Bone density among infants of gestational diabetic mothers and macrosomic neonates.

PubMed

Schushan-Eisen, Irit; Cohen, Mor; Leibovitch, Leah; Maayan-Metzger, Ayala; Strauss, Tzipora

2015-03-01

Decreased bone density has been found among infants of diabetic mothers and among large-for-gestational-age newborns. To evaluate which etiologies (physical or metabolic effect) have the greatest impact on neonatal bone density. A case-control study was conducted that included two study groups: one comprising 20 appropriate-for-gestational-age (AGA) infants of gestational diabetic mothers (IGDM) and matched controls, and the other comprising 20 macrosomic infants (birth weight > 4 kg) and matched controls. Bone density was examined along the tibia bone using quantitative ultrasound that measured speed of sound. Bone density among the group of macrosomic infants was significantly lower than among the control group (2,976 vs. 3,120 m/s respectively, p < 0.005). No differences in bone density were found between infants of diabetic mothers and their controls (3,005 vs. 3,043 m/s respectively, p = 0.286). Low bone density was predicted only by birth weight (for every increase of 100 g) (OR 1.148 [CI 1.014-1.299], p = 0.003). Bone density was found to be low among macrosomic newborn infants, whereas among AGA-IGDM infants bone density was similar to that of the control group. These findings strengthen the hypothesis that reduced fetal movements secondary to fetal macrosomia constitute the mechanism for reduced bone density.

The peripheral quantitative computed tomographic and densitometric analysis of skeletal tissue in male Wistar rats after chromium sulfate treatment.

PubMed

Bieńko, Marek; Radzki, Radosław Piotr; Wolski, Dariusz

2017-09-21

This study evaluates the effects of three different doses of chromium sulphate on bone density and the tomographic parameters of skeletal tissue of rats. The experiment was performed on 40 male Wistar rats which received, by gavage, during 90 days, a chromium sulphate in either a daily dose of 400, 600 or 800 µg/kg BW. At the end of experiment, the rats were scanned using the densitometry method (DXA) to determine the bone mineral density, bone mineral content of total skeleton and vertebral column (L2-L4) and parameters of body composition (Lean Mass and Fat Mass). The isolated femora were scanned using peripheral a quantitative computed tomography method (pQCT) for a separate analysis of the trabecular and cortical bone tissue. The ultimate strength, work to ultimate and the Young modulus of femora was also investigated by the three-point bending test. The negative impact of chromium was observed in relation to bone tissue. All doses significantly decreased total skeleton density and mineral content, and also had impact upon the isolated femora and vertebral column. Trabecular volumetric bone mineral density and trabecular bone mineral content measured by pQCT in distal femur metaphysis were significantly lower in the experimental groups than in the control. Higher doses of chromium also significantly decreased values of ultimate strength and Young modulus in the investigated femora. The results of the experiment demonstrate that chromium sulphate is dose dependent, and exerts a disadvantageous effect on the skeleton, as it decreases bone density and resistance.

Skeletal effects of estrogen deficiency as induced by an aromatase inhibitor in an aged male rat model.

PubMed

Vanderschueren, D; Boonen, S; Ederveen, A G; de Coster, R; Van Herck, E; Moermans, K; Vandenput, L; Verstuyf, A; Bouillon, R

2000-11-01

Aromatization of androgens into estrogens may be important for maintenance of the male skeleton. To address this hypothesis, we evaluated the skeletal effects of selective estrogen deficiency as induced by the aromatase inhibitor vorozole (Vor), with or without 17beta-estradiol (E(2)) administration (1.35 microg/day), in aged (12-month-old) male rats. A baseline group was killed at the start of the experiment (Base). The control group (Control), the group treated with vorozole alone (Vor), the group treated with E(2) alone (E(2)), or the group with a combination of both (Vor + E(2)) were killed 15 weeks later. Vorozole significantly increased serum testosterone (T) and reduced serum E(2) compared with Control. Body weight gain and serum insulin-like growth factor-I (IGF-I) were also lower in Vor, whereas significant weight loss and decrease of serum IGF-I occurred as a result of E(2) administration. Bone formation as assessed by serum osteocalcin was unaffected but osteoid surface in the proximal metaphysis of the tibia was increased in Vor-treated rats. Bone resorption as evaluated by urinary deoxypyridinoline excretion was increased in Vor. Biochemical parameters of bone turnover were reduced significantly in all E(2) treated rats. Premature closure of the growth plates and decreased osteoid and mineralizing surfaces were also observed in E(2) and Vor + E(2). Apparent bone density of lumbar vertebrae and femur, as measured by dual-energy X-ray absorptiometry (DXA), was significantly reduced in Vor. Vorozole decreased femoral bone density mainly in the distal femur (trabecular and cortical region). This decrease of bone density was not present in E(2) and Vor + E(2). Similar findings were observed when bone density was assessed by peripheral quantitative computed tomography (pQCT); that is, trabecular density of the distal femur, the proximal tibia, and the distal lumbar vertebra were all lower in Vor. This decrease in density was not observed in all E(2)-treated animals. In conclusion, administration of the aromatase inhibitor, vorozole, to aged male rats induces net trabecular bone loss in both the appendicular and axial skeleton, despite a concomitant increase in serum testosterone. E(2) administration is able to prevent this trabecular bone loss in vorozole-treated animals.

Evaluation of factors related to bone disease in Polish children and adolescents with cystic fibrosis.

PubMed

Sands, Dorota; Mielus, Monika; Umławska, Wioleta; Lipowicz, Anna; Oralewska, Beata; Walkowiak, Jarosław

2015-09-01

The aim of the study was to evaluate factors related to bone formation and resorption in Polish children and adolescents with cystic fibrosis and to examine the effect of nutritional status, biochemical parameters and clinical status on bone mineral density. The study group consisted of 100 children and adolescents with cystic fibrosis with a mean age 13.4 years old. Anthropometric measurements, included body height, body mass and body mass index (BMI); bone mineral densitometry and biochemical testing were performed. Bone mineral density was measured using a dual-energy X-ray absorption densitometer. Biochemical tests included serum calcium, phosphorus, parathyroid hormone and vitamin D concentrations, as well as 24-h urine calcium and phosphorus excretion. Pulmonary function was evaluated using FEV1%, and clinical status was estimated using the Shwachman-Kulczycki score. Standardized body height, body mass and BMI were significantly lower than in the reference population. Mean serum vitamin D concentration was decreased. Pulmonary disease was generally mild, with a mean FEV1% of 81%. Multivariate linear regression revealed that the only factors that had a significant effect on bone marrow density were BMI and FEV1%. There were no significant correlations between bone mineral density and the results of any of the biochemical tests performed. Nutritional status and bone mineral density were significantly decreased in children and adolescents with cystic fibrosis. In spite of abnormalities in biochemical testing, the factors that were found to have the strongest effect on bone mineral density were standardized BMI and clinical status. Copyright © 2015. Published by Elsevier Urban & Partner Sp. z o.o.

The influence of vegan diet on bone mineral density and biochemical bone turnover markers.

PubMed

Ambroszkiewicz, Jadwiga; Klemarczyk, Witold; Gajewska, Joanna; Chełchowska, Magdalena; Franek, Edward; Laskowska-Klita, Teresa

2010-01-01

Vegetarian diets can be healthy when they are well balanced and if a variety of foods is consumed. However, elimination of animal products from the diet (vegan diets) decreases the intake of some essential nutrients and may influence the bone metabolism. This is especially important in childhood and adolescence, when growth and bone turnover are most intensive. The aim of the study was to assess the effect of vegan diet on bone density (BMD) density and serum concentrations of bone metabolism markers. We examined a family on vegan diet which consisted of parents and two children. Dietary constituents were analysed using a nutritional program. Total and regional BMD were measured by dual-energy X-ray absorptiometry. Concentrations of calcium and phosphate in serum obtained from fasting patients were determined by colorimetric methods, 25-hydroxyvitamin D by the chemiluminescence method and bone turnover markers by specific enzyme immunoassays. In studied vegans, the dietary intake of phosphate was adequate while calcium and vitamin D were below the recommended range. Concentrations of calcium, phosphate and bone turnover markers in the serum of all subjects were within the physiological range, but 25-hydroxyvitamin D level was low. Age-matched Z-score total BMD was between -0.6 and 0.3 in adults, however in children it was lower (-0.9 and -1.0). Z-score BMD lumbar spine (L2-L4) was between -0.9 to -1.9 in parents and -1.5 to -1.7 in children. Our results suggest that an inadequate dietary intake of calcium and vitamin D may impair the bone turnover rate and cause a decrease in bone mineral density in vegans. The parameters of bone density and bone metabolism should be monitored in vegans, especially children, in order to prevent bone abnormalities.

The Consequences of Modern Military Deployment on Calcium Status and Bone Health

DTIC Science & Technology

2010-01-01

Army Medical Center (MAMC) in Tacoma, Washington. At MAMC, data on diet , exercise, and bone mineral density were collected before and after...Studies of basketball players and firefighters, for example, found that athletes experienced a significant decrease in bone mass density (BMD) during the...evidence supporting the link between calcium intake and bone health. We conducted a study to help better define the links between diet , environment

Changes in tibial bone microarchitecture in female recruits in response to 8 weeks of U.S. Army Basic Combat Training.

PubMed

Hughes, Julie M; Gaffney-Stomberg, Erin; Guerriere, Katelyn I; Taylor, Kathryn M; Popp, Kristin L; Xu, Chun; Unnikrishnan, Ginu; Staab, Jeffery S; Matheny, Ronald W; McClung, James P; Reifman, Jaques; Bouxsein, Mary L

2018-08-01

U.S. Army Basic Combat Training (BCT) is a physically-demanding program at the start of military service. Whereas animal studies have shown that increased mechanical loading rapidly alters bone structure, there is limited evidence of changes in bone density and structure in humans exposed to a brief period of unaccustomed physical activity. We aimed to characterize changes in tibial bone density and microarchitecture and serum-based biochemical markers of bone metabolism in female recruits as a result of 8 weeks of BCT. We collected high-resolution peripheral quantitative computed tomographic images of the distal tibial metaphysis and diaphysis (4% and 30% of tibia length from the distal growth plate, respectively) and serum markers of bone metabolism before and after BCT. Linear mixed models were used to estimate the mean difference for each outcome from pre- to post-BCT, while controlling for race/ethnicity, age, and body mass index. 91 female BCT recruits volunteered and completed this observational study (age = 21.5 ± 3.3 yrs). At the distal tibial metaphysis, cortical thickness, trabecular thickness, trabecular number, bone volume/total volume, and total and trabecular volumetric bone density (vBMD) increased significantly by 1-2% (all p < 0.05) over the BCT period, whereas trabecular separation, cortical tissue mineral density (TMD), and cortical vBMD decreased significantly by 0.3-1.0% (all p < 0.05). At the tibial diaphysis, cortical vBMD and cortical TMD decreased significantly (both -0.7%, p < 0.001). Bone strength, estimated by micro finite element analysis, increased by 2.5% and 0.7% at the distal tibial metaphysis and diaphysis, respectively (both p < 0.05). Among the biochemical markers of bone metabolism, sclerostin decreased (-5.7%), whereas bone alkaline phosphatase, C-telopeptide cross-links of type 1 collagen, tartrate-resistance acid phosphatase, and 25(OH)D increased by 10-28% (all p < 0.05). BCT leads to improvements in trabecular bone microarchitecture and increases in serum bone formation markers indicative of new bone formation, as well as increases in serum bone resorption markers and decreases in cortical vBMD consistent with intracortical remodeling. Together, these results demonstrate specific changes in trabecular and cortical bone density and microarchitecture following 8 weeks of unaccustomed physical activity in women. Copyright © 2018 Elsevier Inc. All rights reserved.

