-Campos, Rossana

2018-03-02

Maintaining and building healthy bones during the lifetime requires a complicated interaction between a number of physiological and lifestyle factors. Our goal of this study was to analyze the association between hand grip strength and the maximum peak expiratory flow with bone mineral density and content in adolescent students. The research team studied 1427 adolescent students of both sexes (750 males and 677 females) between the ages of 11.0 and 18.9 years in the Maule Region of Talca (Chile). Weight, standing height, sitting height, hand grip strength (HGS), and maximum peak expiratory flow (PEF) were measured. Furthermore, bone mineral density (BMD) and total body bone mineral content (BMC) were determined by using the Dual-Energy X-Ray Absorptiometry (DXA). Hand grip strength and PEF were categorized in tertiles (lowest, middle, and highest). Linear regression was performed in steps to analyze the relationship between the variables. Differences between categories were determined through ANOVA. In males, the hand grip strength explained 18-19% of the BMD and 20-23% of the BMC. For the females, the percentage of variation occurred between 12 and 13% of the BMD and 17-18% of the BMC. The variation of PEF for the males was observed as 33% of the BMD and 36% of the BMC. For the females, both the BMD and BMC showed a variation of 19%. The HGS and PEF were divided into three categories (lowest, middle, and highest). In both cases, significant differences occurred in bone density health between the three categories. In conclusion, the HGS and the PEF related positively to the bone density health of both sexes of adolescent students. The adolescents with poor values for hand grip strength and expiratory flow showed reduced values of BMD and BMC for the total body. Furthermore, the PEF had a greater influence on bone density health with respect to the HGS of the adolescents of both sexes.

Bone morphogenetic protein 7 (BMP-7) influences tendon-bone integration in vitro.

PubMed

Schwarting, Tim; Lechler, Philipp; Struewer, Johannes; Ambrock, Marius; Frangen, Thomas Manfred; Ruchholtz, Steffen; Ziring, Ewgeni; Frink, Michael

2015-01-01

Successful graft ingrowth following reconstruction of the anterior cruciate ligament is governed by complex biological processes at the tendon-bone interface. The aim of this study was to investigate in an in vitro study the effects of bone morphogenetic protein 7 (BMP-7) on tendon-bone integration. To study the biological effects of BMP-7 on the process of tendon-bone-integration, two independent in vitro models were used. The first model involved the mono- and coculture of bovine tendon specimens and primary bovine osteoblasts with and without BMP-7 exposure. The second model comprised the mono- and coculture of primary bovine osteoblasts and fibroblasts. Alkaline phosphatase (ALP), lactate dehydrogenase (LDH), lactate and osteocalcin (OCN) were analyzed by ELISA. Histological analysis and electron microscopy of the tendon specimens were performed. In both models, positive effects of BMP-7 on ALP enzyme activity were observed (p<0.001). Additionally, similar results were noted for LDH activity and lactate concentration. BMP-7 stimulation led to a significant increase in OCN expression. Whereas the effects of BMP-7 on tendon monoculture peaked during an early phase of the experiment (p<0.001), the cocultures showed a maximal increase during the later stages (p<0.001). The histological analysis showed a stimulating effect of BMP-7 on extracellular matrix formation. Organized ossification zones and calcium carbonate-like structures were only observed in the BMP-stimulated cell cultures. This study showed the positive effects of BMP-7 on the biological process of tendon-bone integration in vitro. Histological signs of improved mineralization were paralleled by increased rates of osteoblast-specific protein levels in primary bovine osteoblasts and fibroblasts. Our findings indicated a role for BMP-7 as an adjuvant therapeutic agent in the treatment of ligamentous injuries, and they emphasized the importance of the transdifferentiation process of tendinous fibroblasts at the tendon-bone interface.

Establishment of peak bone mass.

PubMed

Mora, Stefano; Gilsanz, Vicente

2003-03-01

Among the main areas of progress in osteoporosis research during the last decade or so are the general recognition that this condition, which is the cause of so much pain in the elderly population, has its antecedents in childhood and the identification of the structural basis accounting for much of the differences in bone strength among humans. Nevertheless, current understanding of the bone mineral accrual process is far from complete. The search for genes that regulate bone mass acquisition is ongoing, and current results are not sufficient to identify subjects at risk. However, there is solid evidence that BMD measurements can be helpful for the selection of subjects that presumably would benefit from preventive interventions. The questions regarding the type of preventive interventions, their magnitude, and duration remain unanswered. Carefully designed controlled trials are needed. Nevertheless, previous experience indicates that weight-bearing activity and possibly calcium supplements are beneficial if they are begun during childhood and preferably before the onset of puberty. Modification of unhealthy lifestyles and increments in exercise or calcium assumption are logical interventions that should be implemented to improve bone mass gains in all children and adolescents who are at risk of failing to achieve an optimal peak bone mass.

Fabrication of oriented hydroxyapatite film by RF magnetron sputtering

NASA Astrophysics Data System (ADS)

Hirata, Keishiro; Kubota, Takafumi; Koyama, Daisuke; Takayanagi, Shinji; Matsukawa, Mami

2017-08-01

Hydroxyapatite (HAp) is compatible with bone tissue and is used mainly as a bone prosthetic material, especially as the coating of implants. Oriented HAp film is expected to be a high-quality epitaxial scaffold of the neonatal bone. To fabricate highly oriented HAp thin films via the conventional plasma process, we deposited the HAp film on a Ti coated silica glass substrate using RF magnetron sputtering in low substrate temperature conditions. The X-ray diffraction pattern of the film sample consisted of an intense (002) peak, corresponding to the highly oriented HAp. The (002) peak in XRD diagrams can be attributed either to the monoclinic phase or the hexagonal phase. Pole figure analysis showed that the (002) plane grew parallel to the surface of the substrate, without inclination. Transmission Electron Microscope analysis also showed the fabrication of aligned HAp crystallites. The selected area diffraction patterns indicated the existence of monoclinic phase. The existence of hexagonal phase could not be judged. These results indicate the uniaxial films fabricated by this technique enable to be the epitaxial scaffold of the neonatal bone. This scaffold can be expected to promote connection with the surrounding bone tissue and recovery of the dynamic characteristics of the bone.

Behavioral Intervention in Adolescents Improves Bone Mass, Yet Lactose Maldigestion Is a Barrier

PubMed Central

Lee, Yujin; Savaiano, Dennis A.; McCabe, George P.; Pottenger, Francis M.; Welshimer, Kathleen; Weaver, Connie M.; McCabe, Linda D.; Novotny, Rachel; Read, Marsha; Going, Scott; Mason, April; Van Loan, Marta

2018-01-01

Calcium intake during adolescence is important for attainment of peak bone mass. Lactose maldigestion is an autosomal recessive trait, leading to lower calcium intake. The Adequate Calcium Today study aimed to determine if a school-based targeted behavioral intervention over one year could improve calcium intake and bone mass in early adolescent girls. The school-randomized intervention was conducted at middle schools in six states over one school year. A total of 473 girls aged 10–13 years were recruited for outcome assessments. Bone mineral content (BMC) was determined by dual energy X-ray absorptiometry. Dietary calcium intake was assessed with a semi-quantitative food frequency questionnaire. Baseline calcium intake and BMC were not significantly different between groups. After the intervention period, there were no differences in changes in calcium intake and BMC at any site between groups. An unanticipated outcome was a greater increase in spinal BMC among lactose digesters than lactose maldigesters in the intervention schools only (12 months) (6.9 ± 0.3 g vs. 6.0 ± 0.4 g, p = 0.03) and considering the entire study period (18 months) (9.9 ± 0.4 vs. 8.7 ± 0.5 g, p < 0.01). Overall, no significant differences between the intervention and control schools were observed. However, lactose digesters who received the intervention program increased bone mass to a greater extent than lactose maldigesters. PMID:29597337

Adolescent pregnancy is associated with osteoporosis in postmenopausal women.

PubMed

Cho, Geum Joon; Shin, Jung-Ho; Yi, Kyong Wook; Park, Hyun Tae; Kim, Tak; Hur, Jun Young; Kim, Sun Haeng

2012-04-01

Adolescence is a critical time of life to accumulate bone for peak bone mass. Factors that may interfere with bone mass accrual during this period may increase the risk of osteoporosis. Several studies have reported that pregnancy during adolescence has detrimental effects on bone mass measurements after pregnancy. However, less is known about how adolescent pregnancy affects bone mineral density (BMD) and osteoporosis after menopause. The aim of this study was to evaluate the association between adolescent pregnancy and osteoporosis in postmenopausal Korean women. We conducted a cross-sectional study of 719 postmenopausal women, all of whom were enrolled in the Korean National Health and Nutrition Examination Survey in 2008. BMD was measured using dual-energy x-ray absorptiometry. Postmenopausal women with histories of adolescent pregnancy had lower BMD of the total hip, femoral neck, and lumbar spine than did women without histories of adolescent pregnancy. Multivariate logistic regression analyses revealed that postmenopausal women with history of adolescent pregnancy were at increased risk of osteoporosis (odds ratio, 2.20; 95% CI, 1.12-4.30) compared with women without history of adolescent pregnancy after adjustments for age, body mass index, marital status, education level, household income, alcohol intake, smoking history, exercise, age at menarche, age at menopause, parity, hormone therapy use, intake of energy and calcium, and vitamin D level. Adolescent pregnancy may be a predictor of osteoporosis in postmenopausal women.

[Bone Cell Biology Assessed by Microscopic Approach. Micro- and nanomechanical analysis of bone].

PubMed

Saito, Masami; Hongo, Hiromi

2015-10-01

For Stiffness, we have several ways, Vicker's, Nano Indentor and NanoIndentation with AFM. Recent study needs several nm, tens of nm scale lateral resolution. For this request, AFM supply new technology, PeakForce QNM®, is only way to measure sub molecular level modulus mapping. In this article, introduce several data and specially talk about bone modulus near osteocytic lacunae treated with PTH which is considering to resolve bone matrix around the osteocytic lacunae.

Effects of self-blood on the molding process of polymethyl methacrylate bone cement.

PubMed

Guo, Ying-Jun; Nie, Lin; Zhang, Wen; Mu, Qing

2014-01-01

To evaluate whether the self-blood has influence on the molding process of polymethyl methacrylate (PMMA) bone cement, and to make sure whether it is valuable for the clinical practice. An in vitro study was performed to evaluate the prolonging-effect of self-blood on PMMA bone cement. The effect of prolonging was evaluated by the dough time (TD) and operable time (TO). Moreover, hardness test, squeezing value test and peak temperature test were also conducted to complete the evaluation of this program. The self-blood, especially the plasma, could greatly prolong the handling time of PMMA bone cement without affecting its basic characteristics including hardness, leakage level and peak temperature. On the other hand, we found that in some abnormal conditions, for example with hyperlipemia, self-blood though can also prolong the handling time, would cause some side-effects. We report a new effective way to prolong the handling time of PMMA bone cement by adding moderate amount of self-blood. But "individualized medicine" should be noticed because some abnormal conditions like hyperlipemia would cause undesired side-effects.

Preparation and characterization of hydroxyapatite/sodium alginate biocomposites for bone implant application

NASA Astrophysics Data System (ADS)

Kanasan, Nanthini; Adzila, Sharifah; Suid, Mohd Syafiq; Gurubaran, P.

2016-07-01

In biomedical fields, synthetic scaffolds are being improved by using the ceramics, polymers and composites materials to avoid the limitations of allograft. Ceramic-polymer composites are appearing to be the most successful bone graft substitute in human body. The natural bones itself are well-known as composite of collagen and hydroxyapatite. In this research, precipitation method was used to synthesis hydroxyapatite (HA)/sodium alginate (SA) in various parameters. This paper describes the hydroxyapatite/sodium alginate biocomposite which suitable for use in bone defects or regeneration of bone through the characterizations which include FTIR, FESEM, EDS and DTA. In FTIR, the characteristi peaks of PO4-3 and OH- groups which corresponding to hydroxyapatite are existed in the mixing powders. The needle-size particle of hydroxyapatite/ alginate (HA/SA) are observed in FESEM in the range of 15.8nm-38.2nm.EDS confirmed the existence of HA/SA composition in the mixing powders. There is an endothermic peak which corresponds to the dehydration and the loss of physically adsorbed water molecules of the hydroxyapatite (HA)/sodium alginate (SA) powder which are described in DTA.

Increasing dietary phosphorus intake from food additives: potential for negative impact on bone health.

PubMed

Takeda, Eiji; Yamamoto, Hironori; Yamanaka-Okumura, Hisami; Taketani, Yutaka

2014-01-01

It is important to consider whether habitual high phosphorus intake adversely affects bone health, because phosphorus intake has been increasing, whereas calcium intake has been decreasing in dietary patterns. A higher total habitual dietary phosphorus intake has been associated with higher serum parathyroid hormone (PTH) and lower serum calcium concentrations in healthy individuals. Higher serum PTH concentrations have been shown in those who consume foods with phosphorus additives. These findings suggest that long-term dietary phosphorus loads and long-term hyperphosphatemia may have important negative effects on bone health. In contrast, PTH concentrations did not increase as a result of high dietary phosphorus intake when phosphorus was provided with adequate amounts of calcium. Intake of foods with a ratio of calcium to phosphorus close to that found in dairy products led to positive effects on bone health. Several randomized controlled trials have shown positive relations between dairy intake and bone mineral density. In our loading test with a low-calcium, high-phosphorus lunch provided to healthy young men, serum PTH concentrations showed peaks at 1 and 6 h, and serum fibroblast growth factor 23 (FGF23) concentrations increased significantly at 8 h after the meal. In contrast, the high-calcium, high-phosphorus meal suppressed the second PTH and FGF23 elevations until 8 h after the meal. This implies that adequate dietary calcium intake is needed to overcome the interfering effects of high phosphorus intake on PTH and FGF23 secretion. FGF23 acts on the parathyroid gland to decrease PTH mRNA and PTH secretion in rats with normal kidney function. However, increased serum FGF23 is an early alteration of mineral metabolism in chronic kidney disease, causing secondary hyperthyroidism, and implying resistance of the parathyroid gland to the action of FGF23 in chronic kidney disease. These findings suggest that long-term high-phosphorus diets may impair bone health mediated by FGF23 resistance both in chronic kidney disease patients and in the healthy population.

High-density polymorphisms analysis of 23 candidate genes for association with bone mineral density.

PubMed

Giroux, Sylvie; Elfassihi, Latifa; Clément, Valérie; Bussières, Johanne; Bureau, Alexandre; Cole, David E C; Rousseau, François

2010-11-01

Osteoporosis is a bone disease characterized by low bone mineral density (BMD), a highly heritable and polygenic trait. Women are more prone than men to develop osteoporosis due to a lower peak bone mass and accelerated bone loss at menopause. Peak bone mass has been convincingly shown to be due to genetic factors with heritability up to 80%. Menopausal bone loss has been shown to have around 38% to 49% heritability depending on the site studied. To have more statistical power to detect small genetic effects we focused on premenopausal women. We studied 23 candidate genes, some involved in calcium and vitamin-D regulation and others because estrogens strongly induced their gene expression in mice where it was correlated with humerus trabecular bone density. High-density polymorphisms were selected to cover the entire gene variability and 231 polymorphisms were genotyped in a first sample of 709 premenopausal women. Positive associations were retested in a second, independent, sample of 673 premenopausal women. Ten polymorphisms remained associated with BMD in the combined samples and one was further associated in a large sample of postmenopausal women (1401 women). This associated polymorphism was located in the gene CSF3R (granulocyte colony stimulating factor receptor) that had never been associated with BMD before. The results reported in this study suggest a role for CSF3R in the determination of bone density in women. Copyright © 2010 Elsevier Inc. All rights reserved.

Higher levels of s-RANKL and osteoprotegerin in children and adolescents with type 1 diabetes mellitus may indicate increased osteoclast signaling and predisposition to lower bone mass: a multivariate cross-sectional analysis.

PubMed

Tsentidis, C; Gourgiotis, D; Kossiva, L; Doulgeraki, A; Marmarinos, A; Galli-Tsinopoulou, A; Karavanaki, K

2016-04-01

Simultaneous lower bone mineral density, metabolic bone markers, parathyroid hormone (PTH), magnesium, insulin-like growth factor 1 (IGF1), and higher levels of total soluble receptor activator of nuclear factor-kappa B ligand (s-RANKL), osteoprotegerin (OPG), and alkaline phosphatase (ALP) are indicative of lower osteoblast and increased osteoclast signaling in children and adolescents with type 1 diabetes mellitus, predisposing to adult osteopenia and osteoporosis. Type 1 diabetes mellitus (T1DM) is a risk factor for reduced bone mass, disrupting several bone metabolic pathways. We aimed at identifying association patterns between bone metabolic markers, particularly OPG, s-RANKL, and bone mineral density (BMD) in T1DM children and adolescents, in order to study possible underlying pathophysiologic mechanisms of bone loss. We evaluated 40 children and adolescents with T1DM (mean ± SD age 13.04 ± 3.53 years, T1DM duration 5.15 ± 3.33 years) and 40 healthy age- and gender-matched controls (aged12.99 ± 3.3 years). OPG, s-RANKL, osteocalcin, C-telopeptide cross-links (CTX), IGF1, electrolytes, PTH, and total 25(OH)D were measured, and total body along with lumbar spine BMD were evaluated with dual energy X-ray absorptiometry (DXA). Multivariate regression and factor analysis were performed after classic inference. Patients had significantly lower BMD, with lower bone turnover markers, PTH, magnesium, and IGF1 than controls, indicating lower osteoblast signaling. Higher levels of total s-RANKL, OPG, and total ALP were observed in patients, with log(s-RANKL) and OPG correlation found only in controls, possibly indicating increased osteoclast signaling in patients. Coupling of bone resorption and formation was observed in both groups. Multivariate regression confirmed simultaneous lower bone turnover, IGF1, magnesium, and higher total s-RANKL, OPG, and ALP in patients, while factor analysis indicated possible activation of RANK/RANKL/OPG system in patients and its association with magnesium and IGF1. Patients with longer disease duration or worse metabolic control had lower BMD. T1DM children and adolescents have impaired bone metabolism which seems to be multifactorial. Reduced osteoblast and increased osteoclast signaling, resulting from multiple simultaneous disturbances, could lead to reduced peak bone accrual in early adulthood, predisposing to adult osteopenia and osteoporosis.

Co-registration of multi-modality imaging allows for comprehensive analysis of tumor-induced bone disease

PubMed Central

Seeley, Erin H.; Wilson, Kevin J.; Yankeelov, Thomas E.; Johnson, Rachelle W.; Gore, John C.; Caprioli, Richard M.; Matrisian, Lynn M.; Sterling, Julie A.

2014-01-01

Bone metastases are a clinically significant problem that arises in approximately 70% of metastatic breast cancer patients. Once established in bone, tumor cells induce changes in the bone microenvironment that lead to bone destruction, pain, and significant morbidity. While much is known about the later stages of bone disease, less is known about the earlier stages or the changes in protein expression in the tumor micro-environment. Due to promising results of combining magnetic resonance imaging (MRI) and Matrix-Assisted Laser Desorption/Ionization Imaging Mass Spectrometry (MALDI IMS) ion images in the brain, we developed methods for applying these modalities to models of tumor-induced bone disease in order to better understand the changes in protein expression that occur within the tumor-bone microenvironment. Specifically, we integrated three dimensional-volume reconstructions of spatially resolved MALDI IMS with high-resolution anatomical and diffusion weighted MRI data and histology in an intratibial model of breast tumor-induced bone disease. This approach enables us to analyze proteomic profiles from MALDI IMS data with corresponding in vivo imaging and ex vivo histology data. To the best of our knowledge, this is the first time these three modalities have been rigorously registered in the bone. The MALDI mass-to-charge ratio peaks indicate differential expression of calcyclin, ubiquitin, and other proteins within the tumor cells, while peaks corresponding to hemoglobin A and calgranulin A provided molecular information that aided in the identification of areas rich in red and white blood cells, respectively. This multimodality approach will allow us to comprehensively understand the bone-tumor microenvironment and thus may allow us to better develop and test approaches for inhibiting bone metastases. PMID:24487126

Calcium intake: good for the bones but bad for the heart? An analysis of clinical studies.

PubMed

Lima, Guilherme Alcantara Cunha; Lima, Priscilla Damião Araújo; Barros, Maria da Glória Costa Reis Monteiro de; Vardiero, Lívia Paiva; Melo, Elisa Fernandes de; Paranhos-Neto, Francisco de Paula; Madeira, Miguel; Farias, Maria Lucia Fleiuss de

2016-06-01

The proper dietary calcium intake and calcium supplementation, when indicated, are important factors in the acquisition of peak bone mass during youth and in the prevention of fractures in old age. In addition to its deposition in bone, calcium confers an increase in its resistance and exhibits important activities in different enzymatic pathways in the body (e.g., neural, hormonal, muscle-related and blood clotting pathways). Thus, calcium supplementation can directly or indirectly affect important functions in the body, such as the control of blood pressure, plasma glucose, body weight, lipid profile and endothelial function. Since one publication reported increased cardiovascular risk due to calcium supplementation, many researchers have studied whether this risk actually exists; the results are conflicting, and the involved mechanisms are uncertain. However, studies that have evaluated the influence of the consumption of foods rich in calcium have reported no increase in the cardiovascular risk, which suggests that nutritional intake should be prioritized as a method for supplementation and that the use of calcium supplements should be reserved for patients who truly need supplementation and are unable to achieve the recommended daily nutritional intake of calcium.

Human mesenchymal stromal cells are mechanosensitive to vibration stimuli.

PubMed

Kim, I S; Song, Y M; Lee, B; Hwang, S J

2012-12-01

Low-magnitude high-frequency (LMHF) vibrations have the ability to stimulate bone formation and reduce bone loss. However, the anabolic mechanisms that are mediated by vibration in human bone cells at the cellular level remain unclear. We hypothesized that human mesenchymal stromal cells (hMSCs) display direct osteoblastic responses to LMHF vibration signals. Daily exposure to vibrations increased the proliferation of hMSCs, with the highest efficiency occurring at a peak acceleration of 0.3 g and vibrations at 30 to 40 Hz. Specifically, these conditions promoted osteoblast differentiation through an increase in alkaline phosphatase activity and in vitro matrix mineralization. The effect of vibration on the expression of osteogenesis-related factors differed depending on culture method. hMSCs that underwent vibration in a monolayer culture did not exhibit any changes in the expressions of these genes, while cells in three-dimensional culture showed increased expression of type I collagen, osteoprotegerin, or VEGF, and VEGF induction appeared in 2 different hMSC lines. These results are among the first to demonstrate a dose-response effect upon LMHF stimulation, thereby demonstrating that hMSCs are mechanosensitive to LMHF vibration signals such that they could facilitate the osteogenic process.

Response Of Mineralizing And Non-Mineralizing Bone Cells To Fluid Flow: An In Vitro Model For Mechanotransruction

NASA Technical Reports Server (NTRS)

Makuch, Lauren A.

2004-01-01

Humans reach peak bone mass at age 30. After this point, we lose 1 to 2 percent of bone mass each decade. In the microgravity environment of space, astronauts lose bone mass at an accelerated rate of 1 to 2 percent each month. When astronauts travel to Mars, they may be in space for as long as 3 years. During this time, they may lose about half of their bone mass from weight-bearing bones. This loss may be irreversible. The drastic loss in bone that astronauts experience in space makes them much more vulnerable to fractures. In addition, the corresponding removal of calcium from bone results in higher levels of calcium in the blood, which increases the risk of developing kidney stones. Currently, studies are being conducted which investigate factors governing bone adaptation and mechanotransduction. Bone is constantly adapting in response to mechanical stimuli. Increased mechanical loading stimulates bone formation and suppresses bone resorption. Reduction in mechanical loading caused by bedrest, disuse, or microgravity results in decreased bone formation and possibly increased bone resorption. Osteoblasts and osteoclasts are the two main cell types that participate in bone remodeling. Osteoblasts are anabolic (bone-forming) cells and osteoclasts are catabolic (bone-resorbing) cells. In microgravity, the activity of osteoblasts slows down and the activity of osteoclasts may speed up, causing a loss of bone density. Mechanotransduction, the molecular mechanism by which mechanical stimuli are converted to biochemical signals, is not yet understood. Exposure of cells to fluid flow imposes a shear stress on the cells. Several studies have shown that the shear stress that results from fluid flow induces a cellular response similar to that induced by mechanical loading. Thus, fluid flow can be used as an in vitro model to simulate the mechanical stress that bone cells experience in vivo. Previous in vitro studies have shown that fluid flow induces several responses in osteoblasts, including increased proliferation, osteoblastic differentiation, alkaline phosphatase activity, and production of nitric oxide, prostaglandins, and osteopontin. Several proteins have been implicated in osteoblastic mechanotransduction including Bone Morphogenetic Protein-2 (BMP-2), parathyroid hormone, 1,25-dihydroxyvitamin D3 receptor, osteopontin (OPN), osteoprotegerin (OPG), and alkaline phosphatase (AP). We will characterize relative levels of each protein in mineralizing or non-mineralizing MC3T3 osteoblastic cells that have been exposed to fluid flow compared to non-fluid flow using immunofluorescent staining and two- photon laser microscopy as well as western blotting. Because calcium-mediated pathways are important in osteoblastic signaling, we will transfect MC3T3 cells with cameleon probes for Ca2+ containing YFP and CFP. Results will be analyzed using FRET/FLIM to study differential release of intracellular Ca(2+) in response to fluid flow and conditions inducing matrix mineralization. In addition, we plan to conduct several microarray experiments to determine differential gene expression in MC3T3 cells in response to fluid flow and conditions inducing mineralization.

No association between LRP5 gene polymorphisms and bone and obesity phenotypes in Chinese male-offspring nuclear families.

PubMed

Yu, Jin-bo; Ke, Yao-hua; He, Jin-wei; Zhang, Hao; Hu, Wei-wei; Hu, Yun-qiu; Li, Miao; Liu, Yu-juan; Gu, Jie-mei; Fu, Wen-zhen; Gao, Gao; Yue, Hua; Xiao, Wen-jin; Zhang, Zhen-lin

2010-11-01

To investigate the effect of low-density lipoprotein receptor-related protein 5 (LRP5) gene polymorphisms on bone and obesity phenotypes in young Chinese men. A total of 1244 subjects from 411 Chinese nuclear families were genotyped by using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique at the Q89R, N740N, and A1330V sites in the LRP5 gene. Bone mineral density (BMD) in the lumbar spine and the hip, total fat mass and total lean mass were measured using dual-energy X-ray absorptiometry. The association between LRP5 gene polymorphisms and peak BMD, body mass index (BMI), total fat mass, total lean mass and percentage of fat mass was assessed using a quantitative transmission disequilibrium test (QTDT). No significant within-family associations were found between genotypes or haplotypes of the LRP5 gene and peak BMD, BMI, total fat mass, total lean mass and percentage of fat mass. The 1000 permutations that were subsequently simulated were in agreement with these within-family association results. Our results suggest that common polymorphic variations of the LRP5 gene do not influence peak bone mass acquisition and obesity phenotypes in young Chinese men.

Friction coefficient and effective interference at the implant-bone interface.

PubMed

Damm, Niklas B; Morlock, Michael M; Bishop, Nicholas E

2015-09-18

Although the contact pressure increases during implantation of a wedge-shaped implant, friction coefficients tend to be measured under constant contact pressure, as endorsed in standard procedures. Abrasion and plastic deformation of the bone during implantation are rarely reported, although they define the effective interference, by reducing the nominal interference between implant and bone cavity. In this study radial forces were analysed during simulated implantation and explantation of angled porous and polished implant surfaces against trabecular bone specimens, to determine the corresponding friction coefficients. Permanent deformation was also analysed to determine the effective interference after implantation. For the most porous surface tested, the friction coefficient initially increased with increasing normal contact stress during implantation and then decreased at higher contact stresses. For a less porous surface, the friction coefficient increased continually with normal contact stress during implantation but did not reach the peak magnitude measured for the rougher surface. Friction coefficients for the polished surface were independent of normal contact stress and much lower than for the porous surfaces. Friction coefficients were slightly lower for pull-out than for push-in for the porous surfaces but not for the polished surface. The effective interference was as little as 30% of the nominal interference for the porous surfaces. The determined variation in friction coefficient with radial contact force, as well as the loss of interference during implantation will enable a more accurate representation of implant press-fitting for simulations. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pyridoxine deficiency affects biomechanical properties of chick tibial bone

NASA Technical Reports Server (NTRS)

Masse, P. G.; Rimnac, C. M.; Yamauchi, M.; Coburn, S. P.; Rucker, R. B.; Howell, D. S.; Boskey, A. L.

1996-01-01

The mechanical integrity of bone is dependent on the bone matrix, which is believed to account for the plastic deformation of the tissue, and the mineral, which is believed to account for the elastic deformation. The validity of this model is shown in this study based on analysis of the bones of vitamin B6-deficient and vitamin B6-replete chick bones. In this model, when B6-deficient and control animals are compared, vitamin B6 deficiency has no effect on the mineral content or composition of cortical bone as measured by ash weight (63 +/- 6 vs. 58 +/- 3); mineral to matrix ratio of the FTIR spectra (4.2 +/- 0.6 vs. 4.5 +/- 0.2), line-broadening analyses of the X-ray diffraction 002 peak (beta 002 = 0.50 +/- 0.1 vs. 0.49 +/- 0.01), or other features of the infrared spectra. In contrast, collagen was significantly more extractable from vitamin B6-deficient chick bones (20 +/- 2% of total hydroxyproline extracted vs. 10 +/- 3% p < or = 0.001). The B6-deficient bones also contained an increased amount of the reducible cross-links DHLNL, dehydro-dihydroxylysinonorleucine, (1.03 +/- 0.07 vs. 0.84 +/- 0.13 p < or = 0.001); and a nonsignificant increase in HLNL, dehydro-hydroxylysinonorleucine, (0.51 +/- 0.03 vs. 0.43 +/- 0.03, p < or = 0.10). There were no significant changes in bone length, bone diameter, or area moment of inertia. In four-point bending, no significant changes in elastic modulus, stiffness, offset yield deflection, or fracture deflection were detected. However, fracture load in the B6-deficient animals was decreased from 203 +/- 35 MPa to 151 +/- 23 MPa, p < or = 0.01, and offset yield load was decreased from 165 +/- 9 MPa to 125 +/- 14 MPa, p < or = 0.05. Since earlier histomorphometric studies had demonstrated that the B6-deficient bones were osteopenic, these data suggest that although proper cortical bone mineralization occurred, the alterations of the collagen resulted in changes to bone mechanical performance.

Surface topography of hydroxyapatite promotes osteogenic differentiation of human bone marrow mesenchymal stem cells.

PubMed

Yang, Wanlei; Han, Weiqi; He, Wei; Li, Jianlei; Wang, Jirong; Feng, Haotian; Qian, Yu

2016-03-01

Effective and safe induction of osteogenic differentiation is one of the key elements of bone tissue engineering. Surface topography of scaffold materials was recently found to promote osteogenic differentiation. Utilization of this topography may be a safer approach than traditional induction by growth factors or chemicals. The aim of this study is to investigate the enhancement of osteogenic differentiation by surface topography and its mechanism of action. Hydroxyapatite (HA) discs with average roughness (Ra) of surface topography ranging from 0.2 to 1.65 μm and mean distance between peaks (RSm) ranging from 89.7 to 18.6 μm were prepared, and human bone-marrow mesenchymal stem cells (hBMSCs) were cultured on these discs. Optimal osteogenic differentiation was observed on discs with surface topography characterized by Ra ranging from 0.77 to 1.09 μm and RSm ranging from 53.9 to 39.3 μm. On this surface configuration of HA, hBMSCs showed oriented attachment, F-actin arrangement, and a peak in the expression of Yes-associated protein (YAP) and PDZ binding motif (TAZ) (YAP/TAZ). These results indicated that the surface topography of HA promoted osteogenic differentiation of hBMSCs, possibly by increasing cell attachment and promoting the YAP/TAZ signaling pathway. Copyright © 2015 Elsevier B.V. All rights reserved.

Impact sports and bone fractures among adolescents.

PubMed

Lynch, Kyle R; Kemper, Han C G; Turi-Lynch, Bruna; Agostinete, Ricardo R; Ito, Igor H; Luiz-De-Marco, Rafael; Rodrigues-Junior, Mario A; Fernandes, Rômulo A

2017-12-01

The objective of the present study was to investigate the effects of different sports on stress fractures among adolescents during a 9-month follow-up period. The sample was composed of 184 adolescents divided into three groups (impact sports [n = 102]; swimming [n = 35]; non-sports [n = 47]). The occurrence of stress fracture was reported by participants and coaches. As potential confounders we considered age, sex, resistance training, body composition variables and age at peak of height velocity. There were 13 adolescents who reported fractures during the 9-month period. Bone mineral density values were higher in adolescents engaged in impact sports (P-value = 0.002). Independently of confounders, the risk of stress fracture was lower in adolescents engaged in impact sports than in non-active adolescents (hazard ratio [HR] = 0.23 [95% confidence interval (CI) = 0.05 to 0.98]), while swimming practice was not associated to lower risk of fracture (HR = 0.49 [95% CI = 0.09 to 2.55]). In conclusion, the findings from this study indicate the importance of sports participation among adolescents in the reduction of stress fracture risk, especially with impact sports. More importantly, these results could be relevant for recognising adolescents in danger of not reaching their potential for peak bone mass and later an increased risk of fractures.

Seasonal variation in Internet searches for vitamin D.

PubMed

Moon, Rebecca J; Curtis, Elizabeth M; Davies, Justin H; Cooper, Cyrus; Harvey, Nicholas C

2017-12-01

Internet search rates for "vitamin D" were explored using Google Trends. Search rates increased from 2004 until 2010 and thereafter displayed a seasonal pattern peaking in late winter. This knowledge could help guide the timing of public health interventions aimed at managing vitamin D deficiency. The Internet is an important source of health information. Analysis of Internet search activity rates can provide information on disease epidemiology, health related behaviors and public interest. We explored Internet search rates for vitamin D to determine whether this reflects the increasing scientific interest in this topic. Google Trends is a publically available tool that provides data on Internet searches using Google. Search activity for the term "vitamin D" from 1st January 2004 until 31st October 2016 was obtained. Comparison was made to other bone and nutrition related terms. Worldwide, searches for "vitamin D" increased from 2004 until 2010 and thereafter a statistically significant (p < 0.001) seasonal pattern with a peak in February and nadir in August was observed. This seasonal pattern was evident for searches originating from both the USA (peak in February) and Australia (peak in August); p < 0.001 for both. Searches for the terms "osteoporosis", "rickets", "back pain" or "folic acid" did not display the increase observed for vitamin D or evidence of seasonal variation. Public interest in vitamin D, as assessed by Internet search activity, did increase from 2004 to 2010, likely reflecting the growing scientific interest, but now displays a seasonal pattern with peak interest during late winter. This information could be used to guide public health approaches to managing vitamin D deficiency.

Biomechanical investigation of thread designs and interface conditions of zirconia and titanium dental implants with bone: three-dimensional numeric analysis.

PubMed

Fuh, Lih-Jyh; Hsu, Jui-Ting; Huang, Heng-Li; Chen, Michael Y C; Shen, Yen-Wen

2013-01-01

Bone stress and interfacial sliding at the bone-implant interface (BII) were analyzed in zirconia and titanium implants with various thread designs and interface conditions (bonded BII and contact BIIs with different frictional coefficients) for both conventional and immediately loaded treatments. A total of 18 finite element models comprising two implant materials (zirconia and titanium), three thread designs (different shapes and pitches), and three interface conditions (bonded and contact BIIs) were analyzed to assess the effects on bone stresses and on sliding at the BII. The material properties of the bone model were anisotropic, and a lateral force of 130 N was applied as the loading condition. In the immediately loaded implant, the stress was highly concentrated at one site of the peri-implant bone. The peak bone stress was more than 20% lower in zirconia implants than in titanium implants for a bonded BII and 14% to 20% lower for a contact BII. The bone stresses did not differ significantly between implants with V-shaped threads and square threads. However, sliding at the BII was more than 25% lower with square-thread implants than with V-shaped-thread implants for titanium implants and 36% lower for zirconia implants. Reducing the thread size and pitch in cortical bone (via two V-shaped threads with different pitches) decreased the bone stress by 13%. Increasing the frictional coefficient reduced sliding at the BII in both zirconia and titanium implants. As an implant material, zirconia can reduce the bone stress in the crestal cortical region. Bone stress and sliding at the BII are heavily dependent on the thread design and the frictional coefficient at the BII of immediately loaded implants.

Effects of Gymnastics Activities on Bone Accrual during Growth: A Systematic Review

PubMed Central

Jürimäe, Jaak; Gruodyte-Raciene, Rita; Baxter-Jones, Adam D. G.

2018-01-01

The amount of bone gained during childhood and adolescence impacts greatly on lifetime skeletal health. The purpose of this review is to summarize current evidence of the effects of gymnastics activities on bone mineral accrual during growth and to describe possible factors that influence bone mineral gains. The PubMed and SportDiscus databases were searched, and a total of 24 articles met the selection criteria and were included in this review. Artistic and rhythmic gymnasts presented higher bone mineral density and content values compared to untrained controls, despite possible negative effects associated with hormonal levels, dietary restrictions and body fat. The results suggest that gymnasts had similar bone turnover values compared to untrained controls. High-intensity mechanical loading of gymnastics activity appears to increase bone development and counterbalance negative effects, such as later pubertal development, lower body fat mass and lower hormone levels. In conclusion, gymnasts present higher bone mineral values in comparison with untrained controls. The osteogenic effect of gymnastics athletic activity has a positive influence on bone mineral accrual and overcomes the possible negative influence of high athletic activity that may cause negative energy balance and low body fat mass which are associated with lower bone accrual. Key points Children and adolescent gymnasts present higher bone mineral density and content values compared to untrained controls, despite a variety of possible negative factors. Gymnastics activity with high-impact mechanical loading appears to be especially osteogenic to achieve maximum possible peak bone accrual during growth and maturation. Skeletal benefits of gymnastics activity in childhood are maintained for several years after retirement from gymnastics trainings in young adulthood. PMID:29769826

The Role of Calcium in Osteoporosis

NASA Technical Reports Server (NTRS)

Arnaud, C. D.; Sanchez, S. D.

1991-01-01

Calcium requirements may vary throughout the lifespan. During the growth years and up to age 25 to 30, it is important to maximize dietary intake of calcium to maintain positive calcium balance and achieve peak bone mass, thereby possibly decreasing the risk of fracture when bone is subsequently lost. Calcium intake need not be greater than 800 mg/day during the relatively short period of time between the end of bone building and the onset of bone loss (30 to 40 years). Starting at age 40 to 50, both men and women lose bone slowly, but women lose bone more rapidly around the menopause and for about 10 years after. Intestinal calcium absorption and the ability to adapt to low calcium diets are impaired in many postmenopausal women and elderly persons owing to a suspected functional or absolute decrease in the ability of the kidney to produce 1,25(OH)2D2. The bones then become more and more a source of calcium to maintain critical extracellular fluid calcium levels. Excessive dietary intake of protein and fiber may induce significant negative calcium balance and thus increase dietary calcium requirements. Generally, the strongest risk factors for osteoporosis are uncontrollable (e.g., sex, age, and race) or less controllable (e.g., disease and medications). However, several factors such as diet, physical activity, cigarette smoking, and alcohol use are lifestyle related and can be modified to help reduce the risk of osteoporosis.

Ground reaction forces and bone parameters in females with tibial stress fracture.

PubMed

Bennell, Kim; Crossley, Kay; Jayarajan, Jyotsna; Walton, Elizabeth; Warden, Stuart; Kiss, Z Stephen; Wrigley, Tim

2004-03-01

Tibial stress fracture is a common overuse running injury that results from the interplay of repetitive mechanical loading and bone strength. This research project aimed to determine whether female runners with a history of tibial stress fracture (TSF) differ in ground reaction force (GRF) parameters during running, regional bone density, and tibial bone geometry from those who have never sustained a stress fracture (NSF). Thirty-six female running athletes (13 TSF; 23 NSF) ranging in age from 18 to 44 yr were recruited for this cross-sectional study. The groups were well matched for demographic, training, and menstrual parameters. A force platform measured selected GRF parameters (peak and time to peak for vertical impact and active forces, and horizontal braking and propulsive forces) during overground running at 4.0 m.s.(-1). Lumbar spine, proximal femur, and distal tibial bone mineral density were assessed by dual energy x-ray absorptiometry. Tibial bone geometry (cross-sectional dimensions and areas, and second moments of area) was calculated from a computerized tomography scan at the junction of the middle and distal thirds. There were no significant differences between the groups for any of the GRF, bone density, or tibial bone geometric parameters (P > 0.05). Both TSF and NSF subjects had bone density levels that were average or above average compared with a young adult reference range. Factor analysis followed by discriminant function analysis did not find any combinations of variables that differentiated between TSF and NSF groups. These findings do not support a role for GRF, bone density, or tibial bone geometry in the development of tibial stress fractures, suggesting that other risk factors were more important in this cohort of female runners.

Effects of acute brainstem compression on auditory brainstem response in the guinea pig.

PubMed

Tu, T Y; Yu, L H; Chiu, J H; Shu, C H; Shiao, A S; Lien, C F

1998-11-01

The purpose of this study was to establish the norm for parameters of auditory brainstem response (ABR) in the guinea pig and to investigate if acute brainstem compression results in significant changes to these parameters. Thirty-six guinea pigs with positive Preyer's reflex were anesthetized. A craniectomy was performed to remove the right occipital bone and the dura mater was opened to expose the brain, cerebellum and cerebellopontine angle (CPA). A small inflatable balloon was placed into the CPA precisely and slowly. ABR was recorded before incision of the skin as a baseline value, after placement and after inflation of the balloon with water at 0.1-ml intervals. Five stable peaks were recorded in 27 experimental animals. When the balloon was inflated with 0.1 ml water, the absolute latency (AL) of peaks IV and V and the interpeak latency (IPL) of peaks III and IV, and IV and V were prolonged. The amplitude ratios (AR) of peaks II, III, IV and V to peak I decreased. Inflation of the balloon with 0.2 ml of water caused further elongation of ALs of peaks IV and V and decreases in each AR. When the balloon volume increased to 0.3 ml, peak V became unrecognizable and peaks III and IV showed significant elongation of AL; peaks I and II did not show significant change in ALs. Further increase of the balloon volume to 0.4 ml resulted in disappearance of peaks III, IV and V; AL of peak II was also elongated. However, the amplitude and AL of peak I remained unchanged. Similar changes were observed in IPLs. This study establishes the norm of parameters of ABR in guinea pigs and demonstrates that acute brainstem compression causes elongation of ALs and IPLs of peaks II, III, IV and V. This suggests that peaks II, III, IV and V come from the brainstem and that peak I is not generated from the brainstem in the guinea pig.

Whole-body vibration of mice induces articular cartilage degeneration with minimal changes in subchondral bone.

PubMed

McCann, M R; Yeung, C; Pest, M A; Ratneswaran, A; Pollmann, S I; Holdsworth, D W; Beier, F; Dixon, S J; Séguin, C A

2017-05-01

Low-amplitude, high-frequency whole-body vibration (WBV) has been adopted for the treatment of musculoskeletal diseases including osteoarthritis (OA); however, there is limited knowledge of the direct effects of vibration on joint tissues. Our recent studies revealed striking damage to the knee joint following exposure of mice to WBV. The current study examined the effects of WBV on specific compartments of the murine tibiofemoral joint over 8 weeks, including microarchitecture of the tibia, to understand the mechanisms associated with WBV-induced joint damage. Ten-week-old male CD-1 mice were exposed to WBV (45 Hz, 0.3 g peak acceleration; 30 min/day, 5 days/week) for 4 weeks, 8 weeks, or 4 weeks WBV followed by 4 weeks recovery. The knee joint was evaluated histologically for tissue damage. Architecture of the subchondral bone plate, subchondral trabecular bone, primary and secondary spongiosa of the tibia was assessed using micro-CT. Meniscal tears and focal articular cartilage damage were induced by WBV; the extent of damage increased between 4 and 8-week exposures to WBV. WBV did not alter the subchondral bone plate, or trabecular bone of the tibial spongiosa; however, a transient increase was detected in the subchondral trabecular bone volume and density. The lack of WBV-induced changes in the underlying subchondral bone suggests that damage to the articular cartilage may be secondary to the meniscal injury we detected. Our findings underscore the need for further studies to assess the safety of WBV in the human population to avoid long-term joint damage. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

[The pineal gland's peptides factors and the rhythms of functions of the thymus and bone marrow in animals during aging].

PubMed

Labunets, I F; Butenko, G M; Dragunova, V A; Magdich, L V; Kopylova, G V; Rodnichenko, A E; Mikhal'skiĭ, S A; Khavinson, V Kh; Azarskova, M V; Maksiuk, T V

2004-01-01

It was investigated the influence of pineal peptides on the aging changes both circadian rhythm of thymic serum factor (FTS) titer in male rats Wistar and circannual rhythms of FTS, the amount of stromal cells-precurcors (CFC-F), granulocyte-macrophage cells-precurcors (CFC-GM), CD4+, Mac-1+ and CD19+-cells in bone marrow of male mice CBA. Epithalamin was injected chronically beginning from 6 month in rats and 4 month in mice. In old animals the rhythmical disturbancers of the indices characterized by loss of fluctuations, displacement of seasonal acrophase, increased or diminished amplitude, inversion of rhythm and desynchronization. After epithalamin injections in rats of 11, 17, 27 months the FTS titer at night increased and in old mice of 23-24 months appeared the peak of hormone level in summer-autumn, restored the difference between the amount of CD4+, Mac-1+-cells in bone marrow in spring and autumn, increased CFC-GM amount in spring, diminished CFC-F in autumn and increased this indice in winter. Epithalon also diminished of CFC-GM and CFC-F amount in old mice in autumn. The retarding age-related disturbances of suprachiasmaticus nucleus of hypothalamus structure, the diminishing corticosterone and testosterone levels at night, the increasing hormones level in summer and the falling in winter plays role in the improvement of thymus and bone marrow rhythmical function in old animals, reseaved epithalamin. The rhythms of most indices rhythms in old animals showed a pattern of adult.

The effect of muscle fatigue on in vivo tibial strains.

PubMed

Milgrom, Charles; Radeva-Petrova, Denitsa R; Finestone, Aharon; Nyska, Meir; Mendelson, Stephen; Benjuya, Nisim; Simkin, Ariel; Burr, David

2007-01-01

Stress fracture is a common musculoskeletal problem affecting athletes and soldiers. Repetitive high bone strains and strain rates are considered to be its etiology. The strain level necessary to cause fatigue failure of bone ex vivo is higher than the strains recorded in humans during vigorous physical activity. We hypothesized that during fatiguing exercises, bone strains may increase and reach levels exceeding those measured in the non-fatigued state. To test this hypothesis, we measured in vivo tibial strains, the maximum gastrocnemius isokinetic torque and ground reaction forces in four subjects before and after two fatiguing levels of exercise: a 2km run and a 30km desert march. Strains were measured using strain-gauged staples inserted percutaneously in the medial aspect of their mid-tibial diaphysis. There was a decrease in the peak gastrocnemius isokinetic torque of all four subjects' post-march as compared to pre-run (p=0.0001), indicating the presence of gastrocnemius muscle fatigue. Tension strains increased 26% post-run (p=0.002, 95 % confidence interval (CI) and 29% post-march (p=0.0002, 95% CI) as compared to the pre-run phase. Tension strain rates increased 13% post-run (p=0.001, 95% CI) and 11% post-march (p=0.009, 95% CI) and the compression strain rates increased 9% post-run (p=0.0004, 95% CI) and 17% post-march (p=0.0001, 95% CI). The fatigue state increases bone strains well above those recorded in rested individuals and may be a major factor in the stress fracture etiology.

Infant milk feeding influences adult bone health: a prospective study from birth to 32 years.

PubMed

Pirilä, Satu; Taskinen, Mervi; Viljakainen, Heli; Kajosaari, Merja; Turanlahti, Maila; Saarinen-Pihkala, Ulla M; Mäkitie, Outi

2011-04-27

Peak bone mass, attained by early adulthood, is influenced by genetic and life-style factors. Early infant feeding and duration of breastfeeding in particular, associate with several health-related parameters in childhood. The aim of this study was to examine whether the effects of early infant feeding extend to peak bone mass and other bone health characteristics at adult age. A cohort of 158 adults (76 males) born in Helsinki, Finland, 1975, prospectively followed up from birth, underwent physical examination and bone densitometry to study bone area, bone mineral content (BMC), and bone mineral density (BMD) at 32 years of age. Life-style factors relevant for bone health were recorded. For data analysis the cohort was divided into three equal-size groups according to the total duration of breastfeeding (BF): Short (≤3 months), Intermediate and Prolonged (≥7 months) BF groups. In males short BF is associated with higher bone area, BMC, and BMD compared to longer BF. Males in the Short BF group had on average 4.7% higher whole body BMD than males in the Prolonged BF group. In multivariate analysis, after controlling for multiple confounding factors, the influence of BF duration on adult bone characteristics persisted in males. Differences between the three feeding groups were observed in lumbar spine bone area and BMC, and whole body BMD (MANCOVA; p = 0.025, p = 0.013, and p = 0.048, respectively), favoring the Short BF group. In women no differences were observed. In men, early infant milk feeding may have a significant impact on adult bone health. A potential explanation is that the calcium and phosphate contents were strikingly higher in formula milk and commercial cow milk/cow milk dilutions as opposed to human milk. Our novel finding merits further studies to determine means to ensure optimal bone mass development in infants with prolonged breastfeeding.

Deficiency of Retinaldehyde Dehydrogenase 1 Induces BMP2 and Increases Bone Mass In Vivo

PubMed Central

Nallamshetty, Shriram; Wang, Hong; Rhee, Eun-Jung; Kiefer, Florian W.; Brown, Jonathan D.; Lotinun, Sutada; Le, Phuong; Baron, Roland; Rosen, Clifford J.; Plutzky, Jorge

2013-01-01

The effects of retinoids, the structural derivatives of vitamin A (retinol), on post-natal peak bone density acquisition and skeletal remodeling are complex and compartment specific. Emerging data indicates that retinoids, such as all trans retinoic acid (ATRA) and its precursor all trans retinaldehyde (Rald), exhibit distinct and divergent transcriptional effects in metabolism. Despite these observations, the role of enzymes that control retinoid metabolism in bone remains undefined. In this study, we examined the skeletal phenotype of mice deficient in retinaldehyde dehydrogenase 1 (Aldh1a1), the enzyme responsible for converting Rald to ATRA in adult animals. Bone densitometry and micro-computed tomography (µCT) demonstrated that Aldh1a1-deficient (Aldh1a1−/−) female mice had higher trabecular and cortical bone mass compared to age and sex-matched control C57Bl/6 wild type (WT) mice at multiple time points. Histomorphometry confirmed increased cortical bone thickness and demonstrated significantly higher bone marrow adiposity in Aldh1a1−/− mice. In serum assays, Aldh1a1−/− mice also had higher serum IGF-1 levels. In vitro, primary Aldh1a1−/− mesenchymal stem cells (MSCs) expressed significantly higher levels of bone morphogenetic protein 2 (BMP2) and demonstrated enhanced osteoblastogenesis and adipogenesis versus WT MSCs. BMP2 was also expressed at higher levels in the femurs and tibias of Aldh1a1−/− mice with accompanying induction of BMP2-regulated responses, including expression of Runx2 and alkaline phosphatase, and Smad phosphorylation. In vitro, Rald, which accumulates in Aldh1a1−/− mice, potently induced BMP2 in WT MSCs in a retinoic acid receptor (RAR)-dependent manner, suggesting that Rald is involved in the BMP2 increases seen in Aldh1a1 deficiency in vivo. Collectively, these data implicate Aldh1a1 as a novel determinant of cortical bone density and marrow adiposity in the skeleton in vivo through modulation of BMP signaling. PMID:23951127

Assessment of collagen quality associated with non-enzymatic cross-links in human bone using Fourier-transform infrared imaging.

PubMed

Schmidt, F N; Zimmermann, E A; Campbell, G M; Sroga, G E; Püschel, K; Amling, M; Tang, S Y; Vashishth, D; Busse, B

2017-04-01

Aging and many disease conditions, most notably diabetes, are associated with the accumulation of non-enzymatic cross-links in the bone matrix. The non-enzymatic cross-links, also known as advanced glycation end products (AGEs), occur at the collagen tissue level, where they are associated with reduced plasticity and increased fracture risk. In this study, Fourier-transform infrared (FTIR) imaging was used to detect spectroscopic changes associated with the formation of non-enzymatic cross-links in human bone collagen. Here, the non-enzymatic cross-link profile was investigated in one cohort with an in vitro ribose treatment as well as another cohort with an in vivo bisphosphonate treatment. With FTIR imaging, the two-dimensional (2D) spatial distribution of collagen quality associated with non-enzymatic cross-links was measured through the area ratio of the 1678/1692cm -1 subbands within the amide I peak, termed the non-enzymatic crosslink-ratio (NE-xLR). The NE-xLR increased by 35% in the ribation treatment group in comparison to controls (p<0.005), with interstitial bone tissue being more susceptible to the formation of non-enzymatic cross-links. Ultra high-performance liquid chromatography, fluorescence microscopy, and fluorometric assay confirm a correlation between the non-enzymatic cross-link content and the NE-xLR ratio in the control and ribated groups. High resolution FTIR imaging of the 2D bone microstructure revealed enhanced accumulation of non-enzymatic cross-links in bone regions with higher tissue age (i.e., interstitial bone). This non-enzymatic cross-link ratio (NE-xLR) enables researchers to study not only the overall content of AGEs in the bone but also its spatial distribution, which varies with skeletal aging and diabetes mellitus and provides an additional measure of bone's propensity to fracture. Copyright © 2017 Elsevier Inc. All rights reserved.

Assessment of collagen quality associated with non-enzymatic cross-links in human bone using Fourier-transform infrared imaging

PubMed Central

Schmidt, F.N.; Zimmermann, E.A.; Campbell, G.M.; Sroga, G.E.; Püschel, K.; Amling, M.; Tang, S. Y.; Vashishth, D.; Busse, B.

2017-01-01

Aging and many disease conditions, most notably diabetes, are associated with the accumulation of non-enzymatic cross-links in the bone matrix. The non-enzymatic crosslinks, also known as advanced glycation end products (AGEs), occur at the collagen tissue level, where they are associated with reduced plasticity and increased fracture risk. In this study, Fourier-transform infrared (FTIR) imaging was used to detect spectroscopic changes associated with the formation of non-enzymatic cross-links in human bone collagen. Here, the non-enzymatic cross-link profile was investigated in one cohort with an in vitro ribose treatment as well as another cohort with an in vivo bisphosphonate treatment. With FTIR imaging, the two-dimensional (2D) spatial distribution of collagen quality associated with non-enzymatic cross-links was measured through the area ratio of the 1678/1692 cm−1 subbands within the amide I peak, termed the non-enzymatic crosslink-ratio (NE-xLR). The NE-xLR increased by 35% in the ribation treatment group in comparison to controls (p< 0.005), with interstitial bone tissue being more susceptible to the formation of non-enzymatic cross-links. Ultra high performance liquid chromatography, fluorescence microscopy, and fluorometric assay confirm a correlation between the non-enzymatic cross-link content and the NE-xLR ratio in the control and ribated groups. High resolution FTIR imaging of the 2D bone microstructure revealed enhanced accumulation of non-enzymatic cross-links in bone regions with higher tissue age (i.e., interstitial bone). This non-enzymatic cross-link ratio (NE-xLR) enables researchers to study not only the overall content of AGEs in the bone but also its spatial distribution, which varies with skeletal aging and diabetes mellitus and provides an additional measure of bone's propensity to fracture. PMID:28109917

Sacrificial bonds and hidden length in biomaterials: A kinetic constitutive description of strength and toughness in bone

NASA Astrophysics Data System (ADS)

Lieou, Charles K. C.; Elbanna, Ahmed E.; Carlson, Jean M.

2013-07-01

Sacrificial bonds and hidden length in structural molecules account for the greatly increased fracture toughness of biological materials compared to synthetic materials without such structural features by providing a molecular-scale mechanism for energy dissipation. One example is in the polymeric glue connection between collagen fibrils in animal bone. In this paper we propose a simple kinetic model that describes the breakage of sacrificial bonds and the release of hidden length, based on Bell's theory. We postulate a master equation governing the rates of bond breakage and formation. This enables us to predict the mechanical behavior of a quasi-one-dimensional ensemble of polymers at different stretching rates. We find that both the rupture peak heights and maximum stretching distance increase with the stretching rate. In addition, our theory naturally permits the possibility of self-healing in such biological structures.

Attenuation of radionuclide activity by metal-cup arthroplasties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rosenthall, L.; Rosenthall, S.