Spatial mapping of humeral head bone density.

PubMed

Alidousti, Hamidreza; Giles, Joshua W; Emery, Roger J H; Jeffers, Jonathan

2017-09-01

Short-stem humeral replacements achieve fixation by anchoring to the metaphyseal trabecular bone. Fixing the implant in high-density bone can provide strong fixation and reduce the risk of loosening. However, there is a lack of data mapping the bone density distribution in the proximal humerus. The aim of the study was to investigate the bone density in proximal humerus. Eight computed tomography scans of healthy cadaveric humeri were used to map bone density distribution in the humeral head. The proximal humeral head was divided into 12 slices parallel to the humeral anatomic neck. Each slice was then divided into 4 concentric circles. The slices below the anatomic neck, where short-stem implants have their fixation features, were further divided into radial sectors. The average bone density for each of these regions was calculated, and regions of interest were compared using a repeated-measures analysis of variance with significance set at P < .05. Average apparent bone density was found to decrease from proximal to distal regions, with the majority of higher bone density proximal to the anatomic neck of the humerus (P < .05). Below the anatomic neck, bone density increases from central to peripheral regions, where cortical bone eventually occupies the space (P < .05). In distal slices below the anatomic neck, a higher bone density distribution in the medial calcar region was also observed. This study indicates that it is advantageous with respect to implant fixation to preserve some bone above the anatomic neck and epiphyseal plate and to use the denser bone at the periphery. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Effects of tamoxifen on bone mineral density and metabolism in postmenopausal women with early-stage breast cancer.

PubMed

Zidan, Jamal; Keidar, Zohar; Basher, Walid; Israel, Ora

2004-01-01

At the present time, tamoxifen is the most widely used anti-estrogen for adjuvant therapy and metastatic disease in postmenopausal women with breast cancer, a population at high risk for osteoporosis. This prospective study was designed to evaluate the effect of adjuvant tamoxifen on bone mineral density and all biochemical markers concomitantly in women with early-stage breast cancer in one study. Using dual-energy X-ray absorptiometry, prior to and 12 mo after tamoxifen treatment, bone mineral density in lumbar spine and femoral neck was measured in 44 women with T1-T2N0M0 estrogen-receptor-positive breast cancer receiving adjuvant treatment with tamoxifen 20 mg/d. Biomarkers that can affect bone mineral metabolism were measured before and after 3 and 12 mo of tamoxifen treatment. Bone mineral density was minimally increased in lumbar spine and femoral neck after 12 mo treatment with tamoxifen (p = 0.79 and 0.55, respectively). No differences were found in serum levels of calcium, phosphate, creatinine, ALAT, albumin, LDH, calcitonin, or estradiol. A significant decrease in osteocalcin levels was found after 3 and 12 mo (p < or = 0.01). TSH and PTH levels were increased (p < or = 0.05) after 3 mo, returning to baseline after 12 mo. In conclusion, tamoxifen has an estrogen-like effect on bone metabolism in postmenopausal women and is associated with preservation of bone mineral density in lumbar spine and femoral neck. Changes in serum concentration of biochemical markers may reflect decreased bone turnover or bone remodeling and add to the understanding of tamoxifen's effect on bone mineral density.

Prostaglandin E2 Prevents Ovariectomy-Induced Cancellous Bone Loss in Rats

NASA Technical Reports Server (NTRS)

Ke, Hua Zhu; Li, Mei; Jee, Webster S. S.

1992-01-01

The object of this study was to determine whether prostaglandin E2, (PGE2) can prevent ovariectomy induced cancellous bone loss. Thirty-five 3-month-old female Sprague-Dawley rats were divided into two groups. The rats in the first group were ovariectomized (OVX) while the others received sham operation (sham-OVX). The OVX group was further divided into three treatment groups. The daily doses for the three groups were 0,1 and 6 mg PGE2/kg for 90 days. Bone histomorphometric analyses were performed on double-fluorescent-labeled undecalcified proximal tibial metaphysis (PTM). We confirmed that OVX induces massive cancellous bone loss (-80%) and a higher bone turnover (+143%). The new findings from the present study demonstrate that bone loss due to ovarian hormone deficiency can be prevented by a low-dose (1 mg) daily administration of PGE2. Furthermore, a higher-dose (6 mg) daily administration of PGE2 not only prevents bone loss but also adds extra bone to the proximal tibial metaphyses. PGE, at the 1-mg dose level significantly increased trabecular bone area, trabecular width, trabecular node density, density of node to node, ratio of node to free end, and thus significantly decreased trabecular separation from OVX controls. At this dose level, these same parameters did not differ significantly from sham-OVX controls. However, at the 6-mg dose level PGE2, there were significant increases in trabecular bone area, trabecular width, trabecular node density, density of node to node, and ratio of node to free end, while there was significant decrease in trabecular separation from both OVX and sham-operated controls. The changes in indices of trabecular bone microanatomical structure indicated that PGE2 prevented bone loss as well as the disconnection of existing trabeculae. In summary, PGE2, administration to OVX rats decreased bone turnover and increased bone formation parameters resulting in a positive bone balance that prevented bone loss (in both lower and higher doses) and added extra bone to metaphyses of OVX rats (in higher dose). These findings support the strategy of the use of bone stimulation agents in the prevention of estrogen depletion bone loss (postmenopausal osteoporosis).

Weight loss and bone mineral density.

PubMed

Hunter, Gary R; Plaisance, Eric P; Fisher, Gordon

2014-10-01

Despite evidence that energy deficit produces multiple physiological and metabolic benefits, clinicians are often reluctant to prescribe weight loss in older individuals or those with low bone mineral density (BMD), fearing BMD will be decreased. Confusion exists concerning the effects that weight loss has on bone health. Bone density is more closely associated with lean mass than total body mass and fat mass. Although rapid or large weight loss is often associated with loss of bone density, slower or smaller weight loss is much less apt to adversely affect BMD, especially when it is accompanied with high intensity resistance and/or impact loading training. Maintenance of calcium and vitamin D intake seems to positively affect BMD during weight loss. Although dual energy X-ray absorptiometry is normally used to evaluate bone density, it may overestimate BMD loss following massive weight loss. Volumetric quantitative computed tomography may be more accurate for tracking bone density changes following large weight loss. Moderate weight loss does not necessarily compromise bone health, especially when exercise training is involved. Training strategies that include heavy resistance training and high impact loading that occur with jump training may be especially productive in maintaining, or even increasing bone density with weight loss.

Variable Bone Density of Scaphoid: Importance of Subchondral Screw Placement.

PubMed

Swanstrom, Morgan M; Morse, Kyle W; Lipman, Joseph D; Hearns, Krystle A; Carlson, Michelle G

2018-02-01

Background  Ideal internal fixation of the scaphoid relies on adequate bone stock for screw purchase; so, knowledge of regional bone density of the scaphoid is crucial. Questions/Purpose  The purpose of this study was to evaluate regional variations in scaphoid bone density. Materials and Methods  Three-dimensional CT models of fractured scaphoids were created and sectioned into proximal/distal segments and then into quadrants (volar/dorsal/radial/ulnar). Concentric shells in the proximal and distal pole were constructed in 2-mm increments moving from exterior to interior. Bone density was measured in Hounsfield units (HU). Results  Bone density of the distal scaphoid (453.2 ± 70.8 HU) was less than the proximal scaphoid (619.8 ± 124.2 HU). There was no difference in bone density between the four quadrants in either pole. In both the poles, the first subchondral shell was the densest. In both the proximal and distal poles, bone density decreased significantly in all three deeper shells. Conclusion  The proximal scaphoid had a greater density than the distal scaphoid. Within the poles, there was no difference in bone density between the quadrants. The subchondral 2-mm shell had the greatest density. Bone density dropped off significantly between the first and second shell in both the proximal and distal scaphoids. Clinical Relevance  In scaphoid fracture ORIF, optimal screw placement engages the subchondral 2-mm shell, especially in the distal pole, which has an overall lower bone density, and the second shell has only two-third the density of the first shell.

Effect of low gravity on calcium metabolism and bone formation (L-7)

NASA Technical Reports Server (NTRS)

Suda, Tatsuo

1993-01-01

Recently, attention has been focused on the disorders of bone and calcium metabolism during space flight. The skeletal system has evolved on the Earth under 1-g. Space flights under low gravity appear to cause substantial changes in bone and calcium homeostasis of the animals adapted to 1-g. A space experiment for the First Materials Processing Test (FMPT) was proposed to examine the effects of low gravity on calcium metabolism and bone formation using chick embryos loaded in a space shuttle. This space experiment was proposed based on the following two experimental findings. First, it has been reported that bone density decreases significantly during prolonged space flight. The data obtained from the US Skylab and the U.S.S.R. Salyut-6 cosmonauts have also documented that the degree of bone loss is related to the duration of space flight. Second, the US-Soviet joints space experiment demonstrated that the decrease in bone density under low gravity appears to be due to the decrease in bone formation rather than the increase in bone resorption. The purpose of our space experiment is, therefore, to investigate further the mechanisms of bone growth under low gravity using fertilized chick embryos.

[Bone diseases].

PubMed

Uebelhart, Brigitte; Rizzoli, René

2016-01-13

Calcium intake shows a small impact on bone mineral density and fracture risk. Denosumab is a more potent inhibitor of bone resorption than zoledronate. Abaloparatide, PTHrP analog, increases bone mineral density and decreases fracture incidence. Teriparatide could be delivered via a transdermic device. Romosozumab and odanacatib improve calculated bone strength. Sequential or combined treatments with denosumab and teriparatide could be of interest, but not denosumab followed by teriparatide. Fibrous dysplasia, Paget disease and hypophosphatasia are updated, as well as atypical femoral fracture and osteonecrosis of the jaw.

Bone Growth, Mechanical Stimulus and IGF-1

DTIC Science & Technology

2006-10-01

suffer a bone fracture by the time they reach skeletal maturity. While strenuous physical activity and occupational hazards are key factors in the...females with low bone density. Ultimately, this information could be of great benefit to enhance musculoskeletal development and decrease the risk ...pathogenesis of these fractures , several studies indicate that teenagers who sustain fractures also have decreased bone mass. Therefore, the use of low

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

Silicosis decreases bone mineral density in rats.