1985-04-01

The half-value layers of stainless steel, bone cement, and polyethylene were measured for /sup 99m/Tc, /sup 67/Ga, /sup 111/In, and /sup 201/TI to render some insight into the attenuating effects of the metallic cup and other components used in surface-replacement revision arthroplasty. On theoretic consideration, a twofold increase in /sup 99m/Tc-methylene diphosphonate in bone inside the cup should not be attenuated to the point of escaping detection on the radionuclide images of the hip. /sup 67/Ga, using the 184 and 300 keV peaks, and /sup 111/In have greater half-value layers than /sup 99m/Tc and are subject to less attenuation bymore » the metallic cup.« less

Changes in bone mineral density in response to 24 weeks of resistance training in college-age men and women.

PubMed

Almstedt, Hawley C; Canepa, Jacqueline A; Ramirez, David A; Shoepe, Todd C

2011-04-01

Osteoporosis is a chronic disease of major public health concern. Characterized by low bone mass and increasing risk for fracture, osteoporosis occurs to a greater extent in women. Resistance training is a mode of exercise that can be used to build peak bone mass during youth, thereby preventing osteoporosis later in life. Our aim was to evaluate the effectiveness of a resistance training protocol designed to apply loads to the hip and spine in men and women. We recruited recreationally active men (n = 12) and women (n = 12), ages of 18-23. An additional 10 participants (5 men, 5 women) served as controls. Volunteers completed questionnaires to assess health history, physical activity, dietary intake, and menstrual history. The training program was performed for 24 weeks, on 3 nonconsecutive days per week, including exercises for the upper, lower, and core musculature, marked by an undulating periodization varying between 67 and 95% of 1 repetition maximum (1RM) on the multijoint exercises of bench press, squats, and deadlifts. Dual energy X-ray absorptiometry (Hologic Explorer, Waltham, MA, USA) was used to assess bone mineral density (BMD, g · cm(-2)). A 2-tailed analysis of covariance, controlling for body mass index, revealed that in comparison to women, men had significantly greater increases in BMD at the lateral spine and femoral neck. Male exercisers were found to increase BMD by 2.7-7.7%, whereas percent change in women ranged from -0.8 to 1.5%, depending on the bone site. Both male and female controls demonstrated about 1% change at any bone site. Results indicate that 24 weeks of resistance training, including squat and deadlift exercises, is effective in increasing BMD in young healthy men. Similar benefits were not derived by women who followed the same protocol.

Effects of laser photherapy on bone defects grafted with mineral trioxide aggregate, bone morphogenetic proteins, and guided bone regeneration: a Raman spectroscopic study.

PubMed

Pinheiro, Antonio L B; Aciole, Gilberth T S; Cangussú, Maria Cristina T; Pacheco, Marcos T T; Silveira, Landulfo

2010-12-15

We have used Raman analysis to assess bone healing on different models. Benefits on the isolated or combined use of mineral trioxide aggregate, bone morphogenetic proteins, guided bone regeneration and laser on bone repair have been reported, but not their combination. We studied peaks of hydroxyapatite and CH groups on defects grafted with MTA, treated or not with laser, BMPs, and GBR. Ninety rats were divided in 10 groups each, subdivided into three subgroups. Laser (λ850 nm) was applied at every other day for 2 weeks. Raman readings were taken at the surface of the defect. Statistical analysis (CHA) showed significant differences between all groups (p = 0.001) and between Group II and all other (p < 0.001), but not with Group X (p = 0.09). At day 21 differences were seen between all groups (p = 0.031) and between Groups VIII and X when compared with Groups VI (p = 0.03), V (p < 0.001), IV (p < 0.001), and IX (p = 0.04). At the end of the experimental period no significant differences were seen. On regards CH, significant differences were seen at the 15(th) day (p = 0.002) and between Group II and all other groups (p < 0.0001) but not with control. Advanced maturation on irradiated bone is because of increased secretion of calcium hydroxyapatite (CHA) that is indicative of greater calcification and resistance of the bone. We conclude that the association of the MTA with laser phototherapy (LPT) and/or not with GBR resulted in a better bone repair. The use of the MTA associated to IR LPT resulted in a more advanced and quality bone repair. Copyright © 2010 Wiley Periodicals, Inc.

Finite element study of human pelvis model in side impact for Chinese adult occupants.

PubMed

Ma, Zhengwei; Lan, Fengchong; Chen, Jiqing; Liu, Weiguo

2015-01-01

The occupant's pelvis is very vulnerable to side collision in road accidents. Finite element (FE) studies on pelvic injury help to design occupant protection devices to improve vehicle safety. This study was aimed to develop a highly biofidelic pelvis model of Chinese adults and assess its sensitivity to variations in pelvis cortical bone thickness, bone material properties, and loading conditions. In this study, 4 different FE models of the pelvis were developed from the computed tomography (CT) data of a volunteer representing the 50th percentile Chinese male. Two of them were meshed using entirely hexahedral elements with variable and constant cortical thickness distribution (the V-Hex and C-Hex models), and the others were modeled with hexahedral elements for cancellous bone and variable or constant thickness shell elements for cortical bone (the V-HS and C-HS models). In model developments, the semi-automatic multiblock meshing approach was employed to maintain the pelvis geometric curvature and generate a high-quality hexahedral mesh. Then, several simulations with postmortem human subjects (PMHS) tests were performed to obtain the most accurate model in predicting pelvic injury. Based on the most accurate model, sensitivity studies were conducted to analyze the effects of the cortex thickness, Young's modulus of the cortical and cancellous bone, impactor velocity, and impactor with or without padding on the biomechanical responses and injuries of pelvis. The results indicate that the models with variable cortical bone thickness can give more accurate predictions than those with constant cortical thickness. Both the V-Hex and V-HS models are favorable for simulating pelvic response and injury, but the simulation results of the V-Hex model agree with the tests better. The sensitivity study shows that pelvic response is more sensitive to alterations in the Young's modulus of cortical bone than cancellous bone. Compared to failure displacement, peak force is more sensitive to the cortical bone thickness. However, displacement is more sensitive to the Young's modulus of cancellous bone than peak force. The padding attached on the impactor plays a significant role in absorbing the impact energy and alleviating pelvic injury. The all-hex meshing method with variable cortical bone thickness has the highest accuracy but is time-consuming. The cortical bone plays a determining role in resisting pelvic fracture. Peak impact force appears to be a reasonable injury predictor for pelvic injury assessment. Some appropriate energy absorbers installed in the car door can significantly reduce pelvic injury and will be beneficial for occupant protection.

Drilling force and temperature of bone under dry and physiological drilling conditions

NASA Astrophysics Data System (ADS)

Xu, Linlin; Wang, Chengyong; Jiang, Min; He, Huiyu; Song, Yuexian; Chen, Hanyuan; Shen, Jingnan; Zhang, Jiayong

2014-11-01

Many researches on drilling force and temperature have been done with the aim to reduce the labour intensiveness of surgery, avoid unnecessary damage and improve drilling quality. However, there has not been a systematic study of mid- and high-speed drilling under dry and physiological conditions(injection of saline). Furthermore, there is no consensus on optimal drilling parameters. To study these parameters under dry and physiological drilling conditions, pig humerus bones are drilled with medical twist drills operated using a wide range of drilling speeds and feed rates. Drilling force and temperature are measured using a YDZ-II01W dynamometer and a NEC TVS-500EX thermal infrared imager, respectively, to evaluate internal bone damage. To evaluate drilling quality, bone debris and hole morphology are observed by SEM(scanning electron microscopy). Changes in drilling force and temperature give similar results during drilling such that the value of each parameter peaks just before the drill penetrates through the osteon of the compact bone into the trabeculae of the spongy bone. Drilling temperatures under physiological conditions are much lower than those observed under dry conditions, while a larger drilling force occurs under physiological conditions than dry conditions. Drilling speed and feed rate have a significant influence on drilling force, temperature, bone debris and hole morphology. The investigation of the effect of drilling force and temperature on internal bone damage reveals that a drilling speed of 4500 r/min and a feed rate of 50 mm/min are recommended for bone drilling under physiological conditions. Drilling quality peaks under these optimal parameter conditions. This paper proposes the optimal drilling parameters under mid- and high-speed surgical drilling, considering internal bone damage and drilling quality, which can be looked as a reference for surgeons performing orthopedic operations.

A Coaxial Dual-element Focused Ultrasound Probe for Guidance of Epidural Catheterization: An Experimental Study.

PubMed

Dong, Guo-Chung; Chiu, Li-Chen; Ting, Chien-Kun; Hsu, Jia-Ruei; Huang, Chih-Chung; Chang, Yin; Chen, Gin-Shin

2017-09-01

Ultrasound guidance for epidural block has improved clinical blind-trial problems but the design of present ultrasonic probes poses operating difficulty of ultrasound-guided catheterization, increasing the failure rate. The purpose of this study was to develop a novel ultrasonic probe to avoid needle contact with vertebral bone during epidural catheterization. The probe has a central circular passage for needle insertion. Two focused annular transducers are deployed around the passage for on-axis guidance. A 17-gauge insulated Tuohy needle containing the self-developed fiber-optic-modified stylet was inserted into the back of the anesthetized pig, in the lumbar region under the guidance of our ultrasonic probe. The inner transducer of the probe detected the shallow echo signals of the peak-peak amplitude of 2.8 V over L3 at the depth of 2.4 cm, and the amplitude was decreased to 0.8 V directly over the L3 to L4 interspace. The outer transducer could detect the echoes from the deeper bone at the depth of 4.5 cm, which did not appear for the inner transducer. The operator tilted the probe slightly in left-right and cranial-caudal directions until the echoes at the depth of 4.5 cm disappeared, and the epidural needle was inserted through the central passage of the probe. The needle was advanced and stopped when the epidural space was identified by optical technique. The needle passed without bone contact. Designs of the hollow probe for needle pass and dual transducers with different focal lengths for detection of shallow and deep vertebrae may benefit operation, bone/nonbone identification, and cost.

Associations between socioeconomic factors and proinflammatory cytokines in children, adolescents and young adults: a systematic review protocol.

PubMed

Fredman, Nick John; Duque, Gustavo; Duckham, Rachel Louise; Green, Darci; Brennan-Olsen, Sharon Lee

2018-02-28

There is now substantial evidence of a social gradient in bone health. Social stressors, related to socioeconomic status, are suggested to produce an inflammatory response marked by increased levels of proinflammatory cytokines. Here we focus on the particular role in the years before the achievement of peak bone mass, encompassing childhood, adolescence and young adulthood. An examination of such associations will help explain how social factors such as occupation, level of education and income may affect later-life bone disorders. This paper presents the protocol for a systematic review of existing literature regarding associations between socioeconomic factors and proinflammatory cytokines in those aged 6-30 years. We will conduct a systematic search of PubMed, OVID and CINAHL databases to identify articles that examine associations between socioeconomic factors and levels of proinflammatory cytokines, known to influence bone health, during childhood, adolescence or young adulthood. The findings of this review have implications for the equitable development of peak bone mass regardless of socioeconomic factors. Two independent reviewers will determine the eligibility of studies according to predetermined criteria, and studies will be assessed for methodological quality using a published scoring system. Should statistical heterogeneity be non-significant, we will conduct a meta-analysis; however, if heterogeneity prevent numerical syntheses, we will undertake a best-evidence analysis to determine whether socioeconomic differences exist in the levels of proinflammatory cytokines from childhood through to young adulthood. This study will be a systematic review of published data, and thus ethics approval is not required. In addition to peer-reviewed publication, these findings will be presented at professional conferences in national and international arenas. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Assessment of the use of LED phototherapy on bone defects grafted with hydroxyapatite on rats with iron-deficiency anemia and nonanemic: a Raman spectroscopy analysis.

PubMed

de Castro, Isabele Cardoso Vieira; Rosa, Cristiane Becher; Dos Reis Júnior, João Alves; Moreira, Luiz Gaudêncio Passos; Aragão, Juliana S; Barbosa, Artur Felipe dos Santos; Silveira, Landulfo; Pinheiro, Antonio L B

2014-09-01

This study aimed to assess bone repair in defects grafted or not with hydroxyapatite (HA) on healthy and iron-deficiency anemia (IDA) rats submitted or not to LED phototherapy (LED-PT) by Raman spectroscopy. The animals were divided in eight groups with five rats each: Clot; Clot + LED; IDA + Clot; IDA + LED; Graft; Graft + LED; IDA + Graft; and IDA + Graft + LED. When appropriated, irradiation with IR LED (λ850 ± 10 nm, 150 mW, CW, Φ = 0.5 cm(2), 16 J/cm(2), 15 days) was carried out. Raman shifts: ∼ 960 [symmetric PO4 stretching (phosphate apatite)], ∼ 1,070 [symmetric CO3 stretching (B-type carbonate apatite)], and ∼ 1,454 cm(-1) [CH2/CH3 bending in organics (protein)] were analyzed. The mean peak values for ∼ 960, ∼ 1,070, and ∼ 1,454 cm(-1) were nonsignificantly different on healthy or anemic rats. The group IDA + Graft + LED showed the lowest mean values for the peak ∼ 960 cm(-1) when compared with the irradiated IDA group or not (p ≤ 0.001; p ≤ 0.001). The association of LED-PT and HA-graft showed lowest mean peak at ∼ 1,454 cm(-1) for the IDA rats. The results of this study indicated higher HA peaks as well as a decrease in the level of organic components on healthy animals when graft and LED phototherapy are associated. In the other hand, IDA condition interfered in the graft incorporation to the bone as LED phototherapy only improved bone repair when graft was not used.

Is BMD testing appropriate for all menopausal women?

PubMed

Kleerekoper, Michael; Nelson, Dorothy A

2005-01-01

The United States Preventive Services Task Force has provided an evidence-based guideline indicating that bone mineral density (BMD) testing is appropriate for all women aged 65 or older. This does not preclude BMD testing in younger postmenopausal women but places the onus on the treating physician to justify the procedure to the patient and often the patient's insurance carrier. There are very few circumstances in which BMD testing is appropriate for healthy premenopausal women, but BMD testing in younger postmenopausal women is often appropriate: when there is a family history of osteoporosis with fracture, a personal history of fracture as an adult, and a medical, surgical or therapeutic history that might be associated with accelerated bone loss or increased risk of fracture. Medical conditions include intestinal diseases associated with malabsorption, such as non-tropical sprue, or primary hyperparathyroidism. Women who have neurologic conditions that increase the risk of falling should also be tested. There are data to suggest that patients with hemoglobinopathy are at increased risk for osteoporosis. Surgical conditions include the increasingly performed surgery for obesity and other surgery resulting in bowel resection (e.g., for inflammatory bowel disease). The major medication-related concern is corticosteroid therapy, but chronic or over-treatment with thyroxine, and chronic heparin therapy, should also be considered risk factors for osteoporosis. When performing a BMD test for the first time, it is essential to remember that 50% of women at menopause will have a negative T-score, but this does not imply that the patient has indeed lost any bone from her peak bone mass.

Saw palmetto extract induces nuclear heterogeneity in mice.

PubMed

Trinachartvanit, Wachareeporn; Francis, Bettina M; Rayburn, A Lane

2009-01-01

Saw palmetto (SW), a phytotherapeutic compound used in the treatment of prostate disease, was examined for potential nuclear effects. SW extract was incorporated into a complete casein-based semisynthetic rodent chow at 0%, 0.1% and 1% SW. SW was fed to mice for 6 weeks, after which the mice received a single i/p injection of either the known genotoxic agent methyl methanesulfonate (MMS) in saline or just saline. Forty-eight hours after injection, blood and bone marrow were collected for flow cytometric analysis. A significant effect of MMS was observed in both male and female mice with respect to: an increase in nuclear heterogeneity in bone marrow cells as measured by the coefficient of variation of the G1 peak in a flow histogram (6.32 versus 4.8 in male mice, 7.0 versus 4.9 in female mice) and an increase in the number of micronucleated blood cells (3.4% versus 0.56% male mice, 3.1% versus 0.6 in female mice) indicating a positive genotoxic response. SW also appears to increase the heterogeneity of bone marrow nuclei in a dose dependent manner (0-5.1%, 0.1-5.5% and 1-5.7% in male mice, 0-5.7%, 0.1-6.0% and 1-6.2% in female mice) without a concomitant increase in blood cell micronuclei. These results indicate that SW is not genotoxic with respect to physical DNA damage and that the changes observed in the bone marrow are due to chromatin conformation modifications in the nuclei of in vivo treated mouse cells. Copyright © 2008 Elsevier B.V. All rights reserved.

Morphologic and molecular alteration during tibia fracture healing in rat.

PubMed

Yu, M-D; Su, B-H; Zhang, X-X

2018-03-01

To monitor morphological feature and related osteogenic and bone metabolic change during healing of tibia fracture in a rat model. Tibia density and trabecular thickness were evaluated. Histopathology was examined by HE staining. Serous inflammatory factors IL-4, IL-6, TNF-α and metabolic biomarkers ALP, β-CTX, P1NP, were determined by ELISA. The expression of RUNX2, TGF-β1, VEGF-α, BMP-2, BMP-4, and BMP-7 in callus tissue were qualified by RT-PCR. Bone density decreased until week 4 and then increased post-operation. Trabeculae in callus were thickened over time with active osteogenesis. ELISA indicated the most severe inflammation at week 2, with the highest level of TNF-α, IL-6, and the lowest level of IL-4. After 4 weeks, the inflammation was alleviated accompanying with the decline of TNF-α and IL-6, while there was the elevation of IL-4. Bone metabolism showed active osteogenesis and resorption at week 6 with high P1NP and β-CTX. The expression of RUNX2, TGF-β1, VEGF-α, BMP-2, BMP-4, and BMP-7 increased progressively from week 1 to 6. The major lesions at week 2 in sham were tissue necrosis, periosteal reactive hyperplasia, inflammatory cell infiltration, capillary hyperplasia and slight fibro-blast cytopoiesis. At week 4, proliferation was greatly activated, fibrous callus shaped and chondrogenesis and some osteogenesis occurred at week 8. In rat model, bone density started to increase at week 6 after fracture, accompanied with trabeculae thickening, serous inflammatory factors decline, and peaked bone morphogenetic protein/growth factors, which indicated active osteogenesis was conforming to the classical phase of secondary fracture healing.

The effects of transducer geometry on artifacts common to diagnostic bone imaging with conventional medical ultrasound.

PubMed

Mauldin, F William; Owen, Kevin; Tiouririne, Mohamed; Hossack, John A

2012-06-01

The portability, low cost, and non-ionizing radiation associated with medical ultrasound suggest that it has potential as a superior alternative to X-ray for bone imaging. However, when conventional ultrasound imaging systems are used for bone imaging, clinical acceptance is frequently limited by artifacts derived from reflections occurring away from the main axis of the acoustic beam. In this paper, the physical source of off-axis artifacts and the effect of transducer geometry on these artifacts are investigated in simulation and experimental studies. In agreement with diffraction theory, the sampled linear-array geometry possessed increased off-axis energy compared with single-element piston geometry, and therefore, exhibited greater levels of artifact signal. Simulation and experimental results demonstrated that the linear-array geometry exhibited increased artifact signal when the center frequency increased, when energy off-axis to the main acoustic beam (i.e., grating lobes) was perpendicularly incident upon off-axis surfaces, and when off-axis surfaces were specular rather than diffusive. The simulation model used to simulate specular reflections was validated experimentally and a correlation coefficient of 0.97 between experimental and simulated peak reflection contrast was observed. In ex vivo experiments, the piston geometry yielded 4 and 6.2 dB average contrast improvement compared with the linear array when imaging the spinous process and interlaminar space of an animal spine, respectively. This work indicates that off-axis reflections are a major source of ultrasound image artifacts, particularly in environments comprising specular reflecting (i.e., bone or bone-like) objects. Transducer geometries with reduced sensitivity to off-axis surface reflections, such as a piston transducer geometry, yield significant reductions in image artifact.

The effect of locally delivered recombinant human bone morphogenetic protein-2 with hydroxyapatite/tri-calcium phosphate on the biomechanical properties of bone in diabetes-related osteoporosis.

PubMed

Liporace, Frank A; Breitbart, Eric A; Yoon, Richard S; Doyle, Erin; Paglia, David N; Lin, Sheldon

2015-06-01

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is particularly effective in improving osteogenesis in patients with diminished bone healing capabilities, such as individuals with type 1 diabetes mellitus (T1DM) who have impaired bone healing capabilities and increased risk of developing osteoporosis. This study measured the effects of rhBMP-2 treatment on osteogenesis by observing the dose-dependent effect of localized delivery of rhBMP-2 on biomechanical parameters of bone using a hydroxyapatite/tri-calcium phosphate (HA/TCP) carrier in a T1DM-related osteoporosis animal model. Two different doses of rhBMP-2 (LD low dose, HD high dose) with a HA/TCP carrier were injected into the femoral intramedullary canal of rats with T1DM-related osteoporosis. Two more diabetic rat groups were injected with saline alone and with HA/TCP carrier alone. Radiographs and micro-computed tomography were utilized for qualitative assessment of bone mineral density (BMD). Biomechanical testing occurred at 4- and 8-week time points; parameters tested included torque to failure, torsional rigidity, shear stress, and shear modulus. At the 4-week time point, the LD and HD groups both exhibited significantly higher BMD than controls; at the 8-week time point, the HD group exhibited significantly higher BMD than controls. Biomechanical testing revealed dose-dependent, higher trends in all parameters tested at the 4- and 8-week time points, with minimal significant differences. Groups treated with rhBMP-2 demonstrated improved bone mineral density at both 4 and 8 weeks compared to control saline groups, in addition to strong trends towards improvement of intrinsic and extrinsic biomechanical properties when compared to control groups. Data revealed trends toward dose-dependent increases in peak torque, torsional rigidity, shear stress, and shear modulus 4 weeks after rhBMP-2 treatment. Not applicable.

Osteoporosis in young adults: pathophysiology, diagnosis, and management.

PubMed

Ferrari, S; Bianchi, M L; Eisman, J A; Foldes, A J; Adami, S; Wahl, D A; Stepan, J J; de Vernejoul, M-C; Kaufman, J-M

2012-12-01

Postmenopausal osteoporosis is mainly caused by increased bone remodeling resulting from estrogen deficiency. Indications for treatment are based on low areal bone mineral density (aBMD, T-score  ≤ -2.5), typical fragility fractures (spine or hip), and more recently, an elevated 10-year fracture probability (by FRAX®). In contrast, there is no clear definition of osteoporosis nor intervention thresholds in younger individuals. Low aBMD in a young adult may reflect a physiologically low peak bone mass, such as in lean but otherwise healthy persons, whereas fractures commonly occur with high-impact trauma, i.e., without bone fragility. Furthermore, low aBMD associated with vitamin D deficiency may be highly prevalent in some regions of the world. Nevertheless, true osteoporosis in the young can occur, which we define as a T-score below -2.5 at spine or hip in association with a chronic disease known to affect bone metabolism. In the absence of secondary causes, the presence of fragility fractures, such as in vertebrae, may point towards genetic or idiopathic osteoporosis. In turn, treatment of the underlying condition may improve bone mass as well. In rare cases, a bone-specific treatment may be indicated, although evidence is scarce for a true benefit on fracture risk. The International Osteoporosis Foundation (IOF) convened a working group to review pathophysiology, diagnosis, and management of osteoporosis in the young, excluding children and adolescents, and provide a screening strategy including laboratory exams for a systematic approach of this condition.

[Prevention of osteoporosis by foods and dietary supplements. Chocolate malt drink MILO: nutrition in children and calcium absorption].

PubMed

Fukushima, Yoichi; Kumagai, Akiko

2006-10-01

Calcium is not sufficiently consumed by Japanese at any age groups. Childhood is an important period, when they should earn bone minerals to reach higher peak bone mass for reducing the risk of osteoporosis in their later life. Children require higher calcium consumption per body weight than adults, and also establish their dietary pattern in this period. MILO has attracted widespread popularity as a good-taste chocolate-flavored malt drink with balanced nutrients for children. We developed FOSHU MILO with fructooligosaccharides (FOS) aiming at improving absorption of calcium, which is originally rich in the products. Using the calcium stable isotope (44)Ca, we found that the urinary excretion in the subject fed the products with FOS was higher than that of control product without FOS, suggesting that the FOSHU MILO is effective in promoting calcium absorption from the intestines. MILO could contribute to bone health by increasing consumption of calcium and/or improving the calcium bioavailability.

Functional adaptation to mechanical loading in both cortical and cancellous bone is controlled locally and is confined to the loaded bones.

PubMed

Sugiyama, Toshihiro; Price, Joanna S; Lanyon, Lance E

2010-02-01

In order to validate whether bones' functional adaptation to mechanical loading is a local phenomenon, we randomly assigned 21 female C57BL/6 mice at 19 weeks of age to one of three equal numbered groups. All groups were treated with isoflurane anesthesia three times a week for 2 weeks (approximately 7 min/day). During each anaesthetic period, the right tibiae/fibulae in the DYNAMIC+STATIC group were subjected to a peak dynamic load of 11.5 N (40 cycles with 10-s intervals between cycles) superimposed upon a static "pre-load" of 2.0 N. This total load of 13.5 N engendered peak longitudinal strains of approximately 1400 microstrain on the medial surface of the tibia at a middle/proximal site. The right tibiae/fibulae in the STATIC group received the static "pre-load" alone while the NOLOAD group received no artificial loading. After 2 weeks, the animals were sacrificed and both tibiae, fibulae, femora, ulnae and radii analyzed by three-dimensional high-resolution (5 mum) micro-computed tomography (microCT). In the DYNAMIC+STATIC group, the proximal trabecular percent bone volume and cortical bone volume at the proximal and middle levels of the right tibiae as well as the cortical bone volume at the middle level of the right fibulae were markedly greater than the left. In contrast, the left bones in the DYNAMIC+STATIC group showed no differences compared to the left or right bones in the NOLOAD or STATIC group. These microCT data were confirmed by two-dimensional examination of fluorochrome labels in bone sections which showed the predominantly woven nature of the new bone formed in the loaded bones. We conclude that the adaptive response in both cortical and trabecular regions of bones subjected to short periods of dynamic loading, even when this response is sufficiently vigorous to stimulate woven bone formation, is confined to the loaded bones and does not involve changes in other bones that are adjacent, contra-lateral or remote to them. (c) 2009 Elsevier Inc. All rights reserved.

Stress distribution of the foot during mid-stance to push-off in barefoot gait: a 3-D finite element analysis.

PubMed

Chen, W P; Tang, F T; Ju, C W

2001-08-01

To quantify stress distribution of the foot during mid-stance to push-off in barefoot gait using 3-D finite element analysis. To simulate the foot structure and facilitate later consideration of footwear. Finite element model was generated and loading condition simulating barefoot gait during mid-stance to push-off was used to quantify the stress distributions. A computational model can provide overall stress distributions of the foot subject to various loading conditions. A preliminary 3-D finite element foot model was generated based on the computed tomography data of a male subject and the bone and soft tissue structures were modeled. Analysis was performed for loading condition simulating barefoot gait during mid-stance to push-off. The peak plantar pressure ranged from 374 to 1003 kPa and the peak von Mises stress in the bone ranged from 2.12 to 6.91 MPa at different instants. The plantar pressure patterns were similar to measurement result from previous literature. The present study provides a preliminary computational model that is capable of estimating the overall plantar pressure and bone stress distributions. It can also provide quantitative analysis for normal and pathological foot motion. This model can identify areas of increased pressure and correlate the pressure with foot pathology. Potential applications can be found in the study of foot deformities, footwear, surgical interventions. It may assist pre-treatment planning, design of pedorthotic appliances, and predict the treatment effect of foot orthosis.

Blunted seasonal variation in serum 25-hydroxy vitamin D and increased risk of osteomalacia in vegetarian London Asians.

PubMed

Finch, P J; Ang, L; Colston, K W; Nisbet, J; Maxwell, J D

1992-07-01

Serum 25-hydroxy vitamin D levels were measured in 297 adult Asians and 68 white subjects at different times of year and seasonal variation compared between subjects grouped according to ethnic origin, religion and dietary habit. A sub-group of Asians with symptoms and biochemical changes suggestive of osteomalacia underwent bone biopsy, and static bone histomorphometry was performed. Histological osteomalacia was detected in 15 Asians and borderline changes in 13. The majority of these cases were among vegetarian Hindus. Significant seasonal variation in 25-hydroxy vitamin D was observed in all groups, but with lower peak and trough levels among Asians, and especially the Hindus and vegetarian Asians. Summer rises in 25-hydroxy vitamin D levels were blunted among Hindus and vegetarian Asians, compared to whites, Muslims and non-vegetarian Asians. Vegetarian Asians had significantly lower serum calcium and higher PTH levels than non-vegetarians, but multivariate analysis indicated that this was an effect of osteomalacia, not vegetarianism. We conclude that solar exposure has a significant effect on vitamin D status in Asians resident in London. Non-vegetarian Asians have similar rise and peak levels to whites, but those taking a vegetarian diet (in particular, Hindus) have an impaired seasonal rise in 25-hydroxy vitamin D levels, and are at particular risk of metabolic bone disease. This effect did not appear to be mediated through secondary hyperparathyroidism consequent on a vegetarian diet.

Influence of underpreparation on primary stability of implants inserted in poor quality bone sites: an in vitro study.

PubMed

Degidi, Marco; Daprile, Giuseppe; Piattelli, Adriano

2015-06-01

The purpose of this present study was to investigate the relation between implant site underpreparation and primary stability in the presence of poor-quality bone. A study was performed on fresh humid bovine bone; samples presented no cortical layer with a cancellous structure inside and were obtained from the hip. The bones were firmly attached to a base device. Sixty sites were prepared according to the protocol provided by the manufacturer: a 2-mm pilot drill was introduced to the proper depth and then twist drills of 3 and 3.4 mm were used. After site preparation, 20 3.4- × 11-mm (standard protocol group), 20 3.8- × 11-mm (10% undersized group), and 20 4.5- × 11-mm (25% undersized group) implants were inserted at a calibrated maximum torque of 70 N-cm at the predetermined speed of 30 rpm. After implant insertion, variable torque work (VTW), maximum insertion torque (peak IT), and resonance frequency analysis (RFA) values were recorded. The standard protocol group showed a mean VTW of 565.77 ± 219.12 N-cm, a peak IT of 11.3 ± 4.44 N-cm, and an RFA of 69.35 ± 7.35 implant stability quotient (ISQ). The 10% undersized group showed a mean VTW of 1,240.24 ± 407.78 N-cm, a peak IT of 20.26 ± 7.03 N-cm, and an RFA of 73.40 ± 2.33 ISQ. The 25% undersized group showed a mean VTW of 1,254.96 ± 727.49 N-cm, a peak IT of 17.15 ± 10.39 N-cm, and an RFA of 72.30 ± 6.70 ISQ. For VTW, the difference between the standard and undersized protocol values was statistically significant; for peak IT, the difference between the standard and 10% undersized protocol values was statistically significant; no other statistical differences were found between mean values. In the presence of poor-bone quality, a 10% undersized protocol is sufficient to improve the primary stability of the implant; additional decreases do not seem to enhance primary stability values. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Role of Prostaglandin Pathway and Alendronate-Based Carriers to Enhance Statin-induced Bone

PubMed Central

Lee, Yeonju; Liu, Xinming; Nawshad, Ali; Marx, David B.; Wang, Dong; Reinhardt, Richard A.

2011-01-01

Objective This study investigated the role of the prostaglandin (PG) pathway in locally-applied, simvastatin-induced oral bone growth. The possibility of enhancing long-term bone augmentation with an alendronate-based carrier was initiated. Methods Mandibles of 44 mature female rats were treated bilaterally with the following combinations: 2 mg simvastatin in ethanol (SIM-EtOH), EtOH, 2 mg simvastatin acid complexed with alendronate-beta-cyclodextrin conjugate (SIM/ALN-CD), ALN-CD, or ALN. Bone wash technology (injection of PBS and recollection by suction) was used to sample injection sites at baseline (day 0), and 3, 7, 14 and 21 days post-treatment. After 21-24 or 48 days, histomorphometric analysis was done. The amount of PGE2 in bone wash fluid was measured by ELISA, normalized by total protein, and compared between high and low bone growth groups (ANOVA) and correlated with subsequent bone histology at 21 days (Spearman). SIM-stimulated PGE2 synthase and EP4 receptor mRNA in murine osteoblast and fibroblast cell lines were evaluated with real-time PCR. Results Single injections of 2 mg SIM-EtOH induced significantly more new bone than control side after 21 days. PGE2/protein ratios peaked at day 7 and were correlated with the subsequent 21-day new bone width. The correlations at day 14 between PGE2 and new bone width changed to a negative relationship in the test group. SIM-stimulated osteoblasts expressed increased mRNA levels of PGE receptor EP4, while SIM activated PGE synthesis in fibroblasts. SIM/ALN-CD tended to preserve bone long-term. Conclusion Findings suggest that PGE pathway activation and higher levels of PGE2 during the first week following SIM-induced bone growth are desirable, and alendronate-beta-cyclodextrin conjugates not only act as tissue-specific carriers, but preserve new bone. PMID:21438610

Histomorphometric assessment of bone necrosis produced by two cryosurgery protocols using liquid nitrogen: an experimental study on rat femurs.

PubMed

Costa, Fábio Wildson Gurgel; Brito, Gerly Anne de Castro; Pessoa, Rosana Maria Andrade; Studart-Soares, Eduardo Costa

2011-01-01

The aim of this study was to evaluate the effects of liquid nitrogen cryosurgery on the femoral diaphysis of rats. The femoral diaphyses of 42 Wistar rats were exposed to three local and sequential applications of liquid nitrogen for 1 or 2 min, intercalated with periods of 5 min of passive thawing. The animals were sacrificed after 1, 2, 4 and 12 weeks and the specimens obtained were processed and analyzed histomorphometrically. The depth and extent of peak bone necrosis were 124.509 µm and 2087.094 µm for the 1-min protocol, respectively, and 436.424 µm and 12046.426 µm for the 2-min protocol. Peak necrosis was observed in the second experimental week with both cryotherapy protocols. The present results indicate that the 2-min protocol produced more marked bone necrosis than the 1-min protocol. Although our results cannot be entirely extrapolated to clinical practice, they contribute to the understanding of the behavior of bone tissue submitted to different cycles of liquid nitrogen freezing and may serve as a basis for new studies.

Progressive cell-mediated changes in articular cartilage and bone in mice are initiated by a single session of controlled cyclic compressive loading

PubMed Central

Ko, Frank C.; Dragomir, Cecilia L.; Plumb, Darren A.; Hsia, Allison W.; Adebayo, Olufunmilayo O.; Goldring, Steven R.; Wright, Timothy M.; Goldring, Mary B.; van der Meulen, Marjolein C.H.

2017-01-01

We previously showed that repetitive cyclic loading of the mouse knee joint causes changes that recapitulate the features of osteoarthritis (OA) in humans. By applying a single loading session, we characterized the temporal progression of the structural and compositional changes in subchondral bone and articular cartilage. We applied loading during a single 5-minute session to the left tibia of adult (26-week-old) C57Bl/6 male mice at a peak load of 9.0N for 1200 cycles. Knee joints were collected at times 0, 1, and 2 weeks after loading. The changes in articular cartilage and subchondral bone were analyzed by histology, immunohistochemistry (caspase-3 and cathepsin K), and microcomputed tomography. At time 0, no change was evident in chondrocyte viability or cartilage or subchondral bone integrity. However, cartilage pathology demonstrated by localized thinning and proteoglycan loss occurred at 1 and 2 weeks after the single session of loading. Transient cancellous bone loss was evident at 1 week, associated with increased osteoclast number. Bone loss was reversed to control levels at 2 weeks. We observed formation of fibrous and cartilaginous tissues at the joint margins at 1 and 2 weeks. Our findings demonstrate that a single session of noninvasive loading leads to the development of OA-like morphological and cellular alterations in articular cartilage and subchondral bone. The loss in subchondral trabecular bone mass and thickness returns to control levels at 2 weeks, whereas the cartilage thinning and proteoglycan loss persist. PMID:26896841

Genetic and Dynamic Analyses of Murine Peak Bone Density

DTIC Science & Technology

1999-10-01

DAMD17-96-1-6309 differences, the location of bone regulatory genes with strong and modifier effects , the mode of inheritance for each gene, the...estimate the cortical cross-sectional area, most likely due to partial volume effects . Thus, the high density bone area was consistently estimated to be...significant or highly significant linkage with BMD; b) 9 Beamer, WG DAMD17-96-1-6309 none of the loci exhibited significant interaction effects by ANOVA

A metabolite of leucine (β-hydroxy-β-methylbutyrate) given to sows during pregnancy alters bone development of their newborn offspring by hormonal modulation

PubMed Central

Blicharski, Tomasz; Dobrowolski, Piotr; Hułas-Stasiak, Monika; Muszyński, Siemowit

2017-01-01

The effects of dietary β-hydroxy-β-methylbutyrate (HMB) supplementation during gestation on bone, growth plate, and articular cartilage in newborns were determined. Thermal analysis of articular cartilage was performed to examine the structural changes in collagen. At day 70 of gestation, a total of 12 sows (Large White Polish breed, at the second parity) were randomly assigned to two groups, with each group receiving either a basal diet or the same diet supplemented with 0.2 g/day HMB until the 90th day. Maternal HMB supplementation enhanced body weight, bone length, and diameter in males. It also improved geometric and mechanical properties contributing to increased bone morphology and endurance. In turn, alteration of the length was only observed in females. The positive effects were mediated by increased serum concentrations of insulin-like growth factor-1 and leptin. HMB-treatment enhanced the concentration of FSH, LH, estradiol, and testosterone. Serum TAP was enhanced by the HMB-treatment by 34% in females and 138% in males. Beneficial effects of the HMB-treatment on trabecular bone and content of proteoglycans in articular cartilage were shown. The HMB-treatment significantly changed the collagen structure in cartilages, especially in the females, which was demonstrated by the PSR analysis. Differences between the HMB-supplemented and the control females in the calorimetric peak temperatures were presumably related to different collagen fibril density in the articular cartilage structure. In summary, maternal HMB supplementation in the mid-gestation period significantly improved general growth and mechanical endurance of long bones by the influence on the somatotropic and pituitary-gonadal axes in the offspring. PMID:28617846

Pulsed Electromagnetic Fields Improve Bone Microstructure and Strength in Ovariectomized Rats through a Wnt/Lrp5/β-Catenin Signaling-Associated Mechanism

PubMed Central

Cai, Jing; Wu, Yan; Xie, Kangning; Wu, Xiaoming; Tang, Chi; Liu, Juan; Guo, Wei; Shen, Guanghao; Luo, Erping

2013-01-01

Growing evidence has demonstrated that pulsed electromagnetic field (PEMF), as an alternative noninvasive method, could promote remarkable in vivo and in vitro osteogenesis. However, the exact mechanism of PEMF on osteopenia/osteoporosis is still poorly understood, which further limits the extensive clinical application of PEMF. In the present study, the efficiency of PEMF on osteoporotic bone microarchitecture and bone quality together with its associated signaling pathway mechanisms was systematically investigated in ovariectomized (OVX) rats. Thirty rats were equally assigned to the Control, OVX and OVX+PEMF groups. The OVX+PEMF group was subjected to daily 8-hour PEMF exposure with 15 Hz, 2.4 mT (peak value). After 10 weeks, the OVX+PEMF group exhibited significantly improved bone mass and bone architecture, evidenced by increased BMD, Tb.N, Tb.Th and BV/TV, and suppressed Tb.Sp and SMI levels in the MicroCT analysis. Three-point bending test suggests that PEMF attenuated the biomechanical strength deterioration of the OVX rat femora, evidenced by increased maximum load and elastic modulus. RT-PCR analysis demonstrated that PEMF exposure significantly promoted the overall gene expressions of Wnt1, LRP5 and β-catenin in the canonical Wnt signaling, but did not exhibit obvious impact on either RANKL or RANK gene expressions. Together, our present findings highlight that PEMF attenuated OVX-induced deterioration of bone microarchitecture and strength in rats by promoting the activation of Wnt/LRP5/β-catenin signaling rather than by inhibiting RANKL-RANK signaling. This study enriches our basic knowledge to the osteogenetic activity of PEMF, and may lead to more efficient and scientific clinical application of PEMF in inhibiting osteopenia/osteoporosis. PMID:24244491

Automated HPLC assay for urinary collagen cross-links: effect of age, menopause, and metabolic bone diseases.

PubMed

Kraenzlin, Marius E; Kraenzlin, Claude A; Meier, Christian; Giunta, Cecilia; Steinmann, Beat

2008-09-01

The pyridinium cross-links pyridinoline (PYD) and deoxypyridinoline (DPD) are established markers of bone resorption. We evaluated the analytical and clinical performance of a commercially available PYD HPLC assay and established reference intervals in children and adults. We used a commercially available reagent set (Chromsystems Instruments & Chemicals) to measure PYD and DPD in 319 healthy controls (156 premenopausal women, 80 healthy men, and 83 healthy children age 1 month to 14 years) and 397 patients with metabolic bone diseases (postmenopausal osteoporosis, n = 175; male osteoporosis, n = 176; hyperparathyroidism, n = 17; hyperthyroidism, n = 19; Paget disease, n = 10). The mean intraassay and interassay CVs were <6% and <8% for both PYD and DPD, respectively. The reference interval was constant for premenopausal women in the age group 20-49 years. In men, cross-link values peaked at 20-29 years and decreased thereafter. Women with postmenopausal osteoporosis had significantly higher PYD (51%) and DPD (58%) values compared to premenopausal women. Similar results were found in osteoporotic men. In children the highest values were found in the first weeks and months after birth, followed by a decrease of 50%-60% at age 11-14 years. In metabolic bone diseases cross-link concentrations were significantly increased. The DPD:PYD ratio (mean value approximately 0.2) was remarkably constant in all populations evaluated. The automated HPLC assay is a precise and convenient method for PYD and DPD measurement. We established reference intervals for adult women and men and for children up to 14 years old. The cross-link concentrations we determined by use of this HPLC method confirm its clinical value in enabling identification of increased bone resorption in patients with metabolic bone diseases.

Genetic evidence that thyroid hormone is indispensable for prepubertal insulin-like growth factor-I expression and bone acquisition in mice.

PubMed

Xing, Weirong; Govoni, Kristen E; Donahue, Leah Rae; Kesavan, Chandrasekhar; Wergedal, Jon; Long, Carlin; Bassett, J H Duncan; Gogakos, Apostolos; Wojcicka, Anna; Williams, Graham R; Mohan, Subburaman

2012-05-01

Understanding how bone growth is regulated by hormonal and mechanical factors during early growth periods is important for optimizing the attainment of peak bone mass to prevent or postpone the occurrence of fragility fractures later in life. Using genetic mouse models that are deficient in thyroid hormone (TH) (Tshr(-/-) and Duox2(-/-)), growth hormone (GH) (Ghrhr(lit/lit)), or both (Tshr(-/-); Ghrhr(lit/lit)), we demonstrate that there is an important period prior to puberty when the effects of GH are surprisingly small and TH plays a critical role in the regulation of skeletal growth. Daily administration of T3/T4 during days 5 to 14, the time when serum levels of T3 increase rapidly in mice, rescued the skeletal deficit in TH-deficient mice but not in mice lacking both TH and GH. However, treatment of double-mutant mice with both GH and T3/T4 rescued the bone density deficit. Increased body fat in the TH-deficient as well as TH/GH double-mutant mice was rescued by T3/T4 treatment during days 5 to 14. In vitro studies in osteoblasts revealed that T3 in the presence of TH receptor (TR) α1 bound to a TH response element in intron 1 of the IGF-I gene to stimulate transcription. In vivo studies using TRα and TRβ knockout mice revealed evidence for differential regulation of insulin-like growth factor (IGF)-I expression by the two receptors. Furthermore, blockade of IGF-I action partially inhibited the biological effects of TH, thus suggesting that both IGF-I-dependent and IGF-I-independent mechanisms contribute to TH effects on prepubertal bone acquisition. Copyright © 2012 American Society for Bone and Mineral Research.

Epidemiology, etiology, and diagnosis of osteoporosis.

PubMed

Lane, Nancy E

2006-02-01

Osteoporosis, a major public health problem, is becoming increasingly prevalent with the aging of the world population. Osteoporosis is a skeletal disorder characterized by compromised bone strength, which predisposes the individual to an increased risk of fractures of the hip, spine, and other skeletal sites. The clinical consequences and economic burden of this disease call for measures to assess individuals who are at high risk to allow for appropriate intervention. Many risk factors are associated with osteoporotic fracture, including low peak bone mass, hormonal factors, the use of certain drugs (eg, glucocorticoids), cigarette smoking, low physical activity, low intake of calcium and vitamin D, race, small body size, and a personal or a family history of fracture. All of these factors should be taken into account when assessing the risk of fracture and determining whether further treatment is required. Because osteoporotic fracture risk is higher in older women than in older men, all postmenopausal women should be evaluated for signs of osteoporosis during routine physical examinations. Radiologic laboratory assessments of bone mineral density generally should be reserved for patients at highest risk, including all women over the age of 65, younger postmenopausal women with risk factors, and all postmenopausal women with a history of fractures. The evaluation of biochemical markers of bone turnover has been useful in clinical research. However, the predictive factor of these measurements is not defined clearly, and these findings should not be used as a replacement for bone density testing. Together, clinical assessment of osteoporotic risk factors and objective measures of bone mineral density can help to identify patients who will benefit from intervention and, thus, can potentially reduce the morbidity and mortality associated with osteoporosis-associated fractures in this population.

Increasing Dietary Phosphorus Intake from Food Additives: Potential for Negative Impact on Bone Health123

PubMed Central

Takeda, Eiji; Yamamoto, Hironori; Yamanaka-Okumura, Hisami; Taketani, Yutaka

2014-01-01

It is important to consider whether habitual high phosphorus intake adversely affects bone health, because phosphorus intake has been increasing, whereas calcium intake has been decreasing in dietary patterns. A higher total habitual dietary phosphorus intake has been associated with higher serum parathyroid hormone (PTH) and lower serum calcium concentrations in healthy individuals. Higher serum PTH concentrations have been shown in those who consume foods with phosphorus additives. These findings suggest that long-term dietary phosphorus loads and long-term hyperphosphatemia may have important negative effects on bone health. In contrast, PTH concentrations did not increase as a result of high dietary phosphorus intake when phosphorus was provided with adequate amounts of calcium. Intake of foods with a ratio of calcium to phosphorus close to that found in dairy products led to positive effects on bone health. Several randomized controlled trials have shown positive relations between dairy intake and bone mineral density. In our loading test with a low-calcium, high-phosphorus lunch provided to healthy young men, serum PTH concentrations showed peaks at 1 and 6 h, and serum fibroblast growth factor 23 (FGF23) concentrations increased significantly at 8 h after the meal. In contrast, the high-calcium, high-phosphorus meal suppressed the second PTH and FGF23 elevations until 8 h after the meal. This implies that adequate dietary calcium intake is needed to overcome the interfering effects of high phosphorus intake on PTH and FGF23 secretion. FGF23 acts on the parathyroid gland to decrease PTH mRNA and PTH secretion in rats with normal kidney function. However, increased serum FGF23 is an early alteration of mineral metabolism in chronic kidney disease, causing secondary hyperthyroidism, and implying resistance of the parathyroid gland to the action of FGF23 in chronic kidney disease. These findings suggest that long-term high-phosphorus diets may impair bone health mediated by FGF23 resistance both in chronic kidney disease patients and in the healthy population. PMID:24425727

The effect of phototherapies on bone repair of euthyroid and hypothyroid rats: Raman spectroscopic study

NASA Astrophysics Data System (ADS)

Soares, Amanda P.; Rodriguez, Tania T.; Soares, Luiz G. P.; dos Santos, Jean Nunes; Silveira, Landulfo; Pinheiro, Antonio Luiz B.

2018-04-01

The repair of bone tissue is complex and can be influenced by several local and systemic factors that can delay the repair. Laser and LED phototherapies have shown positive results in the repair of bone tissue. The aim of this study was to evaluate, through Raman spectroscopy, the influence of laser (λ780 nm) and LED (λ850 nm) phototherapies in the repair of surgical defects in femurs of euthyroid and hypothyroid rats. Thirty Albinus Wistar rats were randomly divided into 6 groups. The animals of the hypothyroid groups were submitted to surgical removal of the thyroid gland. After general anesthesia, a surgical bone defect was created in the femur of each animal and filled with blood clot in all groups. In group I (Euthyroid) the defect was created in euthyroid animals; In Group II (Hypo) the defect was created in hypothyroid animals; In Group III (Euthyroid Laser) the defect was irradiated with Laser; on Group IV (Hypo Laser) the defect was made in a hypothyroid animal and irradiated with Laser; on Group V (Euthyroid LED) the defect was irradiated with LED and on Group VI (Hypo LED) the defect was created in hypothyroid animals and LED irradiated. Irradiation was carried out at every 48-h for 15 days. Specimens were taken and stored in liquid nitrogen. Intensity of peaks of phosphate HA ( 960 cm-1), carbonated HA ( 1,070 cm-1) and collagen ( 1,414 cm-1) were measured by Raman Spectroscopy. The results showed that the health status had significant influence all peaks. Irradiation influenced only the peak of 1454 cm-1. It is concluded that phototherapies influences bone repair in cases of thyroid diseases.

Raman and Fourier Transform Infrared (FT-IR) Mineral to Matrix Ratios Correlate with Physical Chemical Properties of Model Compounds and Native Bone Tissue.

PubMed

Taylor, Erik A; Lloyd, Ashley A; Salazar-Lara, Carolina; Donnelly, Eve

2017-10-01

Raman and Fourier transform infrared (FT-IR) spectroscopic imaging techniques can be used to characterize bone composition. In this study, our objective was to validate the Raman mineral:matrix ratios (ν 1 PO 4 :amide III, ν 1 PO 4 :amide I, ν 1 PO 4 :Proline + hydroxyproline, ν 1 PO 4 :Phenylalanine, ν 1 PO 4 :δ CH 2 peak area ratios) by correlating them to ash fraction and the IR mineral:matrix ratio (ν 3 PO 4 :amide I peak area ratio) in chemical standards and native bone tissue. Chemical standards consisting of varying ratios of synthetic hydroxyapatite (HA) and collagen, as well as bone tissue from humans, sheep, and mice, were characterized with confocal Raman spectroscopy and FT-IR spectroscopy and gravimetric analysis. Raman and IR mineral:matrix ratio values from chemical standards increased reciprocally with ash fraction (Raman ν 1 PO 4 /Amide III: P < 0.01, R 2  = 0.966; Raman ν 1 PO 4 /Amide I: P < 0.01, R 2  = 0.919; Raman ν 1 PO 4 /Proline + Hydroxyproline: P < 0.01, R 2  = 0.976; Raman ν 1 PO 4 /Phenylalanine: P < 0.01, R 2  = 0.911; Raman ν 1 PO 4 /δ CH 2 : P < 0.01, R 2  = 0.894; IR P < 0.01, R 2  = 0.91). Fourier transform infrared mineral:matrix ratio values from native bone tissue were also similar to theoretical mineral:matrix ratio values for a given ash fraction. Raman and IR mineral:matrix ratio values were strongly correlated ( P < 0.01, R 2  = 0.82). These results were confirmed by calculating the mineral:matrix ratio for theoretical IR spectra, developed by applying the Beer-Lambert law to calculate the relative extinction coefficients of HA and collagen over the same range of wavenumbers (800-1800 cm -1 ). The results confirm that the Raman mineral:matrix bone composition parameter correlates strongly to ash fraction and to its IR counterpart. Finally, the mineral:matrix ratio values of the native bone tissue are similar to those of both chemical standards and theoretical values, confirming the biological relevance of the chemical standards and the characterization techniques.

Hypermineralization and High Osteocyte Lacunar Density in Osteogenesis Imperfecta Type V Bone Indicate Exuberant Primary Bone Formation.

PubMed

Blouin, Stéphane; Fratzl-Zelman, Nadja; Glorieux, Francis H; Roschger, Paul; Klaushofer, Klaus; Marini, Joan C; Rauch, Frank

2017-09-01

In contrast to "classical" forms of osteogenesis imperfecta (OI) types I to IV, caused by a mutation in COL1A1/A2, OI type V is due to a gain-of-function mutation in the IFITM5 gene, encoding the interferon-induced transmembrane protein 5, or bone-restricted interferon-inducible transmembrane (IFITM)-like protein (BRIL). Its phenotype distinctly differs from OI types I to IV by absence of blue sclerae and dentinogenesis imperfecta, by the occurrence of ossification disorders such as hyperplastic callus and forearm interosseous membrane ossification. Little is known about the impact of the mutation on bone tissue/material level in untreated and bisphosphonate-treated patients. Therefore, investigations of transiliac bone biopsy samples from a cohort of OI type V children (n = 15, 8.7 ± 4 years old) untreated at baseline and a subset (n = 8) after pamidronate treatment (2.6 years in average) were performed. Quantitative backscattered electron imaging (qBEI) was used to determine bone mineralization density distribution (BMDD) as well as osteocyte lacunar density. The BMDD of type V OI bone was distinctly shifted toward a higher degree of mineralization. The most frequently occurring calcium concentration (CaPeak) in cortical (Ct) and cancellous (Cn) bone was markedly increased (+11.5%, +10.4%, respectively, p < 0.0001) compared to healthy reference values. Treatment with pamidronate resulted in only a slight enhancement of mineralization. The osteocyte lacunar density derived from sectioned bone area was elevated in OI type V Ct and Cn bone (+171%, p < 0.0001; +183.3%, p < 0.01; respectively) versus controls. The high osteocyte density was associated with an overall immature primary bone structure ("mesh-like") as visualized by polarized light microscopy. In summary, the bone material from OI type V patients is hypermineralized, similar to other forms of OI. The elevated osteocyte lacunar density in connection with lack of regular bone lamellation points to an exuberant primary bone formation and an alteration of the bone remodeling process in OI type V. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

Does the cortical bone resorption rate change due to 90Sr-radiation exposure? Analysis of data from Techa Riverside residents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tolstykh, E I; Shagina, N B; Degteva, M O

2011-08-01

The Mayak Production Association released large amounts of 90Sr into the Techa River (Southern Urals, Russia) with peak amounts in 1950-1951. Techa Riverside residents ingested an average of about 3,000 kBq of 90Sr. The 90Sr-body burden of approximately 15,000 individuals has been measured in the Urals Research Center for Radiation Medicine in 1974-1997 with use of a special whole-body counter (WBC). Strontium-90 had mainly deposited in the cortical part of the skeleton by 25 years following intake, and 90Sr elimination occurs as a result of cortical bone resorption. The effect of 90Sr-radiation exposure on the rate of cortical bone resorptionmore » was studied. Data on 2,022 WBC measurements were selected for 207 adult persons, who were measured three or more times before they were 50-55 years old. The individual-resorption rates were calculated with the rate of strontium recirculation evaluated as 0.0018 year -1. Individual absorbed doses in red bone marrow (RBM) and bone surface (BS) were also calculated. Statistically significant negative relationships of cortical bone resorption rate were discovered related to 90Sr-body burden and dose absorbed in the RBM or the BS. The response appears to have a threshold of about 1.5-Gy RBM dose. The radiation induced decrease in bone resorption rate may not be significant in terms of health. However, a decrease in bone remodeling rate can be among several causes of an increased level of degenerative dystrophic bone pathology in exposed persons.« less

Raman study of the effect of LED light on grafted bone defects

NASA Astrophysics Data System (ADS)

Soares, Luiz G. G. P.; Aciole, Jouber M. S.; Aciole, Gilbeth T. S.; Barbosa, Artur F. S.; Silveira-Júnior, Landulfo; Pinheiro, Antônio L. B.

2013-03-01

Benefits of the isolated or combined use light and biomaterials on bone healing have been suggested. Our group has used several models to assess the effects of laser on bone. A Raman spectral analysis on surgical bone defects grafted or not with Hydroxyapatite (HA), treated or not with LED was carried out. 40 rats were divided into 4 groups. On Group I the defect was filled with the clot. On Group II, the defect was filled with the HA. On groups III the defect was filled with Clot and further irradiated with LED and on group IV the defects was filled with the HA and further irradiated with LED. LED (λ850 +/- 10nm, 150mW, A= 0.5cm2, 68s, 20 J/cm2 per session, 140 J/cm2 per treatment) was applied at 48 h intervals during 15 days. Specimens were taken after 15 and 30 days after surgery and kept on liquid nitrogen, and underwent Raman analysis. For this, the peak of hydroxyapatite (~960 cm-1) was used as marker of bone mineralization. Significant difference was observed at both times (p<0.05). When the biomaterial was used higher peaks were observed. Association with LED further improved the intensity. Conclusion: It is concluded that LED light improved the effect of the HA.

PIXE study of the kinetics of biomaterials ossification

NASA Astrophysics Data System (ADS)

Weber, G.; Robaye, G.; Braye, F.; Oudadesse, H.; Irigaray, J. L.

1994-05-01

Biomaterials are frequently implanted in bones. This implantation is followed by a phenomenon of ossification. The purpose of this work was to study the time evolution of the gradient of characteristic atomic element's concentrations in the bone, the implant and the bone-implant interface. We have studied two types of neutral biomaterials: pure synthetic hydroxyapatite and porite's asteroid coral. The animal implantations have been made on sheep of the same age and sex having received the same basic diet. The implantations have been made in the cortical femur. On both sides of the implant, at the same distance, two screws were placed to allow further determination of the position of the implant. The PIXE method is particularly suitable here because of the possibility to analyze directly the samples without any preparation and to choose easily the dimensions of beam used for the gradient study. The X-rays have been detected with an ultra LEGe instead of the usual Si(Li) device to avoid the Si escape peak associated with the K α X-ray of calcium, the major constituent of bone. This peak is particularly disturbing here because its energy corresponds to the K α line of phosphorus, an important constituent of bone. The results of these determinations are presented and discussed.

Bone mineralization in childhood and adolescence.

PubMed

Bachrach, L K

1993-08-01

Prevention of osteoporosis depends on establishing adequate peak bone mass in the first two decades of life. Achievement of this goal requires an understanding of factors that promote skeletal health. Genetic factors are important determinants of adult bone mass, but nonheritable variables, including body mass, calcium nutriture, sex steroids, and activity can strongly influence whether maximal bone mineral is achieved. Acquisition of bone mineral continues throughout childhood and adolescence, reaching a lifetime maximum in early adulthood. Adolescence is a particularly critical time for bone mineral accretion as more than half of the bone calcium is normally laid down during the teen years. Chronic illness, malnutrition, or endocrine deficiencies at this age may result in profound deficits in bone mass, which may not be fully reversible. These risk factors contribute to the osteopenia associated with anorexia nervosa, exercise-induced amenorrhea, delayed puberty, Turner's syndrome, and growth hormone deficiency.

Exposure to urban air pollution and bone health in clinically healthy six-year-old children.

PubMed

Calderón-Garcidueñas, Lilian; Mora-Tiscareño, Antonieta; Francolira, Maricela; Torres-Jardón, Ricardo; Peña-Cruz, Bernardo; Palacios-López, Carolina; Zhu, Hongtu; Kong, Linglong; Mendoza-Mendoza, Nicolás; Montesinoscorrea, Hortencia; Romero, Lina; Valencia-Salazar, Gildardo; Kavanaugh, Michael; Frenk, Silvestre

2013-01-01

Air pollution induces systemic inflammation, as well as respiratory, myocardial and brain inflammation in children. Peak bone mass is influenced by environmental factors. We tested the hypothesis that six-year-olds with lifetime exposures to urban air pollution will have alterations in inflammatory markers and bone mineral density (BMD) as opposed to low-polluted city residents when matched for BMI, breast feeding history, skin phototype, age, sex and socioeconomic status. This pilot study included 20 children from Mexico City (MC) (6.17 years ± 0.63 years) and 15 controls (6.27 years ± 0.76 years). We performed full paediatric examinations, a history of outdoor exposures, seven-day dietary recalls, serum inflammatory markers and dual-energy X-ray absorptiometry (DXA). Children in MC had significantly higher concentrations of IL-6 (p=0.001), marked reductions in total blood neutrophils (p= 0.0002) and an increase in monocytes (p=0.005). MC children also had an insufficient Vitamin D intake and spent less time outdoors than controls (p<0.001) in an environment characterized by decreased UV light, with ozone and fine particulates concentrations above standard values. There were no significant differences between the cohorts in DXA Z scores. The impact of systemic inflammation, vitamin D insufficiency, air pollution, urban violence and poverty may have long-term bone detrimental outcomes in exposed paediatric populations as they grow older, increasing the risk of low bone mass and osteoporosis. The selection of reference populations for DXA must take into account air pollution exposures.

The effect of implant design and bone quality on insertion torque, resonance frequency analysis, and insertion energy during implant placement in low or low- to medium-density bone.

PubMed

Wang, Tong-Mei; Lee, Ming-Shu; Wang, Juo-Song; Lin, Li-Deh

2015-01-01

This study investigated the effect of implant design and bone quality on insertion torque (IT), implant stability quotient (ISQ), and insertion energy (IE) by monitoring the continuous change in IT and ISQ while implants were inserted in artificial bone blocks that simulate bone of poor or poor-to-medium quality. Polyurethane foam blocks (Sawbones) of 0.16 g/cm³ and 0.32 g/cm³ were respectively used to simulate low density and low- to medium-density cancellous bone. In addition, some test blocks were laminated with a 1-mm 0.80 g/cm³ polyurethane layer to simulate cancellous bone with a thin cortical layer. Four different implants (Nobel Biocare Mk III-3.75, Mk III-4.0, Mk IV-4.0, and NobelActive-4.3) were placed into the different test blocks in accordance with the manufacturer's instructions. The IT and ISQ were recorded at every 0.5-mm of inserted length during implant insertion, and IE was calculated from the torque curve. The peak IT (PIT), final IT (FIT), IE, and final ISQ values were statistically analyzed. All implants showed increasing ISQ values when the implant was inserted more deeply. In contrast to the ISQ, implants with different designs showed dissimilar IT curve patterns during the insertion. All implants showed a significant increase in the PIT, FIT, IE, and ISQ when the test-block density increased or when the 1-mm laminated layer was present. Tapered implants showed FIT or PIT values of more than 40 Ncm for all of the laminated test blocks and for the nonlaminated test blocks of low to medium density. Parallel-wall implants did not exhibit PIT or FIT values of more than 40 Ncm for all of the test blocks. NobelActive-4.3 showed a significantly higher FIT, but a significantly lower IE, than Mk IV-4.0. While the existence of cortical bone or implant designs significantly affects the dynamic IT profiles during implant insertion, it does not affect the ISQ to a similar extent. Certain implant designs are more suitable than others if high IT is required in bone of poor quality. The manner in which IT, IE, and ISQ represent the implant primary stability requires further study.

Immediate fall of bone formation and transient increase of bone resorption in the course of high-dose, short-term glucocorticoid therapy in young patients with multiple sclerosis.

PubMed

Dovio, Andrea; Perazzolo, Laura; Osella, Giangiacomo; Ventura, Massimo; Termine, Angela; Milano, Eva; Bertolotto, Antonio; Angeli, Alberto

2004-10-01

Glucocorticoid (GC)-induced osteoporosis is the leading form of secondary osteoporosis. Bone loss can be rapid. However, longitudinal studies at the very beginning of treatment are scarce. Patients relapsing from multiple sclerosis are treated with high-dose, short-term iv GCs. A number of them are young, without concomitant disease affecting bone and with no substantial impairment of mobility. Such patients were selected for the present study. Thirteen patients suffering from multiple sclerosis [11 females, two males; age 32 +/- 2 yr (mean +/- se)] and receiving iv methylprednisolone 15 mg/kg daily for 10 d completed the study. We measured serum osteocalcin (OC), aminoterminal propeptide of type I collagen (PINP), bone isoform of alkaline phosphatase (bALP), carboxyterminal telopeptide of type I collagen (CTX), and urinary calcium/creatinine ratio (uCa/Cr) during the 10-d cycle and 3 months later. Dual-energy x-ray absorptiometry and calcaneal quantitative ultrasonometry were performed before and 6 months after therapy. We found an immediate, impressive fall of OC and PINP (-80 +/- 3 and -54 +/- 5% at d 2, respectively), which persisted throughout the whole treatment period (P < 0.0001 for both markers). bALP levels showed only a modest decrease at d 6 (-19 +/- 7%, P < 0.05), with subsequent return to baseline in d 7-10. After 3 months, OC, PINP, and bALP levels rose to +51 +/- 22, +37 +/- 16 (not significant), and +61 +/- 17% (P < 0.01) with respect to baseline, respectively. uCa/Cr and CTX showed a progressive, marked increase during treatment, peaking at d 7-9 (+92 +/- 44 and +149 +/- 63%, respectively), with subsequent decrement at d 10 (P < 0.01 and P < 0.05, respectively) despite continuing GC administration. After 3 months, uCa/Cr and CTX levels were also higher than baseline. No change in quantitative ultrasonometry parameters and bone mineral density was observed 6 months after therapy. In conclusion, high-dose, short-term iv GC regimens cause an immediate and persistent decrease in bone formation and a rapid and transient increase of bone resorption. Our data also support the concept that discontinuation of such regimens is followed by a high bone turnover phase.

Protocol for a randomized controlled trial to compare bone-loading exercises with risedronate for preventing bone loss in osteopenic postmenopausal women.

PubMed

Bilek, Laura D; Waltman, Nancy L; Lappe, Joan M; Kupzyk, Kevin A; Mack, Lynn R; Cullen, Diane M; Berg, Kris; Langel, Meghan; Meisinger, Melissa; Portelli-Trinidad, Ashlee; Lang, Molly

2016-08-30

In the United States, over 34 million American post-menopausal women have low bone mass (osteopenia) which increases their risk of osteoporosis and fractures. Calcium, vitamin D and exercise are recommended for prevention of osteoporosis, and bisphosphonates (BPs) are prescribed in women with osteoporosis. BPs may also be prescribed for women with low bone mass, but are more controversial due to the potential for adverse effects with long-term use. A bone loading exercise program (high-impact weight bearing and resistance training) promotes bone strength by preserving bone mineral density (BMD), improving bone structure, and by promoting bone formation at sites of mechanical stress. The sample for this study will be 309 women with low bone mass who are within 5 years post-menopause. Subjects are stratified by exercise history (≥2 high intensity exercise sessions per week; < 2 sessions per week) and randomized to a control or one of two treatment groups: 1) calcium + vitamin D (CaD) alone (Control); 2) a BP plus CaD (Risedronate); or 3) a bone loading exercise program plus CaD (Exercise). After 12 months of treatment, changes in bone structure, BMD, and bone turnover will be compared in the 3 groups. Primary outcomes for the study are bone structure measures (Bone Strength Index [BSI] at the tibia and Hip Structural Analysis [HSA] scores). Secondary outcomes are BMD at the hip and spine and serum biomarkers of bone formation (alkaline phosphase, AlkphaseB) and resorption (Serum N-terminal telopeptide, NTx). Our central hypothesis is that improvements in bone strength will be greater in subjects randomized to the Exercise group compared to subjects in either Control or Risedronate groups. Our research aims to decrease the risk of osteoporotic fractures by improving bone strength in women with low bone mass (pre-osteoporotic) during their first 5 years' post-menopause, a time of rapid and significant bone loss. Results of this study could be used in developing a clinical management pathway for women with low bone mass at their peak period of bone loss that would involve lifestyle modifications such as exercises prior to medications such as BPs. Clinicaltrials.gov NCT02186600 . Initial registration: 7/7/2014.

[Analysis of stress in periodontal ligament of the maxillary first molar on distal movement by nonlinear finite element method].

PubMed

Dong, Jing; Zhang, Zhe-chen; Zhou, Guo-liang

2015-06-01

To analyze the stress distribution in periodontal ligament of maxillary first molar during distal movement with nonlinear finite element analysis, and to compare it with the result of linear finite element analysis, consequently to provide biomechanical evidence for clinical application. The 3-D finite element model including a maxillary first molar, periodontal ligament, alveolar bone, cancellous bone, cortical bone and a buccal tube was built up by using Mimics, Geomagic, ProE and Ansys Workbench. The material of periodontal ligament was set as nonlinear material and linear elastic material, respectively. Loads of different combinations were applied to simulate the clinical situation of distalizing the maxillary first molar. There were channels of low stress in peak distribution of Von Mises equivalent stress and compressive stress of periodontal ligament in nonlinear finite element model. The peak of Von Mises equivalent stress was lower when it was satisfied that Mt/F minus Mr/F approximately equals 2. The peak of compressive stress was lower when it was satisfied that Mt/F was approximately equal to Mr/F. The relative stress of periodontal ligament was higher and violent in linear finite element model and there were no channels of low stress in peak distribution. There are channels in which stress of periodontal ligament is lower. The condition of low stress should be satisfied by applied M/F during the course of distalizing the maxillary first molar.

Voluntary run training but not estradiol deficiency alters the tibial bone-soleus muscle functional relationship in mice.

PubMed

Warren, Gordon L; Moran, Amy L; Hogan, Harry A; Lin, Angela S; Guldberg, Robert E; Lowe, Dawn A

2007-11-01

The study's objective was to investigate how estrogen deficiency and run training affect the tibial bone-soleus muscle functional relationship in mice. Female mice were assigned into one of two surgical conditions, ovariectomy (OVX) or sham ovariectomy (sham), and one of two activity conditions, voluntary wheel running (Run) or sedentary (Sed). To determine whether differences observed between OVX and sham conditions could be attributed to estradiol (E(2)), additional OVX mice were supplemented with E(2). Tibial bones were analyzed for their functional capacities, ultimate load, and stiffness. Soleus muscles were analyzed for their functional capacities, maximal isometric tetanic force (P(o)), and peak eccentric force. The ratios of bone functional capacities to those of muscle were calculated. The bone functional capacities were affected by both surgical condition and activity but more strongly by surgical condition. Ultimate load and stiffness for the sham group were 7-12% greater than those for OVX animals (P = 0.002), whereas only stiffness was greater for Run than for Sed animals (9%; P = 0.015). The muscle functional capacities were affected by both surgical condition and activity; however, in contrast to the bone, the muscle was more affected by activity. P(o) and peak eccentric force were 10-21% greater for Run than for Sed animals (P < or = 0.016), whereas only P(o) was greater in sham than in OVX animals (9%; P = 0.011). The bone-to-muscle ratios of functional capacities were affected by activity but not by surgical condition or E(2) supplementation. Thus a mismatch of bone-muscle function occurred in mice that voluntarily ran on wheels, irrespective of estrogen status.

Reproductive factors affecting the bone mineral density in postmenopausal women.

PubMed

Ozdemir, Ferda; Demirbag, Derya; Rodoplu, Meliha

2005-03-01

Osteoporosis has been defined as a metabolic bone disease characterized by a loss of bone mineral density (BMD) greater than 2.5 standard deviations below young adult peak bone mass or the presence of fracture. By considering that some factors related to female reproductive system might influence the ultimate risk of osteoporosis, we aimed to investigate if a relationship exists between the present BMD of postmenopausal women with their past and present reproductive characteristics. The present study focused on how BMD could be affected by the following factors in postmenopausal women, such as age at menarche, age at first pregnancy, the number of pregnancies and total breast-feeding time. We reviewed detailed demographic history of 303 postmenopausal women. According to the results of the present study, a negative correlation was found between the number of parities and BMD. The BMD values decreased as the number of pregnancies increased. When the BMD values for lumbar vertebrae 2 and Ward's triangle were investigated, it was observed that a significant difference exists between the women with no child birth and those with more than five parities. There was a significant relationship between age at first pregnancy and BMD values at the lumbar vertebrae 2 and Ward's triangle. Women who had five or more abortions were found to have significantly lower spine BMD values compared to women who had no abortions or women who had one or two abortions. These findings indicate that the increased risk of osteoporosis is associated with the increased number of pregnancies and abortions and higher age at first pregnancy.

Effects of long term treatment with high doses of odanacatib on bone mass, bone strength, and remodeling/modeling in newly ovariectomized monkeys.

PubMed

Duong, L T; Pickarski, M; Cusick, T; Chen, C M; Zhuo, Y; Scott, K; Samadfam, R; Smith, S Y; Pennypacker, B L

2016-07-01

The objectives here were to evaluate the effects of odanacatib (ODN) at doses exceeding the clinical exposure on biomechanical properties of lumbar vertebrae (LV), hip and central femur (CF), and compare ODN to alendronate (ALN) on bone remodeling/modeling in ovariectomized (OVX) monkeys. Ten days post-surgery, animals were treated with vehicle (VEH), ODN-L (2mg/kg/day, p.o.), ODN-H (8/4mg/kg/day), or ALN (30μg/kg/week, s.c.) for 20months. An intact group was also included. ODN-L provided systemic exposures of 1.8-fold of clinical exposure. ODN-H started at 20-fold for 5.5months, and then reduced to 7.8-fold of clinical exposure, compared to ALN at approximated clinical exposure. From cross sectional analyses, LV density and peak load in ODN at both doses or ALN were not different from VEH or Intact. However, cortical thickness of femoral neck (FN) and CF in ODN were higher (21-34%, p<0.05) than VEH, due to smaller endocortical (Ec) perimeter of FN (10-11%; p<0.05) and CF (9-12%; ODN-L, p<0.05), and larger CF periosteal (Ps) perimeter (2-12%; ODN-H, p<0.001) versus VEH. ODN groups also showed slightly higher cortical porosity and Ps non-lamellar bone in CF. ODN-H treatment resulted in higher CF peak load (p<0.05) versus VEH. For all bone sites analyzed, a positive, linear relationship (r(2)=0.46-0.69, p<0.0001) of peak load to density or structural parameters was demonstrated. No treatment-related differences in the derived intrinsic strength properties were evidenced as compared between groups. ALN reduced all remodeling surfaces without affecting Ps modeling. Trabecular and intracortical remodeling were reduced in ODN groups, similar to ALN. Ec mineralizing surface in ODN-H trended to be lower than VEH by month 20, but Ec bone formation indices in ODN groups generally were not different from VEH. Ps modeling in ODN groups was significantly higher than other treatment groups. This study overall demonstrated the bone safety profile of ODN and its unique mechanism on cortical bone supporting the clinical application for osteoporosis treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Long bone robustness during growth: A cross-sectional pQCT examination of children and young adults aged 5-29years.

PubMed

Rantalainen, Timo; Weeks, Benjamin K; Nogueira, Rossana C; Beck, Belinda R

2016-12-01

Skeletal robustness (cross-section size relative to length) is associated with stress fractures in adults, and appears to explain the high incidence of distal radius fractures in adolescents. However, little is known about the ontogeny of long bone robustness during the first three decades of life. Therefore, we explored the ontogeny of tibial, fibular, ulnar and radial robustness in a cross-sectional sample of 5 to 29year-old volunteers of both sexes. Peripheral quantitative computed tomography (pQCT) was used to evaluate cross-sections of the leg (4%, 14%, 38% and 66%), and forearm (4%, and 66%) in N=432 individuals. Robustness was evaluated as the total bone area divided by bone length. Differences between age-groups, sexes, and age-group×sex interactions were evaluated with ANOVA with Tukey's post hocs where appropriate. Most bone sites exhibited more robust bones in men than women (P<0.001 to 0.02), and in older age-groups than younger (P<0.001). Sex×age-group interaction was observed at the 66% and 38% tibia sites with robustness increasing more with age in men than in women (P=0.006 to 0.042). Post-hoc analyses indicated no sex differences prior to 13years-of-age, and notable exceptions to increasing robustness with age at the 4% radial and 66% tibial sites, which exhibited reduced robustness in age groups close to peak height velocity. In conclusion, the present results suggest that very little sexual dimorphism in long bone robustness exists prior to puberty, and that divergence occurs primarily after cessation of longitudinal growth. A period of relative diaphyseal slenderness was identified at age-groups coinciding with the adolescent growth spurt, which may be related to the relatively high incidence of frank and stress fracture in adolescents. Copyright © 2016 Elsevier Inc. All rights reserved.

[THE IMPORTANCE OF "MILK BONES" TO "WISDOM BONES" - COW MILK AND BONE HEALTH - LESSONS FROM MILK ALLERGY PATIENTS].

PubMed

Nachshon, Liat; Katz, Yitzhak

2016-03-01

The necessity of milk consumption in the western diet is a subject of intense controversy. One of the main benefits of milk is that it is the main source of dietary calcium. Calcium is a major bone mineral, mandatory for bone health. Its supply is derived exclusively from external dietary sources. During the growth period, an increased calcium supply is needed for the process of bone mass accumulation. An optimal bone mass achieved by the end of the growth period may be protective later in life against the bone mass loss that commonly occurs. This in turn, can be preventative against the occurrence of osteoporosis and the development of spontaneous bone fractures. Over the past several decades, an increased incidence of osteoporosis has been documented in western countries, leading to high rates of morbidity and mortality in the middle-aged and geriatric population. Many studies have investigated the dietary calcium requirements for different ages, to achieve and maintain proper bone health. Based on their results, guidelines concerning calcium intake in every stage of life have been published by national and international organizations. In the western diet, it is difficult to achieve the recommended calcium intake without milk consumption. Moreover, calcium bioavailability for intestinal absorption is high. Several studies have recently raised doubts concerning the amounts of calcium intake in the western diet and its effectiveness in preventing osteoporosis. The main disadvantage of these studies is their being based on the patient's past memory recall of milk consumption. Patients with IgE-mediated cow's milk protein allergy are a unique population. Their lifetime negligible milk consumption is undisputed. A recent study investigated for the first time, the bone density of young adults with milk allergy at the end of their growth period. Their severe reduction in bone mineral density and dietary calcium intake defines them as a high risk group for the development of early osteoporosis. Another finding of this study was that normal bone density was found in milk allergic patients who started to consume milk after a successful desensitization program. Interestingly, these patients had consumed milk for a period of only 12-36 months and had only partially achieved the recommended dietary intake for calcium. It appears that dietary milk is essential for optimal peak bone mass. The required amounts of calcium and the preferred form for consumption, however, requires further investigation.

Static vs dynamic loads as an influence on bone remodelling.

PubMed

Lanyon, L E; Rubin, C T

1984-01-01

Remodelling activity in the avian ulna was assessed under conditions of disuse alone, disuse with a superimposed continuous compressive load, and disuse interrupted by a short daily period of intermittent loading. The ulnar preparation consisted of the 110mm section of the bone shaft between two submetaphyseal osteotomies. Each end of the preparation was transfixed by a stainless steel pin and the shaft either protected from normal functional loading with the pins joined by external fixators, loaded continuously in compression by joining the pins with springs, or loaded intermittently in compression for a single 100s period per day by engaging the pins in an Instron machine. Similar loads (525 N) were used in both static and dynamic cases. The strains engendered were determined by strain gauges, and at their maximum around the bone's midshaft were -0.002. The intermittent load was applied at a frequency of 1 Hz as a ramped square wave, with a rate of change of strain during the ramp of 0.01 s-1. Peak strain at the midshaft of the ulna during wing flapping in the intact bone was recorded from bone bonded strain gauges in vivo as -0.0033 with a maximum rate of change of strain of 0.056 s-1. Examination of bone sections from the midpoint of the preparation after an 8 week period indicated that in both non-loaded and statically loaded bones there was an increase in both endosteal diameter and intra cortical porosity. These changes produced a decrease in cross sectional area which was similar in the two groups (-13%).(ABSTRACT TRUNCATED AT 250 WORDS)

Serum Albumin and Body Weight as Biomarkers for the Antemortem Identification of Bone and Gastrointestinal Disease in the Common Marmoset

PubMed Central

Baxter, Victoria K.; Shaw, Gillian C.; Sotuyo, Nathaniel P.; Carlson, Cathy S.; Olson, Erik J.; Zink, M. Christine; Mankowski, Joseph L.; Adams, Robert J.

2013-01-01

The increasing use of the common marmoset (Callithrix jacchus) in research makes it important to diagnose spontaneous disease that may confound experimental studies. Bone disease and gastrointestinal disease are two major causes of morbidity and mortality in captive marmosets, but currently no effective antemortem tests are available to identify affected animals prior to the terminal stage of disease. In this study we propose that bone disease and gastrointestinal disease are associated disease entities in marmosets and aim to establish the efficacy of several economical antemortem tests in identifying and predicting disease. Tissues from marmosets were examined to define affected animals and unaffected controls. Complete blood count, serum chemistry values, body weight, quantitative radiographs, and tissue-specific biochemical markers were evaluated as candidate biomarkers for disease. Bone and gastrointestinal disease were associated, with marmosets being over seven times more likely to have either concurrent bone and gastrointestinal disease or neither disease as opposed to lesions in only one organ system. When used in tandem, serum albumin <3.5 g/dL and body weight <325 g identified 100% of the marmosets affected with concurrent bone and gastrointestinal disease. Progressive body weight loss of 0.05% of peak body weight per day predicted which marmosets would develop disease prior to the terminal stage. Bone tissue-specific tests, such as quantitative analysis of radiographs and serum parathyroid hormone levels, were effective for distinguishing between marmosets with bone disease and those without. These results provide an avenue for making informed decisions regarding the removal of affected marmosets from studies in a timely manner, preserving the integrity of research results. PMID:24324827

Progressive cell-mediated changes in articular cartilage and bone in mice are initiated by a single session of controlled cyclic compressive loading.

PubMed

Ko, Frank C; Dragomir, Cecilia L; Plumb, Darren A; Hsia, Allison W; Adebayo, Olufunmilayo O; Goldring, Steven R; Wright, Timothy M; Goldring, Mary B; van der Meulen, Marjolein C H

2016-11-01

We previously showed that repetitive cyclic loading of the mouse knee joint causes changes that recapitulate the features of osteoarthritis (OA) in humans. By applying a single loading session, we characterized the temporal progression of the structural and compositional changes in subchondral bone and articular cartilage. We applied loading during a single 5-minute session to the left tibia of adult (26-week-old) C57Bl/6 male mice at a peak load of 9.0N for 1,200 cycles. Knee joints were collected at times 0, 1, and 2 weeks after loading. The changes in articular cartilage and subchondral bone were analyzed by histology, immunohistochemistry (caspase-3 and cathepsin K), and microcomputed tomography. At time 0, no change was evident in chondrocyte viability or cartilage or subchondral bone integrity. However, cartilage pathology demonstrated by localized thinning and proteoglycan loss occurred at 1 and 2 weeks after the single session of loading. Transient cancellous bone loss was evident at 1 week, associated with increased osteoclast number. Bone loss was reversed to control levels at 2 weeks. We observed formation of fibrous and cartilaginous tissues at the joint margins at 1 and 2 weeks. Our findings demonstrate that a single session of noninvasive loading leads to the development of OA-like morphological and cellular alterations in articular cartilage and subchondral bone. The loss in subchondral trabecular bone mass and thickness returns to control levels at 2 weeks, whereas the cartilage thinning and proteoglycan loss persist. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1941-1949, 2016. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

A time-dependent degeneration manner of condyle in rat CFA-induced inflamed TMJ.

PubMed

Xu, Liqin; Guo, Huilin; Li, Cheng; Xu, Jie; Fang, Wei; Long, Xing

2016-01-01

Temporomandibular joint (TMJ) inflammation is a potential risk factor of osteoarthritis (OA) but the detailed degenerative changes in the inflamed TMJ remain unclear. In this study, we evaluated the changes of condylar cartilage and subchondral bone in rat inflamed TMJ induced by Freund's complete adjuvant (CFA). Articular cavity was injected with CFA and the TMJ samples were collected 1, 2, 3, and 4-week post-injection. Hematoxylin & Eosin (H&E) staining, toluidine blue (TB) staining, Safranin O (S.O) staining, Masson trichrome staining and micro-CT were used to assess TMJ degeneration during inflammation. Osteoclast and osteoblast activities were analyzed by tartrate-resistant acid phosphatase (TRAP) staining and osteocalcin (OCN) immunohistochemistry staining respectively. The expression of receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG) in condylar cartilage and subchondral bone was also evaluated through immunohistochemistry and RANKL/OPG ratio was evaluated. Reduced cartilage thickness, decreased number of chondrocytes, and down-regulated proteoglycan expression were observed in the condylar cartilage in the inflamed TMJ. Enhanced osteoclast activity, and expanded bone marrow cavity were reached the peak in the 2-week after CFA-injection. Meanwhile the RANKL/OPG ratio in the cartilage and subchondral bone also increased in the 2-week CFA-injection. Immature, unmineralized new bones with irregular trabecular bone structure, atypical condylar shape, up-regulated OCN expression, and decreased bone mineral density (BMD) were found in the inflamed TMJ. The time-dependent degeneration manner of TMJ cartilage and subchondral bone was found in CFA-induced arthritis rat model. The degeneration in the TMJ with inflammation might be a risk factor and should be concerned.

MRI-measured pelvic bone marrow adipose tissue is inversely related to DXA-measured bone mineral in younger and older adults.

PubMed

Shen, W; Chen, J; Gantz, M; Punyanitya, M; Heymsfield, S B; Gallagher, D; Albu, J; Engelson, E; Kotler, D; Pi-Sunyer, X; Gilsanz, V

2012-09-01

Recent research has shown an inverse relationship between bone marrow adipose tissue (BMAT) and bone mineral density (BMD). There is a lack of evidence at the macro-imaging level to establish whether increased BMAT is a cause or effect of bone loss. This cross-sectional study compared the BMAT and BMD relationship between a younger adult group at or approaching peak bone mass (PBM; age 18.0-39.9 years) and an older group with potential bone loss (PoBL; age 40.0-88.0 years). Pelvic BMAT was evaluated in 560 healthy men and women with T1-weighted whole-body magnetic resonance imaging. BMD was measured using whole-body dual-energy X-ray absorptiometry. An inverse correlation was observed between pelvic BMAT and pelvic, total and spine BMD in the younger PBM group (r=-0.419 to -0.461, P<0.001) and in the older PoBL group (r=-0.405 to -0.500, P<0.001). After adjusting for age, sex, ethnicity, menopausal status, total body fat, skeletal muscle, subcutaneous and visceral adipose tissue, neither subject group (younger PBM vs older PoBL) nor its interaction with pelvic BMAT significantly contributed to the regression models with BMD as dependent variable and pelvic BMAT as independent variable (P=0.434-0.928). Our findings indicate that an inverse relationship between pelvic BMAT and BMD is present both in younger subjects who have not yet experienced bone loss and also in older subjects. These results provide support at the macro-imaging level for the hypothesis that low BMD may be a result of preferential differentiation of mesenchymal stem cells from osteoblasts to adipocytes.

MRI-measured pelvic bone marrow adipose tissue is inversely related to DXA-measured bone mineral in younger and older Adults

PubMed Central

Shen, Wei; Chen, Jun; Gantz, Madeleine; Punyanitya, Mark; Heymsfield, Steven B; Gallagher, Dympna; Albu, Jeanine; Engelson, Ellen; Kotler, Donald; Pi-Sunyer, Xavier; Gilsanz, Vicente

2012-01-01

Background/Objective Recent research has shown an inverse relationship between bone marrow adipose tissue (BMAT) and bone mineral density (BMD). There is a lack of evidence at the macro-imaging level to establish whether increased BMAT is a cause or effect of bone loss. This cross-sectional study compared the BMAT and BMD relationship between a younger adult group at or approaching peak bone mass (PBM) (age 18.0-39.9 yrs) and an older group with potential bone loss (PoBL) (age 40.0-88 yrs). Subjects/Methods Pelvic BMAT was evaluated in 560 healthy men and women with T1-weighted whole body magnetic resonance imaging. BMD was measured using whole body dual-energy x-ray absorptiometry. Results An inverse correlation was observed between pelvic BMAT and pelvic, total, and spine BMD in the younger PBM group (r=-0.419 to -0.461, P<0.001) and in the older PoBL group (r=-0.405 to -0.500, P<0.001). After adjusting for age, sex, ethnicity, menopausal status, total body fat, skeletal muscle, subcutaneous and visceral adipose tissue, neither subject group (younger PBM vs. older PoBL) nor its interaction with pelvic BMAT significantly contributed to the regression models with BMD as dependent variable and pelvic BMAT as independent variable (P=0.434 to 0.928). Conclusion Our findings indicate that an inverse relationship between pelvic BMAT and BMD is present both in younger subjects who have not yet experienced bone loss and also in older subjects. These results provide support at the macro-imaging level for the hypothesis that low BMD may be a result of preferential differentiation of mesenchymal stem cells from osteoblasts to adipocytes. PMID:22491495

An update on childhood bone health: mineral accrual, assessment and treatment.

PubMed

Sopher, Aviva B; Fennoy, Ilene; Oberfield, Sharon E

2015-02-01

To update the reader's knowledge about the factors that influence bone mineral accrual and to review the advances in the assessment of bone health and treatment of bone disorders. Maternal vitamin D status influences neonatal calcium levels, bone mineral density (BMD) and bone size. In turn, BMD z-score tends to track in childhood. These factors highlight the importance of bone health as early as fetal life. Dual-energy x-ray absorptiometry is the mainstay of clinical bone health assessment in this population because of the availability of appropriate reference data. Recently, more information has become available about the assessment and treatment of bone disease in chronically ill pediatric patients. Bone health must become a health focus starting prenatally in order to maximize peak bone mass and to prevent osteoporosis-related bone disease in adulthood. Vitamin D, calcium and weight-bearing activity are the factors of key importance throughout childhood in achieving optimal bone health as BMD z-score tracks through childhood and into adulthood. Recent updates of the International Society for Clinical Densitometry focus on the appropriate use of dual-energy x-ray absorptiometry in children of all ages, including children with chronic disease, and on the treatment of pediatric bone disease.

Image analysis for dental bone quality assessment using CBCT imaging

NASA Astrophysics Data System (ADS)

Suprijanto; Epsilawati, L.; Hajarini, M. S.; Juliastuti, E.; Susanti, H.

2016-03-01

Cone beam computerized tomography (CBCT) is one of X-ray imaging modalities that are applied in dentistry. Its modality can visualize the oral region in 3D and in a high resolution. CBCT jaw image has potential information for the assessment of bone quality that often used for pre-operative implant planning. We propose comparison method based on normalized histogram (NH) on the region of inter-dental septum and premolar teeth. Furthermore, the NH characteristic from normal and abnormal bone condition are compared and analyzed. Four test parameters are proposed, i.e. the difference between teeth and bone average intensity (s), the ratio between bone and teeth average intensity (n) of NH, the difference between teeth and bone peak value (Δp) of NH, and the ratio between teeth and bone of NH range (r). The results showed that n, s, and Δp have potential to be the classification parameters of dental calcium density.

Very high serum ferritin levels are associated with increased mortality and critical care in pediatric patients.

PubMed

Bennett, Tellen D; Hayward, Kristen N; Farris, Reid W D; Ringold, Sarah; Wallace, Carol A; Brogan, Thomas V

2011-11-01

To determine whether an elevated serum ferritin level is independently associated with mortality and receipt of critical care in pediatric patients. Retrospective cohort study, open population. Seattle Children's Hospital, Seattle, WA, from September 2, 2003, to February 15, 2008. All patients tested for serum ferritin level from September 2, 2003, to August 16, 2007, with a level ≥1000 ng/mL. None. MAIN ANALYSIS: Cox regression. The predictor of interest was the patient-specific peak serum ferritin level, dichotomized a priori at 3000 ng/mL. The outcomes were mortality and intensive care unit admission. A total of 171 patients met the inclusion criteria. The observation time without death or intensive care unit admission ranged from 184 to 1621 days. The hazard ratio of death with peak ferritin of >3000 ng/mL was 4.32 (95% confidence interval 2.21-8.47, p < .001) compared to peak ferritin of 1000-3000 ng/mL. The hazard ratio of intensive care unit admission with peak ferritin of >3000 ng/mL was 2.49 (95% confidence interval 1.53-4.05, p < .001) compared to peak ferritin of 1000-3000 ng/mL. Both estimates were adjusted for bone marrow transplant, solid organ transplant, hemoglobinopathy, and existing rheumatologic disease. In this pediatric population, with serum ferritin levels of >3000 ng/mL, there was increased risk for both receipt of critical care and subsequent death.

Vitamin K3 increased BMD at 1 and 2 months post-surgery and the maximum stress of the middle femur in the rat.

PubMed

Hong, You-jia; Liu, Sheng; Jiang, Ning-yi; Jiang, Sen; Liang, Jiu-gen

2015-02-01

The therapeutic effects of vitamin K3 (VK3) on osteoporosis are still unknown. In this study, we hypothesized that VK3 possesses therapeutic effects on osteoporosis; to verify this hypothesis, the ovariectomized rat was used as an osteoporosis model. Fifty-six Sprague-Dawley female rats aged 8 to 9 months were randomly assigned to 4 groups: sham surgery, ovariectomy with saline, ovariectomy with low-dose VK3, and ovariectomy with high-dose VK3. Intramuscular injection of VK3 was performed every other day beginning 1 month postoperatively. The therapeutic effects of VK3 on osteoporosis were evaluated by measurement of bone mineral density (BMD), bone biochemical markers, biomechanical properties, and bone morphometric parameters. The overall average BMD in VK3-treated groups increased to a level between those of the ovariectomy group and the sham surgery group. The procollagen I N-terminal peptide level peaked at 2 months after surgery in all groups except in the group that had undergone ovariectomy with low-dose VK3. The tartrate-resistant acid phosphatase 5b level increased more slowly at 4 months after surgery than at 2 months after surgery in the VK3-treated groups. The ovariectomy with high-dose VK3 group had the highest maximum stress of the middle femur of all groups. With VK3 treatment, the trabecular bone area percentage increased. All morphometric indicators for the middle tibia in the VK3-treated groups reached the levels found in the sham surgery group. In summary, VK3 therapy increased BMD at 1 and 2 months postsurgery and the maximum stress of the middle femur. In addition, VK3 therapy slowed the increase in bone turnover in ovariectomized rats. Furthermore, VK3 can improve morphometric indicators for the middle tibia. Our preliminary study indicates that VK3 has a potential therapeutic effect on osteoporosis and is worthy of further investigation. Copyright © 2015 Elsevier Inc. All rights reserved.

Osteoblast-Specific Overexpression of Human WNT16 Increases Both Cortical and Trabecular Bone Mass and Structure in Mice

PubMed Central

Alkhouli, Mohammed; Gerard-O'Riley, Rita L.; Wright, Weston B.; Acton, Dena; Gray, Amie K.; Patel, Bhavmik; Reilly, Austin M.; Lim, Kyung-Eun; Robling, Alexander G.; Econs, Michael J.

2016-01-01

Previous genome-wide association studies have identified common variants in genes associated with bone mineral density (BMD) and risk of fracture. Recently, we identified single nucleotide polymorphisms (SNPs) in Wingless-type mouse mammary tumor virus integration site (WNT)16 that were associated with peak BMD in premenopausal women. To further identify the role of Wnt16 in bone mass regulation, we created transgenic (TG) mice overexpressing human WNT16 in osteoblasts. We compared bone phenotypes, serum biochemistry, gene expression, and dynamic bone histomorphometry between TG and wild-type (WT) mice. Compared with WT mice, WNT16-TG mice exhibited significantly higher whole-body areal BMD and bone mineral content (BMC) at 6 and 12 weeks of age in both male and female. Microcomputer tomography analysis of trabecular bone at distal femur revealed 3-fold (male) and 14-fold (female) higher bone volume/tissue volume (BV/TV), and significantly higher trabecular number and trabecular thickness but lower trabecular separation in TG mice compared with WT littermates in both sexes. The cortical bone at femur midshaft also displayed significantly greater bone area/total area and cortical thickness in the TG mice in both sexes. Serum biochemistry analysis showed that male TG mice had higher serum alkaline phosphatase, osteocalcin, osteoprotegerin (OPG), OPG to receptor activator of NF-kB ligand (tumor necrosis family ligand superfamily, number 11; RANKL) ratio as compared with WT mice. Also, lower carboxy-terminal collagen cross-link (CTX) to tartrate-resistant acid phosphatase 5, isoform b (TRAPc5b) ratio was observed in TG mice compared with WT littermates in both male and female. Histomorphometry data demonstrated that both male and female TG mice had significantly higher cortical and trabecular mineralizing surface/bone surface and bone formation rate compared with sex-matched WT mice. Gene expression analysis demonstrated higher expression of Alp, OC, Opg, and Opg to Rankl ratio in bone tissue in the TG mice compared with WT littermates. Our data indicate that WNT16 is critical for positive regulation of both cortical and trabecular bone mass and structure and that this molecule might be targeted for therapeutic interventions to treat osteoporosis. PMID:26584014

Exercise, Hormones, and Skeletal Adaptations During Childhood and Adolescence

PubMed Central

Farr, Joshua N.; Laddu, Deepika R.; Going, Scott B.

2015-01-01

Although primarily considered a disorder of the elderly, emerging evidence suggests the antecedents of osteoporosis are established during childhood and adolescence. A complex interplay of genetic, environmental, hormonal and behavioral factors determines skeletal development, and a greater effort is needed to identify the most critical factors that establish peak bone strength. Indeed, knowledge of modifiable factors that determine skeletal development may permit optimization of skeletal health during growth and could potentially offset reductions in bone strength with aging. The peripubertal years represent a unique period when the skeleton is particularly responsive to loading exercises, and there is now overwhelming evidence that exercise can optimize skeletal development. While this is not controversial, the most effective exercise prescription and how much investment in this prescription is needed to significantly impact bone health continues to be debated. Despite considerable progress, these issues are not easy to address, and important questions remain unresolved. This review focuses on the key determinants of skeletal development, whether exercise during childhood and adolescence should be advocated as a safe and effective strategy for optimizing peak bone strength, and whether investment in exercise early in life protects against the development of osteoporosis and fractures later in life. PMID:25372373

Influences of physical fitness on bone mass in women with fibromyalgia.

PubMed

Gómez-Cabello, Alba; Vicente-Rodríguez, Germán; Navarro-Vera, Isabel; Martinez-Redondo, Diana; Díez-Sánchez, Carmen; Casajús, José Antonio

2015-04-01

The aim of this study was to provide information about the relationship of bone mineral content (BMC) and density (BMD) with some physical-fitness-related variables in a sample of women with fibromyalgia (FM) and age-matched women without FM. Twenty-eight women clinically diagnosed with FM (age 51.1 ± 8.4 yr, M ± SD) and 22 age-matched controls participated in the study. Whole-body BMC and BMD, lean mass, handgrip strength, quadriceps strength, and cardiovascular fitness were measured in all participants. The association between physical-fitness variables and bone-related variables was tested by linear regression controlling for body weight as a possible confounder. There were no differences in BMC or BMD between groups. Women with FM had lower values of handgrip strength, quadriceps strength, and VO2peak than the control group. Handgrip strength and aerobic capacity were associated with BMC and BMD and quadriceps strength was associated with BMD in women with FM; however, only VO2peak was associated with BMC in the group of women without FM. Bone mass of women with FM may be more susceptible to changes in physical fitness than that of the women without fibromyalgia.

Do Bilateral Vertical Jumps With Reactive Jump Landings Achieve Osteogenic Thresholds With and Without Instruction in Premenopausal Women?

PubMed

Clissold, Tracey L; Winwood, Paul W; Cronin, John B; De Souza, Mary Jane

2018-04-01

Jumps have been investigated as a stimulus for bone development; however, effects of instruction, jump type, and jump-landing techniques need investigation. This study sought to identify whether ground reaction forces (GRFs) for bilateral vertical jumps (countermovement jumps and drop jumps) with reactive jump-landings (ie, jumping immediately after initial jump-landing), with instruction and with instruction withdrawn, achieve magnitudes and rates of strain previously shown to improve bone mass among premenopausal women. Twenty-one women (Mean ± SD: 43.3 ± 5.9 y; 69.4 ± 9.6 kg; 167 ± 5.5 cm; 27.5 ± 8.7% body fat) performed a testing session 'with instruction' followed by a testing session performed 1 week later with 'instruction withdrawn.' The magnitudes (4.59 to 5.49 body weight [BW]) and rates of strain (263 to 359 BW·s -1 ) for the jump-landings, performed on an AMTI force plate, exceeded previously determined thresholds (>3 BWs and >43 BW·s -1 ). Interestingly, significantly larger peak resultant forces, (↑10%; P = .002) and peak rates of force development (↑20%; P < .001) values (in relation to BW and BW·s -1 , respectively) were observed for the second jump-landing (postreactive jump). Small increases (ES = 0.22-0.42) in all landing forces were observed in the second jump-landing with 'instruction withdrawn.' These jumps represent a unique training stimulus for premenopausal women and achieve osteogenic thresholds thought prerequisite for bone growth.

Impaired skeletal growth in mice with haploinsufficiency of IGF-I: genetic evidence that differences in IGF-I expression could contribute to peak bone mineral density differences

PubMed Central

Mohan, S; Baylink, D J

2010-01-01

Although it is well established that there is considerable inter-individual variation in the circulating levels of IGF-I in normal, healthy individuals and that a genetic component contributes substantially to this variation, the direct evidence that inter-individual variation in IGF-I contributes to differences in peak bone mineral density (BMD) is lacking. To examine if differences in IGF-I expression could contribute to peak BMD differences, we measured skeletal changes at days 23 (prepubertal), 31 (pubertal) and 56 (postpubertal) in mice with haploinsufficiency of IGF-I (+/−) and corresponding control mice (+/+). Mice (MF1/DBA) heterozygous for the IGF-I knockout allele were bred to generate +/+ and +/− mice (n=18–20 per group). Serum IGF-I was decreased by 23% (P<0·001) in mice with IGF-I haploinsufficiency (+/−) group at day 56 compared with the control (+/+) group. Femoral bone mineral content and BMD, as determined by dual energy X-ray absorptiometry, were reduced by 20% (P<0·001) and 12% respectively in the IGF-I (+/−) group at day 56 compared with the control group. The peripheral quantitative computed tomography measurements at the femoral mid-diaphysis revealed that periosteal circumference (7%, P<0·01) and total volumetric BMD (5%, P<0·05) were decreased significantly in the +/− group compared with the +/+ group. Furthermore, serum IGF-I showed significant positive correlations with both areal BMD (r=0·55) and periosteal circumference (r=0·66) in the pooled data from the +/+ and +/− groups. Our findings that haploinsufficiency of IGF-I caused significant reductions in serum IGF-I level, BMD and bone size, together with the previous findings, are consistent with the notion that genetic variations in IGF-I expression could, in part, contribute to inter-individual differences in peak BMD among a normal population. PMID:15930167

Sequencing analysis of mutations induced by N-ethyl-N-nitrosourea at different sampling times in mouse bone marrow.

PubMed

Wang, Jianyong; Chen, Tao

2010-03-01

In our previous study (Wang et al., 2004, Toxicol. Sci. 82: 124-128), we observed that the cII gene mutant frequency (MF) in the bone marrow of Big Blue mice showed significant increase as early as day 1, reached the maximum at day 3 and then decreased to a plateau by day 15 after a single dose of carcinogen N-ethyl-N-nitrosourea (ENU) treatment, which is different from the longer mutation manifestation time and the constancy of MFs after reaching their maximum in some other tissues. To determine the mechanism underlying the quick increase in MF and the peak formation in the mutant manifestation, we examined the mutation frequencies and spectra of the ENU-induced mutants collected from different sampling times in this study. The cII mutants from days 1, 3 and 120 after ENU treatment were randomly selected from different animals. The mutation frequencies were 33, 217, 305 and 144 x 10(-6) for control, days 1, 3, and 120, respectively. The mutation spectra at days 1 and 3 were significantly different from that at day 120. Considering that stem cells are responsible for the ultimate MF plateau (day 120) and transit cells are accountable for the earlier MF induction (days 1 or 3) in mouse bone marrow, we conclude that transit cells are much more sensitive to mutation induction than stem cells in mouse bone marrow, which resulted in the specific mutation manifestation induced by ENU.

The measurement of intracranial pressure and brain displacement due to short-duration dynamic overpressure loading

NASA Astrophysics Data System (ADS)

Iwaskiw, A. S.; Ott, K. A.; Armiger, R. S.; Wickwire, A. C.; Alphonse, V. D.; Voo, L. M.; Carneal, C. M.; Merkle, A. C.

2018-01-01

The experimental measurement of biomechanical responses that correlate with blast-induced traumatic brain injury (bTBI) has proven challenging. These data are critical for both the development and validation of computational and physical head models, which are used to quantify the biomechanical response to blast as well as to assess fidelity of injury mitigation strategies, such as personal protective equipment. Therefore, foundational postmortem human surrogate (PMHS) experimental data capturing the biomechanical response are necessary for human model development. Prior studies have measured short-duration pressure transmission to the brain (Kinetic phase), but have failed to reproduce and measure the longer-duration inertial loading that can occur (Kinematic phase). Four fully instrumented PMHS were subjected to short-duration dynamic overpressure in front-facing and rear-facing orientations, where intracranial pressure (ICP), global head kinematics, and brain motion (as measured by high-speed X-ray) with respect to the skull were recorded. Peak ICP results generally increased with increased dose, and a mirrored pressure response was seen when comparing the polarity of frontal bone versus occipital bone ICP sensors. The head kinematics were delayed when compared to the pressure response and showed higher peak angles for front-facing tests as compared to rear-facing. Brain displacements were approximately 2-6 mm, and magnitudes did not change appreciably between front- and rear-facing tests. These data will be used to inform and validate models used to assess bTBI.

Effect of exercise on thicknesses of mature hyaline cartilage, calcified cartilage, and subchondral bone of equine tarsi.

PubMed

Tranquille, Carolyne A; Blunden, Antony S; Dyson, Sue J; Parkin, Tim D H; Goodship, Allen E; Murray, Rachel C

2009-12-01

OBJECTIVE-To investigate effects of exercise on hyaline cartilage (HC), calcified cartilage (CC), and subchondral bone (SCB) thickness patterns of equine tarsi. SAMPLE POPULATION-30 tarsi from cadavers of horses with known exercise history. PROCEDURES-Tarsi were assigned to 3 groups according to known exercise history as follows: pasture exercise only (PE tarsi), low-intensity general-purpose riding exercise (LE tarsi), and high-intensity elite competition riding exercise (EE tarsi). Osteochondral tissue from distal tarsal joints underwent histologic preparation. Hyaline cartilage, CC, and SCB thickness were measured at standard sites at medial, midline, and lateral locations across joints with a histomorphometric technique. RESULTS-HC, CC, and SCB thickness were significantly greater at all sites in EE tarsi, compared with PE tarsi; this was also true when LE tarsi were compared with PE tarsi. At specific sites, HC, CC, and SCB were significantly thicker in EE tarsi, compared with LE tarsi. Along the articular surface of the proximal aspect of the third metatarsal bone, SCB was thickest in EE tarsi and thinnest in LE tarsi; increases were greatest at sites previously reported to undergo peak strains and osteochondral damage. CONCLUSIONS AND CLINICAL RELEVANCE-Increased exercise was associated with increased HC, CC, and SCB thickness in mature horses. At sites that undergo high compressive strains, with a reported predisposition to osteoarthritic change, there was increased CC and SCB thickness. These results may provide insight into the interaction between adaptive response to exercise and pathological change.

The Contribution of Experimental in vivo Models to Understanding the Mechanisms of Adaptation to Mechanical Loading in Bone

PubMed Central

Meakin, Lee B.; Price, Joanna S.; Lanyon, Lance E.

2014-01-01

Changing loading regimens by natural means such as exercise, with or without interference such as osteotomy, has provided useful information on the structure:function relationship in bone tissue. However, the greatest precision in defining those aspects of the overall strain environment that influence modeling and remodeling behavior has been achieved by relating quantified changes in bone architecture to quantified changes in bones’ strain environment produced by direct, controlled artificial bone loading. Jiri Hert introduced the technique of artificial loading of bones in vivo with external devices in the 1960s using an electromechanical device to load rabbit tibiae through transfixing stainless steel pins. Quantifying natural bone strains during locomotion by attaching electrical resistance strain gages to bone surfaces was introduced by Lanyon, also in the 1960s. These studies in a variety of bones in a number of species demonstrated remarkable uniformity in the peak strains and maximum strain rates experienced. Experiments combining strain gage instrumentation with artificial loading in sheep, pigs, roosters, turkeys, rats, and mice has yielded significant insight into the control of strain-related adaptive (re)modeling. This diversity of approach has been largely superseded by non-invasive transcutaneous loading in rats and mice, which is now the model of choice for many studies. Together such studies have demonstrated that over the physiological strain range, bone’s mechanically adaptive processes are responsive to dynamic but not static strains; the size and nature of the adaptive response controlling bone mass is linearly related to the peak loads encountered; the strain-related response is preferentially sensitive to high strain rates and unresponsive to static ones; is most responsive to unusual strain distributions; is maximized by remarkably few strain cycles, and that these are most effective when interrupted by short periods of rest between them. PMID:25324829

A method for continuous monitoring of the Ground Reaction Force during daily activity

NASA Technical Reports Server (NTRS)

Whalen, Robert; Quintana, Jason; Emery, Jeff

1993-01-01

Theoretical models and experimental studies of bone remodeling have identified peak cyclic force levels (or cyclic tissue strain energy density), number of daily loading cycles, and load (strain) rate as possible contributors to bone modeling and remodeling stimulus. To test our theoretical model and further investigate the influence of mechanical forces on bone density, we have focused on the calcaneus as a model site loaded by calcaneal surface tractions which are predominantly determined by the magnitude of the external ground reaction force (GRF).

A two-year program of aerobics and weight training enhances bone mineral density of young women.

PubMed

Friedlander, A L; Genant, H K; Sadowsky, S; Byl, N N; Glüer, C C

1995-04-01

Previous research suggests that physical activity may have a beneficial effect on bone mineral density (BMD) in women. This relationship was explored in a 2-year, randomized, intervention trial investigating the efficacy of exercise and calcium supplementation on increasing peak bone mass in young women. One hundred and twenty-seven subjects (ages of 20-35 years) were randomly assigned either to an exercise program that contained both aerobics and weight training components or to a stretching program. Calcium supplementation (up to 1500 mg/day including dietary intake) or placebo was given in a double-blinded design to all subjects. Spinal trabecular BMD was determined using quantitative computed tomography (QCT). Spinal integral, femoral neck, and trochanteric BMD were measured by dual X-ray absorptiometry (DXA) and calcaneal BMD by single photon absorptiometry (SPA). Fitness variables included maximal aerobic capacity (VO2max), and isokinetic muscle performance of the trunk and thigh. Measurements were made at baseline, 1 year, and 2 years. Sixty-three subjects (32 exercise, 31 stretching) completed the study, and all the measured bone parameters indicated a positive influence of the exercise intervention. There were significant positive differences in BMD between the exercise and stretching groups for spinal trabecular (2.5%), femoral neck (2.4%), femoral trochanteric (2.3%), and calcaneal (6.4%) measurements. The exercise group demonstrated a significant gain in BMD for spinal integral (1.3 +/- 2.8%, p < 0.02), femoral trochanteric (2.6 +/- 6.1%, p < 0.05), and calcaneal (5.6 +/- 5.1, p < 0.01) measurements. In contrast to exercise, the calcium intervention had no positive effect on any of the bone parameters. In regard to fitness parameters, the exercise group completed the study with significant gains in VO2max and isokinetic (peak torque) values for the knee flexion and extension and trunk extension. This study indicates that over a 2-year period, a combined regimen of aerobics and weight training has beneficial effects on BMD and fitness parameters in young women. However, the addition of daily calcium supplementation does not add significant benefit to the intervention.

A two-year program of aerobics and weight training enhances bone mineral density of young women

NASA Technical Reports Server (NTRS)

Friedlander, A. L.; Genant, H. K.; Sadowsky, S.; Byl, N. N.; Gluer, C. C.

1995-01-01

Previous research suggests that physical activity may have a beneficial effect on bone mineral density (BMD) in women. This relationship was explored in a 2-year, randomized, intervention trial investigating the efficacy of exercise and calcium supplementation on increasing peak bone mass in young women. One hundred and twenty-seven subjects (ages of 20-35 years) were randomly assigned either to an exercise program that contained both aerobics and weight training components or to a stretching program. Calcium supplementation (up to 1500 mg/day including dietary intake) or placebo was given in a double-blinded design to all subjects. Spinal trabecular BMD was determined using quantitative computed tomography (QCT). Spinal integral, femoral neck, and trochanteric BMD were measured by dual X-ray absorptiometry (DXA) and calcaneal BMD by single photon absorptiometry (SPA). Fitness variables included maximal aerobic capacity (VO2max), and isokinetic muscle performance of the trunk and thigh. Measurements were made at baseline, 1 year, and 2 years. Sixty-three subjects (32 exercise, 31 stretching) completed the study, and all the measured bone parameters indicated a positive influence of the exercise intervention. There were significant positive differences in BMD between the exercise and stretching groups for spinal trabecular (2.5%), femoral neck (2.4%), femoral trochanteric (2.3%), and calcaneal (6.4%) measurements. The exercise group demonstrated a significant gain in BMD for spinal integral (1.3 +/- 2.8%, p < 0.02), femoral trochanteric (2.6 +/- 6.1%, p < 0.05), and calcaneal (5.6 +/- 5.1, p < 0.01) measurements. In contrast to exercise, the calcium intervention had no positive effect on any of the bone parameters. In regard to fitness parameters, the exercise group completed the study with significant gains in VO2max and isokinetic (peak torque) values for the knee flexion and extension and trunk extension. This study indicates that over a 2-year period, a combined regimen of aerobics and weight training has beneficial effects on BMD and fitness parameters in young women. However, the addition of daily calcium supplementation does not add significant benefit to the intervention.

Vitamin D in adolescents: Are current recommendations enough?