PubMed

Hui, Zhang; Dingjie, Xu; Yuan, Yuan; Zhongqiu, Wei; Na, Mao; Mingjian, Bei; Yu, Gou; Guangyuan, Liu; Xuemin, Gao; Shifeng, Li; Yucong, Geng; Fang, Yang; Summer, Ross; Hong, Xu

2018-06-01

Silicosis is the most common occupational lung disease in China, and is associated with a variety of complications, many of which are poorly understood. For example, recent data indicate that silicosis associates with the development of osteopenia, and in some cases this bone loss is severe, meeting criteria for osteoporosis. Although many factors are likely to contribute to this relationship, including a sedentary lifestyle in patients with advanced silicotic lung disease, we hypothesized that silica might directly reduce bone mineral density. In the present study, six Wistar rats were exposed to silica for 24 weeks in order to induce pulmonary silicosis and examine the relationship to bone mineral density. As expected, all rats exposed to silica developed severe pulmonary fibrosis, as manifested by the formation of innumerable silicotic nodules and the deposition of large amounts of interstitial collagen. Moreover, micro-CT results showed that bone mineral density (BMD) was also significantly reduced in rats exposed to silica when compared control animals and this associated with a modest reduction in serum calcium and 25-hydroxyvitamin D levels. In addition, we found that decreased BMD was also linked to increased osteoclast activity as well as fibrosis-like changes, and to the deposition of silica within bone marrow. In summary, our findings support the hypothesis that silicosis reduces bone mineral density and provide support for ongoing investigations into the mechanisms causing osteopenia in silicosis patients. Copyright © 2018. Published by Elsevier Inc.

Daily intermittent decreases in serum levels of parathyroid hormone have an anabolic-like action on the bones of uremic rats with low-turnover bone and osteomalacia.

PubMed

Ishii, H; Wada, M; Furuya, Y; Nagano, N; Nemeth, E F; Fox, J

2000-02-01

The calcium receptor agonist (calcimimetic) compound NPS R-568 causes rapid decreases in circulating levels of parathyroid hormone (PTH) in rats and humans. We hypothesized that daily intermittent decreases in serum PTH levels may have different effects on bone than do chronically sustained decreases. To test this hypothesis, we compared two NPS R-568 dosing regimens in rats with chronic renal insufficiency induced by two intravenous injections of adriamycin. Fourteen weeks after the second adriamycin injection, creatinine clearance was reduced by 52%, PTH levels were elevated approximately 2.5-fold, and serum 25(OH)D3 and 1,25(OH)2D3 levels were reduced substantially. Treatment by daily per os gavage, which decreased PTH levels intermittently, or continuous subcutaneous infusion, which resulted in a sustained suppression of serum PTH levels, then began for 8 weeks. Despite the hyperparathyroidism, the adriamycin-injected rats developed a low-turnover bone lesion with osteomalacia (fourfold increase in osteoid volume in the proximal tibial metaphysis) and osteopenia (67% decrease in cancellous bone volume and an 18% reduction in bone mineral density at the distal femur). Daily administered (but not infused) NPS R-568 significantly increased cancellous bone volume solely by normalizing trabecular thickness, and increased femoral bone mineral density by 14%. These results indicate that daily intermittent, but not sustained, decreases in PTH levels have an "anabolic-like" effect on bones with a low-turnover lesion in this animal model of chronic renal insufficiency.

Subchondral bone remodeling is related to clinical improvement after joint distraction in the treatment of ankle osteoarthritis

PubMed Central

Intema, F.; Thomas, T.P.; Anderson, D.D.; Elkins, J.M.; Brown, T.D.; Amendola, A.; Lafeber, F.P.J.G.; Saltzman, C.L.

2011-01-01

Objective In osteoarthritis (OA), subchondral bone changes alter the joint’s mechanical environment and potentially influence progression of cartilage degeneration. Joint distraction as a treatment for OA has been shown to provide pain relief and functional improvement through mechanisms that are not well understood. This study evaluated whether subchondral bone remodeling was associated with clinical improvement in OA patients treated with joint distraction. Method Twenty-six patients with advanced post-traumatic ankle OA were treated with joint distraction for three months using an Ilizarov frame in a referral center. Primary outcome measure was bone density change analyzed on CT scans. Longitudinal, manually segmented CT datasets for a given patient were brought into a common spatial alignment. Changes in bone density (Hounsfield Units (HU), relative to baseline) were calculated at the weight-bearing region, extending subchondrally to a depth of 8 mm. Clinical outcome was assessed using the ankle OA scale. Results Baseline scans demonstrated subchondral sclerosis with local cysts. At one and two years of follow-up, an overall decrease in bone density (−23% and −21%, respectively) was observed. Interestingly, density in originally low-density (cystic) areas increased. Joint distraction resulted in a decrease in pain (from 60 to 35, scale of 100) and functional deficit (from 67 to 36). Improvements in clinical outcomes were best correlated with disappearance of low-density (cystic) areas (r=0.69). Conclusions Treatment of advanced post-traumatic ankle OA with three months of joint distraction resulted in bone density normalization that was associated with clinical improvement. PMID:21324372

Evaluation of the parameters affecting bone temperature during drilling using a three-dimensional dynamic elastoplastic finite element model.

PubMed

Chen, Yung-Chuan; Tu, Yuan-Kun; Zhuang, Jun-Yan; Tsai, Yi-Jung; Yen, Cheng-Yo; Hsiao, Chih-Kun

2017-11-01

A three-dimensional dynamic elastoplastic finite element model was constructed and experimentally validated and was used to investigate the parameters which influence bone temperature during drilling, including the drill speed, feeding force, drill bit diameter, and bone density. Results showed the proposed three-dimensional dynamic elastoplastic finite element model can effectively simulate the temperature elevation during bone drilling. The bone temperature rise decreased with an increase in feeding force and drill speed, however, increased with the diameter of drill bit or bone density. The temperature distribution is significantly affected by the drilling duration; a lower drilling speed reduced the exposure duration, decreases the region of the thermally affected zone. The constructed model could be applied for analyzing the influence parameters during bone drilling to reduce the risk of thermal necrosis. It may provide important information for the design of drill bits and surgical drilling powers.

[Serum sclerostin levels and metabolic bone diseases].

PubMed

Yamauchi, Mika; Sugimoto, Toshitsugu

2013-06-01

Serum sclerostin levels are being investigated in various metabolic bone diseases. Since serum sclerostin levels are decreased in primary hyperparathyroidism and elevated in hypoparathyroidism, parathyroid hormone (PTH) is thought to be a regulatory factor for sclerostin. Serum sclerostin levels exhibit a significant positive correlation with bone mineral density. On the other hand, a couple of studies on postmenopausal women have shown that high serum sclerostin levels are a risk factor for fracture. Although glucocorticoid induced osteoporosis and diabetes are both diseases that reduce bone formation, serum sclerostin levels have been reported to be decreased in the former and elevated in the latter, suggesting differences in the effects of sclerostin in the two diseases. Serum sclerostin levels are correlated with renal function, and increase with reduction in renal function. Serum sclerostin level may be a new index of bone assessment that differs from bone mineral density and bone metabolic markers.

Oral administration of vitamin C prevents alveolar bone resorption induced by high dietary cholesterol in rats.

PubMed

Sanbe, Toshihiro; Tomofuji, Takaaki; Ekuni, Daisuke; Azuma, Tetsuji; Tamaki, Naofumi; Yamamoto, Tatsuo

2007-11-01

A high-cholesterol diet stimulates alveolar bone resorption, which may be induced via tissue oxidative damage. Vitamin C reduces tissue oxidative damage by neutralizing free radicals and scavenging hydroxyl radicals, and its antioxidant effect may offer the clinical benefit of preventing alveolar bone resorption in cases of hyperlipidemia. We examined whether vitamin C could suppress alveolar bone resorption in rats fed a high-cholesterol diet. In this 12-week study, rats were divided into four groups: a control group (fed a regular diet) and three experimental groups (fed a high-cholesterol diet supplemented with 0, 1, or 2 g/l vitamin C). Vitamin C was provided by adding it to the drinking water. The bone mineral density of the alveolar bone was analyzed by microcomputerized tomography. As an index of tissue oxidative damage, the 8-hydroxydeoxyguanosine level in the periodontal tissue was determined using a competitive enzyme-linked immunosorbent assay. Hyperlipidemia, induced by a high-cholesterol diet, decreased rat alveolar bone density and increased the number of tartrate-resistant acid phosphatase-positive osteoclasts. The expression of 8-hydroxydeoxyguanosine was upregulated in the periodontal tissues. Intake of vitamin C reduced the effect of a high-cholesterol diet on alveolar bone density and osteoclast differentiation and decreased periodontal 8-hydroxydeoxyguanosine expression. In the rat model, vitamin C suppressed alveolar bone resorption, induced by high dietary cholesterol, by decreasing the oxidative damage of periodontal tissue.

A Numeric Analysis of Bone Density in the Edentulous Interforaminal Region.

PubMed

Tavitian, Patrick; Ruquet, Michel; Mensé, Chloe; Nicolas, Emmanuel; Hue, Olivier

The purpose of this study was to assess the density of interforaminal bone using quantitative computed tomography (QCT) in simulated case histories to be prescribed an All-on-Five fixed implant treatment protocol. QCT scans from 30 edentulous patients (15 men and 15 women; mean age 63.33 ± 9.3 years) were analyzed using the Nobel Clinician software. Densities (in Hounsfield units [HU]) were recorded at the neck, middle part of the body, and apex of the lingual and buccal parts of proposed implant sites. The highest bone densities were measured at the neck of the implant (1,187 ± 382 HU), with lower densities at the apex (774 ± 571 HU) (P < .01). Bone densities decreased on the lingual interforaminal portion of the implant, especially on the two intermediate implants. Bone density was lower in women (917 ± 510 HU) than in men (1,095 ± 601 HU) (P < .01). The interforaminal measured bone densities are lower on the paramedian region of the symphysis and in women. However, these levels are in accordance with immediate loading with a fixed partial denture.

Factors associated with menstrual irregularities and decreased bone mineral density in female athletes.

PubMed

Fruth, S J; Worrell, T W

1995-07-01

Menstrual irregularities occur in some female athletes. The most extreme form of menstrual irregularity is amenorrhea, which has been linked to significant decreases in vertebral bone density and increases in injury prevalence. Many authors have sought to determine the causal factors of athletic amenorrhea, some of which include hormonal status, training and physical parameters, nutritional balance, and psychological stress. The purpose of this paper was to compare studies that have examined the relationship of these variables to menstrual irregularities and bone density. Controversy exists regarding the relative contribution of these variables. The etiology is likely multifactorial and should be evaluated as such. Clinicians treating female athletes must be knowledgeable about the negative consequences associated with menstrual irregularities. Furthermore, it is critical that clinicians provide thorough patient education in order to prevent injuries and the long-term loss of bone density. Appropriate medical and/or psychological referral of the athlete with menstrual irregularities may be necessary.

Osteoinductive effects of glyceollins on adult mesenchymal stromal/stem cells from adipose tissue and bone marrow

USDA-ARS?s Scientific Manuscript database

Osteoporosis is characterized by destruction of bone architecture, resulting in decreased bone mass density (BMD) and increased fracture susceptibility. While current therapies focus on reducing bone resorption, the development of therapies to regenerate bone may also be beneficial. Promising anabol...

Osteoporotic-like effects of cadmium on bone mineral density and content in aged ovariectomized beagles

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

Sacco-Gibson, N.; Abrams, J.; Chaudhry, S.

1992-12-31

Our purpose was to evaluate the effects of ovariectomy in conjunction with cadmium (Cd) exposure on bone. Aged female beagles with {sup 45}Ca-labeled skeletons ovariectomized and exposed to Cd. Successive vertebral scans by dual photon absorptiometry monitored changes in bone mineral density (BMD) in each dog with time. Results showed that ovariectomy or Cd exposure alone caused significant decreases in BMD; ovariectomy with Cd exposure caused the greatest decrease. Ovariectomy alone did not decrease BMD in the distal end or mid-shaft of the tibia while BMD of the distal tibia decreased significantly due to Cd exposure alone. Combination treatment resultedmore » in significant decreases in BMD of both tibial regions. At necropsy, tibiae, humeri, lumbar vertebrae and ribs were obtained for biochemical analysis. No group-to-group differences in bone weights (wet, dry, ash), in ash/dry ratios, or in long bone and vertebral Ca/dry or Ca/ash ratios were observed. Significantly higher total {sup 45}Ca content and {sup 45}Ca/dry and {sup 45}Ca/ash ratios were observed in long bones and vertebrae of OV- and OV+ groups. In contrast, intact ribs showed significantly decreased Ca/dry and Ca/ash ratios compared to the SO-group. Quartered ribs demonstrated regional responses to specific treatment; decreases in total Ca content were greatest in the mid-rib region ({minus}36 to {minus}46%). Results suggest that in the aged female beagle, bone mineral loss associated with estrogen depletion is not only related to bone type (trabecular versus cortical) but also to bone Ca pools. Our results also suggest that a regional heterogeneity of bone plays a role in responsiveness to ovariectomy and Cd exposure. These aspects suggest that Cd is an exogenous factor affecting bone mineral loss independently of estrogen depletion. However, estrogen depletion primes bone for responsiveness to Cd-induced bone mineral loss.« less

Anorexia Nervosa, Obesity and Bone Metabolism

PubMed Central

Misra, Madhusmita; Klibanski, Anne

2014-01-01

Anorexia nervosa and obesity are conditions at the extreme ends of the nutritional spectrum, associated with marked reductions versus increases respectively in body fat content. Both conditions are also associated with an increased risk for fractures. In anorexia nervosa, body composition and hormones secreted or regulated by body fat content are important determinants of low bone density, impaired bone structure and reduced bone strength. In addition, anorexia nervosa is characterized by increases in marrow adiposity and decreases in cold activated brown adipose tissue, both of which are related to low bone density. In obese individuals, greater visceral adiposity is associated with greater marrow fat, lower bone density and impaired bone structure. In this review, we discuss bone metabolism in anorexia nervosa and obesity in relation to adipose tissue distribution and hormones secreted or regulated by body fat content. PMID:24079076

Effects of developmental exposure to perfluorooctanoic acid (PFOA) on long bone morphology and bone cell differentiation

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

Koskela, A., E-mail: antti.koskela@oulu.fi

Perfluorooctanoic acid (PFOA) is a ubiquitous and persistent environmental chemical, which has been used extensively due to its stability and surface tension-lowering properties. Toxicological effects include induction of neonatal mortality and reproductive toxicity. In this study, pregnant C57BL/6 mice were exposed orally to 0.3 mg PFOA/kg/day throughout pregnancy, and female offspring were studied at the age of 13 or 17 months. Morphometrical and biomechanical properties of femurs and tibias were analyzed with micro-computed tomography and 3-point bending, and bone PFOA concentrations were determined by mass spectrometry. The effects of PFOA on bone cell differentiation were studied in osteoclasts from C57BL/6more » mice and in the MC3T3 pre-osteoblast cell line. PFOA exposed mice showed increased femoral periosteal area as well as decreased mineral density of tibias. Biomechanical properties of these bones were not affected. Bone PFOA concentrations were clearly elevated even at the age of 17 months. In osteoblasts, low concentrations of PFOA increased osteocalcin (OCN) expression and calcium secretion, but at PFOA concentrations of 100 μM and above osteocalcin (OCN) expression and calcium secretion were decreased. The number of osteoclasts was increased at all PFOA concentrations tested and resorption activity dose-dependently increased from 0.1–1.0 μM, but decreased at higher concentrations. The results show that PFOA accumulates in bone and is present in bones until the old age. PFOA has the potential to influence bone turnover over a long period of time. Therefore bone is a target tissue for PFOA, and altered bone geometry and mineral density seem to persist throughout the life of the animal. - Highlights: • Bone is a target tissue for PFOA both in vivo and in vitro. • Maternal exposure during pregnancy results in PFOA accumulation in bone of the offspring. • PFOA is present in bones until the old age. • PFOA causes mild alterations in bone morphometry and decreases bone mineral density. • Low PFOA concentrations stimulate the resorption activity of osteoclasts.« less

[Numeric simulation of functional remodeling of the anterior alveolar bone].

PubMed

Wang, Wei-feng; Xin, Hai-tao; Zang, Shun-lai; Ding, Jie

2012-04-01

To study the remodeling of the anterior alveolar bone with parodontium under physiology loading using finite element method (FEM) and theory of bone remodeling. A FEM model of the maxillary central incisor with parodontium was established, and the change of bone density during the remodeling of alveolar bone was investigated under physiology loading (60 - 150 N) based on the theory of bone remodeling about strain energy density (SED). The finite element analysis software Abaqus user material subroutine (UMAT) were used. With the increase of physiology loading, the pressure stress on the buccal cervical margin increased gradually while the density was decreased gradually. The cortical bone was lower than its initial density 1.74 g/cm(3), which was 1.74 - 1.63 g/cm(3). The density of cancellous bone was 0.90 - 0.77 g/cm(3), which was lower than its intial density 0.90 g/cm(3). The lingual cervical margin was under tensile stress which also increased with loading, the density had no significant change. When the achieve to 120 N, the density of cortical bone was 1.74 - 1.73 g/cm(3). No significant change was found in the cancellous bone. The simulation of the perodontium remodeling is achieved and proved to be effective by the relevant research based on the method of the study. And the result will be helpful to form the basis of analysis bone remodeling process and predict the results in the clinical work.

Protecting Bone Health in Pediatric Rheumatic Diseases: Pharmacological Considerations.

PubMed

Zhang, Yujuan; Milojevic, Diana

2017-06-01

Bone health in children with rheumatic conditions may be compromised due to several factors related to the inflammatory disease state, delayed puberty, altered life style, including decreased physical activities, sun avoidance, suboptimal calcium and vitamin D intake, and medical treatments, mainly glucocorticoids and possibly some disease-modifying anti-rheumatic drugs. Low bone density or even fragility fractures could be asymptomatic; therefore, children with diseases of high inflammatory load, such as systemic onset juvenile idiopathic arthritis, juvenile dermatomyositis, systemic lupus erythematosus, and those requiring chronic glucocorticoids may benefit from routine screening of bone health. Most commonly used assessment tools are laboratory testing including serum 25-OH-vitamin D measurement and bone mineral density measurement by a variety of methods, dual-energy X-ray absorptiometry as the most widely used. Early disease control, use of steroid-sparing medications such as disease-modifying anti-rheumatic drugs and biologics, supplemental vitamin D and calcium, and promotion of weight-bearing physical activities can help optimize bone health. Additional treatment options for osteoporosis such as bisphosphonates are still controversial in children with chronic rheumatic diseases, especially those with decreased bone density without fragility fractures. This article reviews common risk factors leading to compromised bone health in children with chronic rheumatic diseases and discusses the general approach to prevention and treatment of bone fragility.

Bone Metabolism on ISS Missions

NASA Technical Reports Server (NTRS)

Smith, S. M.; Heer, M. A.; Shackelford, L. C.; Zwart, S. R.

2014-01-01

Spaceflight-induced bone loss is associated with increased bone resorption (1, 2), and either unchanged or decreased rates of bone formation. Resistive exercise had been proposed as a countermeasure, and data from bed rest supported this concept (3). An interim resistive exercise device (iRED) was flown for early ISS crews. Unfortunately, the iRED provided no greater bone protection than on missions where only aerobic and muscular endurance exercises were available (4, 5). In 2008, the Advanced Resistive Exercise Device (ARED), a more robust device with much greater resistance capability, (6, 7) was launched to the ISS. Astronauts who had access to ARED, coupled with adequate energy intake and vitamin D status, returned from ISS missions with bone mineral densities virtually unchanged from preflight (7). Bone biochemical markers showed that while the resistive exercise and adequate energy consumption did not mitigate the increased bone resorption, bone formation was increased (7, 8). The typical drop in circulating parathyroid hormone did not occur in ARED crewmembers. In 2014, an updated look at the densitometry data was published. This study confirmed the initial findings with a much larger set of data. In 42 astronauts (33 male, 9 female), the bone mineral density response to flight was the same for men and women (9), and those with access to the ARED did not have the typical decrease in bone mineral density that was observed in early ISS crewmembers with access to the iRED (Figure 1) (7). Biochemical markers of bone formation and resorption responded similarly in men and women. These data are encouraging, and represent the first in-flight evidence in the history of human space flight that diet and exercise can maintain bone mineral density on long-duration missions. However, the maintenance of bone mineral density through bone remodeling, that is, increases in both resorption and formation, may yield a bone with strength characteristics different from those that existed before space flight. Studies to assess bone strength after flight are underway at NASA, to better understand the results of bone remodeling. Studies are also underway to evaluate optimized exercise protocols and nutritional countermeasures. Regardless, there is clear evidence of progress being made to protect bone during spaceflight.

Soy protein is beneficial but high-fat diet and voluntary running are detrimental to bone structure in mice.

PubMed

Yan, Lin; Graef, George L; Nielsen, Forrest H; Johnson, LuAnn K; Cao, Jay

2015-06-01

Physical activity and soy protein isolate (SPI) augmentation have been reported to be beneficial for bone health. We hypothesized that combining voluntary running and SPI intake would alleviate detrimental changes in bone induced by a high-fat diet. A 2 × 2 × 2 experiment was designed with diets containing 16% or 45% of energy as corn oil and 20% SPI or casein fed to sedentary or running male C57BL/6 mice for 14 weeks. Distal femurs were assessed for microstructural changes. The high-fat diet significantly decreased trabecular number (Tb.N) and bone mineral density (BMD) and increased trabecular separation (Tb.Sp). Soy protein instead of casein, regardless of fat content, in the diet significantly increased bone volume fraction, Tb.N, connectivity density, and BMD and decreased Tb.Sp. Voluntary running, regardless of fat content, significantly decreased bone volume fraction, Tb.N, connectivity density, and BMD and increased Tb.Sp. The high-fat diet significantly decreased osteocalcin and increased tartrate-resistant acid phosphatase 5b (TRAP 5b) concentrations in plasma. Plasma concentrations of osteocalcin were increased by both SPI and running. Running alleviated the increase in TRAP 5b induced by the high-fat diet. These findings demonstrate that a high-fat diet is deleterious, and SPI is beneficial to trabecular bone properties. The deleterious effect of voluntary running on trabecular structural characteristics indicates that there may be a maximal threshold of running beyond which beneficial effects cease and detrimental effects occur. Increases in plasma osteocalcin and decreases in plasma TRAP 5b in running mice suggest that a compensatory response occurs to counteract the detrimental effects of excessive running. Published by Elsevier Inc.

Hypercholesterolemia Promotes an Osteoporotic Phenotype

PubMed Central

Pelton, Kristine; Krieder, Jaclynn; Joiner, Danese; Freeman, Michael R.; Goldstein, Steven A.; Solomon, Keith R.