PubMed

Smith, Taryn J; Lanham-New, Susan A; Hart, Kathryn H

2017-10-01

Vitamin D is essential for bone development during adolescence and low vitamin D status during this critical period of growth may impact bone mineralization, potentially reducing peak bone mass and consequently increasing the risk of osteoporosis in adulthood. Therefore, the high prevalence of vitamin D inadequacy and deficiency in adolescent populations is of great concern. However, there is currently a lack of consensus on the 25-hydroxyvitamin D [25(OH)D] concentration, the widely accepted biomarker of vitamin D status, that defines adequacy, and the vitamin D intake requirements to maintain various 25(OH)D thresholds are not well established. While the current intake recommendations of 10-15μg/day may be sufficient to prevent vitamin D deficiency (25(OH)D<25-30nmol/l), greater intakes may be needed to achieve the higher threshold levels proposed to represent adequacy (25(OH)D>50nmol/l). This review will address these concerns and consider if the current dietary recommendations for vitamin D in adolescents are sufficient. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Synchrotron Ultraviolet Microspectroscopy on Rat Cortical Bone: Involvement of Tyrosine and Tryptophan in the Osteocyte and Its Environment

PubMed Central

Pallu, Stéphane; Rochefort, Gael Y.; Jaffre, Christelle; Refregiers, Matthieu; Maurel, Delphine B.; Benaitreau, Delphine; Lespessailles, Eric; Jamme, Frédéric; Chappard, Christine; Benhamou, Claude-Laurent

2012-01-01

Alcohol induced osteoporosis is characterized by a bone mass decrease and microarchitecture alterations. Having observed an excess in osteocyte apoptosis, we aimed to assess the bone tissue biochemistry, particularly in the osteocyte and its environment. For this purpose, we used a model of alcohol induced osteoporosis in rats. Bone sections of cortical bone were investigated using synchrotron UV-microspectrofluorescence at subcellular resolution. We show that bone present three fluorescence peaks at 305, 333 and 385 nm, respectively corresponding to tyrosine, tryptophan and collagen. We have determined that tyrosine/collagen and tryptophan/collagen ratios were higher in the strong alcohol consumption group. Tryptophan is related to the serotonin metabolism involved in bone formation, while tyrosine is involved in the activity of tyrosine kinases and phosphatases in osteocytes. Our experiment represents the first combined synchrotron UV microspectroscopy analysis of bone tissue with a quantitative biochemical characterization in the osteocyte and surrounding matrix performed separately. PMID:22937127

Conversion of glycerol to polyglycerol over waste duck-bones as a catalyst in solvent free etherification process

NASA Astrophysics Data System (ADS)

Ayoub, Muhammad; Sufian, Suriati; Mekuria Hailegiorgis, Sintayehu; Ullah, Sami; Uemura, Yoshimitsu

2017-08-01

The alkaline catalyst derived from the duck-bones was used for conversion of glycerol to polyglycerol via solvent free etherification process. The physicochemical properties of prepared materials were duck-bones were systematically investigated as a catalyst by latest techniques of Thermo gravimetric analysis (TGA), X-ray diffraction (XRD), and Brunauer-Emmett-Teller (BET) surface properties. TGA showed different trends of duck-bones decomposition from room temperature to 1000C. XRD pattern showed a clear and sharp peaks of a crystalline phase of CaO. The activity of the catalysts was in line with the basic amount of the strong base sites, surface area, and crystalline phase in the catalysts. The prepared catalyst derived from duck-bones provided high activity (99 %) for glycerol conversion and around 68 % yield for polyglycerol production. These ample wastes of duck-bones have good potential to be used as polyglycerol production catalysts due to have high quantity of Ca compare to other types of bones like cow, chicken and fish bones.

Vanishing testes syndrome-related osteoporosis and high cardio-metabolic risk in an adult male with long term untreated hypergonadotropic hypogonadism.

PubMed

Carsote, Mara; Capatina, Cristina; Valea, Ana; Dumitrascu, Anda

2016-02-01

The male hypogonadism-related bone mass loss is often under diagnosed. Peak bone mass is severely affected if the hypogonadism occurs during puberty and is left untreated. We present an interesting; almost bizarre case of a male with non-functional testes early during childhood and undiagnosed and untreated hypogonadism until his fifth decade of life. Forty six year male is referred for goitre, complaining of back pain. Phenotype suggested intersexuality: gynoid proportions, micropenis, no palpable testes into the scrotum, no facial or truncal hair. His medical history had been unremarkable until the previous year when primary hypothyroidism was diagnosed and levothyroxine replacement was initiated. Later, he was diagnosed with ischemic heart disease, with inaugural unstable angina. On admission, the testosterone was 0.2 ng/mL (normal: 1.7-7.8 ng/mL), FSH markedly increased (56 mUI/mL), with normal adrenal axis, and TSH (under thyroxine replacement). High bone turnover markers, and blood cholesterol, and impaired glucose tolerance were diagnosed. The testes were not present in the scrotum. Abdominal computed tomography suggested bilateral masses of 1.6 cm diameter within the abdominal fat that were removed but no gonadal tissue was confirmed histopathologically. Vanishing testes syndrome was confirmed. The central DXA showed lumbar bone mineral density of 0.905 g/cm2, Z-score of -2.9SD. The spine profile X-Ray revealed multiple thoracic vertebral fractures. Alendronate therapy together with vitamin D and calcium supplements and trans-dermal testosterone were started. Four decades of hypogonadism associate increased cardiac risk, as well as decreased bone mass and high fracture risk.

Reversing resistance to vascular-disrupting agents by blocking late mobilization of circulating endothelial progenitor cells.

PubMed

Taylor, Melissa; Billiot, Fanny; Marty, Virginie; Rouffiac, Valérie; Cohen, Patrick; Tournay, Elodie; Opolon, Paule; Louache, Fawzia; Vassal, Gilles; Laplace-Builhé, Corinne; Vielh, Philippe; Soria, Jean-Charles; Farace, Françoise

2012-05-01

The prevailing concept is that immediate mobilization of bone marrow-derived circulating endothelial progenitor cells (CEP) is a key mechanism mediating tumor resistance to vascular-disrupting agents (VDA). Here, we show that administration of VDA to tumor-bearing mice induces 2 distinct peaks in CEPs: an early, unspecific CEP efflux followed by a late yet more dramatic tumor-specific CEP burst that infiltrates tumors and is recruited to vessels. Combination with antiangiogenic drugs could not disrupt the early peak but completely abrogated the late VDA-induced CEP burst, blunted bone marrow-derived cell recruitment to tumors, and resulted in striking antitumor efficacy, indicating that the late CEP burst might be crucial to tumor recovery after VDA therapy. CEP and circulating endothelial cell kinetics in VDA-treated patients with cancer were remarkably consistent with our preclinical data. These findings expand the current understanding of vasculogenic "rebounds" that may be targeted to improve VDA-based strategies. Our findings suggest that resistance to VDA therapy may be strongly mediated by late, rather than early, tumor-specific recruitment of CEPs, the suppression of which resulted in increased VDA-mediated antitumor efficacy. VDA-based therapy might thus be significantly enhanced by combination strategies targeting late CEP mobilization. © 2012 AACR

LRP5 coding polymorphisms influence the variation of peak bone mass in a normal population of French-Canadian women.

PubMed

Giroux, Sylvie; Elfassihi, Latifa; Cardinal, Guy; Laflamme, Nathalie; Rousseau, François

2007-05-01

Bone mineral density has a strong genetic component but it is also influenced by environmental factors making it a complex trait to study. LRP5 gene was previously shown to be involved in rare diseases affecting bone mass. Mutations associated with gain-of-function were described as well as loss-of-function mutations. Following this discovery, many frequent LRP5 polymorphisms were tested against the variation of BMD in the normal population. Heel bone parameters (SOS, BUA) were measured by right calcaneal QUS in 5021 healthy French-Canadian women and for 2104 women, BMD evaluated by DXA at two sites was available (femoral neck (FN) and lumbar spine (LS)). Among women with QUS measures and those with DXA measures, 26.5% and 32.8% respectively were premenopausal, 9.2% and 10.7% were perimenopausal and 64.2% and 56.5% were postmenopausal. About a third of the peri- and postmenopausal women never received hormone therapy. Two single nucleotide coding polymorphisms (Val667Met and Ala1330Val) in LRP5 gene were genotyped by allele-specific PCR. All bone measures were tested individually for associations with each polymorphism by analysis of covariance with adjustment for non genetic risk factors. Furthermore, haplotype analysis was performed to take into account the strong linkage disequilibrium between the two polymorphisms. The two LRP5 polymorphisms were found to be associated with all five bone measures (L2L4 and femoral neck DXA as well as heel SOS, BUA and stiffness index) in the whole sample. Premenopausal women drove the association as expected from the proposed role of LRP5 in peak bone mass. Our results suggest that the Val667Met polymorphism is the causative variant but this remains to be functionally proven.

Control of bone remodelling by applied dynamic loads

NASA Technical Reports Server (NTRS)

Lanyon, L. E.; Rubin, C. T.

1984-01-01

The data showing the relationship between bone mass and peak strain magnitude prepared and submitted for publication. The data from experiments relating remodelling activity with static or dynamic loads were prepared and submitted for publication. Development of programs to relate the location of remodelling activity with he natural and artificial dynamic strain distributions continued. Experiments on the effect of different strain rates on the remodelling response continued.

Current and potential future drug treatments for osteoporosis.

PubMed Central

Patel, S

1996-01-01

There has been a major interest in the drug treatment of osteoporosis and an increase in the number of drugs available in most countries. The ideal drug (one which increases or restores bone density and trabecular connectivity) is still not available. However, in patients with relatively preserved trabecular connectivity and moderately reduced bone density, several agents have shown substantial clinical benefit. Oestrogens are still the mainstay of drug treatment, but the risks of breast cancer versus the cardiovascular and skeletal benefits with long term use have to be assessed in the individual. Newer tissue specific oestrogens show some promise in this respect. The bisphosphonates and possibly fluoride are likely to be the major alternatives to oestrogens in the medium term. The newer bisphosphonates, alendronate and in the future risedronate, are likely to supersede etidronate. Calcitriol probably has a limited role, confined to those patients in whom HRT or bisphosphonates are not appropriate. Calcium supplementation, or an increase in dietary intake if deficient, irrespective of which agent is used, is also of benefit. In older patients there is considerable support for using a combination of calcium and vitamin D. Whether combination treatment, for example oestrogens, bisphosphonates, and calcium together, will result in greater efficacy remains to be conclusively shown, but may be an attractive option in younger patients with higher bone turnover. Apart from fluoride, bone formation stimulators are unlikely to have a major role until the next century, although it may be possible to use growth factors as part of an ADFR regimen (A = activate remodelling, D = depress resorption, F = free formation, and R = repeat). This is still an important theoretical approach and needs further work with newer agents to see if increased efficacy can be found. In addition sequential treatment may be necessary in view of the limited time periods over which particular agents, such as intermittent fluoride (four years), have been examined, and this will have to be individually tailored. Other approaches include trying to increase peak bone mineral density, although influencing the young to prevent a disease that may not manifest itself for half a century is daunting. PMID:8984934

A Wolff in sheep's clothing: trabecular bone adaptation in response to changes in joint loading orientation.

PubMed

Barak, Meir M; Lieberman, Daniel E; Hublin, Jean-Jacques

2011-12-01

This study tests Wolff's law of trabecular bone adaptation by examining if induced changes in joint loading orientation cause corresponding adjustments in trabecular orientation. Two groups of sheep were exercised at a trot, 15 min/day for 34 days on an inclined (7°) or level (0°) treadmills. Incline trotting caused the sheep to extend their tarsal joints by 3-4.5° during peak loading (P<0.01) but has no effect on carpal joint angle (P=0.984). Additionally, tarsal joint angle in the incline group sheep were maintained more extended throughout the day using elevated platform shoes on their forelimbs. A third "sedentary group" group did not run but wore platform shoes throughout the day. As predicted by Wolff's law, trabecular orientation in the distal tibia (tarsal joint) were more obtuse by 2.7 to 4.3° in the incline group compared to the level group; trabecular orientation was not significantly different in the sedentary and level groups. In addition, trabecular orientations in the distal radius (carpal joint) of the sedentary, level and incline groups did not differ between groups, and were aligned almost parallel to the radius long axis, corresponding to the almost straight carpal joint angle at peak loading. Measurements of other trabecular bone parameters revealed additional responses to loading, including significantly higher bone volume fraction (BV/TV), Trabecular number (Tb.N) and trabecular thickness (Tb.Th), lower trabecular spacing (Tb.Sp), and less rod-shaped trabeculae (higher structure model index, SMI) in the exercised than sedentary sheep. Overall, these results demonstrate that trabecular bone dynamically adjusts and realigns itself in very precise relation to changes in peak loading direction, indicating that Wolff's law is not only accurate but also highly sensitive. Copyright © 2011 Elsevier Inc. All rights reserved.

Monte Carlo investigation of backscatter point spread function for x-ray imaging examinations

NASA Astrophysics Data System (ADS)

Xiong, Zhenyu; Vijayan, Sarath; Rudin, Stephen; Bednarek, Daniel R.

2017-03-01

X-ray imaging examinations, especially complex interventions, may result in relatively high doses to the patient's skin inducing skin injuries. A method was developed to determine the skin-dose distribution for non-uniform x-ray beams by convolving the backscatter point-spread-function (PSF) with the primary-dose distribution to generate the backscatter distribution that, when added to the primary dose, gives the total-dose distribution. This technique was incorporated in the dose-tracking system (DTS), which provides a real-time color-coded 3D-mapping of skin dose during fluoroscopic procedures. The aim of this work is to investigate the variation of the backscatter PSF with different parameters. A backscatter PSF of a 1-mm x-ray beam was generated by EGSnrc Monte-Carlo code for different x-ray beam energies, different soft-tissue thickness above bone, different bone thickness and different entrance-beam angles, as well as for different locations on the SK-150 anthropomorphic head phantom. The results show a reduction of the peak scatter to primary dose ratio of 48% when X-ray beam voltage is increased from 40 keV to 120 keV. The backscatter dose was reduced when bone was beneath the soft tissue layer and this reduction increased with thinner soft tissue and thicker bone layers. The backscatter factor increased about 21% as the angle of incidence of the beam with the entrance surface decreased from 90° (perpendicular) to 30°. The backscatter PSF differed for different locations on the SK-150 phantom by up to 15%. The results of this study can be used to improve the accuracy of dose calculation when using PSF convolution in the DTS.

Antidepressant medications and osteoporosis.

PubMed

Rizzoli, R; Cooper, C; Reginster, J-Y; Abrahamsen, B; Adachi, J D; Brandi, M L; Bruyère, O; Compston, J; Ducy, P; Ferrari, S; Harvey, N C; Kanis, J A; Karsenty, G; Laslop, A; Rabenda, V; Vestergaard, P

2012-09-01

Use of antidepressant medications that act on the serotonin system has been linked to detrimental impacts on bone mineral density (BMD), and to osteoporosis. This article reviews current evidence for such effects, and identifies themes for future research. Serotonin receptors are found in all major types of bone cell (osteoblasts, osteocytes, and osteoclasts), indicating an important role of the neuroendocrine system in bone. Observational studies indicate a complex relationship between depression, antidepressants, and fracture. First, the presence of depression itself increases fracture risk, in relation with decreased BMD and an increase in falls. A range of aspects of depression may operate, including behavioral factors (e.g., smoking and nutrition), biological changes, and confounders (e.g., comorbidities and concomitant medications). A substantial proportion of depressed patients receive antidepressants, mostly selective serotonin reuptake inhibitors (SSRIs). Some of these have been linked to decreased BMD (SSRIs) and increased fracture risk (SSRIs and tricyclic agents). Current use of SSRIs and tricyclics increases fracture risk by as much as twofold versus nonusers, even after adjustment for potential confounders. While there is a dose-response relationship for SSRIs, the effect does not appear to be homogeneous across the whole class of drugs and may be linked to affinity for the serotonin transporter system. The increase in risk is the greatest in the early stages of treatment, with a dramatic increase after initiation, reaching a peak within 1 month for tricyclics and 8 months for SSRIs. Treatment-associated increased risk diminishes towards baseline in the year following discontinuation. The body of evidence suggests that SSRIs should be considered in the list of medications that are risk factors for osteoporotic fractures. Copyright © 2012 Elsevier Inc. All rights reserved.

Raman study of the repair of surgical bone defects grafted with biphasic synthetic microgranular HA + β-calcium triphosphate and irradiated or not with λ780 nm laser.

PubMed

Soares, Luiz Guilherme P; Marques, Aparecida Maria C; Barbosa, Artur Felipe S; Santos, Nicole R; Aciole, Jouber Mateus S; Souza, Caroline Mathias C; Pinheiro, Antonio Luiz B; Silveira, Landulfo

2014-09-01

The treatment of bone loss due to different etiologic factors is difficult, and many techniques aim to improve repair, including a wide range of biomaterials and, recently, photobioengineering. This work aimed to assess, through Raman spectroscopy, the level of bone mineralization using the intensities of the Raman peaks of both inorganic (∼ 960, ∼ 1,070, and ∼ 1,077 cm(-1)) and organic (∼ 1,454 and ∼ 1,666 cm(-1)) contents of bone tissue. Forty rats were divided into four groups each subdivided into two subgroups according to the time of killing (15 and 30 days). Surgical bone defects were made on femur of each animal with a trephine drill. On animals of group Clot, the defect was filled only by blood clot; on group Laser, the defect filled with the clot was further irradiated. On animals of groups Biomaterial and Laser + Biomaterial, the defect was filled by biomaterial and the last one was further irradiated (λ780 nm, 70 mW, Φ ∼ 0.4 cm(2), 20 J/cm(2) session, 140 J/cm(2) treatment) in four points around the defect at 48-h intervals and repeated for 2 weeks. At both 15th and 30th day following killing, samples were taken and analyzed by Raman spectroscopy. At the end of the experimental time, the intensities of both inorganic and organic contents were higher on group Laser + Biomaterial. It is concluded that the use of laser phototherapy associated to biomaterial was effective in improving bone healing on bone defects as a result of the increasing deposition of calcium hydroxyapatite measured by Raman spectroscopy.

Prevalence and Risk Factors of Osteoporosis in Women Referring to the Bone Densitometry Academic Center in Urmia, Iran

PubMed Central

Naz, Marzieh Saei Ghare; Ozgoli, Giti; Aghdashi, Mir Amir; Salmani, Fatemeh

2016-01-01

Background: Osteoporosis is one of the fastest growing health problems around the world. Several factors can affect this silent disease. The current study aimed to determine the prevalence and risk factors of osteoporosis in women in Urmia, a city in northwestern Iran. Methods: This cross-sectional study was performed on 360 non-pregnant women over the age of 15 who referred for bone density testing to the Urmia Imam Khomeini Academic Hospital. Data were collected by questionnaire, and bone mineral density of the femoral neck and lumbar spines L1- L4 was evaluated by dual X-ray absorptiometry. Results: The total prevalence of osteoporosis in this study was 42.2%; prevalence of osteoporosis among women 45 years old or less was 14.3% and over the age of 45 years was 50.7%. The factors such as level of education, history of bone fracture, disease history (rheumatoid arthritis, diabetes, high blood pressure), gravidity and parity values, duration of lactation (p<0.001), nutrition dimension of lifestyle (p=0.03), and green tea consumption (p=002) showed a statistically significant association with the bone mineral density. According to the regression model, age (OR=1.081), history of bone fracture (OR=2.75), and gravidity (OR=1.14) were identified as significant risk factors for osteoporosis, while the body mass index (OR=0.94) was identified as a protector against osteoporosis. Conclusion: The prevalence of osteoporosis in this study was high, and findings showed that the advancement of age, lifestyle, and reproductive factors (especially gravidity and duration of lactation) were determining factors for osteoporosis. Appropriate educational programs and interventions could help to increase the women’s peak bone mass therefore reducing their risk of developing osteoporosis. PMID:26925890

Bone Health in Adolescent Athletes with a Focus on Female Athlete Triad

PubMed Central

Ackerman, Kathryn E.; Misra, Madhusmita

2013-01-01

Peak bone mass (PBM) is a negative predictor of osteoporosis and life-long fracture risk. Because osteoporosis is such a prevalent disease with life-threatening consequences later in life, it is important to try to maximize PBM. Adolescence is a critical time for bone acquisition. This review discusses some of the differences in male and female skeletal development and modifiable factors that enhance bone accrual in this age group, particularly in athletes. Hormonal influences, physical activity effects, and nutritional contributions are presented, with a focus on the adolescent athlete. Emphasis is placed on the importance of appropriate energy availability in this age group. The Female Athlete Triad (the inter-relationship of decreased energy availability, menstrual irregularity, and low bone density) is an important issue for adolescent, athletic women, and is therefore reviewed, including prevention and treatment strategies. Recommendations for maximizing bone density in both male and female adolescents are discussed. PMID:21378496

Os incae: variation in frequency in major human population groups

PubMed Central

HANIHARA, TSUNEHIKO; ISHIDA, HAJIME

2001-01-01

The variation in frequency of the Inca bone was examined in major human populations around the world. The New World populations have generally high frequencies of the Inca bone, whereas lower frequencies occur in northeast Asians and Australians. Tibetan/Nepalese and Assam/Sikkim populations in northeast India have more Inca bones than do neighbouring populations. Among modern populations originally derived from eastern Asian population stock, the frequencies are highest in some of the marginal isolated groups. In Central and West Asia as well as in Europe, frequency of the Inca bone is relatively low. The incidence of the complete Inca bone is, moreover, very low in the western hemisphere of the Old World except for Subsaharan Africa. Subsaharan Africans show as a whole a second peak in the occurrence of the Inca bone. Geographical and ethnographical patterns of the frequency variation of the Inca bone found in this study indicate that the possible genetic background for the occurrence of this bone cannot be completely excluded. Relatively high frequencies of the Inca bone in Subsaharan Africans indicate that this trait is not a uniquely eastern Asian regional character. PMID:11273039

Marrow Adipose Tissue Expansion Coincides with Insulin Resistance in MAGP1-Deficient Mice

PubMed Central

Walji, Tezin A.; Turecamo, Sarah E.; Sanchez, Alejandro Coca; Anthony, Bryan A.; Abou-Ezzi, Grazia; Scheller, Erica L.; Link, Daniel C.; Mecham, Robert P.; Craft, Clarissa S.

2016-01-01

Marrow adipose tissue (MAT) is an endocrine organ with the potential to influence skeletal remodeling and hematopoiesis. Pathologic MAT expansion has been studied in the context of severe metabolic challenge, including caloric restriction, high fat diet feeding, and leptin deficiency. However, the rapid change in peripheral fat and glucose metabolism associated with these models impedes our ability to examine which metabolic parameters precede or coincide with MAT expansion. Microfibril-associated glycoprotein-1 (MAGP1) is a matricellular protein that influences cellular processes by tethering signaling molecules to extracellular matrix structures. MAGP1-deficient (Mfap2−/−) mice display a progressive excess adiposity phenotype, which precedes insulin resistance and occurs without changes in caloric intake or ambulation. Mfap2−/− mice were, therefore, used as a model to associate parameters of metabolic disease, bone remodeling, and hematopoiesis with MAT expansion. Marrow adiposity was normal in Mfap2−/− mice until 6 months of age; however, by 10 months, marrow fat volume had increased fivefold relative to wild-type control at the same age. Increased gonadal fat pad mass and hyperglycemia were detectable in Mfap2−/− mice by 2 months, but peaked by 6 months. The development of insulin resistance coincided with MAT expansion. Longitudinal characterization of bone mass demonstrated a disconnection in MAT volume and bone volume. Specifically, Mfap2−/− mice had reduced trabecular bone volume by 2 months, but this phenotype did not progress with age or MAT expansion. Interestingly, MAT expansion in the 10-month-old Mfap2−/− mice was associated with modest alterations in basal hematopoiesis, including a shift from granulopoiesis to B lymphopoiesis. Together, these findings indicate MAT expansion is coincident with insulin resistance, but not excess peripheral adiposity or hyperglycemia in Mfap2−/− mice; and substantial MAT accumulation does not necessitate a proportional decrease in either bone mass or bone marrow cellularity. PMID:27445989

Bioenergetics during calvarial osteoblast differentiation reflect strain differences in bone mass.

PubMed

Guntur, Anyonya R; Le, Phuong T; Farber, Charles R; Rosen, Clifford J

2014-05-01

Osteoblastogenesis is the process by which mesenchymal stem cells differentiate into osteoblasts that synthesize collagen and mineralize matrix. The pace and magnitude of this process are determined by multiple genetic and environmental factors. Two inbred strains of mice, C3H/HeJ and C57BL/6J, exhibit differences in peak bone mass and bone formation. Although all the heritable factors that differ between these strains have not been elucidated, a recent F1 hybrid expression panel (C3H × B6) revealed major genotypic differences in osteoblastic genes related to cellular respiration and oxidative phosphorylation. Thus, we hypothesized that the metabolic rate of energy utilization by osteoblasts differed by strain and would ultimately contribute to differences in bone formation. In order to study the bioenergetic profile of osteoblasts, we measured oxygen consumption rates (OCR) and extracellular acidification rates (ECAR) first in a preosteoblastic cell line MC3T3-E1C4 and subsequently in primary calvarial osteoblasts from C3H and B6 mice at days 7, 14, and 21 of differentiation. During osteoblast differentiation in media containing ascorbic acid and β-glycerophosphate, all 3 cell types increased their oxygen consumption and extracellular acidification rates compared with the same cells grown in regular media. These increases are sustained throughout differentiation. Importantly, C3H calvarial osteoblasts had greater oxygen consumption rates than B6 consistent with their in vivo phenotype of higher bone formation. Interestingly, osteoblasts utilized both oxidative phosphorylation and glycolysis during the differentiation process although mature osteoblasts were more dependent on glycolysis at the 21-day time point than oxidative phosphorylation. Thus, determinants of oxygen consumption reflect strain differences in bone mass and provide the first evidence that during collagen synthesis osteoblasts use both glycolysis and oxidative phosphorylation to synthesize and mineralize matrix.

Bioenergetics During Calvarial Osteoblast Differentiation Reflect Strain Differences in Bone Mass

PubMed Central

Le, Phuong T.; Farber, Charles R.; Rosen, Clifford J.

2014-01-01

Osteoblastogenesis is the process by which mesenchymal stem cells differentiate into osteoblasts that synthesize collagen and mineralize matrix. The pace and magnitude of this process are determined by multiple genetic and environmental factors. Two inbred strains of mice, C3H/HeJ and C57BL/6J, exhibit differences in peak bone mass and bone formation. Although all the heritable factors that differ between these strains have not been elucidated, a recent F1 hybrid expression panel (C3H × B6) revealed major genotypic differences in osteoblastic genes related to cellular respiration and oxidative phosphorylation. Thus, we hypothesized that the metabolic rate of energy utilization by osteoblasts differed by strain and would ultimately contribute to differences in bone formation. In order to study the bioenergetic profile of osteoblasts, we measured oxygen consumption rates (OCR) and extracellular acidification rates (ECAR) first in a preosteoblastic cell line MC3T3-E1C4 and subsequently in primary calvarial osteoblasts from C3H and B6 mice at days 7, 14, and 21 of differentiation. During osteoblast differentiation in media containing ascorbic acid and β-glycerophosphate, all 3 cell types increased their oxygen consumption and extracellular acidification rates compared with the same cells grown in regular media. These increases are sustained throughout differentiation. Importantly, C3H calvarial osteoblasts had greater oxygen consumption rates than B6 consistent with their in vivo phenotype of higher bone formation. Interestingly, osteoblasts utilized both oxidative phosphorylation and glycolysis during the differentiation process although mature osteoblasts were more dependent on glycolysis at the 21-day time point than oxidative phosphorylation. Thus, determinants of oxygen consumption reflect strain differences in bone mass and provide the first evidence that during collagen synthesis osteoblasts use both glycolysis and oxidative phosphorylation to synthesize and mineralize matrix. PMID:24437492

Molecular changes in articular cartilage and subchondral bone in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis.

PubMed

Pickarski, Maureen; Hayami, Tadashi; Zhuo, Ya; Duong, Le T

2011-08-24

Osteoarthritis (OA) is a debilitating, progressive joint disease. Similar to the disease progression in humans, sequential events of early cartilage degradation, subchondral osteopenia followed by sclerosis, and late osteophyte formation were demonstrated in the anterior cruciate ligament transection (ACLT) or ACLT with partial medial meniscectomy (ACLT + MMx) rat OA models. We describe a reliable and consistent method to examine the time dependent changes in the gene expression profiles in articular cartilage and subchondral bone. Local regulation of matrix degradation markers was demonstrated by a significant increase in mRNA levels of aggrecanase-1 and MMP-13 as early as the first week post-surgery, and expression remained elevated throughout the 10 week study. Immunohistochemistry confirmed MMP-13 expression in differentiated chondrocytes and synovial fibroblasts at week-2 and cells within osteophytes at week-10 in the surgically-modified-joints. Concomitant increases in chondrocyte differentiation markers, Col IIA and Sox 9, and vascular invasion markers, VEGF and CD31, peaked around week-2 to -4, and returned to Sham levels at later time points in both models. Indeed, VEGF-positive cells were found in the deep articular chondrocytes adjacent to subchondral bone. Osteoclastic bone resorption markers, cathepsin K and TRAP, were also elevated at week-2. Confirming bone resorption is an early local event in OA progression, cathepsin K positive osteoclasts were found invading the articular cartilage from the subchondral region at week 2. This was followed by late disease events, including subchondral sclerosis and osteophyte formation, as demonstrated by the upregulation of the osteoanabolic markers runx2 and osterix, toward week-4 to 6 post-surgery. In summary, this study demonstrated the temporal and cohesive gene expression changes in articular cartilage and subchondral bone using known markers of OA progression. The findings here support genome-wide profiling efforts to elucidate the sequential and complex regulation of the disease.

Molecular changes in articular cartilage and subchondral bone in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis

PubMed Central

2011-01-01

Background Osteoarthritis (OA) is a debilitating, progressive joint disease. Methods Similar to the disease progression in humans, sequential events of early cartilage degradation, subchondral osteopenia followed by sclerosis, and late osteophyte formation were demonstrated in the anterior cruciate ligament transection (ACLT) or ACLT with partial medial meniscectomy (ACLT + MMx) rat OA models. We describe a reliable and consistent method to examine the time dependent changes in the gene expression profiles in articular cartilage and subchondral bone. Results Local regulation of matrix degradation markers was demonstrated by a significant increase in mRNA levels of aggrecanase-1 and MMP-13 as early as the first week post-surgery, and expression remained elevated throughout the 10 week study. Immunohistochemistry confirmed MMP-13 expression in differentiated chondrocytes and synovial fibroblasts at week-2 and cells within osteophytes at week-10 in the surgically-modified-joints. Concomitant increases in chondrocyte differentiation markers, Col IIA and Sox 9, and vascular invasion markers, VEGF and CD31, peaked around week-2 to -4, and returned to Sham levels at later time points in both models. Indeed, VEGF-positive cells were found in the deep articular chondrocytes adjacent to subchondral bone. Osteoclastic bone resorption markers, cathepsin K and TRAP, were also elevated at week-2. Confirming bone resorption is an early local event in OA progression, cathepsin K positive osteoclasts were found invading the articular cartilage from the subchondral region at week 2. This was followed by late disease events, including subchondral sclerosis and osteophyte formation, as demonstrated by the upregulation of the osteoanabolic markers runx2 and osterix, toward week-4 to 6 post-surgery. Conclusions In summary, this study demonstrated the temporal and cohesive gene expression changes in articular cartilage and subchondral bone using known markers of OA progression. The findings here support genome-wide profiling efforts to elucidate the sequential and complex regulation of the disease. PMID:21864409

Young's modulus and SEM analysis of leg bones exposed to simulated microgravity by hind limb suspension (HLS)

NASA Astrophysics Data System (ADS)

Patel, Niravkumar D.; Mehta, Rahul; Ali, Nawab; Soulsby, Michael; Chowdhury, Parimal

2013-04-01

The aim of this study was to determine composition of the leg bone tissue of rats that were exposed to simulated microgravity by Hind-Limb Suspension (HLS) by tail for one week. The leg bones were cross sectioned, cleaned of soft tissues, dried and sputter coated, and then placed horizontally on the stage of a Scanning Electron Microscope (SEM) for analysis. Interaction of a 17.5 keV electron beam, incident from the vertical direction on the sample, generated images using two detectors. X-rays emitted from the sample during electron bombardment were measured with an Energy Dispersive Spectroscopy (EDS) feature of SEM using a liquid-nitrogen cooled Si(Li) detector with a resolution of 144 eV at 5.9 keV (25Mn Kα x-ray). Kα- x-rays from carbon, oxygen, phosphorus and calcium formed the major peaks in the spectrum. Relative percentages of these elements were determined using a software that could also correct for ZAF factors namely Z(atomic number), A(X-ray absorption) and F(characteristic fluorescence). The x-rays from the control groups and from the experimental (HLS) groups were analyzed on well-defined parts (femur, tibia and knee) of the leg bone. The SEM analysis shows that there are definite changes in the hydroxyl or phosphate group of the main component of the bone structure, hydroxyapatite [Ca10(PO4)6(OH)2], due to hind limb suspension. In a separate experiment, entire leg bones (both from HLS and control rats) were subjected to mechanical stress by mean of a variable force. The stress vs. strain graph was fitted with linear and polynomial function, and the parameters reflecting the mechanical strength of the bone, under increasing stress, were calculated. From the slope of the linear part of the graph the Young's modulus for HLS bones were calculated and found to be 2.49 times smaller than those for control bones.

The roles of exercise and fall risk reduction in the prevention of osteoporosis.

PubMed

Henderson, N K; White, C P; Eisman, J A

1998-06-01

In summary, the optimal model for the prevention of osteoporotic fractures includes maximization and maintenance of bone strength and minimization of trauma. Numerous determinants of each have been identified, but further work to develop preventative strategies based on these determinants remains to be undertaken. Physical activity is a determinant of peak BMD. There also is evidence that activity during growth modulates the external geometry and trabecular architecture, potentially enhancing skeletal strength, while during the adult years activity may reduce age-related bone loss. The magnitude of the effect of a 7% to 8% increase in peak BMD, if maintained through the adult years, could translate to a 1.5-fold reduction in fracture risk. Moreover, in the older population, appropriate forms of exercise could reduce the risk of falling and, thus, further reduce fracture risk. These data must be considered as preliminary in view of the paucity of long-term fracture outcome data from randomized clinical trials. However, current information suggests that the optimal form of exercise to achieve these objectives may vary through life. Vigorous physical activity (including weight-bearing, resistance, and impact components) during childhood may maximize peak BMD. This type of activity seems optimal through the young adult years, but as inevitable age-related degeneration occurs, activity modification to limit the impact component of exercise may become necessary. In the elderly, progressive strength training has been demonstrated to be a safe and effective form of exercise that reduces risk factors for falling and may also enhance BMD. In the frail elderly, activity to improve balance and confidence also may be valuable. Group activities such as Tai Chi may be cost-effective. Precise prescriptions must await the outcome of well-designed, controlled longitudinal studies that include fracture as an outcome. However, increased physical activity seems to be a sensible component of strategies to reduce osteoporotic fracture.

Contact mechanics of reverse engineered distal humeral hemiarthroplasty implants.

PubMed

Willing, Ryan; King, Graham J W; Johnson, James A

2015-11-26

Erosion of articular cartilage is a concern following distal humeral hemiarthroplasty, because native cartilage surfaces are placed in contact with stiff metallic implant components, which causes decreases in contact area and increases in contact stresses. Recently, reverse engineered implants have been proposed which are intended to promote more natural contact mechanics by reproducing the native bone or cartilage shape. In this study, finite element modeling is used in order to calculate changes in cartilage contact areas and stresses following distal humeral hemiarthroplasty with commercially available and reverse engineered implant designs. At the ulna, decreases in contact area were -34±3% (p=0.002), -27±1% (p<0.001) and -14±2% (p=0.008) using commercially available, bone reverse engineered and cartilage reverse engineered designs, respectively. Peak contact stresses increased by 461±57% (p=0.008), 387±127% (p=0.229) and 165±16% (p=0.003). At the radius, decreases in contact area were -21±3% (p=0.013), -13±2% (p<0.006) and -6±1% (p=0.020), and peak contact stresses increased by 75±52% (p>0.999), 241±32% (p=0.010) and 61±10% (p=0.021). Between the three different implant designs, the cartilage reverse engineered design yielded the largest contact areas and lowest contact stresses, but was still unable to reproduce the contact mechanics of the native joint. These findings align with a growing body of evidence indicating that although reverse engineered hemiarthroplasty implants can provide small improvements in contact mechanics when compared with commercially available designs, further optimization of shape and material properties is required in order reproduce native joint contact mechanics. Copyright © 2015 Elsevier Ltd. All rights reserved.

Normative Standards for HRpQCT Parameters in Chinese Men and Women.

PubMed

Zhu, Tracy Y; Yip, Benjamin Hk; Hung, Vivian Wy; Choy, Carol Wy; Cheng, Ka-Lo; Kwok, Timothy Cy; Cheng, Jack Cy; Qin, Ling

2018-06-12

Assessing bone architecture using high resolution peripheral quantitative computed tomography (HRpQCT) has the potential to improve fracture risk assessment. The Normal Reference Study aimed to establish sex-specific reference centile curves for HRpQCT parameters. This was an age-stratified cross-sectional study and 1,072 ambulatory Chinese men (n = 544) and women (n = 528) aged 20-79yrs, who were free from conditions and medications that could affect bone metabolism and had no history of fragility fracture, were recruited from local communities of Hong Kong. Reference centile curves for each HRpQCT parameter were constructed using Generalized Additive Models for Location, Scale and Shape with age as the only explanatory variable. Patterns of reference centile curves reflected age-related changes of bone density, microarchitecture, and estimated bone strength. In both sexes, loss of cortical bone was only evident in mid-adulthood, particularly in women with a more rapid fashion probably concurrent with the onset of menopause. In contrast, loss of trabecular bone was subtle or gradual or occurred at an earlier age. Expected values of HRpQCT parameters for a defined sex and age, and a defined percentile or z-score were obtained from these curves. T-scores were calculated using the population with the peak values as the reference and reflected age- or menopause-related bone loss in an older individual or the room to reach the peak potential in a younger individual. These reference centile curves produced a standard describing a norm or desirable target that enables value clinical judgements. Percentiles, z-scores and T-scores would be helpful in detecting abnormalities in bone density and microarchitecture arising from various conditions and establishing entry criteria for clinical trials. They also hold the potential to refine the diagnosis of osteoporosis and assessment of fracture risk. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Sun Exposure Behavior, Seasonal Vitamin D Deficiency, and Relationship to Bone Health in Adolescents.

PubMed

Farrar, Mark D; Mughal, M Zulf; Adams, Judith E; Wilkinson, Jack; Berry, Jacqueline L; Edwards, Lisa; Kift, Richard; Marjanovic, Elizabeth; Vail, Andy; Webb, Ann R; Rhodes, Lesley E

2016-08-01

Vitamin D is essential for bone health in adolescence, when there is rapid bone mineral content accrual. Because cutaneous sun exposure provides vitamin D, there is no recommended oral intake for UK adolescents. Our objective was to assess seasonal vitamin D status and its contributors in white Caucasian adolescents and examine bone health in those found deficient. Prospective cohort study was undertaken. Six schools in Greater Manchester, UK, were included. Participants were 131 adolescents between 12 and 15 years of age. Seasonal assessment of circulating 25-hydroxyvitamin D (25OHD), personal sun exposure, and dietary vitamin D. Adolescents deficient (25OHD <10 ng/ml/25 nmol/liter) in at least one season underwent dual-energy X-ray absorptiometry (lumbar spine, femoral neck), with bone mineral apparent density correction for size, and peripheral quantitative computed tomography (distal radius) for volumetric bone mineral density (BMD). Serum 25OHD and BMD measurements. Mean 25OHD was highest in September: 24.1 (SD, 6.9) ng/ml and lowest in January: 15.5 (5.9) ng/ml. Over the year, 16% were deficient in ≥ one season and 79% insufficient (25OHD <20 ng/ml/50 nmol/liter) including 28% in September. Dietary vitamin D was low year-round, whereas personal sun exposure was seasonal and predominantly across the school week. Holidays accounted for 17% variation in peak 25OHD (P < .001). Nineteen adolescents underwent bone assessment, which showed low femoral neck bone mineral apparent density vs matched reference data (P = .0002), three with Z less than or equal to -2.0 distal radius trabecular volumetric BMD. Sun exposure levels failed to provide adequate vitamin D, with approximately one-quarter of adolescents insufficient even at summer peak. Seasonal vitamin D deficiency was prevalent and those affected had low BMD. Recommendations on vitamin D acquisition are indicated in this age-group.

Ultrasonic Wave Properties in Bone Axis Direction of Bovine Cortical Bone

NASA Astrophysics Data System (ADS)

Yamamoto, Kazufumi; Yaoi, Yuichiro; Yamato, Yu; Yanagitan, Takahiko; Matsukawa, Mami; Yamazaki, Kaoru

2008-05-01

Quantitative ultrasonography (QUS) is a good method for measuring elastic properties of bone in vivo. Bovine cortical bone has two typical microstructures, plexiform and Haversian. In this study, the relationship between the speed of sound (SOS) and the hydroxyapatite (HAp) crystallite orientation in the axial direction was investigated in two different aged bovine cortical bones. The dependence of attenuation on anatomical position was also investigated. Two ring-permanent hyphen shaped cortical bone samples were obtained from 36- and 24-month-old bovine femurs. SOS was measured with a conventional ultrasonic pulse system. The integrated intensity of the (0002) peak obtained by X-ray diffraction was determine to evaluate the amount of preferred orientation. Regardless of the age of the bovine femurs, a significant correlation between SOS and the preferred orientation of HAp crystallites was observed in parts of the plexiform structure, and the gradient of the relationship showed a similar tendency. Attenuation seemed to depend on bone microstructure.

New bone formation and trabecular bone microarchitecture of highly porous tantalum compared to titanium implant threads: A pilot canine study.

PubMed

Lee, Jin Whan; Wen, Hai Bo; Gubbi, Prabhu; Romanos, Georgios E

2018-02-01

This study evaluated new bone formation activities and trabecular bone microarchitecture within the highly porous region of Trabecular Metal™ Dental Implants (TM) and between the threads of Tapered Screw-Vent® Dental Implants (TSV) in fresh canine extraction sockets. Eight partially edentulated dogs received four implants (4.1 mmD × 13 mmL) bilaterally in mandibular fresh extraction sockets (32 TM, 32 TSV implants), and allowed to heal for 2, 4, 8, and 12 weeks. Calcein was administered to label mineralizing bone at 11 and 4 days before euthanasia for dogs undergoing all four healing periods. Biopsies taken at each time interval were examined histologically. Histomorphometric assay was conducted for 64 unstained and 64 stained slides at the region of interest (ROI) (6 mm long × 0.35 mm deep) in the midsections of the implants. Topographical and chemical analyses were also performed. Histomorphometry revealed significantly more new bone in the TM than in the TSV implants at each healing time (p = .0014, .0084, .0218, and .0251). Calcein-labeled data showed more newly mineralized bone in the TM group than in the TSV group at 2, 8, and 12 weeks (p = .045, .028, .002, respectively) but not at 4 weeks (p = .081). Histologically TM implants exhibited more bone growth and dominant new immature woven bone at an earlier time point than TSV implants. The parameters representing trabecular bone microarchitecture corroborated faster new bone formation in the TM implants when compared to the TSV implants. TM exhibited an irregular faceted topography compared to a relatively uniform microtextured surface for TSV. Chemical analysis showed peaks associated with each implant's composition material, and TSV also showed peaks reflecting the elements of the calcium phosphate blasting media. Results suggest that the healing pathway associated with the highly porous midsection of TM dental implant could enable faster and stronger secondary implant stability than conventional osseointegration alone; however, prospective clinical studies are needed to confirm these potential benefits in patients with low bone density, compromised healing, or prior implant failure. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Expression of Novel Gene Products Upregulated by Disuse is Normalized by an Osteogenic Mechanical Stimulus: Evidence for the Molecular Basis of a Low Level Biomechanical Countermeasure for Osteoporosis?

NASA Technical Reports Server (NTRS)

Rubin, C.; Zhi, J.; Xu, G.; Cute, M.; McLeod, K.; Hadjiargyrou, M.

1999-01-01

The National Research Council's report entitled: A Strategy for Space Biology and Medical Science, highlighted several areas of fundamental scientific investigation which must be addressed to make long-term space exploration not only feasible, but safe. This "Goldberg Strategy," as well as several subsequent reports published by the NRC's Space Studies Board (e.g., Assessment of Programs in Space Biology and Medicine, Smith et. al., 1991), suggests that the principal hurdle to man's extended presence in space is the osteopenia which parallels reduced gravity. Ironically, the most significant risk to the skeleton may only be realized on return to normal gravitational fields, and full recovery of bone mass may never occur. Effective counter-measures to this microgravity induced bone loss are thus essential. Considering the similarities of space and aging induced osteopenia, an indisputable benefit of such a prophylaxis would be its potential as a treatment for the bone loss which plagues over 25 million people in the U.S. The osteogenic potential of mechanical strain is strongly frequency dependent, with sensitivity increasing up through at least 60 Hz (cycles per second). One hundred seconds per day of a 1 Hz cyclic loading will inhibit disuse osteopenia only if sufficient in magnitude to engender 1000 microstrain (mu(epsilon)) in the tissue. When loading is applied at 30 Hz, however, mechanical strains on the order of 5O mu(epsilon) (approx. 1% of the peak strains which occur in bone during vigorous functional activity), can stimulate bone formation in a duration dependent manner. In longer term animal studies, strains of less than 10 mu(epsilon), induced non-invasively via a whole body vibration, will stimulate bone formation on the surfaces of trabeculae, increase bone density, and improve strength. Finally, preliminary results from a double blind prospective clinical trial shows promise in inhibiting the bone loss which parallels the menopause. Based on these observations, we propose that these high frequency, low magnitude, mechanical strains effectively serve as a "surrogate" for musculoskeletal ground reaction forces, and thus represent an ideal countermeasure to the osteopenia which parallels microgravity conditions. The specific goal of this NASA funded work is to identify genes in bone upregulated by disuse, and to determine the efficacy of an osteogenic mechanical stimulus to downregulate their expression.

Biomechanical Evaluation of Glenoid Reconstruction With an Implant-Free J-Bone Graft for Anterior Glenoid Bone Loss.

PubMed

Pauzenberger, Leo; Dyrna, Felix; Obopilwe, Elifho; Heuberer, Philipp R; Arciero, Robert A; Anderl, Werner; Mazzocca, Augustus D

2017-10-01

The anatomic restoration of glenoid morphology with an implant-free J-shaped iliac crest bone graft offers an alternative to currently widely used glenoid reconstruction techniques. No biomechanical data on the J-bone grafting technique are currently available. To evaluate (1) glenohumeral contact patterns, (2) graft fixation under cyclic loading, and (3) the initial stabilizing effect of anatomic glenoid reconstruction with the implant-free J-bone grafting technique. Controlled laboratory study. Eight fresh-frozen cadaveric shoulders and J-shaped iliac crest bone grafts were used for this study. J-bone grafts were harvested, prepared, and implanted according to a previously described, clinically used technique. Glenohumeral contact patterns were measured using dynamic pressure-sensitive sensors under a compressive load of 440 N with the humerus in (a) 30° of abduction, (b) 30° of abduction and 60° of external rotation, (c) 60° of abduction, and (d) 60° of abduction and 60° of external rotation. Using a custom shoulder-testing system allowing positioning with 6 degrees of freedom, a compressive load of 50 N was applied, and the peak force needed to translate the humeral head 10 mm anteriorly at a rate of 2.0 mm/s was recorded. All tests were performed (1) for the intact glenoid, (2) after the creation of a 30% anterior osseous glenoid defect parallel to the longitudinal axis of the glenoid, and (3) after anatomic glenoid reconstruction with an implant-free J-bone graft. Furthermore, after glenoid reconstruction, each specimen was translated anteriorly for 5 mm at a rate of 4.0 mm/s for a total of 3000 cycles while logging graft protrusion and mediolateral bending motions. Graft micromovements were recorded using 2 high-resolution, linear differential variable reluctance transducer strain gauges placed in line with the long leg of the graft and the mediolateral direction, respectively. The creation of a 30% glenoid defect significantly decreased glenohumeral contact areas ( P < .05) but significantly increased contact pressures at all abduction and rotation positions ( P < .05). Glenoid reconstruction restored the contact area and contact pressure back to levels of the native glenohumeral joint in all tested positions. The mean (±SD) force to translate the humeral head anteriorly for 10 mm (60° of abduction: 31.7 ± 12.6 N; 60° of abduction and 60° of external rotation: 28.6 ± 7.6 N) was significantly reduced after the creation of a 30% anterior bone glenoid defect (60° of abduction: 12.2 ± 6.8 N; 60° of abduction and 60° of external rotation: 11.4 ± 5.4 N; P < .001). After glenoid reconstruction with a J-bone graft, the mean peak translational force significantly increased (60° of abduction: 85.0 ± 8.2 N; 60° of abduction and 60° of external rotation: 73.6 ± 4.5 N; P < .001) compared with the defect state and baseline. The mean total graft protrusion under cyclical translation of the humeral head over 3000 cycles was 138.3 ± 169.8 µm, whereas the mean maximal mediolateral graft deflection was 320.1 ± 475.7 µm. Implant-free anatomic glenoid reconstruction with the J-bone grafting technique restored near-native glenohumeral contact areas and pressures, provided secure initial graft fixation, and demonstrated excellent osseous glenohumeral stability at time zero. The implant-free J-bone graft is a viable alternative to commonly used glenoid reconstruction techniques, providing excellent graft fixation and glenohumeral stability immediately postoperatively. The normalization of glenohumeral contact patterns after reconstruction could potentially avoid the progression of dislocation arthropathy.

Does maximum torque mean optimal pullout strength of screws?

PubMed

Tankard, Sara E; Mears, Simon C; Marsland, Daniel; Langdale, Evan R; Belkoff, Stephen M

2013-04-01

To determine the relationship between insertion torque and pullout strength of 3.5-mm-diameter cortical screws in cadaveric humeri with different bone mineral densities (BMDs). Five pairs of human humeri from each of 3 BMD groups (normal, osteopenic, and osteoporotic) were used. Holes were drilled in each humerus, and maximum insertion torque (T(max)) was measured by tightening a screw until stripping occurred. In the remaining holes, screws were tightened to 50%, 70%, or 90% of the T(max). A servohydraulic testing machine pulled each screw out at 1 mm/s while resulting force and axial displacement were recorded at 10 Hz. The authors checked for an effect of insertion torque (percent T(max)) on pullout strength using a general linearized and latent mixed model (Stata10), controlling for cortical thickness and BMD (T-score). Pullout strength for normal and osteoporotic bone was greatest for screws inserted to 50% T(max) and was significantly greater than that at T(max) but not significantly different from that at 70% or 90% T(max). For osteopenic bone, pullout strength was greatest at 70% peak torque, but it was not significantly different from the pullout strength at the 50% or 90% T(max) levels. Tightening screws beyond 50% T(max) does not increase pullout strength of the screw and may place bone at risk for damage that might result in loss of fixation. Even after adjusting for bone thickness and density, there is no clear relationship between pullout strength and screw torque.

Different Movement of Hyolaryngeal Structures by Various Application of Electrical Stimulation in Normal Individuals

PubMed Central

Kim, Sae Hyun; Oh, Byung-Mo; Han, Tae Ryun; Jeong, Ho Joong

2015-01-01

Objective To identify the differences in the movement of the hyoid bone and the vocal cord with and without electrical stimulation in normal subjects. Methods Two-dimensional motion analysis using a videofluoroscopic swallowing study with and without electrical stimulation was performed. Surface electrical stimulation was applied during swallowing using electrodes placed at three different locations on each subject. All subjects were analyzed three times using the following electrode placements: with one pair of electrodes on the suprahyoid muscles and a second pair on the infrahyoid muscles (SI); with placement of the electrode pairs on only the infrahyoid muscles (IO); and with the electrode pairs placed vertically on the suprahyoid and infrahyoid muscles (SIV). Results The main outcomes of this study demonstrated an initial downward displacement as well as different movements of the hyoid bone with the three electrode placements used for electrical stimulation. The initial positions of the hyoid bone with the SI and IO placements resulted in an inferior and anterior displaced position. During swallowing, the hyoid bone moved in a more superior and less anterior direction, resulting in almost the same peak position compared with no electrical stimulation. Conclusion These results demonstrate that electrical stimulation caused an initial depression of the hyoid bone, which had nearly the same peak position during swallowing. Electrical stimulation during swallowing was not dependent on the position of the electrode on the neck, such as on the infrahyoid or on both the suprahyoid and infrahyoid muscles. PMID:26361589

Osteoblastoma of the sternum--case report and review of the literature.

PubMed

Villalobos, Camilo E; Rybak, Leon D; Steiner, German C; Wittig, James C

2010-01-01

Osteoblastoma is an extremely rare entity that represents less than 1% of all bone tumors, and affects twice as many males as females with peak incidence between 15 and 20 years. Osteoblastomas commonly affect axial bones, long bones, bones of the foot and hand, and less commonly the pelvis, scapula, ribs, and clavicle. Osteoblastoma does not have a classic presentation, but can vary with the location and size of the tumor. The main complaint is often progressive pain localized at the tumor site. Osteoblastoma is a benign tumor with an aggressive behavior. The treatment is wide surgical resection, otherwise it continues to enlarge and destroy the bone and surrounding structures. We report a 32-year-old male with an osteoblastoma of this sternum who was treated with an en-bloc resection and reconstruction with Marlex((R)) and a methylmethacrylate plate.

Phosphonated Near-Infrared Fluorophores for Biomedical Imaging of Bone**

PubMed Central

Hyun, Hoon; Wada, Hideyuki; Bao, Kai; Gravier, Julien; Yadav, Yogesh; Laramie, Matt; Henary, Maged; Frangioni, John V.

2014-01-01

The conventional method for creating targeted contrast agents is to conjugate separate targeting and fluorophore domains. In this study we report a new strategy based on incorporation of targeting moieties into the non-resonant structure of pentamethine and heptamethine indocyanines. Using the known affinity of phosphonates for bone minerals as a model system, we have synthesized two families of bifunctional molecules that target bone without the need for a traditional bisphosphonate. With peak fluorescence emission at ≈ 700 nm or ≈ 800 nm, these molecules can be used for FLARE dual-channel imaging. Longitudinal FLARE studies in mice demonstrate that phosphonated near-infrared fluorophores remain stable in bone for over 5 weeks, and histological analysis demonstrates incorporation into bone matrix. Taken together, we describe a new strategy for creating ultracompact, targeted, near-infrared fluorophores for various bioimaging applications. PMID:25139079

Detection of changes in bone quality of osteoporotic model induced by sciatic nerve resection by using Raman spectroscopy

NASA Astrophysics Data System (ADS)

Ishimaru, Yasumitsu; Oshima, Yusuke; Imai, Yuuki; Iimura, Tadahiro; Takanezawa, Sota; Hino, Kazunori; Miura, Hiromasa

2018-02-01

To detect the bone quality loss in osteoporosis, we performed Raman spectroscopic analysis of sciatic nerve resection (NX) mice. Eight months after surgery, lower limbs were collected from the mice and fixed with 70% ethanol. Raman spectra of anterior cortical surface of the proximal tibia at 5 points in each bone were measured by RENISHAW inVia Raman Microscope. Excitation wave length was 785 nm. We also performed DXA and micro CT measurement to confirm the bone mineral density and bone microstructure in the osteoporotic model induced by sciatic nerve resection. In the result of Raman spectroscopy, we detected changes of Raman peak intensity ratio in carbonate/phosphate, mineral/combined proline and hydroxyproline and mineral/phenylalanine. In addition, in the result of micro CT, we found significant changes in VOX BV/TV, Trabecular number, thickness, cancellous bone mineral density, cortical thickness and cortical bone mineral density. The results suggest that not only the bone mineral density but also bone quality reduced in the NX mice. We conclude that Raman spectroscopy is a useful for bone quality assessment as a complementary technique for conventional diagnostics.

Effect of swimming on bone metabolism in adolescents.

PubMed

Derman, Orhan; Cinemre, Alphan; Kanbur, Nuray; Doğan, Muhsin; Kiliç, Mustafa; Karaduman, Erdem

2008-01-01

Physical activity has been shown to have a positive effect on bone metabolism among adolescents. The objective of this study was to determine the effect of swimming on bone metabolism during adolescence. Swimming, as a non-weight-bearing sport, has been considered to be insignificant in the maintenance of bone mass. We studied whether swimming is associated with a higher peak bone mass. Forty swimmers (males aged 10-17 years and females aged 9-16 years) were studied. The control group consisted of the same number of adolescents aged between 10-16 years who did not swim; distribution of male and female gender was similar in the non-swimming control group compared to the swimming group. Adolescents were matched for age, gender and pubertal stages based on Tanner staging. All subjects underwent combined measurement of bone mineral metabolism by dual-energy X-ray absorptiometry of total body calcium content, and specific biochemical markers of turnover including osteocalcin, calcium, phosphorus and alkaline phosphatase. Bone age (determined by Greulich and Pyle's Radiographic Atlas of Skeletal Development of the Hand and Wrist), weight, height, ideal body weight, ideal body weight ratio, body mass index, Tanner classification (rated by examiner), diet, history of tobacco and alcohol exposure, exercise, socioeconomic status and history of chronic illness and medications were recorded to evaluate potential mediators that would affect bone metabolism. Tanner staging was used to assess puberty, and diet was evaluated based on reported consumption of milk, yogurt and cheese and cola/caffeine beverage consumption daily. There was significant difference in bone mineral content between adolescent male swimmers and the control group males. Consumption of cola beverages were significantly higher among the control group compared with the swimmer group. Ideal body weight ratio was significantly high among the female control group compared with female swimmers. Milk consumption was significantly higher for both male and female swimmer groups, whereas yogurt consumption was only significantly higher in the male swimmer group compared with control group. These results indicate that a highly active nonimpact sport such as swimming may lead to increased bone mineral content only for male swimmers. However, dietary behaviors may be more important than swimming on bone metabolism among adolescents.