2013-01-01

A role for hypercholesterolemia in the development of osteoporosis has been suggested in published reports. However, few studies contain direct evidence of a role for maintenance of cholesterol homeostasis in bone health. Using isocaloric high-fat/high-cholesterol and low-fat/no-cholesterol diets in a 4-month feeding study combined with micro computed tomography analysis, we demonstrated in two different mouse strains that mice with hypercholesterolemia lose cortical and trabecular bone in the femurs and vertebrae (bone mineral density was decreased on average by ≈90 mg/mL in the cortical vertebrae in one strain) and cortical bone in the calvariae (bone mineral density was decreased on average by ≈60 mg/mL in one strain). Mechanical testing of the femurs demonstrated that loss of bone in the mice with hypercholesterolemia caused changes in the mechanical properties of the bone including loss of failure load (failure load was decreased by ≈10 N in one strain) and energy to failure. Serologic and histomorphologic analyses suggested that hypercholesterolemia promotes osteoclastogenesis. These studies support a role for hypercholesterolemia in the development of osteoporosis and provide a model with which to test intervention strategies to reduce the effects of hypercholesterolemia on bone health. PMID:22770664

Local variations in bone mineral density: a comparison of OCT versus x-ray micro-CT

NASA Astrophysics Data System (ADS)

Ugryumova, Nadya; Stevens-Smith, Jenna; Scutt, Andrew; Matcher, Stephen J.

2008-02-01

We describe variations in the degree of mineralisation within the subchondral bone plate of the equine metacarpophalangeal joint. A comparison of Optical Coherence Tomography, Micro CT, and SEM techniques was performed. These data are compared between sites on a healthy sample and at points on an osteoarthritically degenerated sample. No significant correlation was found between the optical scattering coefficient and the micro-CT derived BMD for comparisons between different sites on the bone surface. Also OCT demonstrated a larger regional variation in scattering coefficient than did micro CT for bone mineral density. This suggests that the optical scattering coefficient of bone is not related solely to the volume-density of calcium-phosphate. Patches of lower optical scattering coefficient were found in the bone structure that was related to the osteoarthritic lesion area on the overlying cartilage. Areas of microcracking, as revealed by both SEM and micro CT produced distinctive granularity in the OCT images. In further experiments, OCT was compared with micro CT and mechanical strength testing (3-point bending) in a small animal model of cardiovascular disease (cholesterol overload in mice). In the cardiovascular diseased mice, micro-CT of the trabecular bone did not demonstrate a significant change in trabecular bone mineral density before and after administration of the high cholesterol diet. However mechanical testing demonstrated a decrease in mechanical strength and OCT demonstrated a corresponding statistically significant decrease in optical scattering of the bone.

Hibernating little pocket mice show few seasonal changes in bone properties

Treesearch

Noellyn Pineda; Marjorie Owen; Claire Tucker; Samantha Wojda; Stanley Kitchen; Hal Black; Seth Donahue

2017-01-01

Periods of disuse or physical inactivity increases bone porosity and decreases bone mineral density, resulting in a loss of bone mechanical competence in many animals. Although large hibernators like bears and marmots prevent bone loss during hibernation, despite long periods of physical inactivity, some small hibernators do lose bone during hibernation. Little pocket...

Aromatization of androgens is important for skeletal maintenance of aged male rats.

PubMed

Vanderschueren, D; Van Herck, E; De Coster, R; Bouillon, R

1996-09-01

A nonsteroidal aromatase inhibitor vorozole (VOR) was administered to aged (12 months old) male Wistar rats and its effect was compared with the effect of androgen deficiency. The rats were either sham-operated (SHAM) or orchidectomized (ORCH) and treated with or without VOR. Thus, four experimental groups were created (SHAM, ORCH, SHAM + VOR, ORCH + VOR). The follow-up period was 4 months. At the end of the experimental period, bone mineral density (BMD) of the first four lumbar vertebrae and right femur was measured ex vivo with dual-energy X-ray absorptiometry, bone formation was evaluated by serum osteocalcin, and bone resorption by urinary excretion of (deoxy)pyridinoline. Orchidectomy increased bone resorption 2- to 3-fold whereas bone formation was only slightly increased. Treatment of intact male rats with VOR also increased bone resorption (+30% increase) whereas bone formation was not increased in this SHAM + VOR group. Their BMD was 7% lower in the femur (P < 0.01) and 6% lower in the lumbar vertebrae (P < 0.01) compared with the SHAM group that had not received VOR. Moreover, this decrease of bone mineral density was not significantly different from the expected decrease of bone density observed in the ORCH groups (6-10%). This was also reflected by a decrease of calcium content of the first four lumbar vertebrae of 15% (P < 0.001) in the SHAM + VOR group and 9-14% (P < 0.05) in the ORCH groups compared with the SHAM group, respectively. These data therefore suggest that inhibition of aromatization of androgens into estrogens increases bone resorption and bone loss similar to that observed after complete removal of androgens. Aromatization of androgens into estrogens may therefore, at least partly, explain the effects of androgens on skeletal maintenance.

Decreased bone density in carriers and patients of an Israeli family with the osteoporosis-pseudoglioma syndrome.

PubMed

Lev, Dorit; Binson, Inga; Foldes, A Joseph; Watemberg, Nathan; Lerman-Sagie, Tally

2003-06-01

The osteoporosis-pseudoglioma syndrome is a rare autosomal recessive disorder characterized by severe juvenile-onset osteoporosis and congenital or early-onset blindness. Other manifestations include muscular hypotonia, ligamentous laxity, mild mental retardation and seizures. The gene responsible was recently identified to be the low density lipoprotein receptor-related family member LRP5 on chromosome 11q11-12. To measure bone density in two siblings with the OPPG syndrome as well as in their family members (parents and siblings). Bone mineral density was determined in the lumbar spine (antero-posterior), femoral neck, two-thirds distal forearm (> 95% cortical bone) and ultradistal forearm (predominantly trabecular bone) by dual-energy X-ray absorptiometry. The studies revealed osteoporotic changes both in the patients and the carriers. The findings demonstrate that OPPG carriers have reduced bone mass, which is a risk factor for development of early osteoporotic changes.

Assessing the effects of lumbar posterior stabilization and fusion to vertebral bone density in stabilized and adjacent segments by using Hounsfield unit

PubMed Central

Öksüz, Erol; Deniz, Fatih Ersay; Demir, Osman

2017-01-01

Background Computed tomography (CT) with Hounsfield unit (HU) is being used with increasing frequency for determining bone density. Established correlations between HU and bone density have been shown in the literature. The aim of this retrospective study was to determine the bone density changes of the stabilized and adjacent segment vertebral bodies by comparing HU values before and after lumbar posterior stabilization. Methods Sixteen patients who had similar diagnosis of lumbar spondylosis and stenosis were evaluated in this study. Same surgical procedures were performed to all of the patients with L2-3-4-5 transpedicular screw fixation, fusion and L3-4 total laminectomy. Bone mineral density measurements were obtained with clinical CT. Measurements were obtained from stabilized and adjacent segment vertebral bodies. Densities of vertebral bodies were evaluated with HU before the surgeries and approximately one year after the surgeries. The preoperative HU value of each vertebra was compared with postoperative HU value of the same vertebrae by using statistical analysis. Results The HU values of vertebra in the stabilized and adjacent segments consistently decreased after the operations. There were significant differences between the preoperative HU values and the postoperative HU values of the all evaluated vertebral bodies in the stabilized and adjacent segments. Additionally first sacral vertebra HU values were found to be significantly higher than lumbar vertebra HU values in the preoperative group and postoperative group. Conclusions Decrease in the bone density of the adjacent segment vertebral bodies may be one of the major predisposing factors for adjacent segment disease (ASD). PMID:29354730

Cortical bone is more sensitive to alcohol dose effects than trabecular bone in the rat.

PubMed

Maurel, Delphine B; Boisseau, Nathalie; Benhamou, Claude-Laurent; Jaffré, Christelle

2012-10-01

While chronic alcohol consumption is known to decrease bone mineral content (BMC), bone mineral density (BMD), and negatively modify trabecular bone microarchitecture, the impact of alcohol on cortical microarchitecture is still unclear. The aim of this study was to investigate the effects of various doses of alcohol on bone density, trabecular and cortical parameters and bone strength in rats. Forty-eight male Wistar rats were divided into four groups: control (C), alcohol 25% v/v (A25), alcohol 30% v/v (A30) and alcohol 35% v/v (A35). Rats in the alcohol groups were fed a solution composed of ethanol and water for 17 weeks while the control group drank only water. Bone quality and quantity were evaluated through the analysis of density, trabecular and cortical bone microarchitectural parameters, osteocalcin and N-Telopeptide concentrations and a 3-point bending test. Bone density along with trabecular and cortical thickness were lower in alcohol groups compared to C. BMD was lower in A35 vs. A30 and cortical thickness was lower in A35 vs. A25 and A30. Pore number was increased by alcohol and the porosity was greater in A35 compared to C. N-Telopeptide concentration was decreased in alcohol groups compared to control whereas no differences were observed in osteocalcin concentrations. Maximal energy to failure was lower in A25 and A35 compared to C. Chronic ethanol consumption increases cortical bone damage in rats and may have detrimental effects on bone strength. These effects were dose-dependent, with greater negative effects proportionate to greater alcohol doses. Copyright © 2011 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

The effects of low environmental cadmium exposure on bone density

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

Trzcinka-Ochocka, M., E-mail: ochocka@imp.lodz.pl; Jakubowski, M.; Szymczak, W.

2010-04-15

Recent epidemiological data indicate that low environmental exposure to cadmium, as shown by cadmium body burden (Cd-U), is associated with renal dysfunction as well as an increased risk of cadmium-induced bone disorders. The present study was designed to assess the effects of low environmental cadmium exposure, at the level sufficient to induce kidney damage, on bone metabolism and mineral density (BMD). The project was conducted in the area contaminated with cadmium, nearby a zinc smelter located in the region of Poland where heavy industry prevails. The study population comprised 170 women (mean age=39.7; 18-70 years) and 100 men (mean age=31.9;more » 18-76 years). Urinary and blood cadmium and the markers of renal tubular dysfunction ({beta}{sub 2}M-U RBP, NAG), glomerular dysfunction (Alb-U and {beta}{sub 2}M-S) and bone metabolism markers (BAP-S, CTX-S) as well as forearm BMD, were measured. The results of this study based on simple dose-effect analysis showed the relationship between increasing cadmium concentrations and an increased excretion of renal dysfunction markers and decreasing bone density. However, the results of the multivariate analysis did not indicate the association between exposure to cadmium and decrease in bone density. They showed that the most important factors that have impact on bone density are body weight and age in the female subjects and body weight and calcium excretion in males. Our investigation revealed that the excretion of low molecular weight proteins occurred at a lower level of cadmium exposure than the possible loss of bone mass. It seems that renal tubular markers are the most sensitive and significant indicators of early health effects of cadmium intoxication in the general population. The correlation of urinary cadmium concentration with markers of kidney dysfunction was observed in the absence of significant correlations with bone effects. Our findings did not indicate any effects of environmental cadmium exposure on bone density.« less

Raloxifen prevents bone loss in castrated male mice.