Sacral Bone Mass Distribution Assessed by Averaged Three-Dimensional CT Models: Implications for Pathogenesis and Treatment of Fragility Fractures of the Sacrum.

PubMed

Wagner, Daniel; Kamer, Lukas; Sawaguchi, Takeshi; Richards, R Geoff; Noser, Hansrudi; Rommens, Pol M

2016-04-06

Fragility fractures of the sacrum are increasing in prevalence due to osteoporosis and epidemiological changes and are challenging in their treatment. They exhibit specific fracture patterns with unilateral or bilateral fractures lateral to the sacral foramina, and sometimes an additional transverse fracture leads to spinopelvic dissociation. The goal of this study was to assess sacral bone mass distribution and corresponding changes with decreased general bone mass. Clinical computed tomography (CT) scans of intact pelves in ninety-one individuals (mean age and standard deviation, 61.5 ± 11.3 years) were used to generate three-dimensional (3D) models of the sacrum averaging bone mass in Hounsfield units (HU). Individuals with decreased general bone mass were identified by measuring bone mass in L5 (group 1 with <100 HU; in contrast to group 2 with ≥100 HU). In group 1, a large zone of negative Hounsfield units was located in the paraforaminal lateral region from S1 to S3. Along the trans-sacral corridors, a Hounsfield unit peak was observed laterally, corresponding to cortical bone of the auricular surface. The lowest Hounsfield unit values were found in the paraforaminal lateral region in the sacral ala. An intermediate level of bone mass was observed in the area of the vertebral bodies, which also demonstrated the largest difference between groups 1 and 2. Overall, the Hounsfield units were lower at S2 than S1. The models of averaged bone mass in the sacrum revealed a distinct 3D distribution pattern. The negative values in the paraforaminal lateral region may explain the specific fracture patterns in fragility fractures of the sacrum involving the lateral areas of the sacrum. Transverse fractures located between S1 and S2 leading to spinopelvic dissociation may occur because of decreased bone mass in S2. The largest difference between the studied groups was found in the vertebral bodies and might support the use of transsacral or cement-augmented implants. Copyright © 2016 by The Journal of Bone and Joint Surgery, Incorporated.

Modified femoral pressuriser generates a longer lasting high pressure during cement pressurisation

PubMed Central

2011-01-01

Background The strength of the cement-bone interface in hip arthroplasty is strongly related to cement penetration into the bone. A modified femoral pressuriser has been investigated, designed for closer fitting into the femoral opening to generate higher and more constant cement pressure compared to a commercial (conventional) design. Methods Femoral cementation was performed in 10 Sawbones® models, five using the modified pressuriser and five using a current commercial pressuriser as a control. Pressure during the cementation was recorded at the proximal and distal regions of the femoral implant. The peak pressure and the pressure-time curves were analysed by student's t-test and Two way ANOVA. Results The modified pressuriser showed significantly and substantially longer durations at higher cementation pressures and slightly, although not statistically, higher peak pressures compared to the conventional pressuriser. The modified pressuriser also produced more controlled cement leakage. Conclusion The modified pressuriser generates longer higher pressure durations in the femoral model. This design modification may enhance cement penetration into cancellous bone and could improve femoral cementation. PMID:22004662

Ontogenetic relationships between in vivo strain environment, bone histomorphometry and growth in the goat radius

PubMed Central

Main, Russell P

2007-01-01

Vertebrate long bone form, at both the gross and the microstructural level, is the result of many interrelated influences. One factor that is considered to have a significant effect on bone form is the mechanical environment experienced by the bone during growth. The work presented here examines the possible relationships between in vivo bone strains, bone geometry and histomorphology in the radii of three age/size groups of domestic goats. In vivo bone strain data were collected from the radii of galloping goats, and the regional cortical distribution of peak axial strain magnitudes, radial and circumferential strain gradients, and longitudinal strain rates related to regional patterns in cortical growth, porosity, remodelling and collagen fibre orientation. Although porosity and remodelling decreased and increased with age, respectively, these features showed no significant regional differences and did not correspond to regional patterns in the mechanical environment. Thicker regions of the radius's cortex were significantly related to high strain levels and higher rates of periosteal, but not endosteal, growth. However, cortical growth and strain environment were not significantly related. Collagen fibre orientation varied regionally, with a higher percentage of transverse fibres in the caudal region of the radius and primarily longitudinal fibres elsewhere, and, although consistent through growth, also did not generally correspond to regional strain patterns. Although strain magnitudes increased during ontogeny and regional strain patterns were variable over the course of a stride, mean regional strain patterns were generally consistent with growth, suggesting that regional growth patterns and histomorphology, in combination with external loads, may play some role in producing a relatively ‘predictable’ strain environment within the radius. It is further hypothesized that the absence of correlation between regional histomorphometric patterns and the measured strain environments is the result of the variable mechanical environment. However, the potential effects of other physiological and mechanical factors, such as skeletal metabolism and adjacent muscle insertions, that can influence the gross and microstructural morphology of the radius during ontogeny, cannot be ignored. PMID:17331177

Sacrificial bonds and hidden length in biomaterials -- a kinetic description of strength and toughness in bone

NASA Astrophysics Data System (ADS)

Lieou, Charles K. C.; Elbanna, Ahmed E.; Carlson, Jean M.

2013-03-01

Sacrificial bonds and hidden length in structural molecules account for the greatly increased fracture toughness of biological materials compared to synthetic materials without such structural features, by providing a molecular-scale mechanism of energy dissipation. One example of occurrence of sacrificial bonds and hidden length is in the polymeric glue connection between collagen fibrils in animal bone. In this talk, we propose a simple kinetic model that describes the breakage of sacrificial bonds and the revelation of hidden length, based on Bell's theory. We postulate a master equation governing the rates of bond breakage and formation, at the mean-field level, allowing for the number of bonds and hidden lengths to take up non-integer values between successive, discrete bond-breakage events. This enables us to predict the mechanical behavior of a quasi-one-dimensional ensemble of polymers at different stretching rates. We find that both the rupture peak heights and maximum stretching distance increase with the stretching rate. In addition, our theory naturally permits the possibility of self-healing in such biological structures.

Bone tissue heterogeneity is associated with fracture toughness: a polarization Raman spectroscopy study

NASA Astrophysics Data System (ADS)

Makowski, Alexander J.; Granke, Mathilde; Uppuganti, Sasidhar; Mahadevan-Jansen, Anita; Nyman, Jeffry S.

2015-02-01

Polarization Raman Spectroscopy has been used to demonstrate microstructural features and collagen fiber orientation in human and mouse bone, concurrently measuring both organization and composition; however, it is unclear as to what extent these measurements explain the mechanical quality of bone. In a cohort of age and gender matched cadaveric cortical bone samples (23-101 yr.), we show homogeneity of both composition and structure are associated with the age related decrease in fracture toughness. 64 samples were machined into uniform specimens and notched for mechanical fracture toughness testing and polished for Raman Spectroscopy. Fingerprint region spectra were acquired on wet bone prior to mechanical testing by sampling nine different microstructural features spaced in a 750x750 μm grid in the region of intended crack propagation. After ASTM E1820 single edge notched beam fracture toughness tests, the sample was dried in ethanol and the osteonal-interstitial border of one osteon was samples in a 32x32 grid of 2μm2 pixels for two orthogonal orientations relative to the long bone axis. Standard peak ratios from the 9 separate microstructures show heterogeneity between structures but do not sufficiently explain fracture toughness; however, peak ratios from mapping highlight both lamellar contrast (ν1Phos/Amide I) and osteon-interstitial contrast (ν1Phos/Proline). Combining registered orthogonal maps allowed for multivariate analysis of underlying biochemical signatures. Image entropy and homogeneity metrics of single principal components significantly explain resistance to crack initiation and propagation. Ultimately, a combination of polarization content and multivariate Raman signatures allowed for the association of microstructural tissue heterogeneity with fracture resistance.

The Effect of Saline Coolant on Temperature Levels during Decortication with a Midas Rex: An in Vitro Model Using Sheep Cervical Vertebrae.

PubMed

Livingston, Asher; Wang, Tian; Christou, Chris; Pelletier, Matthew H; Walsh, William R

2015-01-01

Decortication of bone with a high-speed burr in the absence of coolant may lead to local thermal necrosis and decreased healing ability, which may negatively impact clinical outcome. Little data are available on the impact of applying a coolant during the burring process. This study aims to establish an in vitro model to quantitatively assess peak temperatures during endplate preparation with a high-speed burr. Six sheep cervical vertebrae were dissected and mounted. Both end plates were used to give a total of 12 sites. Two thermocouples were inserted into each vertebra, 2 mm below the end plate surface and a thermal camera set up to measure surface temperature. A 3 mm high-pneumatic speed burr (Midas Rex, Medtronic, Fort Worth, TX, USA) was used to decorticate the bone in a side to side sweeping pattern, using a matchstick burr (M-8/9MH30) with light pressure. This procedure was repeated while dripping saline onto the burr and bone. Data were compared between groups using a Student's t-test. Application of coolant at the bone-burr interface during decortication resulted in a significant decrease in final temperature. Without coolant, maximum temperatures 2 mm from the surface were not sufficient to cause thermal osteonecrosis, although peak surface temperatures would cause local damage. The use of a high-speed burr provides a quick and an effective method of vertebral end plate preparation. Thermal damage to the bone can be minimized through the use of light pressure and saline coolant. This has implications for any bone preparation performed with a high-speed burr.

Symposium on ‘Nutrition and health in children and adolescents’ Session 1: Nutrition in growth and development

PubMed Central

Prentice, Ann; Schoenmakers, Inez; Laskey, M. Ann; de Bono, Stephanie; Ginty, Fiona; Goldberg, Gail R.

2007-01-01

The growth and development of the human skeleton requires an adequate supply of many different nutritional factors. Classical nutrient deficiencies are associated with stunting (e.g. energy, protein, Zn), rickets (e.g. vitamin D) and other bone abnormalities (e.g. Cu, Zn, vitamin C). In recent years there has been interest in the role nutrition may play in bone growth at intakes above those required to prevent classical deficiencies, particularly in relation to optimising peak bone mass and minimising osteoporosis risk. There is evidence to suggest that peak bone mass and later fracture risk are influenced by the pattern of growth in childhood and by nutritional exposures in utero, in infancy and during childhood and adolescence. Of the individual nutrients, particular attention has been paid to Ca, vitamin D, protein and P. There has also been interest in several food groups, particularly dairy products, fruit and vegetables and foods contributing to acid–base balance. However, it is not possible at the present time to define dietary reference values using bone health as a criterion, and the question of what type of diet constitutes the best support for optimal bone growth and development remains open. Prudent recommendations (Department of Health, 1998; World Health Organization/Food and Agriculture Organization, 2003) are the same as those for adults, i.e. to consume a Ca intake close to the reference nutrient intake, optimise vitamin D status through adequate summer sunshine exposure (and diet supplementation where appropriate), be physically active, have a body weight in the healthy range, restrict salt intake and consume plenty of fruit and vegetables. PMID:17181901

Bone mineralization is elevated and less heterogeneous in adults with type 2 diabetes and osteoarthritis compared to controls with osteoarthritis alone

PubMed Central

Pritchard, J.M.; Papaioannou, A.; Tomowich, C.; Giangregorio, L.M.; Atkinson, S.A.; Beattie, K.A.; Adachi, J.D.; DeBeer, J.; Winemaker, M.; Avram, V.; Schwarcz, H.P.

2016-01-01

Purpose The purpose of this study was to determine whether trabecular bone mineralization differed in adults with type 2 diabetes compared to adults without type 2 diabetes. Methods Proximal femur specimens were obtained following a total hip replacement procedure from men and women ≥65 years of age with and without type 2 diabetes. A scanning electron microscope was used for quantitative backscattered electron imaging (qBEI) analysis of trabecular bone samples from the femoral neck. Gray scale images (pixel size=5.6 μm2) were uploaded to ImageJ software and gray level (GL) values were converted to calcium concentrations (weight [wt] % calcium [Ca]) using data obtained with energy dispersive X-ray spectrometry. The following bone mineralization density distribution (BMDD) outcomes were collected: the weighted mean bone calcium concentration (CaMEAN), the most frequently occurring bone calcium concentration (CaPEAK) and mineralization heterogeneity (CaWIDTH). Differences between groups were assessed using the Student’s t-test for normally distributed data and Mann–Whitney U-test for non-normally distributed data. An alpha value of <0.05 was considered significant. Results Thirty-five Caucasian participants were recruited (mean [standard deviation, SD] age, 75.5 [6.5] years): 14 adults with type 2 diabetes (years since type 2 diabetes diagnosis, 13.5 [7.4] years) and 21 adults without type 2 diabetes. In the adults with type 2 diabetes, bone CaMEAN was 4.9% greater (20.36 [0.98] wt.% Ca versus 19.40 [1.07] wt.% Ca, p=0.015) and CaWIDTH was 9.4% lower (median [interquartile range] 3.55 [2.99–4.12] wt.% Ca versus 3.95 [0.71] wt.% Ca, p<0.001) compared to controls. There was no between-group difference in CaPEAK (21.12 [0.97] wt.% Ca for type 2 diabetes versus 20.44 [1.30] wt.% Ca for controls, p=0.121). Conclusion The combination of elevated mean calcium concentration in bone and lower mineralization heterogeneity in adults with type 2 diabetes may have deleterious effects on the biomechanical properties of bone. These microscopic alterations in bone mineralization, which may be mediated by suppressed bone remodeling, further elucidate higher fracture risk in adults with type 2 diabetes. PMID:23356988

Photoluminescence in the characterization and early detection of biomimetic bone-like apatite formation on the surface of alkaline-treated titanium implant: state of the art.

PubMed

Sepahvandi, Azadeh; Moztarzadeh, Fathollah; Mozafari, Masoud; Ghaffari, Maryam; Raee, Nahid

2011-09-01

Photoluminescence (PL) property is particularly important in the characterization of materials that contain significant proportions of noncrystalline components, multiple phases, or low concentrations of mineral phases. In this research, the ability of biomimetic bone-like apatite deposition on the surface of titanium alloy (Ti6Al4V) substrates in simulated body fluid (SBF) right after alkaline-treatment and subsequent heat-treatment was studied by the inherent luminescence properties of apatite. For this purpose, the metallic substrates were treated in 5 M NaOH solution at 60 °C. Subsequently, the substrates were heat-treated at 600 °C for 1 h for consolidation of the sodium titanate hydrogel layer. Then, they were soaked in SBF for different periods of time. Finally, the possibility to use of PL monitoring as an effective method and early detection tool is discussed. According to the obtained results, it was concluded that the PL emission peak did not have any significant shift to the shorter or higher wavelengths, and the PL intensity increased as the exposure time increased. This research proved that the observed inherent PL of the newly formed apatite coatings might be of specific interest for histological probing and bone remodelling monitoring. Copyright © 2011 Elsevier B.V. All rights reserved.

Optimum frequency of exercise for bone health: randomised controlled trial of a high-impact unilateral intervention.

PubMed

Bailey, Christine A; Brooke-Wavell, Katherine

2010-04-01

Exercise can increase bone strength, but to be effective in reducing fracture risk, exercise must be feasible enough to be adopted into daily life and influence potentially vulnerable skeletal sites such as the superolateral cortex of the femoral neck, where thinning is associated with increased fracture risk. Brief, high-impact exercise increases femoral neck bone density but the optimal frequency of such exercise and the location of bone accrual is unknown. This study thus examined (1) the effectiveness of different weekly frequencies of exercise on femoral neck BMD and (2) whether BMD change differed between hip sites using a high-impact, unilateral intervention. Healthy premenopausal women were randomly assigned to exercise 0, 2, 4, or 7 days/week for 6 months. The exercise intervention incorporated 50 multidirectional hops on one randomly selected leg. BMD was measured by DXA at baseline and after 6 months of exercise. Changes in the exercise leg were compared between groups using ANCOVA, with change in the control leg and baseline BMD as covariates. RM-MANOVA was conducted to determine whether bone changes from exercise differed between hip sites. 61 women (age 33.6+/-11.1 years) completed the intervention. Compliance amongst exercisers was 86.7+/-10.6%. Peak ground reaction forces during exercise increased from 2.5 to 2.8 times body weight. The change in femoral neck BMD in the exercise limb (adjusted for change in the control limb and baseline BMD) differed between groups (p=0.015), being -0.3% (-1.2 to 0.6), 0.0% (-1.0 to 1.0), 0.9% (-0.1 to 2.0) and 1.8% (0.8 to 2.8) in those exercising 0, 2, 4 and 7 days per week, respectively. When BMD changes at upper neck, lower neck and trochanter were compared using RM-MANOVA, a significant exercise effect was observed (p=0.048), but this did not differ significantly between sites (p=0.439) despite greatest mean increases at the upper femoral neck. Brief, daily hopping exercises increased femoral neck BMD in premenopausal women but less frequent exercise was not effective. Brief high-impact exercise may have a role in reducing hip fragility, but may need to be performed frequently for optimal response. Copyright 2009 Elsevier Inc. All rights reserved.

Time of flight secondary ion mass spectrometry of bone-Impact of sample preparation and measurement conditions.

PubMed

Henss, Anja; Hild, Anne; Rohnke, Marcus; Wenisch, Sabine; Janek, Juergen

2015-06-07

Time of flight secondary ion mass spectrometry (ToF-SIMS) enables the simultaneous detection of organic and inorganic ions and fragments with high mass and spatial resolution. Due to recent technical developments, ToF-SIMS has been increasingly applied in the life sciences where sample preparation plays an eminent role for the quality of the analytical results. This paper focusses on sample preparation of bone tissue and its impact on ToF-SIMS analysis. The analysis of bone is important for the understanding of bone diseases and the development of replacement materials and new drugs for the cure of diseased bone. The main purpose of this paper is to find out which preparation process is best suited for ToF-SIMS analysis of bone tissue in order to obtain reliable and reproducible analytical results. The influence of the embedding process on the different components of bone is evaluated using principal component analysis. It is shown that epoxy resin as well as methacrylate based plastics (Epon and Technovit) as embedding materials do not infiltrate the mineralized tissue and that cut sections are better suited for the ToF-SIMS analysis than ground sections. In case of ground samples, a resin layer is smeared over the sample surface due to the polishing step and overlap of peaks is found. Beside some signals of fatty acids in the negative ion mode, the analysis of native, not embedded samples does not provide any advantage. The influence of bismuth bombardment and O2 flooding on the signal intensity of organic and inorganic fragments due to the variation of the ionization probability is additionally discussed. As C60 sputtering has to be applied to remove the smeared resin layer, its effect especially on the organic fragments of the bone is analyzed and described herein.

Notched K-wire for low thermal damage bone drilling.

PubMed

Liu, Yao; Belmont, Barry; Wang, Yiwen; Tai, Bruce; Holmes, James; Shih, Albert

2017-07-01

The Kirschner wire (K-wire) is a common bone drilling tool in orthopedic surgery to affix fractured bone. Significant heat is produced due to both the cutting and the friction between the K-wire and the bone debris during drilling. Such heat can result in high temperatures, leading to osteonecrosis and other secondary injuries. To reduce thermal injury and other high-temperature associated complications, a new K-wire design with three notches along the three-plane trocar tip fabricated using a thin micro-saw tool is studied. These notches evacuate bone debris and reduce the clogging and heat generation during bone drilling. A set of four K-wires, one without notches and three notched, with depths of 0.5, 0.75, and 1mm, are evaluated. Bone drilling experiments conducted on bovine cortical bone show that notched K-wires could effectively decrease the temperature, thrust force, and torque during bone drilling. K-wires with notches 1mm deep reduced the thrust force and torque by approximately 30%, reduced peak temperatures by 43%, and eliminated blackened burn marks in bone. This study demonstrates that a simple modification of the tip of K-wires can effectively reduce bone temperatures during drilling. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

The Endocrine Role of Estrogens on Human Male Skeleton

PubMed Central

Rochira, Vincenzo; Kara, Elda; Carani, Cesare

2015-01-01

Before the characterization of human and animal models of estrogen deficiency, estrogen action was confined in the context of the female bone. These interesting models uncovered a wide spectrum of unexpected estrogen actions on bone in males, allowing the formulation of an estrogen-centric theory useful to explain how sex steroids act on bone in men. Most of the principal physiological events that take place in the developing and mature male bone are now considered to be under the control of estrogen. Estrogen determines the acceleration of bone elongation at puberty, epiphyseal closure, harmonic skeletal proportions, the achievement of peak bone mass, and the maintenance of bone mass. Furthermore, it seems to crosstalk with androgen even in the determination of bone size, a more androgen-dependent phenomenon. At puberty, epiphyseal closure and growth arrest occur when a critical number of estrogens is reached. The same mechanism based on a critical threshold of serum estradiol seems to operate in men during adulthood for bone mass maintenance via the modulation of bone formation and resorption in men. This threshold should be better identified in-between the ranges of 15 and 25 pg/mL. Future basic and clinical research will optimize strategies for the management of bone diseases related to estrogen deficiency in men. PMID:25873947

rhG-CSF in healthy donors: mobilization of peripheral hemopoietic progenitors and effect on peripheral blood leukocytes.

PubMed

Sica, S; Rutella, S; Di Mario, A; Salutari, P; Rumi, C; Ortu la Barbera, E; Etuk, B; Menichella, G; D'Onofrio, G; Leone, G

1996-08-01

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) 16 micrograms/kg/day was given to 9 healthy donors to recruit hemopoietic progenitors (HP) for allogeneic transplantation or donor leukocyte infusion. rhG-CSF was administered s.c. for 5 days. No side effects were encountered except for moderate bone pain and lumbago. Mobilization was effective, reaching a peak median value of 187 x 10(3) CD34+ cells/ml (range 51.2-1127) and 2170 x 10(3) colony-forming units-granulocyte macrophage (CFU-GM)/ml (range 1138-4190). Peak values were obtained at a median of 4 days of rhG-CSF and represented, respectively, a 13-fold and a 37-fold increase from baseline values (p = 0.0007 and p = 0.006). White blood cell (WBC) counts increased 6-fold from baseline values (p < 0.0007) and reached a median peak of 34 x 10(6)/ml (23.5-59). Polymorphonuclear (PMN), and mononuclear (MNC) cells increased 10-fold and 2-fold, respectively (p = 0.0039 and p = 0.0026) and reached a median peak of 32.1 x 10(6)/ml (18.2-52) and 4.42 x 10(6)/ml (3.14-12.42). Absolute lymphocyte and monocyte counts increased at peak day in all donors 1.5-fold and 5.7-fold from baseline values (p = 0.0017 and p = 0.0018). In 7 of 9 donors, lymphocyte subsets were analyzed in detail. CD3+ and CD19+ lymphocytes increased 1.5-fold and 3-fold, respectively (p = 0.032 for both). NK and activated T lymphocytes doubled at a median of 4 days of rhG-CSF (p = 0.032 and p = NS, respectively). Similar changes were observed in lymphocytes collected in leukapheresis product. T helper and T suppressor subsets displayed a similar increase. Thus, besides the anticipated priming effect on HP and PMN, rhG-CSF in healthy donors produced an unexpected and still unexplained modification of lymphocyte subsets in peripheral blood.

Osteoporotic Animal Models of Bone Healing: Advantages and Pitfalls.

PubMed

Calciolari, Elena; Donos, Nikolaos; Mardas, Nikos

2017-10-01

The aim of this review was to summarize the advantages and pitfalls of the available osteoporotic animal models of bone healing. A thorough literature search was performed in MEDLINE via OVID and EMBASE to identify animal studies investigating the effect of experimental osteoporosis on bone healing and bone regeneration. The osteotomy model in the proximal tibia is the most popular osseous defect model to study the bone healing process in osteoporotic-like conditions, although other well-characterized models, such as the post-extraction model, might be taken into consideration by future studies. The regenerative potential of osteoporotic bone and its response to biomaterials/regenerative techniques has not been clarified yet, and the critical size defect model might be an appropriate tool to serve this purpose. Since an ideal animal model for simulating osteoporosis does not exist, the type of bone remodeling, the animal lifespan, the age of peak bone mass, and the economic and ethical implications should be considered in our selection process. Furthermore, the influence of animal species, sex, age, and strain on the outcome measurement should be taken into account. In order to make future studies meaningful, standardized international guidelines for osteoporotic animal models of bone healing need to be set up.

Building osteoporosis prevention into dental practice.

PubMed

Stewart, Stacey; Hanning, Rhona

2012-01-01

The National Report Card on Osteoporosis Care (2008) announced the need for comprehensive approaches to risk reduction and improvement in the early diagnosis of osteoporosis. Dental research has suggested that low systemic bone-mineral density also occurs in alveolar bone, and people with osteoporosis may have an increased risk of tooth loss. Whether or not a causal link exists, both conditions share similar modifiable risk factors, including a role for calcium and vitamin D. The purpose of this paper was to critically examine the role calcium and vitamin D play in the relationship between osteoporosis and the risk of tooth loss. Scientific articles were obtained through PubMed, MEDLINE, CINAHL, AgeLine and Web of Science. Publications were restricted to those involving human subjects, and English-language articles on calcium and vitamin D. The search yielded 8 articles relating to osteoporosis and tooth loss that included calcium and vitamin D intake. Despite methodological concerns, the evidence shows a relationship between osteoporosis and tooth loss for people who have an inadequate intake of calcium and vitamin D. Adequate calcium intake positively influences optimal peak bone mass and may also assist in tooth retention in later life. The dental sector can assist with national prevention strategies for osteoporosis care.

Designing the method for optical in vitro monitoring of the cell-mediated scaffold technology for bone regeneration based on laser-induced fluorescence spectroscopy

NASA Astrophysics Data System (ADS)

Larionov, P. M.; Maslov, N. A.; Papaeva, E. O.; Tereshchenko, V. P.; Khlestkin, V. K.; Bogachev, S. S.; Proskurina, A. S.; Titov, A. T.; Filipenko, M. L.; Pavlov, V. V.; Kudrov, G. A.; Orishich, A. M.

2016-08-01

One of the main unsolved problems in traumatology and orthopedics is reconstruction of critical-sized segmental bone defects. We believe that implementation of noninvasive monitoring of the bioengineering stages for cell-mediated bone scaffold by laser-induced fluorescence (LIF) can become a positive aspect in mastering this technique. An electrospun scaffold model (parameters: 10 wt. % polycaprolactone; 5% wt type A gelatin; mean fiber diameter 877.1 ± 169.1, and contact angle 45.3°) seeded with BHK IR cell culture (182 ± 38 cells/mm2) was used to show the principal possibility of differentiating between the scaffold seeded and unseeded with cells. First of all, the fluorescence spectra of the cell-seeded scaffold contain a peak at 305 nm for the excitation range of 230-290 nm, which can be used to differentiate between the samples. An increase in fluorescence intensity of the cell-seeded scaffold in the range of 400- 580 nm upon excitation at 230-340 nm is also noticeable. The wavelength of 250 nm is characterized by high signal intensity and is most suitable for differentiation between the samples.

Adaptations of young adult rat cortical bone to 14 days of spaceflight

NASA Technical Reports Server (NTRS)

Vailas, A. C.; Vanderby, R., Jr.; Martinez, D. A.; Ashman, R. B.; Ulm, M. J.; Grindeland, R. E.; Durnova, G. N.; Kaplanskii, A.

1992-01-01

To determine whether mature humeral cortical bone would be modified significantly by an acute exposure to weightlessness, adult rats (110 days old) were subjected to 14 days of microgravity on the COSMOS 2044 biosatellite. There were no significant changes in peak force, stiffness, energy to failure, and displacement at failure in the flight rats compared with ground-based controls. Concentrations and contents of hydroxyproline, calcium, and mature stable hydroxylysylpyridinoline and lysylpyridinoline collagen cross-links remained unchanged after spaceflight. Bone lengths, cortical and endosteal areas, and regionl thicknesses showed no significant differences between flight animals and ground controls. The findings suggest that responsiveness of cortical bone to microgravity is less pronounced in adult rats than in previous spaceflight experiments in which young growing animals were used. It is hypothesized that 14 days of spaceflight may not be sufficient to impact the biochemical and biomechanical properties of cortical bone in the mature rat skeleton.

Muscle, bone, and the Utah paradigm: a 1999 overview.

PubMed

Frost, H M

2000-05-01

The still-evolving Utah paradigm of skeletal physiology supplements former ideas about the control of postnatal bone strength and "mass" in health and disease, on earth and in orbit, and as functions of physical activities including sports. In its view, peak muscle forces on bone dominate control of the biologic mechanisms that control changes in our postnatal whole-bone strength and mass. This contrasts with former ideas that chiefly nonmechanical factors dominate that control and mechanical factors have little influence on it. The newer view begs the question of how such a bone-muscle relationship would work, and the Utah paradigm offers plausible explanations for that. Whereas many biomechanicians, orthopedists, and sports medicine experts might find the newer view sensible, some people in other disciplines may not. This article summarizes some evidence that support the Utah paradigm and the above-stated view and explores some of the paradigm's features and implications.

High intake of milk, but not meat, decreases bone turnover in prepubertal boys after 7 days.

PubMed

Budek, A Z; Hoppe, C; Michaelsen, K F; Mølgaard, C

2007-08-01

To compare the short-term effect of a high milk and a high meat intake, identical in protein amount, on bone turnover during prepuberty. A University department. From 28, randomly recruited, 8-year-old boys, first 14 were assigned to the milk group and next 14 to the meat group. In each group, 12 boys finished the dietary intervention. Milk (1.5 l/day) and meat (250 g/d), both containing approximately 53 g of protein, were given together with the habitual diet for 7 days. At baseline and day-7, serum osteocalcin (s-OC), bone-specific alkaline phosphatase (s-BAP) and C-terminal telopeptides of type I collagen (s-CTX) were measured (immunoassay) and dietary intake was estimated (a 3-day weighted food record). Baseline s-OC, s-BAP and s-CTX were not significantly different between the groups. After 7 days, the average protein intake increased in both groups by 47.5 g; the milk group had higher (P<0.0001) calcium intake; s-OC and s-CTX decreased (P< or =0.04) in the milk group (-30.9%; -18.7%, respectively) compared with the meat group (+6.4%; -1.0%, respectively) and s-BAP decreased (P=0.06) both in the milk (-3.9%) and the meat group (-7.5%). At the equal protein intake, milk, but not meat, decreased bone turnover in prepubertal boys after 7 days. This effect was probably due to some milk-derived compounds, rather than to the total protein intake. Future studies should elucidate the mechanism(s) of milk-related decline of bone turnover and its relevance for peak bone mass during growth. University PhD scholarships.

Fabrication of hydroxyapatite from fish bones waste using reflux method

NASA Astrophysics Data System (ADS)

Cahyanto, A.; Kosasih, E.; Aripin, D.; Hasratiningsih, Z.

2017-02-01

The aim of this present study was to investigate the fabrication of hydroxyapatites, which were synthesized from fish bone wastes using reflux method. The fish bone wastes collected from the restaurant were brushed and boiled at 100°C for 10 minutes to remove debris and fat. After drying, the fish bones were crushed, and ball milled into a fine powder. The fish bone wastes were then processed by refluxing using KOH and H3PO4 solutions. The samples were calcined at 900°C and characterized by X-Ray Diffraction (XRD) and Fourier Transform Infrared Spectrometry (FT-IR). The XRD pattern of samples after treatment revealed that the peak of hydroxyapatite was observed and the bands of OH- and PO4 3- were observed by FT-IR. The scanning electron microscope evaluation of sample showed the entangled crystal and porous structure of hydroxyapatite. In conclusion, the hydroxyapatite was successfully synthesized from fish bone wastes using reflux method.

Ferromagnetic resonance in the ethmoid bones of salmon and silver carp

NASA Astrophysics Data System (ADS)

Gorobets, Svitlana; Gorobets, Oksana; Golub, Volodymyr; Gromnadska, Marina

2017-10-01

The detection of biogenic magnetic nanoparticles (BMN) with different magnetic properties in biological material was done using magnetic resonance (MR) spectroscopy. MR spectra of biological material of ethmoid bone of salmon (containing ferritin and BMN), bacteria E. coli K13 (containing ferritin and without BMN), yeast S. cerevisiae (without ferritin or BMN) and ethmoid bone of silver carp (containing ferritin and not investigated for the presence of BMN) were investigated. The analysis of MR spectra shows that S. cerevisiae cells produce much lower signal MR than samples of ethmoid bones of salmon and silver carp which is confirming conclusions about the presence of BMN and ferritin in the ethmoid bones of fishes. The narrow MR linewidth indicates that the magnetic particles in the ethmoid bones of salmon and silver carp are in monodisperse state. The presence of a broad line and the absence of a narrow peak in MR spectrum of E. coli K13 cells are typical for ferritin.

Physical activity during life course and bone mass: a systematic review of methods and findings from cohort studies with young adults

PubMed Central

2013-01-01

Background The purpose of this paper was to review the literature of the cohort studies which evaluated the association between physical activity during the life course and bone mineral content or density in young adults. Methods Prospective cohort studies with bone mineral density or content measured in the whole body, lumbar spine and femoral neck by dual energy x-ray absorptiometry as outcome and physical activity as exposure were searched. Two independent reviewers selected studies retrieved from electronic databases (Medline, Lilacs, Web of Science and Scielo) and reviewed references of all selected full text articles. Downs & Black criterion was used in the quality assessment of these studies. Results Nineteen manuscripts met inclusion criteria. Lumbar spine was the skeletal site most studied (n = 15). Different questionnaires were used for physical activity evaluation. Peak strain score was also used to evaluate physical activity in 5 manuscripts. Lack of statistical power calculation was the main problem found in the quality assessment. Positive associations between physical activity and bone mass were found more in males than in females; in weight bearing anatomical sites (lumbar spine and femoral neck) than in total body and when physical activity measurements were done from adolescence to adulthood – than when evaluated in only one period. Physical activity during growth period was associated with greater bone mass in males. It was not possible to conduct pooled analyses due to the heterogeneity of the studies, considering mainly the different instruments used for physical activity measurements. Conclusions Physical activity seems to be important for bone mass in all periods of life, but especially the growth period should be taking into account due to its important direct effect on bone mass and its influence in physical activity practice in later life. Low participation in peak strain activities may also explain the lower number of associations found in females. PMID:23497066

Replication of Previous Genome-wide Association Studies of Bone Mineral Density in Premenopausal American Women

PubMed Central

Ichikawa, Shoji; Koller, Daniel L; Padgett, Leah R; Lai, Dongbing; Hui, Siu L; Peacock, Munro; Foroud, Tatiana; Econs, Michael J

2010-01-01

Bone mineral density (BMD) achieved during young adulthood (peak BMD) is one of the major determinants of osteoporotic fracture in later life. Genetic variants associated with BMD have been identified by three recent genome-wide association studies. The most significant single-nucleotide polymorphisms (SNPs) from these studies were genotyped to test whether they were associated with peak BMD in premenopausal American women. Femoral neck and lumbar spine BMD were determined by dual-energy X-ray absorptiometry in two groups of premenopausal women: 1524 white women and 512 black women. In premenopausal white women, two SNPs in the C6orf97/ESR1 region were significantly associated with BMD (p < 4.8 × 10−4), with suggestive evidence for CTNNBL1 and LRP5 (p < .01). Evidence of association with one of the two SNPs in the C6orf97/ESR1 region also was observed in premenopausal black women. Furthermore, SNPs in SP7 and a chromosome 4 intergenic region showed suggestive association with BMD in black women. Detailed analyses of additional SNPs in the C6orf97/ESR1 region revealed multiple genomic blocks independently associated with femoral neck and lumbar spine BMD. Findings in the three published genome-wide association studies were replicated in independent samples of premenopausal American women, suggesting that genetic variants in these genes or regions contribute to peak BMD in healthy women in various populations. © 2010 American Society for Bone and Mineral Research. PMID:20200978

Development of finite element model for customized prostheses design for patient with pelvic bone tumor.

PubMed

Iqbal, Taimoor; Shi, Lei; Wang, Ling; Liu, Yaxiong; Li, Dichen; Qin, Mian; Jin, Zhongmin

2017-06-01

The aim of this study was to design a hemi-pelvic prosthesis for a patient affected by pelvic sarcoma. To investigate the biomechanical functionality of the pelvis reconstructed with designed custom-made prosthesis, a patient-specific finite element model of whole pelvis with primary ligaments inclusive was constructed based on the computed tomography images of the patient. Then, a finite element analysis was performed to calculate and compare the stress distribution between the normal and implanted pelvis models when undergoing three different static conditions-both-leg standing, single-leg standing for the healthy and the affected one. No significant differences were observed in the stresses between the normal and reconstructed pelvis for both-leg standing, but 20%-40% larger stresses were predicted for the peak stress of the single-leg standing (affected side). Moreover, two- to threefold of peak stresses were predicted within the prostheses compared to that of the normal pelvis especially for single-leg standing case, however, still below the allowable fatigue limitation. The study on the load transmission functionality of prosthesis indicated that it is crucial to carry out finite element analysis for functional evaluation of the designed customized prostheses before three-dimensional printing manufacturing, allowing better understanding of the possible peak stresses within the bone as well as the implants for safety precaution. The finite element model can be equally applicable to other bone tumor model for biomechanical studying.

[Multiple myeloma (IgG-kappa) infiltrating central nervous system, lymph nodes, liver, and kidneys, and with elevation of IgE].

PubMed

Toyota, Shigeo; Nakamura, Norihiko; Dan, Kazuo

2004-05-01

A 63-year-old man was admitted because of general malaise, fever, headache, generalized lymphadenopathy and hepatomegaly in July 2002. He was diagnosed as having multiple myeloma (MM) (IgG-kappa type) with atypical plasma cells in the bone marrow, lymph nodes and cerebrospinal fluid. Systemic and intrathecal chemotherapy were effective. Because of an increase of polyclonal IgE, electrophoretic patterns revealed an M-peak which was not as sharp as that in IgG myeloma. IgE production is not impaired by the pathologic process in MM patients.

[Role of physical activity in the prevention of osteoporosis].

PubMed

Siegrist, Monika

2008-07-01

In recent years, osteoporosis has become a leading cause of morbidity and mortality in elderly women. Research has demonstrated that the prevention of osteoporosis and osteoporosis-related fractures may best be achieved by initiating sound health behaviors early in life and continuing them throughout life. Evidence suggests that osteoporosis is easier to prevent than to treat. In fact, healthy early life practices, including the adequate consumption of most nutrients, calcium in particular, and regular physical activity, contribute to greater bone mineral mass and optimal peak bone mass. Bone is living tissue that responds to exercise by becoming stronger. Two types of exercises are important for building and maintaining bone mass and density: Weight-bearing exercises, in which bones and muscles work against gravity and resistance training that use muscular strength to improve muscle mass and strengthen bone. Exercise can also improve gait, balance, coordination, proprioception, reaction time, and muscle strength, even in very old and frail elderly people. Overall, the evidence strongly suggests that regular physical activity, especially started in childhood and adolescence, is a cheap and safe way of both improving bone strength and reducing the risk to fall.

Bone density changes in premature ovarian insufficiency patients who have had term pregnancies.

PubMed

Velasco, Mariana; Holloway, Debra; Rymer, Janice

2014-12-01

Premature ovarian insufficiency affects 1% of women under the age of 40 and is associated with a hypoestrogenic state, potentially leading to multiple comorbidities including reduced bone density and fertility. An unpredictable ovarian function is observed in 50% of patients with 5-10% being able to achieve a pregnancy. Longitudinal studies have shown a temporary decline in bone mineral density of up to 5% during pregnancy and lactation in healthy women, with the loss of bone density post-partum being proportional to the period of breastfeeding. Effects of pregnancy in women with premature ovarian insufficiency have not been widely documented. Nevertheless, a lower bone mineral density baseline has been observed pre-conceptually, associated with both the hypoestrogenic state of the condition and the possibility that premature ovarian insufficiency was developed prior to achieving peak bone mass. This may suggest that breastfeeding could cause further deterioration in bone mineral density that may not be easy to recover from due to the reduced baseline levels. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Hemorrhage Near Fetal Rat Bone: Preliminary Results

NASA Astrophysics Data System (ADS)

Bigelow, Timothy A.; Miller, Rita J.; Blue, James P.; O'Brien, William D.

2006-05-01

High-intensity ultrasound has shown potential in treating many ailments requiring noninvasive tissue necrosis. However, little work has been done on using ultrasound to ablate pathologies on or near the developing fetus. For example, Congenital Cystic Adenomatoid Malformation (cyst on lungs), Sacrococcygeal Teratoma (benign tumor on tail bone), and Twin-Twin Transfusion Syndrome (one twin pumps blood to other twin) are selected problems that will potentially benefit from noninvasive ultrasound treatments. Before these applications can be explored, potential ultrasound-induced bioeffects should be understood. Specifically, ultrasound-induced hemorrhage near the fetal rat skull was investigated. An f/1 spherically focused transducer (5.1-cm focal length) was used to expose the skull of 18- to 19-day-gestation exteriorized rat fetuses. The ultrasound pulse had a center frequency of 0.92 MHz and pulse duration of 9.6 μs. The fetuses were exposed to 1 of 4 exposure conditions (denoted A, B, C, and D) in addition to a sham exposure. Three of the exposures consisted of a peak compressional pressure of 10 MPa, a peak rarefactional pressure of 6.7 MPa, and pulse repetition frequencies of 100 Hz (A), 250 Hz (B), and 500 Hz (C), corresponding to time-average intensities of 1.9 W/cm2, 4.7 W/cm2, and 9.4 W/cm2, respectively. Exposure D consisted of a peak compressional pressure of 6.7 MPa, a peak rarefactional pressure of 5.0 MPa, and a PRF of 500 Hz corresponding to a time-average intensity of 4.6 W/cm2. Hemorrhage occurrence increased slightly with increasing time-average intensity (i.e., 11% for A, 28% for B, 31% for C, and 19% for D with a 9% occurrence when the fetuses were not exposed). The low overall occurrence of hemorrhaging may be attributed to fetal motion (observed in over half of the fetuses from the backscattered echo during the exposure). The mean hemorrhage sizes were 3.1 mm2 for A, 2.5 mm2 for B, 2.7 mm2 for C, and 5.1 mm2 for D. The larger lesions at D may be related to these fetuses moving less as only 40% of the fetuses were observed moving for this exposure condition.

Effects of 16-week high-intensity interval training using upper and lower body ergometers on aerobic fitness and morphological changes in healthy men: a preliminary study

PubMed Central

Osawa, Yusuke; Azuma, Koichiro; Tabata, Shogo; Katsukawa, Fuminori; Ishida, Hiroyuki; Oguma, Yuko; Kawai, Toshihide; Itoh, Hiroshi; Okuda, Shigeo; Matsumoto, Hideo

2014-01-01

It is unclear whether combined leg and arm high-intensity interval training (HIIT) improves fitness and morphological characteristics equal to those of leg-based HIIT programs. The aim of this study was to compare the effects of HIIT using leg-cycling (LC) and arm-cranking (AC) ergometers with an HIIT program using only LC. Effects on aerobic capacity and skeletal muscle were analyzed. Twelve healthy male subjects were assigned into two groups. One performed LC-HIIT (n=7) and the other LC- and AC-HIIT (n=5) twice weekly for 16 weeks. The training programs consisted of eight to 12 sets of >90% VO2 (the oxygen uptake that can be utilized in one minute) peak for 60 seconds with a 60-second active rest period. VO2 peak, watt peak, and heart rate were measured during an LC incremental exercise test. The cross-sectional area (CSA) of trunk and thigh muscles as well as bone-free lean body mass were measured using magnetic resonance imaging and dual-energy X-ray absorptiometry. The watt peak increased from baseline in both the LC (23%±38%; P<0.05) and the LC–AC groups (11%±9%; P<0.05). The CSA of the quadriceps femoris muscles also increased from baseline in both the LC (11%±4%; P<0.05) and the LC–AC groups (5%±5%; P<0.05). In contrast, increases were observed in the CSA of musculus psoas major (9%±11%) and musculus anterolateral abdominal (7%±4%) only in the LC–AC group. These results suggest that a combined LC- and AC-HIIT program improves aerobic capacity and muscle hypertrophy in both leg and trunk muscles. PMID:25395872

Effects of 16-week high-intensity interval training using upper and lower body ergometers on aerobic fitness and morphological changes in healthy men: a preliminary study.

PubMed

Osawa, Yusuke; Azuma, Koichiro; Tabata, Shogo; Katsukawa, Fuminori; Ishida, Hiroyuki; Oguma, Yuko; Kawai, Toshihide; Itoh, Hiroshi; Okuda, Shigeo; Matsumoto, Hideo

2014-01-01

It is unclear whether combined leg and arm high-intensity interval training (HIIT) improves fitness and morphological characteristics equal to those of leg-based HIIT programs. The aim of this study was to compare the effects of HIIT using leg-cycling (LC) and arm-cranking (AC) ergometers with an HIIT program using only LC. Effects on aerobic capacity and skeletal muscle were analyzed. Twelve healthy male subjects were assigned into two groups. One performed LC-HIIT (n=7) and the other LC- and AC-HIIT (n=5) twice weekly for 16 weeks. The training programs consisted of eight to 12 sets of >90% VO2 (the oxygen uptake that can be utilized in one minute) peak for 60 seconds with a 60-second active rest period. VO2 peak, watt peak, and heart rate were measured during an LC incremental exercise test. The cross-sectional area (CSA) of trunk and thigh muscles as well as bone-free lean body mass were measured using magnetic resonance imaging and dual-energy X-ray absorptiometry. The watt peak increased from baseline in both the LC (23%±38%; P<0.05) and the LC-AC groups (11%±9%; P<0.05). The CSA of the quadriceps femoris muscles also increased from baseline in both the LC (11%±4%; P<0.05) and the LC-AC groups (5%±5%; P<0.05). In contrast, increases were observed in the CSA of musculus psoas major (9%±11%) and musculus anterolateral abdominal (7%±4%) only in the LC-AC group. These results suggest that a combined LC- and AC-HIIT program improves aerobic capacity and muscle hypertrophy in both leg and trunk muscles.

Effect of tibial bone resection on the development of fast- and slow-twitch skeletal muscles in foetal sheep.

PubMed

West, J M; Williams, N A; Luff, A R; Walker, D W

2000-04-01

To determine if longitudinal bone growth affects the differentiation of fast- and slow-twitch muscles, the tibial bone was sectioned at 90 days gestation in foetal sheep so that the lower leg was permanently without structural support. At 140 days (term is approximately 147 days) the contractile properties of whole muscles, activation profiles of single fibres and ultrastructure of fast- and slow-twitch muscles from the hindlimbs were studied. The contractile and activation profiles of the slow-twitch soleus muscles were significantly affected by tibial bone resection (TIBX). The soleus muscles from the TIBX hindlimbs showed: (1) a decrease in the time to peak of the twitch responses from 106.2 +/- 10.7 ms (control, n = 4) to 65.1 +/- 2.48 ms (TIBX, n = 5); (2) fatigue profiles more characteristic of those observed in the fast-twitch muscles: and (3) Ca2+ - and Sr2+ -activation profiles of skinned fibres similar to those from intact hindlimbs at earlier stages of gestation. In the FDL, TIBX did not significantly change whole muscle twitch contraction time, the fatigue profile or the Ca2+ - and Sr2+ -activation profiles of skinned fibres. Electron microscopy showed an increased deposition of glycogen in both soleus and FDL muscles. This study shows that the development of the slow-twitch phenotype is impeded in the absence of the physical support normally provided by the tibial bone. We suggest that longitudinal stretch is an important factor in allowing full expression of the slow-twitch phenotype.

Quantification of osteoblastic activity in epiphyseal growth plates by quantitative bone SPECT/CT.

PubMed

Yamane, Tomohiko; Kuji, Ichiei; Seto, Akira; Matsunari, Ichiro

2018-06-01

Quantifying the function of the epiphyseal plate is worthwhile for the management of children with growth disorders. The aim of this retrospective study was to quantify the osteoblastic activity at the epiphyseal plate using the quantitative bone SPECT/CT. We enrolled patients under the age of 20 years who received Tc-99m hydroxymethylene diphosphonate bone scintigraphy acquired by a quantitative SPECT/CT scanner. The images were reconstructed by ordered subset conjugate-gradient minimizer, and the uptake on the distal margin of the femur was quantified by peak standardized uptake value (SUVpeak). A public database of standard body height was used to calculate growth velocities (cm/year). Fifteen patients (6.9-19.7 years, 9 female, 6 male) were enrolled and a total of 25 legs were analyzed. SUVpeak in the epiphyseal plate was 18.9 ± 2.4 (average ± standard deviation) in the subjects under 15 years and decreased gradually by aging. The SUVpeak correlated significantly with the age- and sex-matched growth velocity obtained from the database (R 2  = 0.83, p < 0.0001). The SUV measured by quantitative bone SPECT/CT was increased at the epiphyseal plates of children under the age of 15 years in comparison with the older group, corresponding to higher osteoblastic activity. Moreover, this study suggested a correlation between growth velocity and the SUV. Although this is a small retrospective pilot study, the objective and quantitative values measured by the quantitative bone SPECT/CT has the potential to improve the management of children with growth disorder.

Influence of ghrelin and adipocytokines on bone mineral density in adolescent female athletes with amenorrhea and eumenorrheic athletes.

PubMed

Russell, Melissa; Misra, Madhusmita

2010-01-01

Adolescent female athletes are at increased risk for low bone mineral density (BMD) secondary to exercise-induced hypogonadism. Of particular concern is that the adolescent years are also a critical time for bone accrual, and deficits incurred during this period could lead to suboptimal peak bone mass acquisition and subsequent fracture risk in later life. Although weight-bearing exercise is typically associated with an increase in BMD, amenorrheic athletes have lower BMD than eumenorrheic athletes and nonathletic controls as a consequence of low energy availability and subsequent hypogonadism. It is important to recognize that critical interactions exist between net energy availability and the hypothalamo-pituitary-gonadal (H-P-G) axis that are key to the development of a hypogonadal state when energy intake cannot keep pace with expenditure. While the link between energy availability and gonadtotropin pulsatility patterns is well established, the actual metabolic signals that link the two are less clear. Decreased energy availability in athletes is associated with decreases in fat mass, and alterations in adipokines (such as leptin and adiponectin) and fat-regulated hormones (such as ghrelin and peptide YY). These hormones impact the H-P-G axis in animal models, and it is possible that in athletes alterations in fat-related hormones signal the state of energy availability to the hypothalamus and contribute to suppression of gonadotropin pulsatility, hypothalamic amenorrhea and consequent decreased BMD. A better understanding of pathways linking low energy availability with functional hypothalamic amenorrhea and low BMD is critical for the development of future therapeutic strategies addressing these issues in amenorrheic athletes. Copyright © 2010 S. Karger AG, Basel.

Influence of Ghrelin and Adipocytokines on Bone Mineral Density in Adolescent Female Athletes with Amenorrhea and Eumenorrheic Athletes

PubMed Central

Russell, Melissa; Misra, Madhusmita

2013-01-01

Adolescent female athletes are at increased risk for low bone mineral density (BMD) secondary to exercise-induced hypogonadism. Of particular concern is that the adolescent years are also a critical time for bone accrual, and deficits incurred during this period could lead to suboptimal peak bone mass acquisition and subsequent fracture risk in later life. Although weight bearing exercise is typically associated with an increase in BMD, amenorrheic athletes have lower BMD than eumenorrheic athletes and non-athletic controls as a consequence of low energy availability and subsequent hypogonadism. It is important to recognize that critical interactions exist between net energy availability and the hypothalamo-pituitary-gonadal (H-P-G) axis that are key to the development of a hypogonadal state when energy intake cannot keep pace with expenditure. While the link between energy availability and gonadtotropin pulsatility patterns is well established, the actual metabolic signals that link the two are less clear. Decreased energy availability in athletes is associated with decreases in fat mass, and alterations in adipokines (such as leptin and adiponectin) and fat-regulated hormones (such as ghrelin and peptide YY). These hormones impact the H-P-G axis in animal models, and it is possible that in athletes alterations in fat-related hormones signal the state of energy availability to the hypothalamus and contribute to suppression of gonadotrophin pulsatility, hypothalamic amenorrhea and consequent decreased BMD. A better understanding of pathways linking low energy availability with functional hypothalamic amenorrhea and low BMD is critical for the development of future therapeutic strategies addressing these issues in amenorrheic athletes. PMID:20956863

Clinically Relevant Concentrations of Ketamine Inhibit Osteoclast Formation In Vitro in Mouse Bone Marrow Cultures.

PubMed

Du, Erxia; McAllister, Patrick; Venna, Venugopal Reddy; Xiao, Liping

2017-04-01

Ketamine has been used safely in clinics for decades for analgesia and anesthesia. It is increasingly popular in clinical practice due to its new uses and importance for emergency procedures. It is known that ketamine is sequestered in the bone marrow and the major receptors for ketamine, noncompetitive N-methyl-d-aspartate receptors (NMDARs), are expressed in osteoclasts (OCs) and osteoblasts. However, the impact of ketamine on OCs or osteoblasts is unknown. In this study, we investigated the effects of ketamine on osteoclastogenesis and regulation of NMDARs expression in vitro. Bone marrows (BMs) or bone marrow macrophages (BMMs) were cultured in the presence of macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-B ligand (RANKL) with or without ketamine for up to 6 days. OC formation peaked at day 5. On day 5 of culture, ketamine inhibited OC formation from both BM and BMM cultures at clinically relevant concentrations (3-200 µM). Ketamine inhibited RANKL-induced expression of nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1) in BMM cultures. Inhibition of ketamine on RANKL-induced osteoclastogenesis is associated with down-regulation of NMDARs. In addition, ketamine significantly inhibited the M-CSF induced migration of BMMs, inhibited cell fusion and significantly increased mature OC apoptosis. We conclude that clinically relevant concentrations of ketamine inhibit OC formation in both BM and BMM cultures in vitro through inhibiting migration and fusion process and enhancing mature OC apoptosis. It is likely that ketamine regulates osteoclastogenesis, at least in part, via its effects on NMDAR expression. J. Cell. Biochem. 118: 914-923, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Bone remodeling and calcium homeostasis in patients with spinal cord injury: a review.

PubMed

Maïmoun, Laurent; Fattal, Charles; Sultan, Charles

2011-12-01

Patients with spinal cord injury exhibit early and acute bone loss with the major functional consequence being a high incidence of pathological fractures. The bone status of these patients is generally investigated by dual-energy x-ray absorptiometry, but this technique does not reveal the pathophysiological mechanism underlying the bone loss. Bone cell activity can be indirectly evaluated by noninvasive techniques, including measurement of specific biochemical markers of bone formation (such as osteocalcin or bone-alkaline phosphatase) and resorption (such as procollagen type I N- or C-terminal propeptide). The bone loss in spinal cord injury is clearly due to an uncoupling of bone remodeling in favor of bone resorption, which starts just after the injury and peaks at about 1 to 4 months. Beyond 6 months, bone resorption activity decreases progressively but remains elevated for many years after injury. Conversely, bone formation is less affected. Antiresorptive treatment induces an early and acute reduction in bone resorption markers. Level of injury and health-related complications do not seem to be implicated in the intensity of bone resorption. During the acute phase, the hypercalcemic status is associated with the suppression of parathyroid hormone and vitamin D metabolites. The high sensitivity of these markers after treatment suggests that they can be used for monitoring treatment efficacy and patient compliance. The concomitant use of bone markers and dual-energy x-ray absorptiometry may improve the physician's ability to detect patients at risk of severe bone loss and subsequent fractures. Copyright © 2011 Elsevier Inc. All rights reserved.

Validation of cortical bone mineral density distribution using micro-computed tomography.