PubMed

Broulík, P D; Broulíková, K

2007-01-01

Raloxifen is a selective estrogen receptor modulator which prevents bone loss in ovariectomized female mice in a fashion similar to estrogens. Since testosterone-deficient male mice also lose bone mass, we were interested in testing the effects of raloxifen on bones in intact and castrated male mice. Bone density was significantly reduced in castrated animals (1.36+/-0.04 g/ml) as compared to intact animals (1.42+/-0.03 g/ml) (p<0.01). When castrated mice with extraordinarily low concentrations of testosterone and with reduced weight of seminal vesicles were treated with raloxifen, the changes in bone density and bone minerals resulting from castration (1.36+/-0.04 g/ml) were entirely prevented (1.40+/-0.01 g/ml). Cortical bone was lost in orchidectomized mice, and this decrease in cortical thickness of the femur was prevented by raloxifen administration. Raloxifen in a dose used in humans for treatment of osteoporosis decreased the weight of seminal vesicles, an organ which is highly sensitive to the androgenic effect, decreased the concentration of testosterone (12.5+/-2.8 micromol/l) (p<0.01) but not to the same level as in the case of castrated animals (0.6+/-0.3 micromol/l), and did not have any effect on bone density or mineral content in intact mice. The results of the present study may thus be interpreted as supporting the hypothesis that raloxifen is an effective agent against the deleterious effects of castration-induced osteopenia in male mice and also support the hypothesis that estrogens may have physiological skeletal effects in male mice.

Age-dependence of power spectral density and fractal dimension of bone mineralized matrix in atomic force microscope topography images: potential correlates of bone tissue age and bone fragility in female femoral neck trabeculae

PubMed Central

Milovanovic, Petar; Djuric, Marija; Rakocevic, Zlatko

2012-01-01

There is an increasing interest in bone nano-structure, the ultimate goal being to reveal the basis of age-related bone fragility. In this study, power spectral density (PSD) data and fractal dimensions of the mineralized bone matrix were extracted from atomic force microscope topography images of the femoral neck trabeculae. The aim was to evaluate age-dependent differences in the mineralized matrix of human bone and to consider whether these advanced nano-descriptors might be linked to decreased bone remodeling observed by some authors and age-related decline in bone mechanical competence. The investigated bone specimens belonged to a group of young adult women (n = 5, age: 20–40 years) and a group of elderly women (n = 5, age: 70–95 years) without bone diseases. PSD graphs showed the roughness density distribution in relation to spatial frequency. In all cases, there was a fairly linear decrease in magnitude of the power spectra with increasing spatial frequencies. The PSD slope was steeper in elderly individuals (−2.374 vs. −2.066), suggesting the dominance of larger surface morphological features. Fractal dimension of the mineralized bone matrix showed a significant negative trend with advanced age, declining from 2.467 in young individuals to 2.313 in the elderly (r = 0.65, P = 0.04). Higher fractal dimension in young women reflects domination of smaller mineral grains, which is compatible with the more freshly remodeled structure. In contrast, the surface patterns in elderly individuals were indicative of older tissue age. Lower roughness and reduced structural complexity (decreased fractal dimension) of the interfibrillar bone matrix in the elderly suggest a decline in bone toughness, which explains why aged bone is more brittle and prone to fractures. PMID:22946475

Age-dependence of power spectral density and fractal dimension of bone mineralized matrix in atomic force microscope topography images: potential correlates of bone tissue age and bone fragility in female femoral neck trabeculae.

PubMed

Milovanovic, Petar; Djuric, Marija; Rakocevic, Zlatko

2012-11-01

There is an increasing interest in bone nano-structure, the ultimate goal being to reveal the basis of age-related bone fragility. In this study, power spectral density (PSD) data and fractal dimensions of the mineralized bone matrix were extracted from atomic force microscope topography images of the femoral neck trabeculae. The aim was to evaluate age-dependent differences in the mineralized matrix of human bone and to consider whether these advanced nano-descriptors might be linked to decreased bone remodeling observed by some authors and age-related decline in bone mechanical competence. The investigated bone specimens belonged to a group of young adult women (n = 5, age: 20-40 years) and a group of elderly women (n = 5, age: 70-95 years) without bone diseases. PSD graphs showed the roughness density distribution in relation to spatial frequency. In all cases, there was a fairly linear decrease in magnitude of the power spectra with increasing spatial frequencies. The PSD slope was steeper in elderly individuals (-2.374 vs. -2.066), suggesting the dominance of larger surface morphological features. Fractal dimension of the mineralized bone matrix showed a significant negative trend with advanced age, declining from 2.467 in young individuals to 2.313 in the elderly (r = 0.65, P = 0.04). Higher fractal dimension in young women reflects domination of smaller mineral grains, which is compatible with the more freshly remodeled structure. In contrast, the surface patterns in elderly individuals were indicative of older tissue age. Lower roughness and reduced structural complexity (decreased fractal dimension) of the interfibrillar bone matrix in the elderly suggest a decline in bone toughness, which explains why aged bone is more brittle and prone to fractures. © 2012 The Authors Journal of Anatomy © 2012 Anatomical Society.

Impaired rib bone mass and quality in end-stage cystic fibrosis patients.

PubMed

Mailhot, Geneviève; Dion, Natalie; Farlay, Delphine; Rizzo, Sébastien; Bureau, Nathalie J; Jomphe, Valérie; Sankhe, Safiétou; Boivin, Georges; Lands, Larry C; Ferraro, Pasquale; Ste-Marie, Louis-Georges

2017-05-01

Advancements in research and clinical care have considerably extended the life expectancy of cystic fibrosis (CF) patients. However, with this extended survival come comorbidities. One of the leading co-morbidities is CF-related bone disease (CFBD), which progresses with disease severity and places patients at high risk for fractures, particularly of the ribs and vertebrae. Evidence that CF patients with vertebral fractures had higher bone mineral density (BMD) than the nonfracture group led us to postulate that bone quality is impaired in these patients. We therefore examined rib specimens resected at the time of lung transplant in CF patients to measure parameters of bone quantity and quality. In this exploratory study, we analysed 19 end-stage CF and 13 control rib specimens resected from otherwise healthy lung donors. BMD, bone microarchitecture, static parameters of bone formation and resorption and microcrack density of rib specimens were quantified by imaging, histomorphometric and histological methods. Variables reflecting the mineralization of ribs were assessed by digitized microradiography. The degree of bone mineralization (g/cm 3 ) and the heterogeneity index of the mineralization (g/cm 3 ) were calculated for trabecular and cortical bone. Compared to controls, CF ribs exhibited lower areal and trabecular volumetric BMD, decreased trabecular thickness and osteoid parameters, and increased microcrack density, that was particularly pronounced in specimens from patients with CF-related diabetes. Static parameters of bone resorption were similar in both groups. Degree of mineralization of total bone, but not heterogeneity index, was increased in CF specimens. The combination of reduced bone mass, altered microarchitecture, imbalanced bone remodeling (maintained bone resorption but decreased formation), increased microdamage and a small increase of the degree of mineralization, may lead to decreased bone strength, which, when coupled with chronic coughing and chest physical therapy, may provide an explanation for the increased incidence of rib fractures previously reported in this population. Copyright © 2017 Elsevier Inc. All rights reserved.

Differences in trabecular bone of leptin-deficient ob/ob mice in response to biomechanical loading.

PubMed

Heep, Hansjoerg; Wedemeyer, Christian; Wegner, Alexander; Hofmeister, Sebastian; von Knoch, Marius

2008-06-15

It is known that bone mineral density (BMD) and the strength of bone is predicted by body mass. Fat mass is a significant predictor of bone mineral density which correlates with body weight. This suggests that body fat regulates bone metabolism first by means of hormonal factors and second that the effects of muscle and loading are signaling factors in mechanotransduction. Leptin, a peptide hormone produced predominantly by white fat cells, is one of these hormonal factors. The aim of this study was to investigate and measure by micro-CT the different effects of weight-bearing on trabecular bone formation in mice without the stimulation of leptin. Animals with an ad-libitum-diet (Group A) were found to increase body weight significantly at the age of six weeks in comparison with lean mice (Group B). From this point on, the difference increased constantly. At the age of twenty weeks the obese mice were almost twice as heavy as the lean mice. Significant statistical differences are shown between the two groups for body weight and bone mineral density. Examination of trabecular bone (BV/TV, trabecular number (Tb.N.), trabecular thickness (Tb.Th.)) revealed that the only statistically significant difference between the two groups was the Tb.N. for the proximal femur. High weight-bearing insignificantly improved all trabecular bone parameters in the obese mice. Compared with the control-diet Group B, the BV/TV and Tb.N. were slightly higher in the controlled-diet Group A, but not the Tb.Th.. However, correlation was found between Tb.N. and BMD on the one hand and body weight on the other hand. biomechanical loading led to decreased bone mineral density by a decrease in the number of trabeculae. Trabecular thickness was not increased by biomechanical loading in growing mice. Decreased body weight in leptin-deficient mice protects against bone loss. This finding is consistent with the principle of light-weight construction of bone. Differences in cortical and trabecular bone will be examined in later studies. It is not possible to conclude that these results also apply to human beings.

Decreased bone mineral density in experimental myasthenia gravis in C57BL/6 mice.

PubMed

Oshima, Minako; Iida-Klein, Akiko; Maruta, Takahiro; Deitiker, Philip R; Atassi, M Zouhair

2017-09-01

Experimental autoimmune myasthenia gravis (EAMG), an animal model of myasthenia gravis (MG), can be induced in C57BL/6 (B6, H-2  b ) mice by 2-3 injections with Torpedo californica AChR (tAChR) in complete Freund's adjuvant. Some EAMG mice exhibit weight loss with muscle weakness. The loss in body weight, which is closely associated with bone structure, is particularly evident in EAMG mice with severe muscle weakness. However, the relationship between muscle weakness and bone loss in EAMG has not been studied before. Recent investigations on bone have shed light on association of bone health and immunological states. It is possible that muscle weakness in EAMG developed by anti-tAChR immune responses might accompany bone loss. We determined whether reduced muscle strength associates with decreased bone mineral density (BMD) in EAMG mice. EAMG was induced by two injections at 4-week interval of tAChR and adjuvants in two different age groups. The first tAChR injection was either at age 8 weeks or at 15 weeks. We measured BMD at three skeletal sites, including femur, tibia, and lumbar vertebrae, using dual energy X-ray absorptiometry. Among these bone areas, femur of EAMG mice in both age groups showed a significant decrease in BMD compared to control adjuvant-injected and to non-immunized mice. Reduction in BMD in induced EAMG at a later-age appears to parallel the severity of the disease. The results indicate that anti-tAChR autoimmune response alone can reduce bone density in EAMG mice. BMD reduction was also observed in adjuvant-injected mice in comparison to normal un-injected mice, suggesting that BMD decrease can occur even when muscle activity is normal. Decreased BMD observed in both tAChR-injected and adjuvant-injected mice groups were discussed in relation to innate immunity and bone-related immunology involving activated T cells and tumour necrosis factor-related cytokines that trigger osteoclastogenesis and bone loss.