PubMed

Mashiatulla, Maleeha; Ross, Ryan D; Sumner, D Rick

2017-06-01

Changes in the bone mineral density distribution (BMDD), due to disease or drugs, can alter whole bone mechanical properties such as strength, stiffness and toughness. The methods currently available for assessing BMDD are destructive and two-dimensional. Micro-computed tomography (μCT) has been used extensively to quantify the three-dimensional geometry of bone and to measure the mean degree of mineralization, commonly called the tissue mineral density (TMD). The TMD measurement has been validated to ash density; however parameters describing the frequency distribution of TMD have not yet been validated. In the current study we tested the ability of μCT to estimate six BMDD parameters: mean, heterogeneity (assessed by the full-width-at-half-maximum (FWHM) and the coefficient of variation (CoV)), the upper and lower 5% cutoffs of the frequency distribution, and peak mineralization) in rat sized femoral cortical bone samples. We used backscatter scanning electron microscopy (bSEM) as the standard. Aluminum and hydroxyapatite phantoms were used to identify optimal scanner settings (70kVp, and 57μA, with a 1500ms integration time). When using hydroxyapatite samples that spanned a broad range of mineralization levels, high correlations were found between μCT and bSEM for all BMDD parameters (R 2 ≥0.92, p<0.010). When using cortical bone samples from rats and various species machined to mimic rat cortical bone geometry, significant correlations between μCT and bSEM were found for mean mineralization (R 2 =0.65, p<0.001), peak mineralization (R 2 =0.61, p<0.001) the lower 5% cutoff (R 2 =0.62, p<0.001) and the upper 5% cutoff (R 2 =0.33, p=0.021), but not for heterogeneity, measured by FWHM (R 2 =0.05, p=0.412) and CoV (R 2 =0.04, p=0.469). Thus, while mean mineralization and most parameters used to characterize the BMDD can be assessed with μCT in rat sized cortical bone samples, caution should be used when reporting the heterogeneity. Copyright © 2017 Elsevier Inc. All rights reserved.

Young's modulus and SEM analysis of leg bones exposed to simulated microgravity by hind limb suspension (HLS)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Patel, Niravkumar D.; Mehta, Rahul; Ali, Nawab

2013-04-19

The aim of this study was to determine composition of the leg bone tissue of rats that were exposed to simulated microgravity by Hind-Limb Suspension (HLS) by tail for one week. The leg bones were cross sectioned, cleaned of soft tissues, dried and sputter coated, and then placed horizontally on the stage of a Scanning Electron Microscope (SEM) for analysis. Interaction of a 17.5 keV electron beam, incident from the vertical direction on the sample, generated images using two detectors. X-rays emitted from the sample during electron bombardment were measured with an Energy Dispersive Spectroscopy (EDS) feature of SEM usingmore » a liquid-nitrogen cooled Si(Li) detector with a resolution of 144 eV at 5.9 keV ({sub 25}Mn K{sub {alpha}} x-ray). K{sub {alpha}}- x-rays from carbon, oxygen, phosphorus and calcium formed the major peaks in the spectrum. Relative percentages of these elements were determined using a software that could also correct for ZAF factors namely Z(atomic number), A(X-ray absorption) and F(characteristic fluorescence). The x-rays from the control groups and from the experimental (HLS) groups were analyzed on well-defined parts (femur, tibia and knee) of the leg bone. The SEM analysis shows that there are definite changes in the hydroxyl or phosphate group of the main component of the bone structure, hydroxyapatite [Ca{sub 10}(PO{sub 4}){sub 6}(OH){sub 2}], due to hind limb suspension. In a separate experiment, entire leg bones (both from HLS and control rats) were subjected to mechanical stress by mean of a variable force. The stress vs. strain graph was fitted with linear and polynomial function, and the parameters reflecting the mechanical strength of the bone, under increasing stress, were calculated. From the slope of the linear part of the graph the Young's modulus for HLS bones were calculated and found to be 2.49 times smaller than those for control bones.« less

Growth hormone treatment of growth failure secondary to total body irradiation and bone marrow transplantation.

PubMed Central

Papadimitriou, A; Urena, M; Hamill, G; Stanhope, R; Leiper, A D

1991-01-01

Growth hormone was given to 13 children (nine boys, four girls) with acute leukaemia who had undergone treatment with cyclophosphamide and total body irradiation before bone marrow transplantation. Mean age at total body irradiation and bone marrow transplantation was 9.0 years (range 3.7-15.8). Endocrinological investigation was carried out at a mean of 2.0 years (range 0.4-4.0) after bone marrow transplantation. Peak serum growth hormone responses to hypoglycaemia were less than 10.0 micrograms/l (less than 20.0 mU/l) in 10, 10.5 micrograms/l (21.0 mU/l) in one, greater than 16.0 micrograms/l (greater than 32.0 mU/l) in two patients. Mean age of the patients at the start of growth hormone treatment was 12.2 years (range 5.8-18.2). The mean time between total body irradiation and bone marrow transplantation and the start of growth hormone treatment was 3.2 years (range, 1.1-5.0). Height velocity SD score (SD) increased from a mean pretreatment value of -1.27 (0.65) to + 0.22 (0.81) in the first year, +0.16 (1.11) in the second year, and +0.42 (0.71) in the third year of treatment. Height SD score (SD) changed only slightly from -1.52 (0.42) to -1.50 (0.47) in the first year, to -1.50 (0.46) in the second year, and -1.74 (0.92) in the third year. Measurement of segmental proportions showed no significant increase in subischial leg length from -0.87 (0.67) to -0.63 (0.65) in the first year, to -0.58 (0.70) in the second year, and -0.80 (1.14) in the third year of treatment. Our data indicate that children who have undergone total body irradiation and bone marrow transplantation respond to treatment with growth hormone in either of two dose regimens, with an increase in height velocity that is adequate to restore a normal growth rate but not to 'catch up', and that total body irradiation impairs not only spinal but also leg growth, possibly by a direct effect of irradiation on the epiphyses and soft tissues. PMID:2053788

Ultra-Deep Bone Diagnostics with Fat-Skin Overlayers Using New Pulsed Photothermal Radar

NASA Astrophysics Data System (ADS)

Sreekumar, K.; Mandelis, A.

2013-09-01

The constraints imposed by the laser safety (maximum permissible exposure) ceiling on pump laser energy and the strong attenuation of thermal-wave signals in tissues significantly limit the photothermally active depth in most biological specimens to a level which is normally insufficient for practical applications (a few mm below the skin surface). A theoretical approach for improvement of the signal-to-noise ratio (SNR), minimizing the static (dc) component of the photothermal (PT) signal and making use of the PT radiometric nonlinearity has been introduced. At low frequencies fixed-pulse-width chirps of large peak power were found to be superior to all other equal energy modalities, with an SNR improvement by up to two orders of magnitude. Compared to radar peak delay and amplitude, the long-delayed radar output amplitude is found to be more sensitive to subsurface conditions. Two-dimensional spatial plots of this parameter depicting the back-surface conditions of bones with and without fat tissue overlayers are presented. Pulsed-chirp radar thermography has been demonstrated to monitor the degree of demineralization in goat rib bone with a substantial SNR and spatial resolution that is not practicable with harmonic radars of the same energy density.

Sensitivity and specificity of radiographic methods for predicting insertion torque of dental implants.

PubMed

Cortes, Arthur Rodriguez Gonzalez; Eimar, Hazem; Barbosa, Jorge de Sá; Costa, Claudio; Arita, Emiko Saito; Tamimi, Faleh

2015-05-01

Subjective radiographic classifications of alveolar bone have been proposed and correlated with implant insertion torque (IT). The present diagnostic study aims to identify quantitative bone features influencing IT and to use these findings to develop an objective radiographic classification for predicting IT. Demographics, panoramic radiographs (taken at the beginning of dental treatment), and cone-beam computed tomographic scans (taken for implant surgical planning) of 25 patients receiving 31 implants were analyzed. Bone samples retrieved from implant sites were assessed with dual x-ray absorptiometry, microcomputed tomography, and histology. Odds ratio, sensitivity, and specificity of all variables to predict high peak IT were assessed. A ridge cortical thickness >0.75 mm and a normal appearance of the inferior mandibular cortex were the most sensitive variables for predicting high peak IT (87.5% and 75%, respectively). A classification based on the combination of both variables presented high sensitivity (90.9%) and specificity (100%) for predicting IT. Within the limitations of this study, the results suggest that it is possible to predict IT accurately based on radiographic findings of the patient. This could be useful in the treatment plan of immediate loading cases.

The effect of short G-CSF administration on the numbers and clonogenic efficiency of hematopoietic progenitor cells in bone marrow and peripheral blood of normal donors.

PubMed

Zaucha, J M; Knopińska-Posłuszny, W; Bieniaszewska, M; Myśliwski, A; Hellmann, A

2000-01-01

We have analysed the cellularity, the number of clonogenic cells and their clonogenic efficiency (the number of clonogenic cells/2 x 10(5) MNC) in peripheral blood (PB) and bone marrow (BM) during and after filgrastim (rhG-CSF) mobilization of CD34+ cells in 12 healthy donors for allogeneic stem cell donation. G-CSF was administrated subcutaneously for 5 consecutive days at a dose of 10 micrograms/kg/day. WBC, MNC, CD34+ cell counts, CFU-GM and BFU-E assays in PB were performed at baseline and then daily 12 hours after each G-CSF dose. BM was assayed before start (day 1) and after the last dose (day 6) of G-CSF. Results are given as medians, with ranges in parentheses. In PB the total WBC and MNC increased 7.4-fold (6.0-12.3) and 3.3-fold (1.5-9.4), respectively, reaching a peak of 49.4 x 10(9)/l (32.5-66.6) on day 6 for WBC and 6.28 x 10(9)/l (4.7-13.3) for MNC on day 5. CD34+ cell number reached a peak value of 48.0 x 10(6)/l (45.6-285) on day 6 whereas CFU-GM and BFU-E reached their peaks on day 5, 0.95 x 10(4)/ml (0.05-6.08) and 1.04 x 10(4)/ml, respectively. CFU-MIX, not detectable at baseline, reached a peak of 0.95 x 10(4)/ml (0.006-0.51) on day 5 as well. This was accompanied by an increase in CFU-GM, BFU-E and CFU-MIX clonogenic efficiency: 23-fold (3-150), 9.75-fold (2.2-27.8) and 20-fold (2.5-210), respectively. In BM the total WBC number increased 2.5-fold (1.3-4.9) from the baseline value of 52.6 x 10(9)/l (7.9-137.0) whereas the MNC count increased 2.0-fold (0.81-3.7) from a baseline of 13.6 x 10(9)/l (3.5-54.8). This was, however, not significant. The number of CD34+ cells increased significantly 2.9-fold (0.8-8.3). In 8 donors CFU-MIX were detectable before but not after G-CSF treatment. A similar decrease in CFU-GM and BFU-E clonogenic efficiency occurred but was not significant. CFU-GM and BFU-E numbers did not change. We conclude that the total body numbers of lineage committed progenitors increased during G-CSF administration, which indicate their proliferation in addition to mobilization. The effect of G-CSF on the number of more primitive progenitors in BM is less clear and needs further investigation.

Heat generated during seating of dental implant fixtures.

PubMed

Flanagan, Dennis

2014-04-01

Frictional heat can be generated during seating of dental implants into a drill-prepared osteotomy. This in vitro study tested the heat generated by implant seating in dense bovine mandible ramus. A thermocouple was placed approximately 0.5 mm from the rim of the osteotomy during seating of each dental implant. Four diameters of implants were tested. The average temperature increases were 0.075°C for the 5.7-mm-diameter implant, 0.97°C for the 4.7-mm-diameter implant, 1.4°C for the 3.7-mm-diameter implant, and 8.6°C for the 2.5-mm-diameter implant. The results showed that heat was indeed generated and a small temperature rise occurred, apparently by the friction of the implant surface against the fresh-cut bone surface. Bone is a poor thermal conductor. The titanium of the implant and the steel of the handpiece are much better heat conductors. Titanium may be 70 times more heat conductive than bone. The larger diameter and displacement implant may act as a heat sink to draw away any heat produced from the friction of seating the implant at the bone-implant interface. The peak temperature duration was momentary, and not measured, but this was approximately less than 1 second. Except for the 2.5-mm-diameter implants, the temperature rises and durations were found to be below those previously deemed to be detrimental, so no clinically significant osseous damage would be expected during dental implant fixture seating of standard and large-diameter-sized implants. A 2.5-mm implant may generate detrimental heat during seating in nonvital bone, but this may be clinically insignificant in vital bone. The surface area and thermal conductivity are important factors in removing generated heat transfer at the bone-implant interface. The F value as determined by analysis of variance was 69.22, and the P value was less than .0001, demonstrating significant differences between the groups considered as a whole.

Monitoring Bacterial Burden, Inflammation and Bone Damage Longitudinally Using Optical and μCT Imaging in an Orthopaedic Implant Infection in Mice

PubMed Central

Niska, Jared A.; Meganck, Jeffrey A.; Pribaz, Jonathan R.; Shahbazian, Jonathan H.; Lim, Ed; Zhang, Ning; Rice, Brad W.; Akin, Ali; Ramos, Romela Irene; Bernthal, Nicholas M.; Francis, Kevin P.; Miller, Lloyd S.

2012-01-01

Background Recent advances in non-invasive optical, radiographic and μCT imaging provide an opportunity to monitor biological processes longitudinally in an anatomical context. One particularly relevant application for combining these modalities is to study orthopaedic implant infections. These infections are characterized by the formation of persistent bacterial biofilms on the implanted materials, causing inflammation, periprosthetic osteolysis, osteomyelitis, and bone damage, resulting in implant loosening and failure. Methodology/Principal Findings An orthopaedic implant infection model was used in which a titanium Kirshner-wire was surgically placed in femurs of LysEGFP mice, which possess EGFP-fluorescent neutrophils, and a bioluminescent S. aureus strain (Xen29; 1×103 CFUs) was inoculated in the knee joint before closure. In vivo bioluminescent, fluorescent, X-ray and μCT imaging were performed on various postoperative days. The bacterial bioluminescent signals of the S. aureus-infected mice peaked on day 19, before decreasing to a basal level of light, which remained measurable for the entire 48 day experiment. Neutrophil EGFP-fluorescent signals of the S. aureus-infected mice were statistically greater than uninfected mice on days 2 and 5, but afterwards the signals for both groups approached background levels of detection. To visualize the three-dimensional location of the bacterial infection and neutrophil infiltration, a diffuse optical tomography reconstruction algorithm was used to co-register the bioluminescent and fluorescent signals with μCT images. To quantify the anatomical bone changes on the μCT images, the outer bone volume of the distal femurs were measured using a semi-automated contour based segmentation process. The outer bone volume increased through day 48, indicating that bone damage continued during the implant infection. Conclusions/Significance Bioluminescent and fluorescent optical imaging was combined with X-ray and μCT imaging to provide noninvasive and longitudinal measurements of the dynamic changes in bacterial burden, neutrophil recruitment and bone damage in a mouse orthopaedic implant infection model. PMID:23082163

Time of flight secondary ion mass spectrometry of bone—Impact of sample preparation and measurement conditions

PubMed Central

Henss, Anja; Hild, Anne; Rohnke, Marcus; Wenisch, Sabine; Janek, Juergen

2015-01-01

Time of flight secondary ion mass spectrometry (ToF-SIMS) enables the simultaneous detection of organic and inorganic ions and fragments with high mass and spatial resolution. Due to recent technical developments, ToF-SIMS has been increasingly applied in the life sciences where sample preparation plays an eminent role for the quality of the analytical results. This paper focusses on sample preparation of bone tissue and its impact on ToF-SIMS analysis. The analysis of bone is important for the understanding of bone diseases and the development of replacement materials and new drugs for the cure of diseased bone. The main purpose of this paper is to find out which preparation process is best suited for ToF-SIMS analysis of bone tissue in order to obtain reliable and reproducible analytical results. The influence of the embedding process on the different components of bone is evaluated using principal component analysis. It is shown that epoxy resin as well as methacrylate based plastics (Epon and Technovit) as embedding materials do not infiltrate the mineralized tissue and that cut sections are better suited for the ToF-SIMS analysis than ground sections. In case of ground samples, a resin layer is smeared over the sample surface due to the polishing step and overlap of peaks is found. Beside some signals of fatty acids in the negative ion mode, the analysis of native, not embedded samples does not provide any advantage. The influence of bismuth bombardment and O2 flooding on the signal intensity of organic and inorganic fragments due to the variation of the ionization probability is additionally discussed. As C60 sputtering has to be applied to remove the smeared resin layer, its effect especially on the organic fragments of the bone is analyzed and described herein. PMID:26253108

Acoustic emission from trabecular bone during mechanical testing: the effect of osteoporosis and osteoarthritis.

PubMed

Leichter, I; Bivas, A; Margulies, J Y; Roman, I; Simkin, A

1990-01-01

This study examines the relation between the nature of acoustic emission signals emitted from cancellous bone under compression and the mechanical properties of the tissue. The examined bone specimens were taken from 12 normal, 31 osteoporotic and six osteoarthritic femoral heads. The mechanical behaviour of the osteoporotic bone specimens was found to be significantly different from that of the normal specimens both in the pre-yield and post-yield ranges. In the osteoarthritic bones only the elastic behaviour was significantly different. The rates of acoustic events before yield and beyond it were found to be significantly higher both in the osteoporotic and osteoarthritic bone specimens. The average peak amplitude of the signals was also significantly higher in the diseased bones. Stepwise regression analysis showed that a combination of the acoustic emission parameters could significantly predict some mechanical properties of the bone. The energy absorbed during compression and the ultimate compressive stress of the specimens could be estimated from the rate of pre-yield acoustic events, the average amplitude of the signals and the rate of post-yield events. However, the explanation power of the acoustic emission parameters was only moderate. The nature of acoustic emission signals was thus demonstrated to be a potential tool for assessing bone quality.

Effects of Amplitude and Frequency of Mechanical Vibration Stimulation on Cultured Osteoblasts

NASA Astrophysics Data System (ADS)

Shikata, Tetsuo; Shiraishi, Toshihiko; Morishita, Shin; Takeuchi, Ryohei; Saito, Tomoyuki

Mechanical stimulation to bones affects bone formation such as decrease of bone mass of astronauts under zero gravity, walking rehabilitation to bone fracture and fracture repair with ultrasound devices. Bone cells have been reported to sense and response to mechanical stimulation at cellular level morphologically and metabolically. In the view of mechanical vibrations, bone cells are deformed according to mechanical stimulation and their mechanical characteristics. In this study, sinusoidal inertia force was applied to cultured osteoblasts, which are a kind of bone cells, and effects of frequency and acceleration amplitude of mechanical vibration on the cells were investigated in respect of the cell proliferation, bone matrix generation and alkaline phosphatase (ALP) gene expression. The results to be obtained are as follows. The significant difference of cell density and bone mass generation between the non-vibrating and vibrating groups is found. ALP gene expression shows a peak to frequency at 50 Hz and the value of it is approximately 4.5 times as high as that of the non-vibrating group in the case of the acceleration amplitude of 0.5 G. ALP gene expression at 0.5 G is significantly larger than at 0, 0.125 or 0.25 G in the case of the frequency of 50 Hz.

Changes in chemical composition of bone matrix in ovariectomized (OVX) rats detected by Raman spectroscopy and multivariate analysis

NASA Astrophysics Data System (ADS)

Oshima, Yusuke; Iimura, Tadahiro; Saitou, Takashi; Imamura, Takeshi

2015-02-01

Osteoporosis is a major bone disease that connotes the risk of fragility fractures resulting from alterations to bone quantity and/or quality to mechanical competence. Bone strength arises from both bone quantity and quality. Assessment of bone quality and bone quantity is important for prediction of fracture risk. In spite of the two factors contribute to maintain the bone strength, only one factor, bone mineral density is used to determine the bone strength in the current diagnosis of osteoporosis. On the other hand, there is no practical method to measure chemical composition of bone tissue including hydroxyapatite and collagen non-invasively. Raman spectroscopy is a powerful technique to analyze chemical composition and material properties of bone matrix non-invasively. Here we demonstrated Raman spectroscopic analysis of the bone matrix in osteoporosis model rat. Ovariectomized (OVX) rat was made and the decalcified sections of tibias were analyzed by a Raman microscope. In the results, Raman bands of typical collagen appeared in the obtained spectra. Although the typical mineral bands at 960 cm-1 (Phosphate) was absent due to decalcified processing, we found that Raman peak intensities of amide I and C-C stretching bands were significantly different between OVX and sham-operated specimens. These differences on the Raman spectra were statistically compared by multivariate analyses, principal component analysis (PCA) and liner discrimination analysis (LDA). Our analyses suggest that amide I and C-C stretching bands can be related to stability of bone matrix which reflects bone quality.

Effect of UV Photofunctionalization on Biologic and Anchoring Capability of Orthodontic Miniscrews.

PubMed

Tabuchi, Masako; Ikeda, Takayuki; Hirota, Makoto; Nakagawa, Kaori; Park, Wonhee; Miyazawa, Ken; Goto, Shigemi; Ogawa, Takahiro

2015-01-01

Treatment of titanium with UV light immediately before use, or photofunctionalization, is gaining traction as a simple method to improve the biologic capability and clinical performance of dental implants. The objective of this study was to examine the effect of photofunctionalization on the biologic capability and mechanical anchorage of orthodontic miniscrews. Untreated and photofunctionalized Ti-6Al-4V orthodontic miniscrews were placed into rat femurs. Photofunctionalization was performed by treating miniscrews with UV light for 12 minutes using a photo device immediately before placement. After 3 weeks of healing, miniscrews were pushed laterally to measure the resistance against the tipping force. The miniscrews were also evaluated for morphology and chemistry of tissue formed around them using scanning electron microscopy and energy dispersive spectroscopy. Rat bone marrow-derived osteoblasts were cultured on Ti-6Al-4V disks with and without photofunctionalization. The number of osteoblasts attached to the disks and the behaviors, alkaline phosphatase activity, and mineralization capability of osteoblasts were evaluated. Photofunctionalization converted both disk and screw surfaces from hydrophobic to superhydrophilic. In vivo biomechanical testing showed that the displacement of untreated screws was 1.5 to 1.7 times greater than that of photofunctionalized screws when subjected to lateral tipping force. Robust bone formation was observed around photofunctionalized miniscrews with strong elemental peaks of calcium and phosphorus, whereas the tissue around untreated miniscrews appeared thin and showed no clear peak of calcium. The attachment, initial spreading, adhesion, and expression of functional phenotypes of osteoblasts were significantly increased on photofunctionalized Ti-6Al-4V disks. These in vivo and in vitro results comprehensively and consistently demonstrate that photofunctionalization increases the bioactivity of Ti-6Al-4V and improves the anchoring capability of orthodontic miniscrews.

Impact insertion of osteochondral grafts: Interference fit and central graft reduction affect biomechanics and cartilage damage.

PubMed

Su, Alvin W; Chen, Yunchan; Wailes, Dustin H; Wong, Van W; Cai, Shengqiang; Chen, Albert C; Bugbee, William D; Sah, Robert L

2018-01-01

An osteochondral graft (OCG) is an effective treatment for articular cartilage and osteochondral defects. Impact of an OCG during insertion into the osteochondral recipient site (OCR) can cause chondrocyte death and matrix damage. The aim of the present study was to analyze the effects of graft-host interference fit and a modified OCG geometry on OCG insertion biomechanics and cartilage damage. The effects of interference fit (radius of OCG - radius of OCR), loose (0.00 mm), moderate (0.05 mm), tight (0.10 mm), and of a tight fit with OCG geometry modification (central region of decreased radius), were analyzed for OCG cylinders and OCR blocks from adult bovine knee joints with an instrumented drop tower apparatus. An increasingly tight (OCG - OCR) interference fit led to increased taps for insertion, peak axial force, graft cartilage axial compression, cumulative and total energy delivery to cartilage, lower time of peak axial force, lesser graft advancement during each tap, higher total crack length in the cartilage surface, and lower chondrocyte viability. The modified OCG, with reduction of diameter in the central area, altered the biomechanical insertion variables and biological consequences to be similar to those of the moderate interference fit scenario. Micro-computed tomography confirmed structural interference between the OCR bone and both the proximal and distal bone segments of the OCGs, with the central regions being slightly separated for the modified OCGs. These results clarify OCG insertion biomechanics and mechanobiology, and introduce a simple modification of OCGs that facilitates insertion with reduced energy while maintaining a structural interference fit. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:377-386, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Physical Activity-Related Injury Profile in Children and Adolescents According to Their Age, Maturation, and Level of Sports Participation.

PubMed

Costa E Silva, Lara; Fragoso, Maria Isabel; Teles, Júlia

Physical activity (PA) is beneficial, enhancing healthy development. However, one-third of school-age children practicing sports regularly suffer from an injury. These injuries are associated with sex, chronological age, and PA level. To identify the importance of age, PA level, and maturity as predictors of injury in Portuguese youth. Descriptive epidemiological study. Level 3. Information about injury and PA level was assessed via 2 questionnaires (LESADO RAPIL II) from 647 subjects aged 10 to 17 years. Maturity offset according to Mirwald (time before or after peak height velocity) and Tanner-Whitehouse III bone age estimates were used to evaluate maturation. Binary logistic regression and gamma regression were used to determine significant predictors of injury and injury rate. Injury occurrence was higher for both sexes in recreational, school, and federated athletes (athletes engaged in sports that are regulated by their respective federations, with formal competition). These injuries also increased with age in boys and in the higher maturity offset group in girls. Injury rate was higher for both sexes in the no sports participation group. Early-maturing girls, with higher bone age and lower maturity offset, showed higher injury rate. Injuries in Portuguese youth were related to PA level, age, and biological maturation. Recreational, school, and federated athletes had more injury ocurrences while subjects with no sports participation had higher injury risk. Older subjects had more injuries. Early-maturing girls that had just passed peak height velocity may be particularly vulnerable to risk of sports injury because of the growing process. Increased knowledge about injury with specific PA exposure data is important to an overall risk management strategy. This study has deepened the association between injury and biological maturation variables.

Association of insulin resistance with near peak bone mass in the femur and lumbar spine of Korean adults aged 25-35: The Korean National Health and Nutrition Examination Survey 2008-2010

PubMed Central

Choo, Min Soo; Choi, Se Rin; Han, Jun Hyun; Lee, Seong Ho

2017-01-01

Objective This study aimed to evaluate the relationship between insulin resistance and the bone mineral density (BMD) of femur and lumbar spine in Korean adults who are expected to exhibit near peak bone mass. Methods Data from the Korean National Health and Nutrition Examination Survey 2008–2010 were analyzed. A total of 2,750 participants aged 25−35 years were included. Insulin resistance was assessed using a homeostatic model assessment of insulin resistance (HOMA-IR) and serum fasting insulin. Results In a multivariate linear regression analysis, the HOMA-IR was significantly inversely associated with the BMD of the total hip (TH, β = −0.052, P = 0.002), femoral neck (FN, β = −0.072, P<0.001), femoral trochanter (FTr, β = −0.055, P = 0.003), femoral intertrochanter (FITr, β = −0.041, P = 0.015), and lumbar spine (LS, β = −0.063, P = 0.001) among all study subjects after adjustment for gender, age, height, weight, whole body fat mass percentage, systolic blood pressure, diastolic blood pressure, total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, vitamin D, smoking, alcohol intake, physical activity, education level, and household income in both genders as well as labor, the use of oral contraceptives, and age at menarche in females. The serum fasting insulin was significantly inversely associated with the BMD of the TH (β = −0.055, P = 0.001), FN (β = −0.072, P<0.001), FTr (β = −0.055, P = 0.003), FITr (β = −0.045, P = 0.009), and LS (β = −0.064, P = 0.001) among all subjects in a multivariate linear regression analysis. Conclusion Our results suggest that insulin resistance may be independently and inversely associated with the near peak bone mass of the femur and lumbar spine. PMID:28704413

Rapid Prototyping Amphiphilic Polymer/Hydroxyapatite Composite Scaffolds with Hydration-Induced Self-Fixation Behavior

PubMed Central

Kutikov, Artem B.; Gurijala, Anvesh

2015-01-01

Two major factors hampering the broad use of rapid prototyped biomaterials for tissue engineering applications are the requirement for custom-designed or expensive research-grade three-dimensional (3D) printers and the limited selection of suitable thermoplastic biomaterials exhibiting physical characteristics desired for facile surgical handling and biological properties encouraging tissue integration. Properly designed thermoplastic biodegradable amphiphilic polymers can exhibit hydration-dependent hydrophilicity changes and stiffening behavior, which may be exploited to facilitate the surgical delivery/self-fixation of the scaffold within a physiological tissue environment. Compared to conventional hydrophobic polyesters, they also present significant advantages in blending with hydrophilic osteoconductive minerals with improved interfacial adhesion for bone tissue engineering applications. Here, we demonstrated the excellent blending of biodegradable, amphiphilic poly(D,L-lactic acid)-poly(ethylene glycol)-poly(D,L-lactic acid) (PLA-PEG-PLA) (PELA) triblock co-polymer with hydroxyapatite (HA) and the fabrication of high-quality rapid prototyped 3D macroporous composite scaffolds using an unmodified consumer-grade 3D printer. The rapid prototyped HA-PELA composite scaffolds and the PELA control (without HA) swelled (66% and 44% volume increases, respectively) and stiffened (1.38-fold and 4-fold increases in compressive modulus, respectively) in water. To test the hypothesis that the hydration-induced physical changes can translate into self-fixation properties of the scaffolds within a confined defect, a straightforward in vitro pull-out test was designed to quantify the peak force required to dislodge these scaffolds from a simulated cylindrical defect at dry versus wet states. Consistent with our hypothesis, the peak fixation force measured for the PELA and HA-PELA scaffolds increased 6-fold and 15-fold upon hydration, respectively. Furthermore, we showed that the low-fouling 3D PELA inhibited the attachment of NIH3T3 fibroblasts or bone marrow stromal cells while the HA-PELA readily supported cellular attachment and osteogenic differentiation. Finally, we demonstrated the feasibility of rapid prototyping biphasic PELA/HA-PELA scaffolds for potential guided bone regeneration where an osteoconductive scaffold interior encouraging osteointegration and a nonadhesive surface discouraging fibrous tissue encapsulation is desired. This work demonstrated that by combining facile and readily translatable rapid prototyping approaches with unique biomaterial designs, biodegradable composite scaffolds with well-controlled macroporosities, spatially defined biological microenvironment, and useful handling characteristics can be developed. PMID:25025950

Pedicle screws with a thin hydroxyapatite coating for improving fixation at the bone-implant interface in the osteoporotic spine: experimental study in a porcine model.

PubMed

Ohe, Makoto; Moridaira, Hiroshi; Inami, Satoshi; Takeuchi, Daisaku; Nohara, Yutaka; Taneichi, Hiroshi

2018-03-30

OBJECTIVE Instrumentation failure caused by the loosening of pedicle screws (PSs) in patients with osteoporosis is a serious problem after spinal surgery. The addition of a thin hydroxyapatite (HA) surface coating applied by using a sputtering process was reported recently to be a promising method for providing bone conduction around an implant without a significant risk of coating-layer breakage. In this study, the authors evaluated the biomechanical and histological features of the bone-implant interface (BII) of PSs with a thin HA coating in an in vivo porcine osteoporotic spine model. METHODS Three types of PSs (untreated/standard [STPS], sandblasted [BLPS], and HA-coated [HAPS] PSs) were implanted into the thoracic and lumbar spine (T9-L6) of 8 mature Clawn miniature pigs (6 ovariectomized [osteoporosis group] and 2 sham-operated [control group] pigs). The spines were harvested from the osteoporosis group at 0, 2, 4, 8, 12, or 24 weeks after PS placement and from the control group at 0 or 24 weeks. Their bone mineral density (BMD) was measured by peripheral quantitative CT. Histological evaluation of the BIIs was conducted by performing bone volume/tissue volume and bone surface/implant surface measurements. The strength of the BII was evaluated with extraction torque testing. RESULTS The BMD decreased significantly in the osteoporosis group (p < 0.01). HAPSs exhibited the greatest mean extraction peak torque at 8 weeks, and HAPSs and BLPSs exhibited significantly greater mean torque than the STPSs at 12 weeks (p < 0.05). The bone surface/implant surface ratio was significantly higher for HAPSs than for STPSs after 2 weeks (p < 0.05), and bonding between bone and the implant surface was maintained until 24 weeks with no detachment of the coating layer. In contrast, the bone volume/tissue volume ratio was significantly higher for HAPSs than for BLPSs or STPSs only at 4 weeks. CONCLUSIONS Using PSs with a thin HA coating applied using a sputtering process strengthens bonding at the BII, which might improve early implant fixation after spinal surgery for osteoporosis. However, the absence of increased bone mass around the screw remains a concern; prescribing osteoporosis treatment to improve bone quality might be necessary to prevent fractures around the screws.

Method for noninvasive intracranial pressure measurement

DOEpatents

Sinha, Dipen N.

2000-01-01

An ultrasonic-based method for continuous, noninvasive intracranial pressure (ICP) measurement and monitoring is described. The stress level in the skull bone is affected by pressure. This also changes the interfacial conditions between the dura matter and the skull bone. Standing waves may be set up in the skull bone and the layers in contact with the bone. At specific frequencies, there are resonance peaks in the response of the skull which can be readily detected by sweeping the excitation frequency on an excitation transducer in contact with a subject's head, while monitoring the standing wave characteristics from the signal received on a second, receiving transducer similarly in contact with the subject's head. At a chosen frequency, the phase difference between the excitation signal and the received signal can be determined. This difference can be related to the intracranial pressure and changes therein.

Antibacterial activity of agricultural waste derived wollastonite doped with copper for bone tissue engineering.

PubMed

Azeena, S; Subhapradha, N; Selvamurugan, N; Narayan, S; Srinivasan, N; Murugesan, R; Chung, T W; Moorthi, A

2017-02-01

Bioactive ceramic materials with metal ions generation brought great attention in the class of biomaterials development and widely employed as a filler material for bone tissue regeneration. The present study aimed to fabricate calcium silicate based ceramic material doped with copper metal particles by sol-gel method. Rice straw of agricultural waste was utilized as a source material to synthesize wollastonite, then wollastonite was doped with copper to fabricate copper doped wollastonite (Cu-Ws) particles. The synthesized materials were subjected to physio-chemical characterization by TEM, DLS, FTIR, XRD and DSC analysis. It was found that the sizes of the WS particles was around 900nm, while adding copper the size was increased upto 1184nm and the addition of copper to the material sharpening the peak. The release of Cu ions was estimated by ICP analysis. The anti-bacterial potentiality of the particles suggested that better microbial growth inhibition against E. coli (Gram negative) and S. aureus (Gram positive) strains from ATCC, in which the growth inhibition was more significant against S. aureus. The biocompatibility in mouse Mesenchymal Stem cells (mMSC) showed the non-toxic effect up to 0.05mg/ml concentration while the increase in concentration was found to be toxic to the cells. So the particles may have better potential application with the challenging prevention of post implantation infection in the field of bone tissue engineering (BTE). Copyright © 2016. Published by Elsevier B.V.

Effect of carbonated hydroxyapatite incorporated advanced platelet rich fibrin intrasulcular injection on the alkaline phosphatase level during orthodontic relapse

NASA Astrophysics Data System (ADS)

Alhasyimi, Ananto Ali; Pudyani, Pinandi Sri; Asmara, Widya; Ana, Ika Dewi

2018-02-01

Nowadays, relapse in orthodontic treatment is considered very important because of high incidence of relapse after the treatment. Alkaline phosphatase (ALP) as a biomarker of bone formation will decrease in compression sites during relapse after orthodontic tooth movement. In this situation, manipulating alveolar bone remodeling to increase ALP level is considered one of the new strategies to prevent relapse properly. In the field of tissue engineering, in this study, carbonated hydroxyapatite (CHA) is expected to have the ability to incorporate advanced platelet rich fibrin (aPRF). Next, CHA will retain the aPRF containing various growth factors (GF) until it reaches into a specific targeted area, gradually degraded, and deliver the GF in a controlled manner to prevent relapse. Here, gingival crevicular fluid (GCF) of 45 samples (n=45) were collected and levels of ALP were analyzed using UV-Vis 6300 Spectrophotometer at 405 nm wavelength. We found that there is a significant difference of ALP levels (p<0.05) in GCF between treatments and control groups. ALP level was elevated significantly in CHA and CHA-aPRF groups at days 7 and 14 after debonding compared with the control groups. The peak level of ALP was observed at days 14 after debonding in groups C (0.789 ± 0.039 U/mg). Therefore, it can be concluded that the application of hydrogel CHA with controlled release manner incorporated aPRF enhances bone regeneration by increasing ALP level.

Hind limb scaling of kangaroos and wallabies (superfamily Macropodoidea): implications for hopping performance, safety factor and elastic savings

PubMed Central

McGowan, C P; Skinner, J; Biewener, A A

2008-01-01

The aim of this study was to examine hind limb scaling of the musculoskeletal system in the Macropodoidea, the superfamily containing wallabies and kangaroos, to re-examine the effect of size on the locomotor mechanics and physiology of marsupial hopping. Morphometric musculoskeletal analyses were conducted of 15 species and skeletal specimens of 21 species spanning a size range from 0.8 to 80 kg that included representatives of 12 of the 16 extant genera of macropodoids. We found that unlike other groups, macropodoids are able to match force demands associated with increasing body size primarily through a combination of positive allometry in muscle area and muscle moment arms. Isometric scaling of primary hind limb bones suggests, however, that larger species experience relatively greater bone stresses. Muscle to tendon area ratios of the ankle extensors scale with strong positive allometry, indicating that peak tendon stresses also increase with increasing body size but to a lesser degree than previously reported. Consistent with previous morphological and experimental studies, large macropodoids are therefore better suited for elastic strain energy recovery but operate at lower safety factors, which likely poses an upper limit to body size. Scaling patterns for extant macropodoids suggest that extinct giant kangaroos (∼250 kg) were likely limited in locomotor capacity. PMID:18086129

Coating with a Modular Bone Morphogenetic Peptide Promotes Healing of a Bone-Implant Gap in an Ovine Model

PubMed Central

Lu, Yan; Lee, Jae Sung; Nemke, Brett; Graf, Ben K.; Royalty, Kevin; Illgen, Richard; Vanderby, Ray; Markel, Mark D.; Murphy, William L.

2012-01-01

Despite the potential for growth factor delivery strategies to promote orthopedic implant healing, there is a need for growth factor delivery methods that are controllable and amenable to clinical translation. We have developed a modular bone growth factor, herein termed “modular bone morphogenetic peptide (mBMP)”, which was designed to efficiently bind to the surface of orthopedic implants and also stimulate new bone formation. The purpose of this study was to coat a hydroxyapatite-titanium implant with mBMP and evaluate bone healing across a bone-implant gap in the sheep femoral condyle. The mBMP molecules efficiently bound to a hydroxyapatite-titanium implant and 64% of the initially bound mBMP molecules were released in a sustained manner over 28 days. The results demonstrated that the mBMP-coated implant group had significantly more mineralized bone filling in the implant-bone gap than the control group in C-arm computed tomography (DynaCT) scanning (25% more), histological (35% more) and microradiographic images (50% more). Push-out stiffness of the mBMP group was nearly 40% greater than that of control group whereas peak force did not show a significant difference. The results of this study demonstrated that mBMP coated on a hydroxyapatite-titanium implant stimulates new bone formation and may be useful to improve implant fixation in total joint arthroplasty applications. PMID:23185610

Cutting moments and grip forces in meat cutting operations and the effect of knife sharpness.

PubMed

McGorry, Raymond W; Dowd, Peter C; Dempsey, Patrick G

2003-07-01

The force exposure associated with meat cutting operations and the effect of knife sharpness on performance and productivity have not been well documented. Specialized hardware was used to measure grip force and reactive moments with 15 professional meat cutters performing lamb shoulder boning, beef rib trimming and beef loin trim operations in a field study conducted in two meat packing plants. A system for measuring relative blade sharpness was developed for this study. Mean and peak cutting moments observed for the meat cutting operations, averaged across subjects were 4.7 and 17.2 Nm for the shoulder boning, 3.5 and 12.9 Nm for the rib trim, and 2.3 and 10.6 Nm for the loin trim, respectively. Expressed as percent of MVC, mean grip forces of 28.3% and peak grip forces of 72.6% were observed overall. Blade sharpness was found to effect grip forces, cutting moments and cutting time, with sharper blades requiring statistically significantly lower peak and mean cutting moments, and grip forces than dull knives. Efforts aimed at providing and maintaining sharp blades could have a significant impact on force exposure.

Static versus dynamic loads as an influence on bone remodelling

NASA Technical Reports Server (NTRS)

Lanyon, L. E.; Rubin, C. T.

1983-01-01

Bone remodelling activity in the avian ulna was assessed under conditions of disuse alone, disuse with a superimposed continuous compressive load, and disuse interrupted by a short daily period of intermittent loading. The ulna preparation is made by two submetaphyseal osteotomies, the cut ends of the bone being covered with stainless steel caps which, together with the bone they enclosed, are pierced by pins emerging transcutaneously on the dorsal and ventral surfaces of the wing. The 110 mm long undisturbed section of the bone shaft can be protected from functional loading, loaded continuously in compression by joining the pins with springs, or loaded intermittently in compression by engaging the pins in an Instron machine. Similar loads (525 n) were used in both static and dynamic cases engendering similar peak strains at the bone's midshaft (-2000 x 10-6). The intermitent load was applied at a frequency of 1 Hz during a single 100 second period per day as a ramped square wave, with a rate of change of strain during the ramp of 0.01 per second.

Assessment of skeletal maturity in scoliosis patients to determine clinical management: a new classification scheme using distal radius and ulna radiographs.

PubMed

Luk, Keith D K; Saw, Lim Beng; Grozman, Samuel; Cheung, Kenneth M C; Samartzis, Dino

2014-02-01

Assessment of skeletal maturity in patients with adolescent idiopathic scoliosis (AIS) is important to guide clinical management. Understanding growth peak and cessation is crucial to determine clinical observational intervals, timing to initiate or end bracing therapy, and when to instrument and fuse. The commonly used clinical or radiologic methods to assess skeletal maturity are still deficient in predicting the growth peak and cessation among adolescents, and bone age is too complicated to apply. To address these concerns, we describe a new distal radius and ulna (DRU) classification scheme to assess skeletal maturity. A prospective study. One hundred fifty young, female AIS patients with hand x-rays and no previous history of spine surgery from a single institute were assessed. Radius and ulna plain radiographs, and various anthropomorphic parameters were assessed. We identified various stages of radius and ulna epiphysis maturity, which were graded as R1-R11 for the radius and U1-U9 for the ulna. The bone age, development of sexual characteristics, standing height, sitting height, arm span, radius length, and tibia length were studied prospectively at each stage of these epiphysis changes. Standing height, sitting height, and arm span growth were at their peak during stages R7 (mean, 11.4 years old) and U5 (mean, 11.0 years old). The long bone growths also demonstrated a common peak at R7 and U5. Cessation of height and arm span growth was noted after stages R10 (mean, 15.6 years old) and U9 (mean, 17.3 years old). The new DRU classification is a practical and easy-to-use scheme that can provide skeletal maturation status. This classification scheme provides close relationship with adolescent growth spurt and cessation of growth. This classification may have a tremendous utility in improving clinical-decision making in the conservative and operative management of scoliosis patients. Copyright © 2014 Elsevier Inc. All rights reserved.

Influence of thread shape and inclination on the biomechanical behaviour of plateau implant systems.

PubMed

Calì, Michele; Zanetti, Elisabetta Maria; Oliveri, Salvatore Massimo; Asero, Riccardo; Ciaramella, Stefano; Martorelli, Massimo; Bignardi, Cristina

2018-03-01

To assess the influence of implant thread shape and inclination on the mechanical behaviour of bone-implant systems. The study assesses which factors influence the initial and full osseointegration stages. Point clouds of the original implant were created using a non-contact reverse engineering technique. A 3D tessellated surface was created using Geomagic Studio ® software. From cross-section curves, generated by intersecting the tessellated model and cutting-planes, a 3D parametric CAD model was created using SolidWorks ® 2017. By the permutation of three thread shapes (rectangular, 30° trapezoidal, 45° trapezoidal) and three thread inclinations (0°, 3° or 6°), nine geometric configurations were obtained. Two different osseointegration stages were analysed: the initial osseointegration and a full osseointegration. In total, 18 different FE models were analysed and two load conditions were applied to each model. The mechanical behaviour of the models was analysed by Finite Element (FE) Analysis using ANSYS ® v. 17.0. Static linear analyses were also carried out. ANOVA was used to assess the influence of each factor. Models with a rectangular thread and 6° inclination provided the best results and reduced displacement in the initial osseointegration stages up to 4.58%. This configuration also reduced equivalent VM stress peaks up to 54%. The same effect was confirmed for the full osseointegration stage, where 6° inclination reduced stress peaks by up to 62%. The FE analysis confirmed the beneficial effect of thread inclination, reducing the displacement in immediate post-operative conditions and equivalent VM stress peaks. Thread shape does not significantly influence the mechanical behaviour of bone-implant systems but contributes to reducing stress peaks in the trabecular bone in both the initial and full osseointegration stages. Copyright © 2018 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

ALOX12 polymorphisms are associated with fat mass but not peak bone mineral density in Chinese nuclear families.

PubMed

Xiao, W-J; He, J-W; Zhang, H; Hu, W-W; Gu, J-M; Yue, H; Gao, G; Yu, J-B; Wang, C; Ke, Y-H; Fu, W-Z; Zhang, Z-L

2011-03-01

Arachidonate 12-lipoxygenase (ALOX12) is a member of the lipoxygenase superfamily, which catalyzes the incorporation of molecular oxygen into polyunsaturated fatty acids. The products of ALOX12 reactions serve as endogenous ligands for peroxisome proliferator-activated receptor γ (PPARG). The activation of the PPARG pathway in marrow-derived mesenchymal progenitors stimulates adipogenesis and inhibits osteoblastogenesis. Our objective was to determine whether polymorphisms in the ALOX12 gene were associated with variations in peak bone mineral density (BMD) and obesity phenotypes in young Chinese men. All six tagging single-nucleotide polymorphisms (SNPs) in the ALOX12 gene were genotyped in a total of 1215 subjects from 400 Chinese nuclear families by allele-specific polymerase chain reaction. The BMD at the lumbar spine and hip, total fat mass (TFM) and total lean mass (TLM) were measured using dual-energy X-ray absorptiometry. The pairwise linkage disequilibrium among SNPs was measured, and the haplotype blocks were inferred. Both the individual SNP markers and the haplotypes were tested for an association with the peak BMD, body mass index, TFM, TLM and percentage fat mass (PFM) using the quantitative transmission disequilibrium test (QTDT). Using the QTDT, significant within-family association was found between the rs2073438 polymorphism in the ALOX12 gene and the TFM and PFM (P=0.007 and 0.012, respectively). Haplotype analyses were combined with our individual SNP results and remained significant even after correction for multiple testing. However, we failed to find significant within-family associations between ALOX12 SNPs and the BMD at any bone site in young Chinese men. Our present results suggest that the rs2073438 polymorphism of ALOX12 contributes to the variation of obesity phenotypes in young Chinese men, although we failed to replicate the association with the peak BMD variation in this sample. Further independent studies are needed to confirm our findings.

Study of the Elasto-plastic Properties of Mineralized Biomaterials via Synchrotron High-energy X-ray Diffraction

NASA Astrophysics Data System (ADS)

Deymier-Black, Alix Christine

Synchrotron high-energy X-ray diffraction was employed to investigate the strains in the hydroxyapatite (HAP) platelets and mineralized collagen fibrils in bovine dentin and cortical bone. The HAP and the fibrillar apparent moduli, defined as the applied stress divided by the phase strain, in dentin were measured as 27+/-7.2 and 16+/-4.9 GPa. The HAP apparent modulus ( EHAPapp ) is less than the lower bound calculated for EHAPapp from the Voigt model. This discrepancy is probably due to stress concentrators or decreases in the HAP Young's modulus due to size or composition effects. EHAPapp and Efibapp in dentin vary significantly within a single tooth in both the apical-cervical direction and the buccal-lingual direction. However, the variation between teeth is minimal. The HAP and fibrillar apparent moduli are not affected by freezing in dentin or by X-ray irradiation in bone and dentin. X-ray irradiation causes a decrease in HAP residual strain in bone. This decrease suggests the presence of HAP-collagen interfacial damage. It was determined from the HAP 00.2 peak broadening that irradiation damage mostly affects the HAP unit cells which are under the highest strain. From this it was theorized that irradiation may damage highly-strained bonds at stress concentrators and/or calcium-mediated electrostatic bonds. The fact that the apparent modulus does not change with irradiation suggests that the interfacial damage must be reversible. Bone and dentin both undergo creep when loaded to high stresses. At low irradiation doses, both the fibrillar and HAP strains increase with creep time indicating that load is being transferred from the matrix to the HAP. However, at high doses, the strain on the HAP decreases with creep time. This supports the interfacial damage theory which would allow the HAP to release its elastic load upon interfacial debonding. At -80 MPa, beyond a dose of 50 kGy, the rate of change in HAP strain with time begins to increase, becoming positive at ˜115 kGy. After 300 kGy the HAP strain rate decreases and plateaus probably due to stiffening of the matrix through cross-linking. The HAP and fibrillar strain rate in irradiated bone and dentin samples increase with increased temperature and applied load.

Raman ratios on the repair of grafted surgical bone defects irradiated or not with laser (λ780 nm) or LED (λ850 nm).

PubMed

Pinheiro, Antonio Luiz B; Soares, Luiz Guilherme P; Marques, Aparecida Maria C; Aciole, Jouber Mateus S; de Souza, Renato Aparecido; Silveira, Landulfo

2014-09-05

This work aimed to assess biochemical changes associated to mineralization and remodeling of bone defects filled with Hydroxyapatite+Beta-Beta-tricalcium phosphate irradiated or not with 2 light sources. Ratios of intensities, band position and bandwidth of selected Raman peaks of collagen and apatites were used. Sixty male Wistar rats were divided into 6 groups subdivided into 2 subgroups (15th and 30th days). A standard surgical defect was created on one femur of each animal. In 3 groups the defects were filled with blood clot (Clot, Clot+Laser and Clot+LED groups) and in the remaining 3 groups the defects were filled with biomaterial (Biomaterial, Biomaterial+Laser and Biomaterial+LED groups). When indicated, the defects were irradiated with either Laser (λ780 nm, 70 mW, Φ∼0.4 cm(2)) or LED (λ850±10 nm, 150 mW, Φ∼0.5 cm(2)), 20 J/cm(2) each session, at 48 h intervals/2 weeks (140 J/cm(2) treatment). Following sacrifice, bone fragments were analyzed by Raman spectroscopy. Statistical analysis (ANOVA General Linear Model, p<0.05) showed that both grafting and time were the variables that presented significance for the ratios of ∼1660/∼1670 cm(-1) (collagen maturation), ∼1077/∼854 cm(-1) (mineralization), ∼1077/∼1070 cm(-1) (carbonate substitution) and the position of the ∼960 cm(-1) (bone maturation). At 30th day, the ratios indicated an increased deposition of immature collagen for both Clot and Biomaterial groups. Biomaterial group showed increased collagen maturation. Only collagen deposition was significantly dependent upon irradiation independently of the light source, being the amount of collagen I increased in the Clot group at the end of the experimental time. On the other hand, collagen I deposition was reduced in biomaterial irradiated groups. Raman ratios of selected protein matrix and phosphate and carbonate HA indicated that the use of biphasic synthetic micro-granular HA+Beta-TCP graft improved the repair of bone defects, associated or not with Laser or LED light, because of the increasing deposition of HA. Copyright © 2014 Elsevier B.V. All rights reserved.

Prevention of disuse osteoporosis: Effect of sodium fluoride during five weeks of bed rest

NASA Technical Reports Server (NTRS)

Schneider, Victor S.

1987-01-01

An attempt was made to modify factors which promote disuse osteoporosis and thereby prevent it from occurring. Since fluoride is currently used to enhance bone formation in the treatment of low turnover osteoporosis, it was hypothesized that if the fluoride ion was available over a long period of time that it would slow the demonstrated loss of calcium by inhibiting bone resorption and enhancing bone formation. This study was used to determine whether oral medication with sodium F will modify or prevent 5 weeks of bed rest induced disuse osteoporosis, to determine the longitudinal effects of 5 weeks of bed rest on PTH, CT and calcitriol, to measure muscle volume changes and metabolic activity by magnetic resonance imaging and magnetic resonance spectroscopy during prolonged bed rest, to measure changes in peak muscle strength and fatigability, and to measure bone turnover in bone biopsies. Subjects were studied during 1 week of equilibration, 4 weeks of control ambulation, 5 weeks of bed rest, and 1 week of reambulation.

Role of IGF1 and EFN-EPH signaling in skeletal metabolism.

PubMed

Lindsey, Richard C; Rundle, Charles H; Mohan, Subburaman

2018-07-01

Insulin-like growth factor 1(IGF1) and ephrin ligand (EFN)-receptor (EPH) signaling are both crucial for bone cell function and skeletal development and maintenance. IGF1 signaling is the major mediator of growth hormone-induced bone growth, but a host of different signals and factors regulate IGF1 signaling at the systemic and local levels. Disruption of the Igf1 gene results in reduced peak bone mass in both experimental animal models and humans. Additionally, EFN-EPH signaling is a complex system which, particularly through cell-cell interactions, contributes to the development and differentiation of many bone cell types. Recent evidence has demonstrated several ways in which the IGF1 and EFN-EPH signaling pathways interact with and depend upon each other to regulate bone cell function. While much remains to be elucidated, the interaction between these two signaling pathways opens a vast array of new opportunities for investigation into the mechanisms of and potential therapies for skeletal conditions such as osteoporosis and fracture repair. © 2018 Society for Endocrinology.

Assessing the age of animal bones and ivories by Raman spectroscopy

NASA Astrophysics Data System (ADS)

Sharikova, Anna; Peerzada, Lubna; Khmaladze, Alexander

2018-02-01

A fast, convenient way to determine the age of bones and ivories is important both in forensics and for classifying art objects in collections of art experts, restorers, art galleries and museums. Knowing the age of elephant tusks is also essential because there are many date-specific regulations of ivory trade. Radiocarbon dating is the standard method used to determine the age of organic materials, but it is expensive, time consuming, and damages the sample in the process. Raman spectroscopy is sensitive to rotational and vibrational molecular transitions, and also intermolecular vibrations. Therefore, it can provide information about sample make up, such as proteins and minerals, as well as detect spectral signatures associated with structural changes in molecules. Since Raman spectroscopy identifies the molecular bonds present in a sample, it is often used to determine its chemical composition. Bones and ivories contain two primary components: collagen and bioapatite. As the protein collagen deteriorates with time, its Raman signal decreases. The ratio of collagen-to-bioapatite peaks, therefore, is smaller in the older samples compared to the younger ones, providing a basis for sample dating. We employed Raman spectroscopy to non-destructively determine the age of several elephant tusk fragments. We have also used it to identify ivory imitations made of vegetable and plastic materials. Such materials have entirely different chemical composition, and their spectra are easily distinguished from those of bone and ivory. Peak fitting was employed to determine collagen and bioapatite components.

Physical development and swimming performance during biological maturation in young female swimmers.

PubMed

Lätt, Evelin; Jürimäe, Jaak; Haljaste, Kaja; Cicchella, Antonio; Purge, Priit; Jürimäe, Toivo

2009-03-01

The present study analyzed the development of physiological, biomechanical and anthropometrical parameters in young female swimmers and assessed the effect of these parameters on swimming performance during biological maturation. In total, 26 female swimmers participated in the study in which data were annually collected for two consecutive years. Body composition, basic anthropometrical parameters and biological age were measured. During the 400-m front-crawl swimming, the energy cost of swimming and stroking parameters were assessed. Peak oxygen consumption (VO2(peak)) was assessed by means of the backward-extrapolation technique recording VO2 during the first 20 sec of the recovery period after a maximal trial of 400-m distance. During the 2-year follow-up study period, age, height, body mass, body fat %, fat free mass, bone mineral mass, total bone mineral density, arm span and biological maturation values significantly increased during each year (p < 0.05). The tracking of the physical characteristics measured over the 2-year study period was relatively high (r > 0.694), except for the body fat% (r > 0.554). The tracking of the Tanner stages was also high (r = 0.759-0.780). Stepwise regression analyses showed that biomechanical factors (R2 > 0.322; p < 0.05) best characterized the 400-metre swimming performance in young female swimmers, followed by bioenergetical (R2 > 0.311; p < 0.05) and physical (R2 > 0.203; p < 0.05) factors during all three measurement times.

Sensitivity of simulated transcranial ultrasound fields to acoustic medium property maps

NASA Astrophysics Data System (ADS)

Robertson, James; Martin, Eleanor; Cox, Ben; Treeby, Bradley E.

2017-04-01

High intensity transcranial focused ultrasound is an FDA approved treatment for essential tremor, while low-intensity applications such as neurostimulation and opening the blood brain barrier are under active research. Simulations of transcranial ultrasound propagation are used both for focusing through the skull, and predicting intracranial fields. Maps of the skull acoustic properties are necessary for accurate simulations, and can be derived from medical images using a variety of methods. The skull maps range from segmented, homogeneous models, to fully heterogeneous models derived from medical image intensity. In the present work, the impact of uncertainties in the skull properties is examined using a model of transcranial propagation from a single element focused transducer. The impact of changes in bone layer geometry and the sound speed, density, and acoustic absorption values is quantified through a numerical sensitivity analysis. Sound speed is shown to be the most influential acoustic property, and must be defined with less than 4% error to obtain acceptable accuracy in simulated focus pressure, position, and volume. Changes in the skull thickness of as little as 0.1 mm can cause an error in peak intracranial pressure of greater than 5%, while smoothing with a 1 \\text{m}{{\\text{m}}3} kernel to imitate the effect of obtaining skull maps from low resolution images causes an increase of over 50% in peak pressure. The numerical results are confirmed experimentally through comparison with sonications made through 3D printed and resin cast skull bone phantoms.

Locomotor loading mechanics in the hindlimbs of tegu lizards (Tupinambis merianae): comparative and evolutionary implications.

PubMed

Sheffield, K Megan; Butcher, Michael T; Shugart, S Katherine; Gander, Jennifer C; Blob, Richard W

2011-08-01

Skeletal elements are usually able to withstand several times their usual load before they yield, and this ratio is known as the bone's safety factor. Limited studies on amphibians and non-avian reptiles have shown that they have much higher limb bone safety factors than birds and mammals. It has been hypothesized that this difference is related to the difference in posture between upright birds and mammals and sprawling ectotherms; however, limb bone loading data from a wider range of sprawling species are needed in order to determine whether the higher safety factors seen in amphibians and non-avian reptiles are ancestral or derived conditions. Tegus (family Teiidae) are an ideal lineage with which to expand sampling of limb bone loading mechanics for sprawling taxa, particularly for lizards, because they are from a different clade than previously sampled iguanas and exhibit different foraging and locomotor habits (actively foraging carnivore versus burst-activity herbivore). We evaluated the mechanics of locomotor loading for the femur of the Argentine black and white tegu (Tupinambus merianae) using three-dimensional measurements of the ground reaction force and hindlimb kinematics, in vivo bone strains and femoral mechanical properties. Peak bending stresses experienced by the femur were low (tensile: 10.4 ± 1.1 MPa; compressive: -17.4 ± 0.9 MPa) and comparable to those in other reptiles, with moderate shear stresses and strains also present. Analyses of peak femoral stresses and strains led to estimated safety factor ranges of 8.8-18.6 in bending and 7.8-17.5 in torsion, both substantially higher than typical for birds and mammals but similar to other sprawling tetrapods. These results broaden the range of reptilian and amphibian taxa in which high femoral safety factors have been evaluated and further indicate a trend for the independent evolution of lower limb bone safety factors in endothermic taxa.

Hematologic interactions of endotoxin, tumor necrosis factor alpha (TNF alpha), interleukin 1, and adrenal hormones and the hematologic effects of TNF alpha in Corynebacterium parvum-primed rats.

PubMed

Ulich, T R; del Castillo, J; Ni, R X; Bikhazi, N

1989-06-01

Endotoxin reduces the release among other cytokines of tumor necrosis factor (TNF) and interleukin 1 (IL-1) and causes peripheral lymphopenia and a dose-response-dependent initial neutropenia followed by a monophasic neutrophilia. TNF alone induces lymphopenia and an initial neutropenia followed by a biphasic neutrophilia. IL-1 alone induces lymphopenia and a monophasic neutrophilia. TNF-plus-IL-1 caused a greater lymphopenia than either monokine alone, suggesting that both monokines contribute to LPS-induced lymphopenia. TNF-plus-IL-1 induced neutropenia similar in magnitude to that induced by TNF alone and induced a neutrophilia significantly greater than that induced by either monokine alone, suggesting that LPS-induced neutropenia is caused by TNF, while LPS-induced neutrophilia is due to the combined effects of TNF and II-1. TNF and IL-1 were administered together with LPS to simulate the in vivo condition of endogenous monokine release during gram-negative bacteremia. TNF combined with LPS increased both the duration and magnitude of LPS-induced lymphopenia, LPS-induced neutropenia, and LPS-induced neutrophilia. TNF-plus-LPS treated rats at 2 hours after injection exhibited a striking 93% decrease in bone marrow neutrophils even though no peripheral neutrophilia was yet apparent, suggesting that the subsequent neutrophilia was due to demargination and recirculation of neutrophils sequestered in the peripheral vasculature immediately after their release from the bone marrow. Epinephrine, which causes neutrophilia by demargination but not by release of marrow neutrophils, reversed the initial neutropenia in TNF-plus-LPS-treated rats and increased the neutrophilia. IL-1 combined with LPS increased LPS-induced neutrophilia, suggesting that endogenous IL-1 also contributed to LPS-induced neutrophilia. Corynebacterium parvum-primed rats with hyperplasia of the monocyte-macrophage system and treated with TNF differed from naive rats treated with TNF in that the second peak was as great as the initial peak of neutrophilia, supporting the hypothesis that the second peak of TNF-induced neutrophilia is due to the release of endogenous monokines. In conclusion, exogenous TNF, IL-1, and adrenal hormones affect circulating numbers of lymphocytes and neutrophils in a fashion consistent with their postulated endogenous role in the regulation of leukocyte trafficking during bacterial infection.

[Toward an anthropometric diagnosis of osteopenia and a biochemical diagnosis of osteoporoses].

PubMed

Cointry, Gustavo R; Capozza, Ricardo F; Ferretti, Jose L; Frost, Harold M

2003-01-01

The current (metabolic) conception of bone-weakening diseases regards bone strength as determined by a systemically-controlled "mineralized mass" which grows until it reaches a peak and then is lost at individually-specific rates. This concept disregards bone biomechanics. Skeletons are structures, it reaches of which depends on the stiffness and the spatial distribution rather than the volume of the calcified material. Rather than allowing a systemic regulation of their "mass" as a way to optimize their strength, bones autocontrol their stiffness by orienting bone formation and destruction as locally determined by the directional sensing, by osteocytes, of the strains caused by mechanical usage (gravity, muscle contractions). Bone mass and strength are just side products of that control. Endocrine-metabolic systems modulate non-directionally the work of bone cells as required for achieving a mineral equilibrium, despite the biomechanical controls, and can determine osteopenias and osteoporoses. Osteoporoses are not "intense osteopenias" (as per the current WHO's conception) but "osteopenic bone fragilities" (as recently stated by the NIH). The diagnosis of osteopenia is an anthropometric problem that can be solved densitometrically; but that of bone fragility is a biomechanical matter that requires evaluation of bone material's stiffness and distribution by other means ("resistometry"). For therapeutic purposes, osteopenias and osteoporoses should be also evaluated according to the relationship between bone mass or strength and muscle mass or strength in order to distinguish between "mechanical" (disuse) and "metabolic" etiologies (intrinsic bone lesion, or systemic disequilibrium), in which the bone/muscle proportionality tends to remain normal or to deteriorate, respectively.

Growth and development of male "little" mice assessed with Parks' theory of feeding and growth.

PubMed

Puche, Rodolfo C; Alloatti, Rosa; Chapo, Gustavo

2002-01-01

This work was designed to characterize the appetite kinetics and growth of male C57BL/6J (lit) mice. Those variables were assessed with Parks' function of ad libitum feeding and growth. Heterozygous mice (lit/+) attained their mature weight at 12-15 weeks of age, peak growth rate (3.5 g/week) at 5 weeks and displayed the normal decay of food conversion efficiency as a function of age. The homozygous genotype has a chronic defect in the synthesis and secretion of growth hormone (GH). Homozygous mice could not be assessed with Park's function. From the 4th to the 15th week of age, body weight increased linearly and exhibited constant food conversion efficiency. Food intake of both genotypes was commensurate with their body weights. Lit/lit mice became progressively obese. At 40 weeks of age, body fat of lit/lit mice was fivefold that of lit/+ and their body weight was similar to their heterozygous controls. The chronic deficiency of growth hormone produced a lower bone mass (compared to heterozygous controls). Bone mass of both genotypes attained maturity at 12-15 weeks with a maximum growth rate at 5 weeks. Body weight and bone mass grow harmoniously in lit/+ but not in lit/lit mice.

Extracurricular sports activity around growth spurt and improved tibial cortical bone properties in late adolescence.

PubMed

Shi, Hui-Jing; Nakamura, Keiko; Kizuki, Masashi; Inose, Tomoko; Seino, Kaoruko; Takano, Takehito

2006-12-01

To elucidate whether extracurricular sports activity during rapid growth correlates with improved bone properties in late adolescence, a longitudinal observation was performed among 96 high-school enrollments (46 boys and 50 girls, born in 1981-1982) in metropolitan Tokyo. In each year of high school, tibial cortical speed of sound (TCSOS) was measured by quantitative ultrasonometry, and participation in extracurricular sports activity (ECSA) since primary school was examined by structured questionnaire. We calculated the number of years since peak height velocity (ysPHV) based on annual records of height from 6 to 18 y of age to indicate progression of puberty. The increase in TCSOS during high school in boys (32.5 m/s) was significantly greater than that in girls (5.4 m/s). The magnitude of positive association between ysPHV and TCSOS attenuated gradually over time. ECSA in grades 7-9 in boys and in grades 4-6 in girls were significant predictors of TCSOS throughout high school, independent of potential confounders. The bone benefits of ECSA around the growth spurt are maintainable in subsequent years. The importance of physical activities that are integrated into the ordinary lifestyle of children and adolescents during this crucial period is emphasized.

Ultrasonic wave propagation in trabecular bone predicted by the stratified model

NASA Technical Reports Server (NTRS)

Lin, W.; Qin, Y. X.; Rubin, C.

2001-01-01

The objective of this study was to investigate ultrasound propagation in trabecular bone by considering the wave reflection and transmission in a multilayered medium. The use of ultrasound to identify those at risk of osteoporosis is a promising diagnostic method providing a measure of bone mineral density (BMD). A stratified model was proposed to study the effect of transmission and reflection of ultrasound wave within the trabecular architecture on the relationship between ultrasound and BMD. The results demonstrated that ultrasound velocity in trabecular bone was highly correlated with the bone apparent density (r=0.97). Moreover, a consistent pattern of the frequency dependence of ultrasound attenuation coefficient has been observed between simulation using this model and experimental measurement of trabecular bone. The normalized broadband ultrasound attenuation (nBUA) derived from the simulation results revealed that nBUA was nonlinear with respect to trabecular porosity and BMD. The curve of the relationship between nBUA and BMD was parabolic in shape, and the peak magnitude of nBUA was observed at approximately 60% of bone porosity. These results agreed with the published experimental data and demonstrated that according to the stratified model, reflection and transmission were important factors in the ultrasonic propagation through the trabecular bone.

Calcium requirements for Asian children and adolescents.

PubMed

Lee, Warren Tak Keung; Jiang, Ji

2008-01-01

Calcium is important for bone health. Over the last 15 years, reference calcium intakes in Western countries have been revised upwards for maximizing bone mass at skeletal maturity and for prevention of osteoporotic fractures. Some of these reference figures have also been adopted for use in Asian countries. However, the scientific data based on for revising reference calcium intakes in the West was largely based on Caucasians. Limited human studies relating to calcium requirements and bone mineralization have been conducted in Asians in Asia. In children and adolescents, a trial has confirmed no effects of calcium supplementation on bone gains in adolescent girls after 7 years. A meta-analysis has also revealed that calcium supplementation has little beneficial effects on bone gain. Given that genetic factors, hormonal status, body size, bone structure, diets, physical activity, vitamin D status and adaptation could modify calcium retention and bone integrity, these factors need to be considered collectively to promote bone health in Asian populations. Furthermore, studies to identify indigenous foods rich in calcium and high in bioavailability are needed to widen sources of dietary calcium. Ethnic differences in calcium retention, hormonal status, bone structure, bone mineral accretion and peak bone mass are evident among Asians, Caucasians and Blacks in USA. Hence, reference calcium intakes for Asians are likely to be unique and different from those of Caucasians. More research has to be conducted in Asian populations in order to develop appropriate reference calcium intakes for the region.

Influence of Alveolar Bone Defects on the Stress Distribution in Quad Zygomatic Implant-Supported Maxillary Prosthesis.

PubMed

Duan, Yuanyuan; Chandran, Ravi; Cherry, Denise

The purpose of this study was to create three-dimensional composite models of quad zygomatic implant-supported maxillary prostheses with a variety of alveolar bone defects around implant sites, and to investigate the stress distribution in the surrounding bone using the finite element analysis (FEA) method. Three-dimensional models of titanium zygomatic implants, maxillary prostheses, and human skulls were created and assembled using Mimics based on microcomputed tomography and cone beam computed tomography images. A variety of additional bone defects were created at the locations of four zygomatic implants to simulate multiple clinical scenarios. The volume meshes were created and exported into FEA software. Material properties were assigned respectively for all the structures, and von Mises stress data were collected and plotted in the postprocessing module. The maximum stress in the surrounding bone was located in the crestal bone around zygomatic implants. The maximum stress in the prostheses was located at the angled area of the implant-abutment connection. The model with anterior defects had a higher peak stress value than the model with posterior defects. All the models with additional bone defects had higher maximum stress values than the control model without additional bone loss. Additional alveolar bone loss has a negative influence on the stress concentration in the surrounding bone of quad zygomatic implant-supported prostheses. More care should be taken if these additional bone defects are at the sites of anterior zygomatic implants.

Quantitative trait locus on chromosome X affects bone loss after maturation in mice.

PubMed

Okudaira, Shuzo; Shimizu, Motoyuki; Otsuki, Bungo; Nakanishi, Rika; Ohta, Akira; Higuchi, Keiichi; Hosokawa, Masanori; Tsuboyama, Tadao; Nakamura, Takashi

2010-09-01

Genetic programming is known to affect the peak bone mass and bone loss after maturation. However, little is known about how polymorphic genes on chromosome X (Chr X) modulate bone loss after maturation. We previously reported a quantitative trait locus (QTL) on Chr X, designated Pbd3, which had a suggestive linkage to bone mass, in male SAMP2 and SAMP6 mice. In this study, we aimed to clarify the effects of Pbd3 on the skeletal phenotype. We generated a congenic strain, P2.P6-X, carrying a 45.6-cM SAMP6-derived Chr X interval on a SAMP2 genetic background. The effects of Pbd3 on the bone phenotype were determined by microcomputed tomography (microCT), whole-body dual-energy X-ray absorptiometry (DXA), serum bone turnover markers, and histomorphometric parameters. Both the bone area fraction (BA/TA) on microCT and whole-body DXA revealed reduced bone loss in P2.P6-X compared with that in SAMP2. The serum concentrations of bone turnover markers at 4 months of age were significantly lower in P2.P6-X than in SAMP2, but did not differ at 8 months of age. These results were observed in female mice, but not in male mice. In conclusion, a QTL within a segregated 45.6-cM interval on Chr X is sex-specifically related to the rate of bone loss after maturation.

Sex steroids during bone growth: a comparative study between mouse models for hypogonadal and senile osteoporosis.

PubMed

Ophoff, J; Venken, K; Callewaert, F; Boonen, S; Bouillon, R; Vanderschueren, D

2009-10-01

In this study, the role of disturbed bone mineral acquisition during puberty in the pathogenesis of osteoporosis was studied. To this end, a mouse model for senile and hypogonadal osteoporosis was used. Longitudinal follow-up showed that bone fragility in both models results from deficient bone build-up during early puberty. Male osteoporosis may result from impaired bone growth. This study characterizes the mechanisms of deficient peak bone mass acquisition in models for senile (SAMP6) and hypogonadal (orchidectomized SAMR1) osteoporosis. Bone mineral acquisition was investigated longitudinally in SAMP6 and orchidectomized SAMR1 mice (eight to ten animals per group) using peripheral quantitative computed tomography and histomorphometry. Additionally, the effects of long-term 5alpha-dihydrotestosterone (DHT) and 17beta-estradiol (E2) replacement were studied. Statistical analysis was performed using ANOVA and Student's t test. SAMP6 mice showed an early (4 weeks) medullary expansion of the cortex due to impaired endocortical bone formation (-43%). Despite compensatory periosteal bone formation (+47%), cortical thickness was severely reduced in 20-week-old SAMP6 versus SAMR1. Orchidectomy reduced periosteal apposition between 4 and 8 weeks of age and resulted in high bone turnover and less trabecular bone gain in SAMP6 and SAMR1. DHT and E2 stimulated periosteal expansion and trabecular bone in orchidectomized SAMP6 and SAMR1. E2 stimulated endocortical apposition in SAMP6. Moreover, sex steroid action occurred between 4 and 8 weeks of age. Bone fragility in both models resulted from deficient bone build-up during early puberty. DHT and E2 improved bone mass acquisition in orchidectomized animals, suggesting a role for AR and ER in male skeletal development.

The role of cross-sectional geometry, curvature, and limb posture in maintaining equal safety factors: a computed tomography study.

PubMed

Brassey, Charlotte A; Kitchener, Andrew C; Withers, Philip J; Manning, Phillip L; Sellers, William I

2013-03-01

The limb bones of an elephant are considered to experience similar peak locomotory stresses as a shrew. "Safety factors" are maintained across the entire range of body masses through a combination of robusticity of long bones, postural variation, and modification of gait. The relative contributions of these variables remain uncertain. To test the role of shape change, we undertook X-ray tomographic scans of the leg bones of 60 species of mammals and birds, and extracted geometric properties. The maximum resistible forces the bones could withstand before yield under compressive, bending, and torsional loads were calculated using standard engineering equations incorporating curvature. Positive allometric scaling of cross-sectional properties with body mass was insufficient to prevent negative allometry of bending (F(b) ) and torsional maximum force (F(t) ) (and hence decreasing safety factors) in mammalian (femur F(b) ∞M(b) (0.76) , F(t) ∞M(b) (0.80) ; tibia F(b) ∞M(b) (0.80) , F(t) ∞M(b) (0.76) ) and avian hindlimbs (tibiotarsus F(b) ∞M(b) (0.88) , F(t) ∞M(b) (0.89) ) with the exception of avian femoral F(b) and F(t) . The minimum angle from horizontal a bone must be held while maintaining a given safety factor under combined compressive and bending loads increases with M(b) , with the exception of the avian femur. Postural erectness is shown as an effective means of achieving stress similarity in mammals. The scaling behavior of the avian femur is discussed in light of unusual posture and kinematics. Copyright © 2013 Wiley Periodicals, Inc.

Diabetes mellitus affects the biomechanical function of the callus and the expression of TGF-beta1 and BMP2 in an early stage of fracture healing.

PubMed

Xu, M T; Sun, S; Zhang, L; Xu, F; Du, S L; Zhang, X D; Wang, D W

2016-01-01

Transforming growth factor beta 1 (TGF-β1) and bone morphogenetic protein-2 (BMP-2) are important regulators of bone repair and regeneration. In this study, we examined whether TGF-β1 and BMP-2 expressions were delayed during bone healing in type 1 diabetes mellitus. Tibial fractures were created in 95 diabetic and 95 control adult male Wistar rats of 10 weeks of age. At 1, 2, 3, 4, and 5 weeks after fracture induction, five rats were sacrificed from each group. The expressions of TGF-β1 and BMP2 in the fractured tibias were measured by immunohistochemistry and quantitative reverse-transcription polymerase chain reaction, weekly for the first 5 weeks post-fracture. Mechanical parameters (bending rigidity, torsional rigidity, destruction torque) of the healing bones were also assessed at 3, 4, and 5 weeks post-fracture, after the rats were sacrificed. The bending rigidity, torsional rigidity and destruction torque of the two groups increased continuously during the healing process. The diabetes group had lower mean values for bending rigidity, torsional rigidity and destruction torque compared with the control group (P<0.05). TGF-β1 and BMP-2 expression were significantly lower (P<0.05) in the control group than in the diabetes group at postoperative weeks 1, 2, and 3. Peak levels of TGF-β1 and BMP-2 expression were delayed by 1 week in the diabetes group compared with the control group. Our results demonstrate that there was a delayed recovery in the biomechanical function of the fractured bones in diabetic rats. This delay may be associated with a delayed expression of the growth factors TGF-β1 and BMP-2.

Bone mineral density, body composition and bone turnover in patients with congenital hypogonadotropic hypogonadism.

PubMed

Laitinen, E-M; Hero, M; Vaaralahti, K; Tommiska, J; Raivio, T

2012-08-01

Patients with congenital hypogonadotropic hypogonadism (HH) may have reduced peak bone mass in early adulthood, and increased risk for osteoporosis despite long-term hormonal replacement therapy (HRT). To investigate the relationship between HRT history and measures of bone health in patients with HH, we recruited 33 subjects (24 men, nine women; mean age 39.8 years, range: 24.0-69.1) with congenital HH (Kallmann syndrome or normosmic HH). They underwent clinical examination, were interviewed and medical charts were reviewed. Twenty-six subjects underwent dual-energy X-ray absorptiometry for evaluation of BMD of lumbar spine, hip, femoral neck and whole body; body composition and vertebral morphology were evaluated in 22 and 23 subjects, respectively. Circulating PINP, ICTP and sex hormone levels were measured. HRT history clearly associated to bone health: BMDs of lumbar spine, femoral neck, hip and whole body were lower in subjects (n = 9) who had had long (≥5 years) treatment pauses or low dose testosterone (T) treatment as compared to subjects without such history (n = 17; all p-values < 0.05). In addition, fat mass and body mass index (BMI) were significantly higher in men with deficient treatment history (median fat mass: 37.5 vs. 23.1%, p = 0.005; BMI: 32.6 vs. 25.2 kg/m(2), p < 0.05). Serum PINP correlated with ICTP (r(s) = 0.61; p < 0.005) in men, but these markers correlated neither with circulating T, nor with serum estradiol levels in women. In conclusion, patients with congenital HH require life-long follow-up to avoid inadequate HRT, long treatment pauses and further morbidity. © 2012 The Authors. International Journal of Andrology © 2012 European Academy of Andrology.

[Osteoclasts and early bone remodeling after orthodontic micro-implant placement].

PubMed

Zhang, Wei; Guo, Jia-jia; Zhu, Wen-qian; Tang, Guo-hua

2013-08-01

To observe the incidence of osteoclasts during early bone remodeling after orthodontic micro-implant placement. Twenty New Zealand rabbits were randomly allotted into 4 groups. One micro-implant was implanted proximal to the epiphyseal plate of the tibia. Animals were sacrificed on day 3, 7, 14 and 28 (n=5). The sequence of histological changes around the micro-implants were evaluated by hematoxylin and eosin (HE) staining. Osteoclasts were identified by TRAP staining. The differences of the number of the osteoclasts among each time point were analyzed by one way ANOVA with SPSS 19.0 software package. After 3 days of implantation, a large number of erythrocytes, inflammatory cells, mesenchymal cells and bone debris were seen at the implant bone interfaces. Few osteoclasts were observed. On day 7, granular woven bone was formed and some osteoclasts were found in the Howship's lacunae. New bone formation and mineralization were apparent on day 14. Meanwhile, large amounts of osteoclasts were found in the latticed woven bone. On day 28, woven trabeculae with lamellate structures connected to lamellar bone and fewer osteoclasts were identified. Semi-quantitative analysis showed that the number of the osteoclasts was at peak on day 14. There were significant differences among each time point (P<0.01). Osteoclast activity is closely related to bone formation and remodeling after micro-implant insertion.

Fortified tuna bone powder supplementation increases bone mineral density of lactating rats and their offspring.

PubMed

Suntornsaratoon, Panan; Charoenphandhu, Narattaphol; Krishnamra, Nateetip

2018-03-01

Breastfeeding leads to bone calcium loss for milk production, resulting in progressive maternal osteopenia. Calcium supplement from natural sources has been postulated to be more beneficial to bone health than purified CaCO 3 because natural sources also contain other nutrients such as certain amino acids that might enhance calcium metabolism. Herein, we examined the effect of calcium supplementation from tuna bone powder and CaCO 3 on bones of dams and the offspring. Both forms of calcium supplement, i.e. tuna bone powder and CaCO 3 , increased maternal bone mineral density (BMD). However, bone histomorphometry revealed that only tuna bone had beneficial effect on maternal bone microstructure, i.e. increased bone formation, decreased bone resorption and increased in bone volume. Regarding the mechanical properties, the decreased ultimate load in non-supplement lactating mothers was restored to the load seen in nulliparous animals by calcium supplementation. Moreover, both tuna bone and CaCO 3 supplementation in mothers led to increased milk calcium concentration and consequently increased BMD in the growing offspring. Calcium supplement from tuna bone powder was effective in preventing maternal osteopenia. Tuna bone, which is a readily available fishing industrial waste, is a good alternative source of calcium supplement that increases BMD in both lactating mothers and the neonates. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

A soluble bone morphogenetic protein type IA receptor increases bone mass and bone strength

PubMed Central

Baud’huin, Marc; Solban, Nicolas; Cornwall-Brady, Milton; Sako, Dianne; Kawamoto, Yoshimi; Liharska, Katia; Lath, Darren; Bouxsein, Mary L.; Underwood, Kathryn W.; Ucran, Jeffrey; Kumar, Ravindra; Pobre, Eileen; Grinberg, Asya; Seehra, Jasbir; Canalis, Ernesto; Pearsall, R. Scott; Croucher, Peter I.

2012-01-01

Diseases such as osteoporosis are associated with reduced bone mass. Therapies to prevent bone loss exist, but there are few that stimulate bone formation and restore bone mass. Bone morphogenetic proteins (BMPs) are members of the TGFβ superfamily, which act as pleiotropic regulators of skeletal organogenesis and bone homeostasis. Ablation of the BMPR1A receptor in osteoblasts increases bone mass, suggesting that inhibition of BMPR1A signaling may have therapeutic benefit. The aim of this study was to determine the skeletal effects of systemic administration of a soluble BMPR1A fusion protein (mBMPR1A–mFc) in vivo. mBMPR1A–mFc was shown to bind BMP2/4 specifically and with high affinity and prevent downstream signaling. mBMPR1A–mFc treatment of immature and mature mice increased bone mineral density, cortical thickness, trabecular bone volume, thickness and number, and decreased trabecular separation. The increase in bone mass was due to an early increase in osteoblast number and bone formation rate, mediated by a suppression of Dickkopf-1 expression. This was followed by a decrease in osteoclast number and eroded surface, which was associated with a decrease in receptor activator of NF-κB ligand (RANKL) production, an increase in osteoprotegerin expression, and a decrease in serum tartrate-resistant acid phosphatase (TRAP5b) concentration. mBMPR1A treatment also increased bone mass and strength in mice with bone loss due to estrogen deficiency. In conclusion, mBMPR1A–mFc stimulates osteoblastic bone formation and decreases bone resorption, which leads to an increase in bone mass, and offers a promising unique alternative for the treatment of bone-related disorders. PMID:22761317

Influence of hyperbaric oxygen on biomechanics and structural bone matrix in type 1 diabetes mellitus rats.

PubMed

Limirio, Pedro Henrique Justino Oliveira; da Rocha Junior, Huberth Alexandre; Morais, Richarlisson Borges de; Hiraki, Karen Renata Nakamura; Balbi, Ana Paula Coelho; Soares, Priscilla Barbosa Ferreira; Dechichi, Paula

2018-01-01

The aim of this study was to evaluate the biomechanics and structural bone matrix in diabetic rats subjected to hyperbaric oxygen therapy (HBO). Twenty-four male rats were divided into the following groups: Control; Control + HBO; Diabetic, and Diabetic + HBO. Diabetes was induced with streptozotocin (STZ) in the diabetic Groups. After 30 days, HBO was performed every 48h in HBO groups and all animals were euthanized 60 days after diabetic induction. The femur was submitted to a biomechanical (maximum strength, energy-to-failure and stiffness) and Attenuated Total Reflectance Fourier transform infrared (ATR-FTIR) analyses (crosslink ratio, crystallinity index, matrix-to-mineral ratio: Amide I + II/Hydroxyapatite (M:MI) and Amide III + Collagen/HA (M:MIII)). In biomechanical analysis, diabetic animals showed lower values of maximum strength, energy and stiffness than non-diabetic animals. However, structural strength and stiffness were increased in groups with HBO compared with non-HBO. ATR-FTIR analysis showed decreased collagen maturity in the ratio of crosslink peaks in diabetic compared with the other groups. The bone from the diabetic groups showed decreased crystallinity compared with non-diabetic groups. M:MI showed no statistical difference between groups. However, M:MIII showed an increased matrix mineral ratio in diabetic+HBO and control+HBO compared with control and diabetic groups. Correlations between mechanical and ATR-FTIR analyses showed significant positive correlation between collagen maturity and stiffness. Diabetes decreased collagen maturation and the mineral deposition process, thus reducing biomechanical properties. Moreover, the study showed that HBO improved crosslink maturation and increased maximum strength and stiffness in the femur of T1DM animals.

Oral Contraceptives Use by Young Woman Reduces Peak Bone Mass

DTIC Science & Technology

1999-09-01

Alphacel 10.0 Lard 5.20 Safflower Oil (linoleic) 1.00 Choline Bitartrate 0.20 Vitamin Mixture, AIN-76A 1.00 Mineral Mix, AIN-76 3.50 On Nov...774-9,1970 Modrowoski D, del Pozo E, Miravet L . Horm Metab Res 24(10):474-477, 1992. Parfitt AM, Drezner MK, Glorieux FH, et al. J Bone Mineral Res...Register.1 C. L . Hughes.*2 U. Blas- Machado.*1 E. Sulistiawati.*’ P. W. Louderback.*1 S. E. Rankin.*1 ’Pathology/Comparative Medicine, Wake Forest

Inhibiting the osteocyte-specific protein sclerostin increases bone mass and fracture resistance in multiple myeloma

PubMed Central

Mohanty, Sindhu T.; Seckinger, Anja; Terry, Rachael L.; Pettitt, Jessica A.; Simic, Marija K.; Le, Lawrence M. T.; Kramer, Ina; Falank, Carolyne; Fairfield, Heather; Ghobrial, Irene M.; Baldock, Paul A.; Little, David G.; Kneissel, Michaela; Vanderkerken, Karin; Bassett, J. H. Duncan; Williams, Graham R.; Oyajobi, Babatunde O.; Hose, Dirk

2017-01-01

Multiple myeloma (MM) is a plasma cell cancer that develops in the skeleton causing profound bone destruction and fractures. The bone disease is mediated by increased osteoclastic bone resorption and suppressed bone formation. Bisphosphonates used for treatment inhibit bone resorption and prevent bone loss but fail to influence bone formation and do not replace lost bone, so patients continue to fracture. Stimulating bone formation to increase bone mass and fracture resistance is a priority; however, targeting tumor-derived modulators of bone formation has had limited success. Sclerostin is an osteocyte-specific Wnt antagonist that inhibits bone formation. We hypothesized that inhibiting sclerostin would prevent development of bone disease and increase resistance to fracture in MM. Sclerostin was expressed in osteocytes from bones from naive and myeloma-bearing mice. In contrast, sclerostin was not expressed by plasma cells from 630 patients with myeloma or 54 myeloma cell lines. Mice injected with 5TGM1-eGFP, 5T2MM, or MM1.S myeloma cells demonstrated significant bone loss, which was associated with a decrease in fracture resistance in the vertebrae. Treatment with anti-sclerostin antibody increased osteoblast numbers and bone formation rate but did not inhibit bone resorption or reduce tumor burden. Treatment with anti-sclerostin antibody prevented myeloma-induced bone loss, reduced osteolytic bone lesions, and increased fracture resistance. Treatment with anti-sclerostin antibody and zoledronic acid combined increased bone mass and fracture resistance when compared with treatment with zoledronic acid alone. This study defines a therapeutic strategy superior to the current standard of care that will reduce fractures for patients with MM. PMID:28515094

Bone formation: roles of genistein and daidzein

USDA-ARS?s Scientific Manuscript database

Bone remodeling consists of a balance between bone formation by osteoblasts and bone resorption by osteoclasts. Osteoporosis is the result of increased bone resorption and decreased bone formation causing a decreased bone mass density, loss of bone microarchitecture, and an increased risk of fractu...

Estrogen regulates the rate of bone turnover but bone balance in ovariectomized rats is modulated by prevailing mechanical strain

NASA Technical Reports Server (NTRS)

Westerlind, K. C.; Wronski, T. J.; Ritman, E. L.; Luo, Z. P.; An, K. N.; Bell, N. H.; Turner, R. T.

1997-01-01

Estrogen deficiency induced bone loss is associated with increased bone turnover in rats and humans. The respective roles of increased bone turnover and altered balance between bone formation and bone resorption in mediating estrogen deficiency-induced cancellous bone loss was investigated in ovariectomized rats. Ovariectomy resulted in increased bone turnover in the distal femur. However, cancellous bone was preferentially lost in the metaphysis, a site that normally experiences low strain energy. No bone loss was observed in the epiphysis, a site experiencing higher strain energy. The role of mechanical strain in maintaining bone balance was investigated by altering the strain history. Mechanical strain was increased and decreased in long bones of ovariectomized rats by treadmill exercise and functional unloading, respectively. Functional unloading was achieved during orbital spaceflight and following unilateral sciatic neurotomy. Increasing mechanical loading reduced bone loss in the metaphysis. In contrast, decreasing loading accentuated bone loss in the metaphysis and resulted in bone loss in the epiphysis. Finally, administration of estrogen to ovariectomized rats reduced bone loss in the unloaded and prevented loss in the loaded limb following unilateral sciatic neurotomy in part by reducing indices of bone turnover. These results suggest that estrogen regulates the rate of bone turnover, but the overall balance between bone formation and bone resorption is influenced by prevailing levels of mechanical strain.

Age-dependent tissue-specific exposure of cell phone users.

PubMed

Christ, Andreas; Gosselin, Marie-Christine; Christopoulou, Maria; Kühn, Sven; Kuster, Niels

2010-04-07

The peak spatial specific absorption rate (SAR) assessed with the standardized specific anthropometric mannequin head phantom has been shown to yield a conservative exposure estimate for both adults and children using mobile phones. There are, however, questions remaining concerning the impact of age-dependent dielectric tissue properties and age-dependent proportions of the skull, face and ear on the global and local absorption, in particular in the brain tissues. In this study, we compare the absorption in various parts of the cortex for different magnetic resonance imaging-based head phantoms of adults and children exposed to different models of mobile phones. The results show that the locally induced fields in children can be significantly higher (>3 dB) in subregions of the brain (cortex, hippocampus and hypothalamus) and the eye due to the closer proximity of the phone to these tissues. The increase is even larger for bone marrow (>10 dB) as a result of its significantly high conductivity. Tissues such as the pineal gland show no increase since their distances to the phone are not a function of age. This study, however, confirms previous findings saying that there are no age-dependent changes of the peak spatial SAR when averaged over the entire head.

Age-dependent tissue-specific exposure of cell phone users

NASA Astrophysics Data System (ADS)

Christ, Andreas; Gosselin, Marie-Christine; Christopoulou, Maria; Kühn, Sven; Kuster, Niels

2010-04-01

The peak spatial specific absorption rate (SAR) assessed with the standardized specific anthropometric mannequin head phantom has been shown to yield a conservative exposure estimate for both adults and children using mobile phones. There are, however, questions remaining concerning the impact of age-dependent dielectric tissue properties and age-dependent proportions of the skull, face and ear on the global and local absorption, in particular in the brain tissues. In this study, we compare the absorption in various parts of the cortex for different magnetic resonance imaging-based head phantoms of adults and children exposed to different models of mobile phones. The results show that the locally induced fields in children can be significantly higher (>3 dB) in subregions of the brain (cortex, hippocampus and hypothalamus) and the eye due to the closer proximity of the phone to these tissues. The increase is even larger for bone marrow (>10 dB) as a result of its significantly high conductivity. Tissues such as the pineal gland show no increase since their distances to the phone are not a function of age. This study, however, confirms previous findings saying that there are no age-dependent changes of the peak spatial SAR when averaged over the entire head.

Posterior root tear fixation of the lateral meniscus combined with arthroscopic ACL double-bundle reconstruction: technical note of a transosseous fixation using the tibial PL tunnel.

PubMed

Forkel, Philipp; Petersen, Wolf

2012-03-01

According to our observation in ACL reconstruction, we find root tears of the posterior horn of the lateral meniscus as a common concomitant injury in ACL-deficient knees. This might be a consequence of initial trauma or of the increased anterior-posterior translation of the tibia and an overload impact on the posterior meniscus root in ACL-deficient knees. A tear of the posterior horn of the medial meniscus causes a 25% increase in peak pressure in the medial compartment compared with that found in the intact condition. The repair restores the peak contact pressure to normal (Allaire et al. in J Bone Joint Surg Am 90(9):1922-1931, [2008]). A tear of the posterior horn of the lateral meniscus might have similar consequences. We hypothesize the surgical anatomical reattachment of the root at the tibia helping to restore knee joint kinematics and helping to advance ACL-graft function. This article presents an arthroscopical technique to reattach the posterior meniscus root in combination with ACL double-bundle reconstruction. The procedure uses the tibial PL tunnel to fix the meniscus suture.

Graphene Oxide-A Tool for the Preparation of Chemically Crosslinking Free Alginate-Chitosan-Collagen Scaffolds for Bone Tissue Engineering.

PubMed

Kolanthai, Elayaraja; Sindu, Pugazhendhi Abinaya; Khajuria, Deepak Kumar; Veerla, Sarath Chandra; Kuppuswamy, Dhandapani; Catalani, Luiz Henrique; Mahapatra, D Roy

2018-04-18

Developing a biodegradable scaffold remains a major challenge in bone tissue engineering. This study was aimed at developing novel alginate-chitosan-collagen (SA-CS-Col)-based composite scaffolds consisting of graphene oxide (GO) to enrich porous structures, elicited by the freeze-drying technique. To characterize porosity, water absorption, and compressive modulus, GO scaffolds (SA-CS-Col-GO) were prepared with and without Ca 2+ -mediated crosslinking (chemical crosslinking) and analyzed using Raman, Fourier transform infrared (FTIR), X-ray diffraction (XRD), and scanning electron microscopy techniques. The incorporation of GO into the SA-CS-Col matrix increased both crosslinking density as indicated by the reduction of crystalline peaks in the XRD patterns and polyelectrolyte ion complex as confirmed by FTIR. GO scaffolds showed increased mechanical properties which were further increased for chemically crosslinked scaffolds. All scaffolds exhibited interconnected pores of 10-250 μm range. By increasing the crosslinking density with Ca 2+ , a decrease in the porosity/swelling ratio was observed. Moreover, the SA-CS-Col-GO scaffold with or without chemical crosslinking was more stable as compared to SA-CS or SA-CS-Col scaffolds when placed in aqueous solution. To perform in vitro biochemical studies, mouse osteoblast cells were grown on various scaffolds and evaluated for cell proliferation by using MTT assay and mineralization and differentiation by alizarin red S staining. These measurements showed a significant increase for cells attached to the SA-CS-Col-GO scaffold compared to SA-CS or SA-CS-Col composites. However, chemical crosslinking of SA-CS-Col-GO showed no effect on the osteogenic ability of osteoblasts. These studies indicate the potential use of GO to prepare free SA-CS-Col scaffolds with preserved porous structure with elongated Col fibrils and that these composites, which are biocompatible and stable in a biological medium, could be used for application in engineering bone tissues.

Development and blood compatibility assessment of electrospun polyvinyl alcohol blended with metallocene polyethylene and plectranthus amboinicus (PVA/mPE/PA) for bone tissue engineering.

PubMed

Qi, Jie; Zhang, Huang; Wang, Yingzhou; Mani, Mohan Prasath; Jaganathan, Saravana Kumar

2018-01-01

Currently, the design of extracellular matrix (ECM) with nanoscale properties in bone tissue engineering is challenging. For bone tissue engineering, the ECM must have certain properties such as being nontoxic, highly porous, and should not cause foreign body reactions. In this study, the hybrid scaffold based on polyvinyl alcohol (PVA) blended with metallocene polyethylene (mPE) and plectranthus amboinicus (PA) was fabricated for bone tissue engineering via electrospinning. The fabricated hybrid nanocomposites were characterized by scanning electron microscopy (SEM), Fourier transform and infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), contact angle measurement, and atomic force microscopy (AFM). Furthermore, activated partial thromboplastin time (APTT), prothrombin time (PT), and hemolytic assays were used to investigate the blood compatibility of the prepared hybrid nanocomposites. The prepared hybrid nanocomposites showed reduced fiber diameter (238±45 nm) and also increased porosity (87%) with decreased pore diameter (340±86 nm) compared with pure PVA. The interactions between PVA, mPE, and PA were identified by the formation of the additional peaks as revealed in FTIR. Furthermore, the prepared hybrid nanocomposites showed a decreased contact angle of 51°±1.32° indicating a hydrophilic nature and exhibited lower thermal stability compared to pristine PVA. Moreover, the mechanical results revealed that the electrospun scaffold showed an improved tensile strength of 3.55±0.29 MPa compared with the pristine PVA (1.8±0.52 MPa). The prepared hybrid nanocomposites showed delayed blood clotting as noted in APTT and PT assays indicating better blood compatibility. Moreover, the hemolysis assay revealed that the hybrid nanocomposites exhibited a low hemolytic index of 0.6% compared with pure PVA, which was 1.6% suggesting the safety of the developed nanocomposite to red blood cells (RBCs). The prepared nanocomposites exhibited better physico-chemical properties, sufficient porosity, mechanical strength, and blood compatibility, which favors it as a valuable candidate in bone tissue engineering for repairing the bone defects.

The Orientation of Nanoscale Apatite Platelets in Relation to Osteoblastic-Osteocyte Lacunae on Trabecular Bone Surface.

PubMed

Shah, Furqan A; Zanghellini, Ezio; Matic, Aleksandar; Thomsen, Peter; Palmquist, Anders

2016-02-01

The orientation of nanoscale mineral platelets was quantitatively evaluated in relation to the shape of lacunae associated with partially embedded osteocytes (osteoblastic-osteocytes) on the surface of deproteinised trabecular bone of adult sheep. By scanning electron microscopy and image analysis, the mean orientation of mineral platelets at the osteoblastic-osteocyte lacuna (Ot.Lc) floor was found to be 19° ± 14° in the tibia and 20° ± 14° in the femur. Further, the mineral platelets showed a high degree of directional coherency: 37 ± 7% in the tibia and 38 ± 9% in the femur. The majority of Ot.Lc in the tibia (69.37%) and the femur (74.77%) exhibited a mean orientation of mineral platelets between 0° and 25°, with the largest fraction within a 15°-20° range, 17.12 and 19.8% in the tibia and femur, respectively. Energy dispersive X-ray spectroscopy and Raman spectroscopy were used to characterise the features observed on the anorganic bone surface. The Ca/P (atomic %) ratio was 1.69 ± 0.1 within the Ot.Lc and 1.68 ± 0.1 externally. Raman spectra of NaOCl-treated bone showed peaks associated with carbonated apatite: ν1, ν2 and ν4 PO4(3-), and ν1 CO3(2-), while the collagen amide bands were greatly reduced in intensity compared to untreated bone. The apatite-to-collagen ratio increased considerably after deproteinisation; however, the mineral crystallinity and the carbonate-to-phosphate ratios were unaffected. The ~19°-20° orientation of mineral platelets in at the Ot.Lc floor may be attributable to a gradual rotation of osteoblasts in successive layers relative to the underlying surface, giving rise to the twisted plywood-like pattern of lamellar bone.

Effects of LED or laser phototherapy on bone defects grafted with MTA and irradiated with laser or LED light: a comparative Raman spectroscopic study

NASA Astrophysics Data System (ADS)

Pinheiro, Antonio L. B.; Soares, Luiz G. P.; Barbosa, Artur Felipe S.; Silveira, Landulfo, Jr.

2012-03-01

We studied peaks of calcium hydroxyapatite - CHA on defects grafted with MTA, treated or not with Light Emitting Diode - LED or IR Laser. 54 rats were divided in 6 groups each subdivided into 3 subgroups (15,21,30d). LED (λ850 +/- 10nm) or IR Laser (λ850 nm) was applied over (LED) or in 4 points around the defect at 48 h intervals for 15 days. Raman readings were taken at the surface of the defect. The smaller overall intensity of the peak was found in Group MTA + Laser (1510.2 +/- 274.1) and the highest on Group LED (2322 +/- 715). There were no statistically significant differences between non-irradiated subjects on regards the CHA peaks. On the other hand, there were statistically significant differences between the Group Clot and LED, Clot and Laser, and Clot and MTA + Laser (p =0.01, p = 0.02, p = 0.003). There were no significant differences between Group MTA and MTA + LED (p=0.2) but significant differences were seen between Groups MTA and MTA + Laser (p=0.01). Significant differences were also observed between Groups LED and Laser (p <0.001) and between Groups MTA + LED and MTA + Laser (p=0.009). MTA, due to its characteristics, seemed to be directly affected by the light. However, the use of either phototherapy positively affected bone healing similarly as observed on different studies using other biomaterials. The overall analysis of our results indicated that the use of either light source resulted in a better, more advanced, and of quality bone repair.

Analysis of multiple bone responses to graded strains above functional levels, and to disuse, in mice in vivo show that the human Lrp5 G171V High Bone Mass mutation increases the osteogenic response to loading but that lack of Lrp5 activity reduces it

PubMed Central

Saxon, Leanne K.; Jackson, Brendan F.; Sugiyama, Toshihiro; Lanyon, Lance E.; Price, Joanna S.

2011-01-01

Introduction To investigate the role of the low-density lipoprotein receptor-related protein 5 (Lrp5) in bones' responses to loading, we analysed changes in multiple measures of bone architecture in tibias subjected to loading or disuse in male and female mice with the Lrp5 loss of function mutation (Lrp5−/−) or heterozygous for the Lrp5 G171V High Bone Mass (HBM) mutation (Lrp5HBM+). Materials and methods The right tibias of these 17 week old male and female mice and their Wild Type (WT) littermates were subjected to short periods of loading three days a week for two weeks. Each tibia was loaded for 40 cycles, to produce peak strains at the midshaft within the low, medium or high physiological range (~ 1500, 2400 and 3000 microstrain, respectively). In similar groups of mice the right sciatic nerve was severed causing disuse of the right tibia for 3 weeks. Data from microCT of loaded, neurectomised and contra-lateral control tibias were analysed to quantify changes in the cortical and cancellous regions of the bone in the absence of functional strains and in response to graded strains in addition to those derived from function. Results and conclusion Male WT+/+ controls showed significant strain:response curves for cortical area and trabecular thickness, but Lrp5−/− mice showed no detectable strain:response in those same outcomes. Female mice of either WT+/+ or Lrp5−/− genotype did not show significant strain:response curves for cortical or trabecular parameters, the one exception being Tb.Th in Lrp5−/− mice. Since female WT+/+ mice did not respond to loading in a significant dose:responsive manner, the similar lack of responsiveness of the Lrp5−/− females could not be ascribed to their Lrp5 status. Cortical bone loss associated with disuse showed no differences between Lrp5−/− mice and WT+/+ controls, but in cancellous bone of both male and females of these mice, there was a greater loss than in WT+/+ controls. In contrast, the tibias of male and female mice heterozygous for the Lrp5 G171V HBM mutation showed greater osteogenic responsiveness to loading and less bone loss associated with disuse than their WTHBM− controls. These data indicate that the presence of the Lrp5 G171V HBM mutation is associated with an increased osteogenic response to loading but support only a marginal gender-related role for normal Lrp5 function in this loading-related response. PMID:21419885

Advanced age diminishes tendon-to-bone healing in a rat model of rotator cuff repair.

PubMed

Plate, Johannes F; Brown, Philip J; Walters, Jordan; Clark, John A; Smith, Thomas L; Freehill, Michael T; Tuohy, Christopher J; Stitzel, Joel D; Mannava, Sandeep

2014-04-01

Advanced patient age is associated with recurrent tearing and failure of rotator cuff repairs clinically; however, basic science studies have not evaluated the influence of aging on tendon-to-bone healing after rotator cuff repair in an animal model. Hypothesis/ This study examined the effect of aging on tendon-to-bone healing in an established rat model of rotator cuff repair using the aged animal colony from the National Institute on Aging of the National Institutes of Health. The authors hypothesized that normal aging decreases biomechanical strength and histologic organization at the tendon-to-bone junction after acute repair. Controlled laboratory study. In 56 F344xBN rats, 28 old and 28 young (24 and 8 months of age, respectively), the supraspinatus tendon was transected and repaired. At 2 or 8 weeks after surgery, shoulder specimens underwent biomechanical testing to compare load-to-failure and load-relaxation response between age groups. Histologic sections of the tendon-to-bone interface were assessed with hematoxylin and eosin staining, and collagen fiber organization was assessed by semiquantitative analysis of picrosirius red birefringence under polarized light. Peak failure load was similar between young and old animals at 2 weeks after repair (31% vs 26% of age-matched uninjured controls, respectively; P > .05) but significantly higher in young animals compared with old animals 8 weeks after repair (86% vs 65% of age-matched uninjured controls, respectively; P < .01). Eight weeks after repair, fibroblasts appeared more organized and uniformly aligned in young animals on hematoxylin and eosin slides compared with old animals. Collagen birefringence analysis of the tendon-to-bone junction demonstrated that young animals had increased collagen fiber organization and similar histologic structure compared with age-matched controls (53.7 ± 2.4 gray scales; P > .05). In contrast, old animals had decreased collagen fiber organization and altered structure compared with age-matched controls (49.8 ± 3.1 gray scales; P < .01). In a rat model of aging, old animals demonstrated diminished tendon-to-bone healing after rotator cuff injury and repair. Old animals had significantly decreased failure strength and collagen fiber organization at the tendon-to-bone junction compared with young animals. This study implies that animal age may need to be considered in future studies of rotator cuff repair in animal models. With increasing age and activity level of the population, the incidence of rotator cuff tears is predicted to rise. Despite advances in rotator cuff repair technique, the retear rate remains specifically high in elderly patients. The findings of this research suggest that aging negatively influences tendon-to-bone healing after rotator cuff repair in a validated animal model.

Contribution of myostatin gene polymorphisms to normal variation in lean mass, fat mass and peak BMD in Chinese male offspring.

PubMed

Yue, Hua; He, Jin-wei; Zhang, Hao; Wang, Chun; Hu, Wei-wei; Gu, Jie-mei; Ke, Yao-hua; Fu, Wen-zhen; Hu, Yun-qiu; Li, Miao; Liu, Yu-juan; Wu, Song-hua; Zhang, Zhen-lin

2012-05-01

Myostatin gene is a member of the transforming growth factor-β (TGF-β) family that negatively regulates skeletal muscle growth. Genetic polymorphisms in Myostatin were found to be associated with the peak bone mineral density (BMD) in Chinese women. The purpose of this study was to investigate whether myostatin played a role in the normal variation in peak BMD, lean mass (LM), and fat mass (FM) of Chinese men. Four hundred male-offspring nuclear families of Chinese Han ethnic group were recruited. Anthropometric measurements, including the peak BMD, body LM and FM were measured using dual-energy X-ray absorptiometry (DXA). The single nucleotide polymorphisms (SNPs) studied were tag-SNPs selected by sequencing. Both rs2293284 and +2278GA were genotyped using TaqMan assay, and rs3791783 was genotyped with PCR-restriction fragment length polymorphism (RFLP) analysis. The associations of the SNPs with anthropometric variations were analyzed using the quantitative transmission disequilibrium test (QTDT). Using QTDT to detect within-family associations, neither single SNP nor haplotype was found to be associated with peak BMD at any bone site. However, rs3791783 was found to be significantly associated with fat mass of the trunk (P<0.001). Moreover, for within-family associations, haplotypes AGG, AAA, and TGG were found to be significantly associated with the trunk fat mass (all P<0.001). Our results suggest that genetic variation within myostatin may play a role in regulating the variation in fat mass in Chinese males. Additionally, the myostatin gene may be a candidate that determines body fat mass in Chinese men.

Calcium ions and osteoclastogenesis initiate the induction of bone formation by coral-derived macroporous constructs

PubMed Central

Klar, Roland M; Duarte, Raquel; Dix-Peek, Therese; Dickens, Caroline; Ferretti, Carlo; Ripamonti, Ugo

2013-01-01

Coral-derived calcium carbonate/hydroxyapatite macroporous constructs of the genus Goniopora with limited hydrothermal conversion to hydroxyapatite (7% HA/CC) initiate the induction of bone formation. Which are the molecular signals that initiate pattern formation and the induction of bone formation? To evaluate the role of released calcium ions and osteoclastogenesis, 7% HA/CC was pre-loaded with either 500 μg of the calcium channel blocker, verapamil hydrochloride, or 240 μg of the osteoclast inhibitor, biphosphonate zoledronate, and implanted in the rectus abdominis muscle of six adult Chacma baboons Papio ursinus. Generated tissues on days 15, 60 and 90 were analysed by histomorphometry and qRT-PCR. On day 15, up-regulation of type IV collagen characterized all the implanted constructs correlating with vascular invasion. Zoledronate-treated specimens showed an important delay in tissue patterning and morphogenesis with limited bone formation. Osteoclastic inhibition yielded minimal, if any, bone formation by induction. 7% HA/CC pre-loaded with the Ca++ channel blocker verapamil hydrochloride strongly inhibited the induction of bone formation. Down-regulation of bone morphogenetic protein-2 (BMP-2) together with up-regulation of Noggin genes correlated with limited bone formation in 7% HA/CC pre-loaded with either verapamil or zoledronate, indicating that the induction of bone formation by coral-derived macroporous constructs is via the BMPs pathway. The spontaneous induction of bone formation is initiated by a local peak of Ca++ activating stem cell differentiation and the induction of bone formation. PMID:24106923

Impact of skeletal maturation on bone metabolism biomarkers and bone mineral density in healthy Brazilian male adolescents.

PubMed

Silva, Carla C; Goldberg, Tamara B L; Nga, Hong S; Kurokawa, Cilmery S; Capela, Renata C; Teixeira, Altamir S; Dalmas, José C

2011-01-01

To evaluate the behavior of biomarkers of bone formation and resorption in healthy male Brazilian adolescents according to their biological maturation. Eighty-seven volunteers were divided into age groups according to bone age (BA): 10-12 years (n = 25), 13-15 years (n = 36), and 16-18 years (n = 26). Weight (kg), height (m), body mass index (kg/m(2)), calcium intake from 3 days assessed by 24-h food recall (mg/day), pubertal event evaluation by Tanner criteria, and serum biomarker levels (osteocalcin [OC] [ng/mL], bone alkaline phosphatase [BAP] [U/L], and serum carboxyterminal telopeptide [S-CTx] [ng/mL]) were recorded and correlated to bone mineral density (BMD) (g/cm(2)) measured by dual energy X-ray absorptiometry of the lumbar spine, proximal femur, and whole body. Biomarkers showed similar behaviors, presenting higher median values in the 13-15 year group (BAP = 154.71 U/L, OC = 43.0 ng/mL, S-CTx = 2.09 ng/mL; p < 0.01) and when adolescents were in the pubertal stage G4. Median biomarker values decreased with advancing BA and sexual maturation. Biomarker values showed parallelism with peak height velocity, and, interestingly, bone formation biomarkers indicated significant negative correlation with BMD in the different evaluated locations, i.e., higher BMD values correlated with lower bone biomarker values. This is the first study of healthy Brazilian adolescents with rigid and careful inclusion and exclusion criteria to assess the correlation of bone markers and BMD with biological maturation indicators. Our results can help understand bone turnover and monitor bone metabolism.

Comparison of parameters of bone profile and homocysteine in physically active and non-active postmenopausal females.

PubMed

Tariq, Sundus; Lone, Khalid Parvez; Tariq, Saba

2016-01-01

Optimal physical activity is important in attaining a peak bone mass. Physically active women have better bone mineral density and reduce fracture risk as compared to females living a sedentary life. The objective of this study was to compare parameters of bone profile and serum homocysteine levels in physically active and non-active postmenopausal females. In this cross sectional study postmenopausal females between 50-70 years of age were recruited and divided into two groups: Physically inactive (n=133) performing light physical activity and Physically active (n=34) performing moderate physical activity. Physical activity (in metabolic equivalents), bone mineral density and serum homocysteine levels were assessed. Spearman's rho correlation was applied to observe correlations. Two independent sample t test and Mann Whitney U test were applied to compare groups. P-value ≤ 0.05 was taken statistically significant. Parameters of bone profile were significantly higher and serum homocysteine levels were significantly lower in postmenopausal females performing moderate physical activity as compared to females performing light physical activity. Homocysteine was not significantly related to T-score and Z-score in both groups. Improving physical activity could be beneficial for improving the quality of bone, decreasing fracture risk and decreasing serum homocysteine levels.

Mechanical signaling in the development of postmenopausal osteoporosis

NASA Technical Reports Server (NTRS)

Turner, R. T.

1999-01-01

Estrogen deficiency results in increased bone turnover and net bone loss in rats as well as humans. The respective roles of bone turnover and mechanical strain in mediating estrogen deficiency-induced cancellous bone loss were investigated in ovariectomized rats. Ovariectomy resulted in increased bone turnover in long bones. However, cancellous bone was preferentially lost in the metaphysis, a site that experiences low strain energy during normal physical activity. No bone loss was observed in the epiphysis, a site experiencing higher strain energy, despite a similar increase in bone turnover. The role of mechanical strain in maintaining bone balance was investigated by altering the strain history. Mechanical strain was increased or decreased in long bones of ovariectomized rats by treadmill exercise or functional unloading, respectively. Increasing mechanical loading reduced bone loss in the metaphysis. In contrast, decreasing weight bearing accentuated bone loss in the metaphysis and resulted in bone loss in the epiphysis. Finally, administration of estrogen to ovariectomized rats reduced bone loss in unloaded limbs and prevented bone loss in the loaded limbs. These results suggest that estrogen alters the mechanosensory (mechanostat) set point for skeletal adaptation, effectively reducing the minimum strain energy levels at which bone is added. Additionally, these studies suggest that physical activity as well as endocrine status play an important role in maintenance of the female skeleton during aging.

The influence of aluminium, steel and polyurethane shoeing systems and of the unshod hoof on the injury risk of a horse kick. An ex vivo experimental study.

PubMed

Sprick, Miriam; Fürst, Anton; Baschnagel, Fabio; Michel, Silvain; Piskoty, Gabor; Hartnack, Sonja; Jackson, Michelle A

2017-09-12

To evaluate the damage inflicted by an unshod hoof and by the various horseshoe materials (steel, aluminium and polyurethane) on the long bones of horses after a simulated kick. Sixty-four equine radii and tibiae were evaluated using a drop impact test setup. An impactor with a steel, aluminium, polyurethane, or hoof horn head was dropped onto prepared bones. An impactor velocity of 8 m/s was initially used with all four materials and then testing was repeated with a velocity of 12 m/s with the polyurethane and hoof horn heads. The impact process was analysed using a high-speed camera, and physical parameters, including peak contact force and impact duration, were calculated. At 8 m/s, the probability of a fracture was 75% for steel and 81% for aluminium, whereas polyurethane and hoof horn did not damage the bones. At 12 m/s, the probability of a fracture was 25% for polyurethane and 12.5% for hoof horn. The peak contact force and impact duration differed significantly between 'hard materials' (aluminium and steel) and 'soft materials' (polyurethane and hoof horn). The observed bone injuries were similar to those seen in analogous experimental studies carried out previously and comparable to clinical fracture cases suggesting that the simulated kick was realistic. The probability of fracture was significantly higher for steel and aluminium than for polyurethane and hoof horn, which suggests that the horseshoe material has a significant influence on the risk of injury for humans or horses kicked by a horse.

Does Increased Coefficient of Friction of Highly Porous Metal Increase Initial Stability at the Acetabular Interface?

PubMed

Goldman, Ashton H; Armstrong, Lucas C; Owen, John R; Wayne, Jennifer S; Jiranek, William A

2016-03-01

Highly porous metal acetabular components illustrate a decreased rate of aseptic loosening in short-term follow-up compared with previous registry data. This study compared the effect of component surface roughness at the bone-implant interface and the quality of the bone on initial pressfit stability. The null hypothesis is that a standard porous coated acetabular cup would show no difference in initial stability as compared with a highly porous acetabular cup when subjected to a bending moment. Second, would bone mineral density (BMD) be a significant variable under these test conditions. In a cadaveric model, acetabular cup micromotion was measured during a 1-time cantilever bending moment applied to 2 generations of pressfit acetabular components. BMD data were also obtained from the femoral necks available for associated specimen. The mean bending moment at 150 μm was not found to be significantly different for Gription (24.6 ± 14.0 N m) cups vs Porocoat (25 ± 10.2 N m; P > .84). The peak bending moment tolerated by Gription cups (33.9 ± 20.3 N m) was not found to be significantly different from Porocoat (33.5 ± 12.2 N m; P > .92). No correlation between BMD and bending moment at 150 μm of displacement could be identified. The coefficient of friction provided by highly porous metal acetabular shells used in this study did not provide better resistance to migration under bending load when compared with a standard porous coated component. Copyright © 2016 Elsevier Inc. All rights reserved.

Additively Manufactured and Surface Biofunctionalized Porous Nitinol.

PubMed

Gorgin Karaji, Z; Speirs, M; Dadbakhsh, S; Kruth, J-P; Weinans, H; Zadpoor, A A; Amin Yavari, S

2017-01-18

Enhanced bone tissue regeneration and improved osseointegration are among the most important goals in design of multifunctional orthopedic biomaterials. In this study, we used additive manufacturing (selective laser melting) to develop multifunctional porous nitinol that combines superelasticity with a rationally designed microarchitecture and biofunctionalized surface. The rational design based on triply periodic minimal surfaces aimed to properly adjust the pore size, increase the surface area (thereby amplifying the effects of surface biofunctionalization), and resemble the curvature characteristics of trabecular bone. The surface of additively manufactured (AM) porous nitinol was biofunctionalized using polydopamine-immobilized rhBMP2 for better control of the release kinetics. The actual morphological properties of porous nitinol measured by microcomputed tomography (e.g., open/close porosity, and surface area) closely matched the design values. The superelasticity originated from the austenite phase formed in the nitinol porous structure at room temperature. Polydopamine and rhBMP2 signature peaks were confirmed by X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy tests. The release of rhBMP2 continued until 28 days. The early time and long-term release profiles were found to be adjustable independent of each other. In vitro cell culture showed improved cell attachment, cell proliferation, cell morphology (spreading, spindle-like shape), and cell coverage as well as elevated levels of ALP activity and increased calcium content for biofunctionalized surfaces as compared to as-manufactured specimens. The demonstrated functionalities of porous nitinol could be used as a basis for deployable orthopedic implants with rationally designed microarchitectures that maximize bone tissue regeneration performance by release of biomolecules with adjustable and well-controlled release profiles.

Influence of stress, temperature, and strain on calcite twins constrained by deformation experiments

NASA Astrophysics Data System (ADS)

Rybacki, E.; Evans, B.; Janssen, C.; Wirth, R.; Dresen, G.

2013-08-01

A series of low-strain triaxial compression and high-strain torsion experiments were performed on marble and limestone samples to examine the influence of stress, temperature, and strain on the evolution of twin density, the percentage of grains with 1, 2, or 3 twin sets, and the twin width—all parameters that have been suggested as either paleopiezometers or paleothermometers. Cylindrical and dog-bone-shaped samples were deformed in the semibrittle regime between 20 °C and 350 °C, under confining pressures of 50-400 MPa, and at strain rates of 10- 4-10- 6 s- 1. The samples sustained shear stresses, τ, up to 280 MPa, failing when deformed to shear strains γ > 1. The mean width of calcite twins increased with both temperature and strain, and thus, measurement of twin width provides only a rough estimation of peak temperature, unless additional constraints on deformation are known. In Carrara marble, the twin density, NL (no of twins/mm), increased as the rock hardened with strain and was approximately related to the peak differential stress, σ (MPa), by the relation σ=19.5±9.8√{N}. Dislocation tangles occurred along twin boundaries, resulting in a complicated cell structure, which also evolved with stress. As previously established, the square root of dislocation density, observed after quench, also correlated with peak stress. Apparently, both twin density and dislocation cell structure are important state variables for describing the strength of these rocks.

External Load Affects Ground Reaction Force Parameters Non-uniformly during Running in Weightlessness

NASA Technical Reports Server (NTRS)

DeWitt, John; Schaffner, Grant; Laughlin, Mitzi; Loehr, James; Hagan, R. Donald

2004-01-01

Long-term exposure to microgravity induces detrimefits to the musculcskdetal system (Schneider et al., 1995; LeBlanc et al., 2000). Treadmill exercise is used onboard the International Space Station as an exercise countermeasure to musculoskeletal deconditioning due to spaceflight. During locomotive exercise in weightlessness (0G), crewmembers wear a harness attached to an external loading mechanism (EL). The EL pulls the crewmember toward the treadmill, and provides resistive load during the impact and propulsive phases of gait. The resulting forces may be important in stimulating bone maintenance (Turner, 1998). The EL can be applied via a bungee and carabineer clip configuration attached to the harness and can be manipulated to create varying amounts of load levels during exercise. Ground-based research performed using a vertically mounted treadmill found that peak ground reaction forces (GRF) during running at an EL of less than one body weight (BW) are less than those that occur during running in normal gravity (1G) (Davis et al., 1996). However, it is not known how the GRF are affected by the EL in a true OG environment. Locomotion while suspended may result in biomechanics that differ from free running. The purpose of this investigation was to determine how EL affects peak impact force, peak propulsive force, loading rate, and impulse of the GRF during running in 0G. It was hypothesized that increasing EL would result in increases in each GRF parameter.

Early-onset type 2 diabetes impairs skeletal acquisition in the male TALLYHO/JngJ mouse.

PubMed

Devlin, M J; Van Vliet, M; Motyl, K; Karim, L; Brooks, D J; Louis, L; Conlon, C; Rosen, C J; Bouxsein, M L

2014-10-01

Type 2 diabetes (T2D) incidence in adolescents is rising and may interfere with peak bone mass acquisition. We tested the effects of early-onset T2D on bone mass, microarchitecture, and strength in the TALLYHO/JngJ mouse, which develops T2D by 8 weeks of age. We assessed metabolism and skeletal acquisition in male TALLYHO/JngJ and SWR/J controls (n = 8-10/group) from 4 weeks to 8 and 17 weeks of age. Tallyho mice were obese; had an approximately 2-fold higher leptin and percentage body fat; and had lower bone mineral density vs SWR at all time points (P < .03 for all). Tallyho had severe deficits in distal femur trabecular bone volume fraction (-54%), trabecular number (-27%), and connectivity density (-82%) (P < .01 for all). Bone formation was higher in Tallyho mice at 8 weeks but lower by 17 weeks of age vs SWR despite similar numbers of osteoblasts. Bone marrow adiposity was 7- to 50-fold higher in Tallyho vs SWR. In vitro, primary bone marrow stromal cell differentiation into osteoblast and adipocyte lineages was similar in SWR and Tallyho, suggesting skeletal deficits were not due to intrinsic defects in Tallyho bone-forming cells. These data suggest the Tallyho mouse might be a useful model to study the skeletal effects of adolescent T2D.

Histological and histomorphometrical analysis of a silica matrix embedded nanocrystalline hydroxyapatite bone substitute using the subcutaneous implantation model in Wistar rats.

PubMed

Ghanaati, Shahram; Orth, Carina; Barbeck, Mike; Willershausen, Ines; Thimm, Benjamin W; Booms, Patrick; Stübinger, Stefan; Landes, Constantin; Sader, Robert Anton; Kirkpatrick, Charles James

2010-06-01

The clinical suitability of a bone substitute material is determined by the ability to induce a tissue reaction specific to its composition. The aim of this in vivo study was to analyze the tissue reaction to a silica matrix-embedded, nanocrystalline hydroxyapatite bone substitute.The subcutaneous implantation model in Wistar rats was chosen to assess the effect of silica degradation on the vascularization of the biomaterial and its biodegradation within a time period of 6 months. Already at day 10 after implantation, histomorphometrical analysis showed that the vascularization of the implantation bed reached its peak value compared to all other time points. Both vessel density and vascularization significantly decreased until day 90 after implantation. In this time period, the bone substitute underwent a significant degradation initiated by TRAP-positive and TRAP-negative multinucleated giant cells together with macrophages and lymphocytes. Although no specific tissue reaction could be related to the described silica degradation, the biomaterial was close to being fully degraded without a severe inflammatory response. These characteristics are advantageous for bone regeneration and remodeling processes.

Increased bone density in mice lacking the proton receptor, OGR1

PubMed Central

Krieger, Nancy S.; Yao, Zhenqiang; Kyker-Snowman, Kelly; Kim, Min Ho; Boyce, Brendan F.; Bushinsky, David A.

2016-01-01

Chronic metabolic acidosis stimulates cell-mediated calcium efflux from bone through osteoblastic prostaglandin E2-induced stimulation of RANKL leading to increased osteoclastic bone resorption. Osteoblasts express the proton-sensing G-protein coupled receptor, OGR1, which activates IP3-mediated intracellular calcium. Proton-induced osteoblastic intracellular calcium signaling requires OGR1, suggesting OGR1 is the sensor activated during acidosis to cause bone resorption. Growing mice produce large amounts of metabolic acids which must be buffered, primarily by bone, prior to excretion by the kidney. Here we tested whether lack of OGR1 inhibits proton-induced bone resorption by measuring bone mineral density by μCT and histomorphometry in 8 week old male OGR1−/− and C57/Bl6 wild type mice. OGR1−/− mice have normal skeletal development with no atypical gross phenotype. Trabecular and cortical bone volume was increased in tibiae and vertebrae from OGR1−/−. There were increased osteoblast numbers on the cortical and trabecular surfaces of tibiae from OGR1−/− mice, increased endocortical and trabecular bone formation rates, and osteoblastic gene expression. Osteoclast numbers and surface were increased in tibiae of OGR1−/− mice. Thus, in rapidly growing mice, lack of OGR1 leads to increased bone mass with increased bone turnover and a greater increase in bone formation than resorption. This supports the important role of the proton receptor, OGR1, in the response of bone to protons. PMID:26880453

Determination of spatial distribution of increase in bone temperature during drilling by infrared thermography: preliminary report.

PubMed

Augustin, Goran; Davila, Slavko; Udiljak, Toma; Vedrina, Denis Stjepan; Bagatin, Dinko

2009-05-01

During the drilling of the bone, the temperature could increase above 47 degrees C and cause irreversible osteonecrosis. The spatial distribution of increase in bone temperature could only be presumed using several thermocouples around the drilling site. The aim of this study was to use infrared thermographic camera for determination of spatial distribution of increase in bone temperature during drilling. One combination of drill parameters was used (drill diameter 4.5 mm; drill speed 1,820 rpm; feed-rate 84 mm/min; drill point angle 100 degrees) without external irrigation on room temperature of 26 degrees C. The increase in bone temperature during drilling was analyzed with infrared thermographic camera in two perpendicular planes. Thermographic pictures were taken before drilling, during drilling with measurement of maximal temperature values and after extraction of the drill from the bone. The thermographic picture shows that the increase in bone temperature has irregular shape with maximal increase along cortical bone, which is the most compact component of the bone. The width of this area with the temperature above critical level is three times broader than the width of cortical bone. From the front, the distribution of increase in bone temperature follows the form of the cortical bone (segment of a ring), which is the most compact part and causes the highest resistance to drilling and subsequent friction. Thermography showed that increase in bone temperature spreads through cortical bone, which is the most compact and dense part, and generates highest frictional heat during drilling. The medullar cavity, because of its gelatinous structure, contributes only to thermal dissipation.

Effects of growth hormone administration for 6 months on bone turnover and bone marrow fat in obese premenopausal women.

PubMed

Bredella, Miriam A; Gerweck, Anu V; Barber, Lauren A; Breggia, Anne; Rosen, Clifford J; Torriani, Martin; Miller, Karen K

2014-05-01

Abdominal adiposity is associated with low BMD and decreased growth hormone (GH) secretion, an important regulator of bone homeostasis. The purpose of our study was to determine the effects of a short course of GH on markers of bone turnover and bone marrow fat in premenopausal women with abdominal adiposity. In a 6-month, randomized, double-blind, placebo-controlled trial we studied 79 abdominally obese premenopausal women (21-45 y) who underwent daily sc injections of GH vs. placebo. Main outcome measures were body composition by DXA and CT, bone marrow fat by proton MR spectroscopy, P1NP, CTX, 25(OH)D, hsCRP, undercarboxylated osteocalcin (ucOC), preadipocyte factor 1 (Pref 1), apolipoprotein B (ApoB), and IGF-1. GH increased IGF-1, P1NP, 25(OH)D, ucOC, bone marrow fat and lean mass, and decreased abdominal fat, hsCRP, and ApoB compared with placebo (p<0.05). There was a trend toward an increase in CTX and Pref-1. Among all participants, a 6-month increase in IGF-1 correlated with 6-month increase in P1NP (p=0.0005), suggesting that subjects with the greatest increases in IGF-1 experienced the greatest increases in bone formation. A six-month decrease in abdominal fat, hsCRP, and ApoB inversely predicted 6-month change in P1NP, and 6-month increase in lean mass and 25(OH)D positively predicted 6-month change in P1NP (p≤0.05), suggesting that subjects with greatest decreases in abdominal fat, inflammation and ApoB, and the greatest increases in lean mass and 25(OH)D experienced the greatest increases in bone formation. A six-month increase in bone marrow fat correlated with 6-month increase in P1NP (trend), suggesting that subjects with the greatest increases in bone formation experienced the greatest increases in bone marrow fat. Forward stepwise regression analysis indicated that increase in lean mass and decrease in abdominal fat were positive predictors of P1NP. When IGF-1 was added to the model, it became the only predictor of P1NP. GH replacement in abdominally obese premenopausal women for 6 months increased bone turnover and bone marrow fat. Reductions in abdominal fat, and inflammation, and increases in IGF-1, lean mass and vitamin D were associated with increased bone formation. The increase in bone marrow fat may reflect changes in energy demand from increased bone turnover. Copyright © 2014 Elsevier Inc. All rights reserved.

Seasonal bone growth and physiology in endotherms shed light on dinosaur physiology.

PubMed

Köhler, Meike; Marín-Moratalla, Nekane; Jordana, Xavier; Aanes, Ronny

2012-07-19

Cyclical growth leaves marks in bone tissue that are in the forefront of discussions about physiologies of extinct vertebrates. Ectotherms show pronounced annual cycles of growth arrest that correlate with a decrease in body temperature and metabolic rate; endotherms are assumed to grow continuously until they attain maturity because of their constant high body temperature and sustained metabolic rate. This apparent dichotomy has driven the argument that zonal bone denotes ectotherm-like physiologies, thus fuelling the controversy on dinosaur thermophysiology and the evolution of endothermy in birds and mammal-like reptiles. Here we show, from a comprehensive global study of wild ruminants from tropical to polar environments, that cyclical growth is a universal trait of homoeothermic endotherms. Growth is arrested during the unfavourable season concurrently with decreases in body temperature, metabolic rate and bone-growth-mediating plasma insulin-like growth factor-1 levels, forming part of a plesiomorphic thermometabolic strategy for energy conservation. Conversely, bouts of intense tissue growth coincide with peak metabolic rates and correlated hormonal changes at the beginning of the favourable season, indicating an increased efficiency in acquiring and using seasonal resources. Our study supplies the strongest evidence so far that homeothermic endotherms arrest growth seasonally, which precludes the use of lines of arrested growth as an argument in support of ectothermy. However, high growth rates are a distinctive trait of mammals, suggesting the capacity for endogenous heat generation. The ruminant annual cycle provides an extant model on which to base inferences regarding the thermophysiology of dinosaurs and other extinct taxa.

A Paradigm for the Development and Evaluation of Novel Implant Topologies for Bone Fixation: In Vivo Evaluation

PubMed Central

Long, Jason P.; Hollister, Scott J.; Goldstein, Steven A.

2012-01-01

While contemporary prosthetic devices restore some function to individuals who have lost a limb, there are efforts to develop bio-integrated prostheses to improve functionality. A critical step in advancing this technology will be to securely attach the device to remnant bone. To investigate mechanisms for establishing robust implant fixation in bone while undergoing loading, we previously used a topology optimization scheme to develop optimized orthopaedic implants and then fabricated selected designs from titanium (Ti)-alloy with selective laser sintering (SLS) technology. In the present study, we examined how implant architecture and mechanical stimulation influence osseointegration within an in vivo environment. To do this, we evaluated three implant designs (two optimized and one non-optimized) using a unique in vivo model that applied cyclic, tension/ compression loads to the implants. Eighteen (six per implant design) adult male canines had implants surgically placed in their proximal, tibial metaphyses. Experimental duration was 12 weeks; daily loading (peak load of ±22N for 1000 cycles) was applied to one of each animal’s bilateral implants for the latter six weeks. Following harvest, osseointegration was assessed by non-destructive mechanical testing, micro-computed tomography (microCT) and back-scatter scanning electron microscopy (SEM). Data revealed that implant loading enhanced osseointegration by significantly increasing construct stiffness, peri-implant trabecular morphology, and percentages of interface connectivity and bone ingrowth. While this experiment did not demonstrate a clear advantage associated with the optimized implant designs, osseointegration was found to be significantly influenced by aspects of implant architecture. PMID:22951278

Cartilage degeneration in the human patellae and its relationship to the mineralisation of the underlying bone: a key to the understanding of chondromalacia patellae and femoropatellar arthrosis?

PubMed

Eckstein, F; Putz, R; Müller-Gerbl, M; Steinlechner, M; Benedetto, K P

1993-01-01

According to the literature subchondral bone plays a significant role in the transmission of load through joints and in the pathogenesis of osteoarthrosis. Therefore the degeneration of the articular cartilage was investigated in the patellae from 30 dissecting-room specimens and of 20 patients, previously submitted to arthroscopy, and subchondral mineralisation of their underlying bone was at the same time assessed by means of CT osteoabsorptiometry. Lateral cartilage lesions were localised over highly mineralised subchondral bone; these appear to be due to long-term stress. They were mainly found in the older specimens and showed a high rate of progression with increasing age. Medially localised cartilage lesions, on the other hand, were situated in a transitional region between moderate and slight subchondral mineralisation; they may be caused by infrequent stress peaks and by shear stress in the articular cartilage, the very medial part of the joint being deprived of mechanical stimulation for much of the time. These lesions were to be found predominantly in the younger specimens and showed little progress with advancing age. Patients with lateral cartilage degeneration exhibited higher, patients with medial chondromalacia patellae lower mineralisation than normals. Their density patterns therefore indicate a different mechanical pathogenesis of the cartilage lesions in the lateral and medial facet. It could be shown that CT osteoabsorptiometry allows an assessment of the mechanical situation, present in individual femoro-patellar joints, and that this situation is highly relevant for the pathogenesis of patellar cartilage degeneration.

A paradigm for the development and evaluation of novel implant topologies for bone fixation: in vivo evaluation.

PubMed

Long, Jason P; Hollister, Scott J; Goldstein, Steven A

2012-10-11

While contemporary prosthetic devices restore some function to individuals who have lost a limb, there are efforts to develop bio-integrated prostheses to improve functionality. A critical step in advancing this technology will be to securely attach the device to remnant bone. To investigate mechanisms for establishing robust implant fixation in bone while undergoing loading, we previously used a topology optimization scheme to develop optimized orthopedic implants and then fabricated selected designs from titanium (Ti)-alloy with selective laser sintering (SLS) technology. In the present study, we examined how implant architecture and mechanical stimulation influence osseointegration within an in vivo environment. To do this, we evaluated three implant designs (two optimized and one non-optimized) using a unique in vivo model that applied cyclic, tension/compression loads to the implants. Eighteen (six per implant design) adult male canines had implants surgically placed in their proximal, tibial metaphyses. Experimental duration was 12 weeks; daily loading (peak load of ±22 N for 1000 cycles) was applied to one of each animal's bilateral implants for the latter six weeks. Following harvest, osseointegration was assessed by non-destructive mechanical testing, micro-computed tomography (microCT) and back-scatter scanning electron microscopy (SEM). Data revealed that implant loading enhanced osseointegration by significantly increasing construct stiffness, peri-implant trabecular morphology, and percentages of interface connectivity and bone ingrowth. While this experiment did not demonstrate a clear advantage associated with the optimized implant designs, osseointegration was found to be significantly influenced by aspects of implant architecture. Copyright © 2012 Elsevier Ltd. All rights reserved.

Protective effect of the Japanese traditional medicine juzentaihoto on myelosuppression induced by the anticancer drug TS-1 and identification of a potential biomarker of this effect.

PubMed

Ogawa, Kazuo; Omatsu, Tatsushi; Matsumoto, Chinami; Tsuchiya, Naoko; Yamamoto, Masahiro; Naito, Yuji; Yoshikawa, Toshikazu

2012-08-09

TS-1 is an oral anticancer drug containing a 5-fluorouracil derivative (Tegafur) that is widely used in Japan for the treatment of cancer, especially gastrointestinal tumors. Frequently, however, TS-1 therapy has to be discontinued because of leukopenia. If it were possible to predict the development of bone marrow suppression before the white blood cell (WBC) count had actually decreased, treatment could be improved by strict dosage control and/or the prophylactic administration of hematopoietic drugs. Juzentaihoto (JTT), a traditional Japanese medicine (Kampo), has been reported to activate hematopoiesis and reduce the side effects associated with chemotherapy and radiotherapy. Here, we 1) evaluate the efficacy of JTT in alleviating myelosuppression induced by TS-1 therapy in mice, and 2) explore biomarkers that reflect both induction by TS-1 and alleviation by JTT of bone marrow suppression using a proteomics approach. Ten mg/kg of TS-1 was administered to Balb/c mice with or without 1 g/kg of oral JTT for 3, 5 and 7 days. WBC count and ratio of CD34+ bone marrow cells (BMCs) were estimated by flow cytometry. Plasma samples were analyzed using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI TOF-MS). A biomarker candidate from SELDI profiling was identified using a combination of cation exchange spin column purification, SDS-PAGE, enzymatic digestion and LC-MS/MS. After administration of TS-1, a significant decrease in WBC count and CD34+ BMC ratio were observed at days 5 and 3, respectively. JTT treatment improved WBC count on day 7 and CD34+ BMC ratio on days 5 and 7. SELDI analysis highlighted three protein peaks that had increased on day 3 after treatment with TS-1 but remained unchanged in mice co-treated with JTT. One of the three peaks, m/z 4223.1, was further investigated and identified as a specific C-terminal fragment of albumin. This study indicates that bone marrow suppression by treatment with TS-1 in mice might be improved by coadministration of JTT. A C-terminal fragment of albumin was identified as a candidate biomarker for predicting TS-1-induced myelosuppression. However, the sensitivity and specificity of the biomarker candidate must be validated in future clinical studies.

Study of tissue engineered bone nodules by Fourier transform infrared spectroscopy.

PubMed

Aydin, Halil Murat; Hu, Bin; Suso, Josep Sulé; El Haj, Alicia; Yang, Ying

2011-02-21

The key criteria for assessing the success of bone tissue engineering are the quality and quantity of the produced minerals within the cultured constructs. The accumulation of calcium ions and inorganic phosphates in culture medium serves as nucleating agents for the formation of hydroxyapatite, which is the main inorganic component of bone. Bone nodule formation is one of the hallmarks of mineralization in such cell cultures. In this study, we developed a new two-step procedure to accelerate bone formation in which mouse bone cell aggregates were produced first on various chemically treated non-adhesive substrates. After this step, the bone cells' growth and mineralization were followed in conventional culture plates. The number and size of cell aggregates were studied with light microscopy. The minerals' formation in the form of nodules produced by the cell aggregates and the bone crystal quality were studied with Fourier Transform Infrared (FTIR) spectroscopy. The FTIR spectra of the ash specimens (mineral phase only) from thermal gravimetric analysis (TGA) provided valuable information of the quality of the minerals. The υ(4) PO(4) region (550-650 cm(-1)), which reveals apatitic and non-apatitic HPO(4) or PO(4) environments, and phosphate region (910-1180 cm(-1)) were examined for the minerals produced in the form of nodules. The peak position and intensity of the spectra demonstrate that the quality of the bone produced by cell aggregates, especially from the bigger ones, which were formed on Plunoric treated substrates, exhibit a composition more similar to that of native bone. This work establishes a new protocol for high quality bone formation and characterization, with the potential to be applied to bone tissue engineering.

Evaluation of bone mineral density in children receiving carbamazepine or valproate monotherapy.

PubMed

Chou, I-Jun; Lin, Kuang-Lin; Wang, Huei-Shyong; Wang, Chao-Jan

2007-01-01

Antiepileptic drugs have been shown to be associated with a lowering of bone mineral density in childhood and adolescence, which are critical periods of skeletal mineralization. A lower peak bone mass attained at the end of adolescence is associated with greater involutional osteoporosis and risk for fracture in the elderly. Our purpose was to evaluate the effects of carbamazepine and valproate monotherapy on bone mineral density in children in Taiwan. From November 1995 to April 2005, forty-two children with uncomplicated epilepsy, who were treated with either carbamazepine (n=21) or valproate (n=21) monotherapy for more than 6 months, were enrolled in this study. All subjects were 5 to 18 years of age, seizure-free for 5 months or more, with normal daily activity, and normal diet. Lumbar bone mineral density of L1 to L4 was measured by dual-energy X-ray absorptiometry. The mean serum levels of carbamazepine and valproate were 5.12 +/- 2.15 mcg/ml and 49.61 +/- 20.84 mcg/ml, respectively. Treatment durations were 37.05 +/- 31.11 months and 22.86 +/- 18.84 months, respectively. The serum levels of calcium and phosphate in both groups were within therapeutic range. The serum level of alkaline phosphatase was significantly higher in the carbamazepine group (264.71 +/- 66.91, U/L) than in the valproate group (179.48 +/- 79.37, U/L). Three patients (140%) had bone mineral density Z-score of -2.0 or lower in the carbamazepine-treated group, but none in the valproate-treated group (p=0.232). Comparing the Z-score in carbamazapine- and valproate-monotherapy children, 7 (33%) had Z-score of -1.5 or lower in the carbamazepine-treated group, and none in the valporate-treated group had Z-score of -1.5 or lower (p=0.009). Four (57%) patients in the 7 carbamazepine-treated children with Z-score of -1.5 or lower had serum drug level lower than therapeutic range. Children receiving carbarmazepine monotherapy had increased frequency of lower bone density than children receiving valproate monotherapy.

Comparison of an experimental bone cement with surgical Simplex P, Spineplex and Cortoss.

PubMed

Boyd, D; Towler, M R; Wren, A; Clarkin, O M

2008-04-01

Conventional polymethylmethacrylate (PMMA) cements and more recently Bisphenol-a-glycidyl dimethacrylate (BIS-GMA) composite cements are employed in procedures such as vertebroplasty. Unfortunately, such materials have inherent drawbacks including, a high curing exotherm, the incorporation of toxic components in their formulations, and critically, exhibit a modulus mismatch between cement and bone. The literature suggests that aluminium free, zinc based glass polyalkenoate cements (Zn-GPC) may be suitable alternative materials for consideration in such applications as vertebroplasty. This paper, examines one formulation of Zn-GPC and compares its strengths, modulus, and biocompatibility with three commercially available bone cements, Spineplex, Simplex P and Cortoss. The setting times indicate that the current formulation of Zn-GPC sets in a time unsuitable for clinical deployment. However during setting, the peak exotherm was recorded to be 33 degrees C, the lowest of all cements examined, and well below the threshold level for tissue necrosis to occur. The data obtained from mechanical testing shows the Zn-GPC has strengths of 63 MPa in compression and 30 MPa in biaxial flexure. Importantly these strengths remain stable with maturation; similar long term stability was exhibited by both Spineplex and Simplex P. Conversely, the strengths of Cortoss were observed to rapidly diminish with time, a cause for clinical concern. In addition to strengths, the modulus of each material was determined. Only the Zn-GPC exhibited a modulus similar to vertebral trabecular bone, with all commercial materials exhibiting excessively high moduli. Such data indicates that the use of Zn-GPC may reduce adjacent fractures. The final investigation used the well established simulated body fluid (SBF) method to examine the ability of each material to bond with bone. The results indicate that the Zn-GPC is capable of producing a bone like apatite layer at its surface within 24 h which increased in coverage and density up to 7 days. Conversely, Spineplex, and Simplex P exhibit no apatite layer formation, while Cortoss exhibits only minimal formation of an apatite layer after 7 days incubation in SBF. This paper shows that Zn-GPC, with optimised setting times, are suitable candidate materials for further development as bone cements.

Virtual monochromatic spectral imaging with fast kilovoltage switching: reduction of metal artifacts at CT.

PubMed

Pessis, Eric; Campagna, Raphaël; Sverzut, Jean-Michel; Bach, Fabienne; Rodallec, Mathieu; Guerini, Henri; Feydy, Antoine; Drapé, Jean-Luc

2013-01-01

With arthroplasty being increasingly used to relieve joint pain, imaging of patients with metal implants can represent a significant part of the clinical work load in the radiologist's daily practice. Computed tomography (CT) plays an important role in the postoperative evaluation of patients who are suspected of having metal prosthesis-related problems such as aseptic loosening, bone resorption or osteolysis, infection, dislocation, metal hardware failure, or periprosthetic bone fracture. Despite advances in detector technology and computer software, artifacts from metal implants can seriously degrade the quality of CT images, sometimes to the point of making them diagnostically unusable. Several factors may help reduce the number and severity of artifacts at multidetector CT, including decreasing the detector collimation and pitch, increasing the kilovolt peak and tube charge, and using appropriate reconstruction algorithms and section thickness. More recently, dual-energy CT has been proposed as a means of reducing beam-hardening artifacts. The use of dual-energy CT scanners allows the synthesis of virtual monochromatic spectral (VMS) images. Monochromatic images depict how the imaged object would look if the x-ray source produced x-ray photons at only a single energy level. For this reason, VMS imaging is expected to provide improved image quality by reducing beam-hardening artifacts.

Gender-specific increase of bone mass by CART peptide treatment is ovary-dependent.

PubMed

Gerrits, Han; Bakker, Nicole Ec; van de Ven-de Laat, Cindy Jm; Bourgondien, Freek Gm; Peddemors, Carolien; Litjens, Ralph Hgm; Kok, Han J; Vogel, Gerard Mt; Krajnc-Franken, Magda Am; Gossen, Jan A

2011-12-01

Cocaine- and amphetamine-regulated transcript (CART) has emerged as a neurotransmitter and hormone that has been implicated in many processes including food intake, maintenance of body weight, and reward, but also in the regulation of bone mass. CART-deficient mice are characterized by an osteoporotic phenotype, whereas female transgenic mice overexpressing CART display an increase in bone mass. Here we describe experiments that show that peripheral subcutaneous sustained release of different CART peptide isoforms for a period up to 60 days increased bone mass by 80% in intact mice. CART peptides increased trabecular bone mass, but not cortical bone mass, and the increase was caused by reduced osteoclast activity in combination with normal osteoblast activity. The observed effect on bone was gender-specific, because male mice did not respond to treatment with CART peptides. In addition, male transgenic CART overexpressing mice did not display increased bone mass. Ovariectomy (OVX) completely abolished the increase of bone mass by CART peptides, both in CART peptide-treated wild-type mice and in CART transgenic mice. The effect of CART peptide treatment on trabecular bone was not mediated by 17β-estradiol (E(2)) because supplementation of OVX mice with E(2) could not rescue the effect of CART peptides on bone. Together, these results indicate that sustained release of CART peptides increases bone mass in a gender-specific way via a yet unknown mechanism that requires the presence of the ovary. Copyright © 2011 American Society for Bone and Mineral Research.

Long-term anabolic effects of prostaglandin-E2 on tibial diaphyseal bone in male rats

NASA Technical Reports Server (NTRS)

Jee, Webster S. S.; Ke, Hua Zhu; Li, Xiao Jian

1991-01-01

The effects of long-term prostaglandin E2 (PGE2) on tibial diaphyseal bone were studied in 7-month-old male Sprague-Dawley rats given daily subcutaneous injections of 0, 1, 3 and 6 mg PGE2/kg/day for 60, 120 and 180 days. The tibial shaft was measured by single photon absorptiometry and dynamic histomorphometric analyses were performed on double-fluorescent labeled undecalcified tibial diaphyseal bone samples. Exogenous PGE2 administration produced the following transient changes in a dose-response manner between zero and 60 days: (1) increased bone width and mineral density; (2) increased total tissue and total bone areas; (3) decreased marrow area; (4) increased periosteal and corticoendosteal lamellar bone formation; (5) activated corticoendosteal lamellar and woven trabecular bone formation; and (6) activated intracortical bone remodeling. A new steady-state of increased tibial diaphyseal bone mass and elevated bone activities were observed from day 60 onward. The elevated bone mass level attained after 60 days of PGE2 treatment was maintained at 120 and 180 days. These observations indicate that the powerful anabolic effects of PGE2 will increase both periosteal and corticoendosteal bone mass and sustain the transient increase in bone mass with continuous daily administration of PGE2.

Regional Variation of Bone Tissue Properties at the Human Mandibular Condyle

PubMed Central

Kim, Do-Gyoon; Jeong, Yong-Hoon; Kosel, Erin; Agnew, Amanda M.; McComb, David W.; Bodnyk, Kyle; Hart, Richard T.; Kim, Min Kyung; Han, Sang Yeun; Johnston, William M.

2015-01-01

The temporomandibular joint (TMJ) bears different types of static and dynamic loading during occlusion and mastication. As such, characteristics of mandibular condylar bone tissue play an important role in determining the mechanical stability of the TMJ under the macro-level loading. Thus, the objective of this study was to examine regional variation of the elastic, plastic, and viscoelastic mechanical properties of human mandibular condylar bone tissue using nanoindentation. Cortical and trabecular bone were dissected from mandibular condyles of human cadavers (9 males, 54 to 96 years). These specimens were scanned using microcomputed tomography to obtain bone tissue mineral distribution. Then, nanoindentation was conducted on the surface of the same specimens in hydration. Plastic hardness (H) at a peak load, viscoelastic creep (Creep/Pmax), viscosity (η), and tangent delta (tan δ) during a 30 second hold period, and elastic modulus (E) during unloading were obtained by a cycle of indentation at the same site of bone tissue. The tissue mineral and nanoindentation parameters were analyzed for the periosteal and endosteal cortex, and trabecular bone regions of the mandibular condyle. The more mineralized periosteal cortex had higher mean values of elastic modulus, plastic hardness, and viscosity but lower viscoelastic creep and tan δ than the less mineralized trabecular bone of the mandibular condyle. These characteristics of bone tissue suggest that the periosteal cortex tissue may have more effective properties to resist elastic, plastic, and viscoelastic deformation under static loading, and the trabecular bone tissue to absorb and dissipate time-dependent viscoelastic loading energy at the TMJ during static occlusion and dynamic mastication. PMID:25913634

Investigating the Prevalence of Low Bone Mass in Children of Southern Iran and Its Associated Factors

PubMed Central

Saki, Forough; Ranjbar Omrani, Gholamhossein; Jeddi, Marjan; Bakhshaieshkaram, Marzie; Dabbaghmanesh, Mohammad Hossein

2017-01-01

Background Improving peak bone mass and bone strength in the first years of life and enhancing it during young adulthood could prevent osteoporosis and fractures in the last years of life. We evaluated the prevalence of low bone mass in the lumbar and femoral neck and its associated factors in southern Iranian children. Methods This is a cross-sectional study on healthy Iranian children aged 9 - 18 years old during 2011 - 2012. Dual energy X-ray absorptiometry (DEXA) was used for measuring bone mineral density (BMD). BMD Z-score ≤ -2 was considered as low. Anthropometric data, physical activity, sun exposure, puberty, and mineral biochemical parameters were assessed. Data were analyzed using SPSS v.15. Results 477 normal children, including 236 (49.5%) girls and 241 (50.5%) boys, aged 13.8 ± 2.7 years were enrolled. Prevalence of low bone mass (LBM) in the femoral and lumbar region was 10.7% and 18.7%, respectively. The prevalence of LBM in femur of girls is twice more than boys. Fat mass index, BMI Z-score, and physical activity were associated with lumbar low bone mass. BMI Z-score and physical activity were associated with femoral low bone mass. Conclusions High prevalence of low bone mineral density in children 9 to 18 years in south of the country is concerned and is needed to plan for prevention and treatment. BMI-Z score, fat mass index, and physical activity were the 3 most important preventive factors in developing low bone mass in children. PMID:29344033

Analysis of the effects of growth hormone, exercise and food restriction on cancellous bone in different bone sites in middle-aged female rats.

PubMed

Banu, J; Orhii, P B; Okafor, M C; Wang, L; Kalu, D N

2001-06-01

The aim of this study is to determine the effects of growth hormone (GH), exercise (EX), GH+EX and food restriction on cancellous bone in middle-aged female rats. Female F344 rats aged 13 months were divided into (1) age-matched controls; (2) GH treated (2.5 mg/kg. 5 day/week); (3) EX (voluntary wheel running); (4) GH+EX; and (5) food restricted (FR) (fed 60% of the ad libitum food intake). The animals were treated for 18 weeks, at the end of which they were sacrificed. Cancellous bone and cortical bone in the fourth lumbar vertebra, proximal tibial metaphysis (PTM), distal femoral metaphysis (DFM) and femoral neck (NF) were analyzed using peripheral quantitative computerized tomography (pQCT) densitometry. Growth hormone increased cancellous bone area, cancellous bone mineral content, cortical bone area and cortical bone mineral content in the vertebra, PTM, DFM and NF. The tibial muscle wet weight was increased significantly after GH treatment. Exercise increased the cancellous bone area in the vertebra, PTM and DFM. Cortical bone area and cortical bone mineral content increased after EX in the vertebra, PTM, DFM and NF. No significant change was seen in the tibial muscle wet weight after EX. Growth hormone+EX increased cancellous bone area in the vertebra PTM and DFM but had no effect in neck of the femur. Cancellous bone mineral content, cortical bone area and cortical bone mineral content increased with GH+EX in the vertebra, PTM, DFM and NF. The tibial muscle wet weight was increased significantly with GH+EX. Food restriction decreased cancellous bone area and cancellous bone mineral content in all the bones studied. The decrease was statistically significant only at the distal femoral metaphysis. The tibial muscle wet weight decreased when compared with the age-matched control, but this decrease was not statistically significant. We conclude that the effect of the dose of GH used and the levels of voluntary wheel running EX used increased cancellous bone in intact rats; the effect of GH is much greater and different bones respond with varying intensities. The effects of combined treatment of GH and EX on cancellous bone are not always significantly higher than those of GH alone. FR at the level studied has a mostly negative effect on cancellous bone.

The uptake by the canine tibia of the bone-scanning agent 99mTc-MDP before and after an osteotomy.

PubMed

Hughes, S; Khan, R; Davies, R; Lavender, P

1978-11-01

The residue and extraction of technetium-labelled methylene diphosphonate (99mTc-MDP), a substance used in bone scanning, was examined in the canine tibia and found to be low. Examination of washout curves suggested that there were four compartments in cortical bone, a vascular, a perivascular, a bone fluid and a bone compartment. After an osteotomy in the canine tibia the residue of 99mTc-MDP increased. This was believed to be due to an increase in the blood supply to the bone and to an associated increase in new bone available for exchange. Bone scanning in a fracture is therefore a reflection of the vascular status of the bone being examined and of the uptake by bone. This is dependent on there being an adequate blood supply to the bone and an increased number of mineral-binding sites.

Increasing Bone Mass and Bone Strength in Individuals with Chronic Spinal Cord Injury: Maximizing Response to Therapy

DTIC Science & Technology

2017-10-01

Award Number: W81XWH-16-1-0763 TITLE: Increasing Bone Mass and Bone Strength in Individuals with Chronic Spinal Cord Injury: Maximizing Response...TYPE Annual 3. DATES COVERED (From - To) 30 Sep 2016-29 Sep 2017 5a. CONTRACT NUMBER Increasing Bone Mass and Bone Strength in Individuals with...DISTRIBUTION / AVAILABILITY STATEMENT Approved for public release; distribution unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Rapid bone loss is a universal

Improved adherence with PTH(1–84) in an extension trial for 24 months results in enhanced BMD gains in the treatment of postmenopausal women with osteoporosis

PubMed Central

Bilezikian, J. P.; Greenspan, S. L.; Wüster, C.; Muñoz-Torres, M.; Bone, H. G.; Rosen, C. J.; Andersen, H. S.; Hanley, D. A.

2016-01-01

Summary The purpose of this study is to examine the effect of PTH(1–84) treatment over 24 months followed by 12 months discontinuation on BMD, bone turnover markers, fractures and the impact of adherence on efficacy. Introduction There is limited information about the effect of PTH(1-84) after 18 months and limited data about the impact of compliance on response to anabolic therapy. Methods Seven hundred and eighty-one subjects who received active PTH(1–84) in the Treatment of Osteoporosis with Parathyroid hormone trial for approximately 18 months were entered into a 6-month open-label extension. Thereafter, they were followed for 12 additional months after discontinuation of treatment. Endpoints examined included changes in BMD and biochemical markers. Results PTH(1–84) treatment over 24 months increased BMD at the lumbar spine by 6.8 % above baseline (p < 0.05). The total corresponding BMD increases at the hip and femoral neck were 1.1 and 2.2% above baseline. Larger increases in spine BMD were observed in participants with ≥80 % adherence to daily injections of PTH(1–84) (8.3% in adherent vs 4.9 % in poorly adherent patients). Total hip BMD gains were 1.7 % in adherent vs 0.6 % in poorly adherent participants. Markers of bone turnover (BSAP and NTx) peaked 6 months after starting PTH(1–84) treatment and declined slowly but remained above baseline at 24 months. After discontinuation of PTH(1–84) treatment (at 24 months), bone turnover markers returned to near baseline levels by 30 months. The adherent group sustained significantly fewer fractures than the poorly adherent group. Conclusions PTH(1–84) treatment over 24 months results in continued increases in lumbar spine BMD. Adherence to treatment with PTH(1–84) for up to 24 months is also associated with greater efficacy. PMID:22930240

Locomotor Behavior of Chickens Anticipating Incline Walking

PubMed Central

LeBlanc, Chantal; Tobalske, Bret; Szkotnicki, Bill; Harlander-Matauschek, Alexandra

2018-01-01

Keel bone damage (KBD) is prevalent in hens raised for egg production, and ramps between different tiers in aviaries have potential to reduce the frequency of falls resulting in KBD. Effective use of ramps requires modulation of locomotion in anticipation of the incline. Inadequate adaptive locomotion may be one explanation why domestic layer hens (Gallus gallus domesticus) exhibit high rates of KBD. To improve understanding of the capacity of hens to modulate their locomotion in anticipation of climbing, we measured the effects of incline angle upon the mechanics of the preparatory step before ascending a ramp. Because the energetic challenge of climbing increases with slope, we predicted that as angle of incline increased, birds during foot contact with the ground before starting to climb would increase their peak force and duration of contact and reduce variation in center of pressure (COP) under their foot. We tested 20 female domestic chickens on ramp inclines at slopes of +0°, +40°, and +70° when birds were 17, 21, 26, 31, and 36 weeks of age. There were significantly higher vertical peak ground reaction forces in preparation at the steepest slope, and ground contact time increased significantly with each increase in ramp angle. Effects upon variation in COP were not apparent; likewise, effects of limb length, age, body mass were not significant. Our results reveal that domestic chickens are capable of modulating their locomotion in response to incline angle. PMID:29376060

Evaluation of a Freezer Mill for Bone Pulverization prior to DNA Extraction: An Improved Workflow for STR Analysis.

PubMed

Morales Colón, Emely; Hernández, Mireya; Candelario, Mariel; Meléndez, María; Dawson Cruz, Tracey

2018-03-01

Traditional methods for bone pulverization typically generate heat, risking stability of DNA sample. SPEX™ has developed cryogenic grinders which introduce liquid nitrogen to cool the sample and aid in the grinding process. In this study, the Freezer Mill 6970 EFM was used with two DNA extraction methods and routine downstream STR analysis procedures. DNA from as little as 0.1 g of bone powder was used to develop full STR profiles after freezer mill pulverization, and the method was reproducible. Further, no contamination was detected upon cleaning/reuse of the sample vials. There were no significant differences in DNA yield, STR alleles detected, or peak heights using the freezer mill as compared to traditional grinding, and successful DNA profiles were achieved from as low as 0.1 g of bone powder with this method. Overall, this work indicates that this cryogenic mill method may be used as a viable alternative to traditional tissue grinders. © 2017 American Academy of Forensic Sciences.

Fourth near-infrared optical window for assessment of bone and other tissues

NASA Astrophysics Data System (ADS)

Sordillo, Diana C.; Sordillo, Laura A.; Sordillo, Peter P.; Alfano, Robert R.

2016-02-01

Recently, additional near-infrared (NIR) optical windows beyond the conventional first therapeutic window have been utilized for deep tissue imaging through scattering media. Biomedical applications using a second optical window (1100 to 1300 nm) and a third (1600 to 1870 nm) are emerging. A fourth window (2100 to 2300 nm) has been largely ignored due to high water absorption and a lack of high sensitivity imaging detectors and ultrafast laser sources. In this study, optical properties of bone in this fourth NIR optical window, were investigated. Results were compared to those seen at the first, second and third windows, and are consistent with our previous work on malignant and benign breast and prostate tissues. Bone and malignant tissues showed highest uptake in the third and fourth windows. As collagen is a major chromophore with prominent spectral peaks between 2100 and 2300 nm, it may be that the fourth optical window is particularly useful for studying tissues with a higher collagen content, such as bone or malignant tumors.

Tridax procumbens flavonoids: a prospective bioactive compound increased osteoblast differentiation and trabecular bone formation.

PubMed

Al Mamun, Md Abdullah; Hosen, Mohammad Jakir; Khatun, Amina; Alam, M Masihul; Al-Bari, Md Abdul Alim

2017-09-08

The Tridax procumbens extracts (TPE) are known for their ethno-medicinal properties to increase osteogenic functioning in mesenchymal stem cells. Recently, we found that the T. procumbens flavonoids (TPF) significantly suppressed the RANKL-induced osteoclasts differentiation and bone resorption. The TPF also promoted osteoblasts differentiation and bone formation demonstrated by increasing bone formation markers in cultured mouse primary osteoblasts. However, the effects of the TPF on in vivo bone formation remain unclear. In this study, we investigated the effects of the TPF on in vivo bone formation, injected the TPF (20 mg/kg) twice a day in the low calcium diet mice and killed them after 21 day. Radiographic and histomorphometric analyses were performed on the dissected bones to determine the anabolic effects of the TPF. Bone mineral density and bone mineral content of the TPF-treated mice were significantly increased compared to the control mice. Bone formation-related indices like osteoblast number, osteoblast surface, bone volume, mineralizing surface, mineral apposition rate and bone formation rate were significantly increased in the TPF-treated mice compared to the control mice. Our findings point towards the stimulation of bone formation by TPF, suggested that the TPF could be a potential natural anabolic agent to treat patients with bone loss-associated diseases such as osteoporosis.

A myostatin and activin decoy receptor enhances bone formation in mice.

PubMed

Bialek, P; Parkington, J; Li, X; Gavin, D; Wallace, C; Zhang, J; Root, A; Yan, G; Warner, L; Seeherman, H J; Yaworsky, P J

2014-03-01

Myostatin is a member of the bone morphogenetic protein/transforming growth factor-β (BMP/TGFβ) super-family of secreted differentiation factors. Myostatin is a negative regulator of muscle mass as shown by increased muscle mass in myostatin deficient mice. Interestingly, these mice also exhibit increased bone mass suggesting that myostatin may also play a role in regulating bone mass. To investigate the role of myostatin in bone, young adult mice were administered with either a myostatin neutralizing antibody (Mstn-mAb), a soluble myostatin decoy receptor (ActRIIB-Fc) or vehicle. While both myostatin inhibitors increased muscle mass, only ActRIIB-Fc increased bone mass. Bone volume fraction (BV/TV), as determined by microCT, was increased by 132% and 27% in the distal femur and lumbar vertebrae, respectively. Histological evaluation demonstrated that increased BV/TV in both locations was attributed to increased trabecular thickness, trabecular number and bone formation rate. Increased BV/TV resulted in enhanced vertebral maximum compressive force compared to untreated animals. The fact that ActRIIB-Fc, but not Mstn-mAb, increased bone volume suggested that this soluble decoy receptor may be binding a ligand other than myostatin, that plays a role in regulating bone mass. This was confirmed by the significant increase in BV/TV in myostatin deficient mice treated with ActRIIB-Fc. Of the other known ActRIIB-Fc ligands, BMP3 has been identified as a negative regulator of bone mass. However, BMP3 deficient mice treated with ActRIIB-Fc showed similar increases in BV/TV as wild type (WT) littermates treated with ActRIIB-Fc. This result suggests that BMP3 neutralization is not the mechanism responsible for increased bone mass. The results of this study demonstrate that ActRIIB-Fc increases both muscle and bone mass in mice. Therefore, a therapeutic that has this dual activity represents a potential approach for the treatment of frailty. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

The Loss of Activating Transcription Factor 4 (ATF4) Reduces Bone Toughness and Fracture Toughness

PubMed Central

Makowski, Alexander J.; Uppuganti, Sasidhar; Waader, Sandra A.; Whitehead, Jack M.; Rowland, Barbara J.; Granke, Mathilde; Mahadevan-Jansen, Anita; Yang, Xiangli; Nyman, Jeffry S.

2014-01-01

Even though age-related changes to bone tissue affecting fracture risk are well characterized, only a few matrix-related factors have been identified as important to maintaining fracture resistance. As a gene critical to osteoblast differentiation, activating transcription factor 4 (ATF4) is possibly one of the seimportant factors. To test the hypothesis that the loss of ATF4 affects the fracture resistance of bone beyond bone mass and structure, we harvested bones from Atf4+/+ and Atf4−/− littermates at 8 and 20 weeks of age (n≥9 per group) for bone assessment across several length scales. From whole bone mechanical tests in bending, femurs from Atf4−/− mice were found to be brittle with reduced toughness and fracture toughness compared to femurs from Atf4+/+ mice. However, there were no differences in material strength and in tissue hardness, as determined by nanoindentation, between the genotypes, irrespective age. Tissue mineral density of the cortex at the point of loading as determined by micro-computed tomography was also not significantly different. However, by analyzing local composition by Raman Spectroscopy (RS), bone tissue of Atf4−/− mice was found to have higher mineral to collagen ratio compared to wild-type tissue, primarily at 20 weeks of age. From RS analysis of intact femurs at 2 orthogonal orientations relative to the polarization axis of the laser, we also found that the organizational-sensitive peak ratio, ν1 Phosphate per Amide I, changed to a greater extent upon bone rotation for Atf4-deficient tissue, implying bone matrix organization may contribute to the brittleness phenotype. Target genes of ATF4 activity are not only important to osteoblast differentiation but also maintaining bone toughness and fracture toughness. PMID:24509412

The loss of activating transcription factor 4 (ATF4) reduces bone toughness and fracture toughness.

PubMed

Makowski, Alexander J; Uppuganti, Sasidhar; Wadeer, Sandra A; Whitehead, Jack M; Rowland, Barbara J; Granke, Mathilde; Mahadevan-Jansen, Anita; Yang, Xiangli; Nyman, Jeffry S

2014-05-01

Even though age-related changes to bone tissue affecting fracture risk are well characterized, only a few matrix-related factors have been identified as important to maintaining fracture resistance. As a gene critical to osteoblast differentiation, activating transcription factor 4 (ATF4) is possibly one of these important factors. To test the hypothesis that the loss of ATF4 affects the fracture resistance of bone beyond bone mass and structure, we harvested bones from Atf4+/+ and Atf4-/- littermates at 8 and 20 weeks of age (n≥9 per group) for bone assessment across several length scales. From whole bone mechanical tests in bending, femurs from Atf4-/- mice were found to be brittle with reduced toughness and fracture toughness compared to femurs from Atf4+/+ mice. However, there were no differences in material strength and in tissue hardness, as determined by nanoindentation, between the genotypes, irrespective of age. Tissue mineral density of the cortex at the point of loading as determined by micro-computed tomography was also not significantly different. However, by analyzing local composition by Raman Spectroscopy (RS), bone tissue of Atf4-/- mice was found to have higher mineral to collagen ratio compared to wild-type tissue, primarily at 20 weeks of age. From RS analysis of intact femurs at 2 orthogonal orientations relative to the polarization axis of the laser, we also found that the organizational-sensitive peak ratio, ν1Phosphate per Amide I, changed to a greater extent upon bone rotation for Atf4-deficient tissue, implying bone matrix organization may contribute to the brittleness phenotype. Target genes of ATF4 activity are not only important to osteoblast differentiation but also in maintaining bone toughness and fracture toughness. Published by Elsevier Inc.

Feeding soy protein isolate and oils rich in omega-3 polyunsaturated fatty acids affected mineral balance, but not bone in a rat model of autosomal recessive polycystic kidney disease.

PubMed

Maditz, Kaitlin H; Smith, Brenda J; Miller, Matthew; Oldaker, Chris; Tou, Janet C

2015-02-10

Polycystic kidney disease (PKD), a genetic disorder characterized by multiple cysts and renal failure at an early age. In children, kidney disease is often accompanied by disordered mineral metabolism, failure to achieve peak bone mass, and reduced adult height. Optimizing bone health during the growth stage may preserve against bone loss associated with early renal dysfunction in PKD. Dietary soy protein and omega-3 polyunsaturated fatty acid (n-3 PUFA) have been reported to ameliorate PKD and to promote bone health. The study objective was to determine the bone effects of feeding soy protein and/or n-3 PUFAs in a rat model of PKD. Weanling female PCK rats (n = 12/group) were randomly assigned to casein + corn oil (Casein + CO), casein + soybean oil (Casein + SO), soy protein isolate + soybean oil (SPI + SO) or soy protein isolate + 1:1 soybean oil:salmon oil blend (SPI + SB) for 12 weeks. Rats fed SPI + SO diet had shorter (P = 0.001) femur length than casein-fed rats. Rats fed SPI + SO and SPI + SB diet had higher (P = 0.04) calcium (Ca) and phosphorus (P) retention. However, there were no significant differences in femur and tibial Ca, P or bone mass between diet groups. There were also no significant difference in bone microarchitecture measured by micro-computed tomography or bone strength determined by three-point bending test between diet groups. Early diet management of PKD using SPI and/or n-3 PUFAs influenced bone longitudinal growth and mineral balance, but neither worsened nor enhanced bone mineralization, microarchitecture or strength.