Effects of antiepileptic drugs on bone mineral density and bone metabolism in children: a meta-analysis*

PubMed Central

Zhang, Ying; Zheng, Yu-xin; Zhu, Jun-ming; Zhang, Jian-min; Zheng, Zhe

2015-01-01

Objective: The aim of our meta-analysis was to assess the effects of antiepileptic drugs on bone mineral density and bone metabolism in epileptic children. Methods: Searches of PubMed and Web of Science were undertaken to identify studies evaluating the association between antiepileptic drugs and bone mineral density and bone metabolism. Results: A total of 22 studies with 1492 subjects were included in our research. We identified: (1) a reduction in bone mineral density at lumbar spine (standardized mean difference (SMD)=−0.30, 95% confidence interval (CI) [−0.61, −0.05]), trochanter (mean difference (MD)=−0.07, 95% CI [−0.10, −0.05]), femoral neck (MD=−0.05, 95% CI [−0.09, −0.02]), and total body bone mineral density (MD=−0.33, 95% CI [−0.51, −0.15]); (2) a reduction in 25-hydroxyvitamin D (MD=−3.37, 95% CI [−5.94, −0.80]) and an increase in serum alkaline phosphatase (SMD=0.71, 95% CI [0.38, 1.05]); (3) no significant changes in serum parathyroid hormone, calcium, or phosphorus. Conclusions: Our meta-analysis suggests that treatment with antiepileptic drugs may be associated with decreased bone mineral density in epileptic children. PMID:26160719

A study of changes in bone metabolism in cases of gender identity disorder.

PubMed

Miyajima, Tsuyoshi; Kim, Yoon Taek; Oda, Hiromi

2012-07-01

The aim of this study was to determine the effect of increasing estrogen and decreasing androgen in males and increasing androgen and decreasing estrogen in females on bone metabolism in patients with gender identity disorder (GID). We measured and examined bone mineral density (BMD) and bone metabolism markers retrospectively in GID patients who were treated in our hospital. In addition, we studied the effects of treatment on those who had osteoporosis. Patients who underwent a change from male to female (MtF) showed inhibition of bone resorption and increased L2-4 BMD whereas those who underwent a change from female to male (FtM) had increased bone resorption and decreased L2-4 BMD. Six months after administration of risedronate to FtM patients with osteoporosis, L2-4 BMD increased and bone resorption markers decreased. These results indicate that estrogen is an important element with regard to bone metabolism in males.

Running exercise alleviates trabecular bone loss and osteopenia in hemizygous β-globin knockout thalassemic mice.

PubMed

Thongchote, Kanogwun; Svasti, Saovaros; Teerapornpuntakit, Jarinthorn; Krishnamra, Nateetip; Charoenphandhu, Narattaphol

2014-06-15

A marked decrease in β-globin production led to β-thalassemia, a hereditary anemic disease associated with bone marrow expansion, bone erosion, and osteoporosis. Herein, we aimed to investigate changes in bone mineral density (BMD) and trabecular microstructure in hemizygous β-globin knockout thalassemic (BKO) mice and to determine whether endurance running (60 min/day, 5 days/wk for 12 wk in running wheels) could effectively alleviate bone loss in BKO mice. Both male and female BKO mice (1-2 mo old) showed growth retardation as indicated by smaller body weight and femoral length than their wild-type littermates. A decrease in BMD was more severe in female than in male BKO mice. Bone histomorphometry revealed that BKO mice had decreases in trabecular bone volume, trabecular number, and trabecular thickness, presumably due to suppression of osteoblast-mediated bone formation and activation of osteoclast-mediated bone resorption, the latter of which was consistent with elevated serum levels of osteoclastogenic cytokines IL-1α and -1β. As determined by peripheral quantitative computed tomography, running increased cortical density and thickness in the femoral and tibial diaphyses of BKO mice compared with those of sedentary BKO mice. Several histomorphometric parameters suggested an enhancement of bone formation (e.g., increased mineral apposition rate) and suppression of bone resorption (e.g., decreased osteoclast surface), which led to increases in trabecular bone volume and trabecular thickness in running BKO mice. In conclusion, BKO mice exhibited pervasive osteopenia and impaired bone microstructure, whereas running exercise appeared to be an effective intervention in alleviating bone microstructural defect in β-thalassemia. Copyright © 2014 the American Physiological Society.

Effect of altered reproductive function and lowered testosterone levels on bone density in male endurance athletes.

PubMed

Bennell, K L; Brukner, P D; Malcolm, S A

1996-09-01

It is apparent that bone density in male athletes can be reduced without a concomitant decrease in testosterone, suggesting that bone density and testosterone concentrations in the normal range are not closely related in male athletes. Further research is necessary to monitor concurrent changes in bone density and testosterone over a period of time in exercising males. In any case, the effect of exercise on the male reproductive system does not appear as extreme as that which can occur in female athletes, and any impact on bone density is not nearly as evident. These results imply that factors apart from testosterone concentrations must be responsible for the observed osteopenia in some male athletes. Many factors have the potential to adversely affect bone density, independently of alterations in reproductive function. These include low calcium intake, energy deficit, weight loss, psychological stress, and low body fat, all of which may be associated with intense endurance training. Future research investigating skeletal health in male athletes should include a thorough assessment of reproductive function in addition to these other factors.

The Oxysterol, 27-Hydroxycholesterol, Links Cholesterol Metabolism to Bone Homeostasis Through Its Actions on the Estrogen and Liver X Receptors

PubMed Central

Nelson, Erik R.; DuSell, Carolyn D.; Wang, Xiaojuan; Howe, Matthew K.; Evans, Glenda; Michalek, Ryan D.; Umetani, Michihisa; Rathmell, Jeffrey C.; Khosla, Sundeep; Gesty-Palmer, Diane

2011-01-01

Osteoporosis and age-related bone loss are important public health concerns. Therefore, there is a high level of interest in the development of medical interventions and lifestyle changes that reduce the incidence of osteoporosis and age-related bone loss. Decreased bone mineral density is associated with high cholesterol, and patients on statins have increased bone mineral densities, strongly implicating cholesterol as a negative regulator of bone homeostasis. In this study, using both molecular and pharmacological approaches, we have been able to demonstrate that the primary cholesterol metabolite, 27-hydroxycholesterol, through its actions on both estrogen receptors and liver X receptors, decreases osteoblast differentiation and enhances osteoclastogenesis, resulting in increased bone resorbtion in mice. Induction of the short heterodimer partner protein by estrogens in osteoblasts can attenuate the liver X receptor-mediated actions of 27-hydroxycholesterol in bone. These data establish a mechanistic link between cholesterol and bone quality, highlight an unexpected target of estrogens in osteoblasts, and define a signaling axis, the therapeutic exploitation of which is likely to yield novel antiosteoporotic drugs. PMID:21933863

A Flexible Method for Producing F.E.M. Analysis of Bone Using Open-Source Software

NASA Technical Reports Server (NTRS)

Boppana, Abhishektha; Sefcik, Ryan; Myers, Jerry G.; Lewandowski, Beth

2016-01-01

Individuals who experience decreases in load-bearing bone densities can be subject to a higher risk of bone fracture during daily activity. Astronauts may lose up to nine percent of their load-bearing bone density for every month they spend in space [1]. Because of this, specialized countermeasures reduce percent loss in bone density and reduce fracture risk upon returning to Earth. Astronauts will typically not be at risk for fracture during spaceflight, because of the lesser loads experienced in microgravity conditions. However, once back on Earth, astronauts have an increased risk for bone fracture as a result of weakened bone and return to 1G conditions [2]. It is therefore important to understand the significance of any bone density loss in addition to developing exercises in an attempt to limit losses in bone strength. NASA seeks to develop a deeper understanding of fracture risk through the development of a computational bone strength model to assess the bone fracture risk of astronauts pre-flight and post-flight. This study addresses the several key processes needed to develop such strength analyses using medical image processing and finite element modeling.

A toxicity profile of osteoprotegerin in the cynomolgus monkey.

PubMed

Smith, Brenda B; Cosenza, Mary Ellen; Mancini, Audrey; Dunstan, Colin; Gregson, Richard; Martin, Steven W; Smith, Susan Y; Davis, Harold

2003-01-01

Osteoprotegerin (OPG) is a novel secreted glycoprotein of the tumor necrosis factor (TNF) receptor superfamily that acts as an antiresorptive agent inhibiting osteoclast maturation. OPG acts by competitively inhibiting the association of the OPG ligand with the RANK receptor on osteoclasts and osteoclast precursors. This inhibition of osteoclasts can lead to excess accumulation of newly synthesized bone and cartilage in vivo. The purpose of this study was to investigate the potential toxicity of a human recombinant form of OPG in the young cynomolgus monkey. OPG was administered by intravenous (i.v.) or subcutaneous (s.c.) injection three times per week for either 4 or 13 weeks. There were no deaths during the study, no clinical signs related to treatment, no effect on body weight, appetence, or ophthalmology. No toxicologically relevant changes in routine laboratory investigations, organ weights, or gross or histopathological findings were observed. Serum ionized calcium and phosphorus were decreased at all dose levels. Evaluations were performed to monitor biochemical markers of bone resorption (N-telopeptide [NTx], deoxypyridinoline [DPD]), bone formation (skeletal alkaline phosphatase [sALP], osteocalcin [OC]), parathyroid hormone [PTH], and bone density of the proximal tibia and distal radius in vivo. Dose-related decreases in NTx and/or DPD were observed at each dose level, with up to a 90% decrease in NTx noted for animals treated i.v. or s.c. at 15 mg/kg. Similar decreases were observed for sALP and OC. PTH was increased for animals treated at 5 and 15 mg/kg (i.v. or s.c.). Trabecular bone density was increased for the majority of males and females treated i.v. or s.c. at 15 mg/kg and males treated i.v. at 5 mg/kg. Microscopic examination of the sternebrae revealed corresponding increases in bone. Decreases in markers of bone turnover, and corresponding increases in bone density, were consistent with the pharmacological action of OPG as an osteoclast inhibitor. The no-observable-adverse-effect level (NOAEL) of OPG was 15 mg/kg.

Osteoporosis: Are we measuring what we intend to measure? In search of the ideal bone strength study

NASA Astrophysics Data System (ADS)

de Riese, Cornelia

2006-02-01

In 1991 the World Health Organization (WHO) defined osteoporosis as a "loss of bone mass and micro architectural deterioration of the skeleton leading to increased risk of fracture." 1,2 Since microarchitecture can not be measured directly, a panel of the WHO recommended that the diagnosis be made according to a quantifiable surrogate marker, calcium mineral, in bone. Subsequently in 1994, the definition focused on the actual bone "density," giving densitometric technology a central place in establishing the diagnosis of osteoporosis. 3,4 But soon it became obvious that there was only limited correlation between bone mineral density (BMD) and actual occurrence of fractures and that decreases in bone mass account for only about 50% of the deterioration of bone strength with aging. In other words only about 60% of bone strength is related to BMD. 5 Recent developments in bone research have shown that bone mineral density in itself is not sufficient to accurately predict fracture risk. Bone is composed of inorganic calcium apatite crystals that mineralize an organic type I collagen matrix. The degree of mineralization, the properties of the collagen matrix, crystal size, trabecular orientation, special distribution of the different components and many more factors are all impacting bone strength. 6-14 Human cadaver studies have confirmed the correlation between bone density and bone. 26 strength. 5,15-20 Changes in cancellous bone morphology appear to lead to a disproportionate decrease in bone strength. 21-26 When postmenopausal women are stratified by age, obvious differences between BMD and actual fracture risk are observed. 24 Felsenberg eloquently summarizes what he calls the "Bone Quality Framework." In great detail he talks about the geometry and micro- architecture of bone and how the different components are related to functional stability. 27 Are our current testing modalities appropriately addressing these structural factors? Are we keeping in mind that in screening for osteoporosis the key variable is fragility, not bone density itself? All currently FDA approved and commercially available equipments for the evaluation of bone status claim that they - at least indirectly - assess the biological fracture risk. This review summarizes an extensive current literature research covering FDA approved as well as experimental devices for the evaluation of bone. The pros and cons of the different techniques are discussed in the context of diagnostic accuracies and practical implications.

Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with antiresorptive drugs.

PubMed

Cummings, Steven R; Karpf, David B; Harris, Fran; Genant, Harry K; Ensrud, Kristine; LaCroix, Andrea Z; Black, Dennis M

2002-03-01

To estimate how much the improvement in bone mass accounts for the reduction in risk of vertebral fracture that has been observed in randomized trials of antiresorptive treatments for osteoporosis. After a systematic search, we conducted a meta-analysis of 12 trials to describe the relation between improvement in spine bone mineral density and reduction in risk of vertebral fracture in postmenopausal women. We also used logistic models to estimate the proportion of the reduction in risk of vertebral fracture observed with alendronate in the Fracture Intervention Trial that was due to improvement in bone mineral density. Across the 12 trials, a 1% improvement in spine bone mineral density was associated with a 0.03 decrease (95% confidence interval [CI]: 0.02 to 0.05) in the relative risk (RR) of vertebral fracture. The reductions in risk were greater than predicted from improvement in bone mineral density; for example, the model estimated that treatments predicted to reduce fracture risk by 20% (RR = 0.80), based on improvement in bone mineral density, actually reduce the risk of fracture by about 45% (RR = 0.55). In the Fracture Intervention Trial, improvement in spine bone mineral density explained 16% (95% CI: 11% to 27%) of the reduction in the risk of vertebral fracture with alendronate. Improvement in spine bone mineral density during treatment with antiresorptive drugs accounts for a predictable but small part of the observed reduction in the risk of vertebral fracture.

[Effect of low-dose or standard-dose conjugated equine estrogen combined with different progesterone on bone density in menopause syndrome women].

PubMed

Zuo, H L; Deng, Y; Wang, Y F; Gao, L L; Xue, W; Zhu, S Y; Ma, X; Sun, A J

2018-04-25

Objective: To explore the effect of low-dose or standard-dose conjugated equine estrogen (CEE) combined with natural progesterone or dydrogesterone on bone density in menopause syndrome women. Methods: Totally 123 patients with menopause syndrome were recruited and randomly assigned to 3 treatment groups: group A (low-dose CEE+progesterone) , group B (standard-dose CEE+progesterone) , group C (standard-dose CEE+dydrogesterone) . Using continuous sequential regimen, the duration of intervention was 12 cycles. The bone mineral density of lumbar 2-4 and neck of femur, the bone metabolic markers, the level of FSH and estradiol were examined just before the drug administration and 12 months after the beginning of experiment. Results: There were 107 cases completed the one year trial. (1) Bone density: after 12 cycles of treatment, there was no significant change in bone density in group A ( P> 0.05) ; lumbar vertebrae of group B and C increased significantly, at 3.0% and 2.1%respectively (all P< 0.05) . The bone density of left femoral neck of group C significantly increased by 2.9% ( P= 0.029) . There was no significant difference among the treatment groups at the beginning of experiment ( P> 0.05) . (2) Bone metabolic markers: after 12 cycles of treatment, the levels of calcium, phosphorus, alkaline phosphatase, Ca/Cr decreased significantly, the difference were statistically significant (all P< 0.05) . There was no significant difference among the treatment groups at the beginning of experiment ( P> 0.05) . (3) Levels of FSH and estradiol: after 12 cycles of treatment, the levels of FSH in three groups were decreased significantly (all P< 0.01) . The levels of estradiol in three groups were increased significantly (all P< 0.01) . There was no significant difference among the treatment groups at the beginning of experiment ( P> 0.05) . Conclusions: Both low-dose and standard-dose menopause hormone therapy (MHT) could elevate the level of estradiol, reduce bone turnover, prevent bone loss of postmenopausal women effectively. The standard dose of MHT could also increase the density of vertebrae and femoral neck, and generate more clinical benefits.

Biochemical Bone Turnover Markers and Osteoporosis in Older Men: Where Are We?

PubMed Central

Szulc, Pawel

2011-01-01

In men aged less than 60, the association of serum and urinary levels of biochemical bone turnover markers (BTMs) and bone mineral density (BMD) is weak or not significant. After this age, higher BTM levels are correlated weakly, but significantly, with lower BMD and faster bone loss. Limited data from the cohort studies suggest that BTM measurement does not improve the prediction of fragility fractures in older men in comparison with age, BMD, history of falls and fragility fractures. Testosterone replacement therapy (TRT) decreases bone resorption. During TRT, bone formation markers slightly increase (direct effect on osteoblasts), then decrease (slowdown of bone turnover). Bisphosphonates (alendronate, risedronate, ibandronate, zoledronate) induce a rapid decrease in bone resorption followed by a milder decrease in bone formation. In men receiving antiresorptive therapy for prostate cancer, zoledronate, denosumab and toremifene decrease significantly levels of bone resorption and bone formation markers. Teriparatide induced a rapid increase in serum concentrations of bone formation markers followed by an increase in bone resorption. We need more studies on the utility of BTM measurement for the improvement of the persistence and adherence to the anti-osteoporotic treatment in men. PMID:22220284

Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss

NASA Technical Reports Server (NTRS)

LeBlanc, Adrian; Matsumoto, Toshio; Jones, Jeffrey A.; Shapiro, Jay; Lang, Thomas F.; Smith, Scott M.; Shackelford, Linda C.; Sibonga, Jean; Evans, Harlan; Spector, Elisabeth;

Effects of Active Mastication on Chronic Stress-Induced Bone Loss in Mice

PubMed Central

Azuma, Kagaku; Furuzawa, Manabu; Fujiwara, Shu; Yamada, Kumiko; Kubo, Kin-ya

2015-01-01

Chronic psychologic stress increases corticosterone levels, which decreases bone density. Active mastication or chewing attenuates stress-induced increases in corticosterone. We evaluated whether active mastication attenuates chronic stress-induced bone loss in mice. Male C57BL/6 (B6) mice were randomly divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube (60 min, 2x/day, 4 weeks). The stress/chewing group was given a wooden stick to chew during the experimental period. Quantitative micro-computed tomography, histologic analysis, and biochemical markers were used to evaluate the bone response. The stress/chewing group exhibited significantly attenuated stress-induced increases in serum corticosterone levels, suppressed bone formation, enhanced bone resorption, and decreased trabecular bone mass in the vertebrae and distal femurs, compared with mice in the stress group. Active mastication during exposure to chronic stress alleviated chronic stress-induced bone density loss in B6 mice. Active mastication during chronic psychologic stress may thus be an effective strategy to prevent and/or treat chronic stress-related osteopenia. PMID:26664256

Effects of Active Mastication on Chronic Stress-Induced Bone Loss in Mice.

PubMed

Azuma, Kagaku; Furuzawa, Manabu; Fujiwara, Shu; Yamada, Kumiko; Kubo, Kin-ya

2015-01-01

Chronic psychologic stress increases corticosterone levels, which decreases bone density. Active mastication or chewing attenuates stress-induced increases in corticosterone. We evaluated whether active mastication attenuates chronic stress-induced bone loss in mice. Male C57BL/6 (B6) mice were randomly divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube (60 min, 2x/day, 4 weeks). The stress/chewing group was given a wooden stick to chew during the experimental period. Quantitative micro-computed tomography, histologic analysis, and biochemical markers were used to evaluate the bone response. The stress/chewing group exhibited significantly attenuated stress-induced increases in serum corticosterone levels, suppressed bone formation, enhanced bone resorption, and decreased trabecular bone mass in the vertebrae and distal femurs, compared with mice in the stress group. Active mastication during exposure to chronic stress alleviated chronic stress-induced bone density loss in B6 mice. Active mastication during chronic psychologic stress may thus be an effective strategy to prevent and/or treat chronic stress-related osteopenia.

ASSOCIATION BETWEEN NON-ENZYMATIC GLYCATION, RESORPTION, AND MICRODAMAGE IN HUMAN TIBIAL CORTICES

PubMed Central

Karim, Lamya; Diab, Tamim; Vashishth, Deepak

2015-01-01

Purpose/Introduction Changes in the quality of bone material contribute significantly to bone fragility. In order to establish a better understanding of the interaction of the different components of bone quality and their influence on bone fragility we investigated the relationship between non-enzymatic glycation, resorption, and microdamage generated in vivo in cortical bone using bone specimens from the same donors. Methods Total fluorescent advanced glycation end-products (AGEs) were measured in 96 human cortical bone samples from 83 donors. Resorption pit density, average resorption pit area, and percent resorption area were quantified in samples from 48 common donors with AGE measurements. Linear microcrack density and diffuse damage were measured in 21 common donors with AGE and resorption measurements. Correlation analyses were performed between all measured variables to establish the relationships among them and their variation with age. Results We found that average resorption pit area and percent resorption area decreased with increasing AGEs independently of age. Resorption pit density and percent resorption area demonstrated negative age-adjusted correlation with diffuse damage. Furthermore, average resorption pit area, resorption pit density, and percent resorption area were found to decrease significantly with age. Conclusions The current study demonstrated the in vivo interrelationship between the organic constituents, remodeling, and damage formation in cortical bone. In addition to the age-related reduction in resorption, there is a negative correlation between AGEs and resorption independent of age. This inverse relationship indicates that AGEs alter the resorption process and/or accumulate in the tissue as a result of reduced resorption and may lead to bone fragility by adversely affecting fracture resistance through altered bone matrix properties. PMID:25326375

Associations between genetic variants and the effect of letrozole and exemestane on bone mass and bone turnover.

PubMed

Oesterreich, Steffi; Henry, N Lynn; Kidwell, Kelley M; Van Poznak, Catherine H; Skaar, Todd C; Dantzer, Jessica; Li, Lang; Hangartner, Thomas N; Peacock, Munro; Nguyen, Anne T; Rae, James M; Desta, Zeruesenay; Philips, Santosh; Storniolo, Anna M; Stearns, Vered; Hayes, Daniel F; Flockhart, David A

2015-11-01

Adjuvant therapy for hormone receptor (HR) positive postmenopausal breast cancer patients includes aromatase inhibitors (AI). While both the non-steroidal AI letrozole and the steroidal AI exemestane decrease serum estrogen concentrations, there is evidence that exemestane may be less detrimental to bone. We hypothesized that single nucleotide polymorphisms (SNP) predict effects of AIs on bone turnover. Early stage HR-positive breast cancer patients were enrolled in a randomized trial of exemestane versus letrozole. Effects of AI on bone mineral density (BMD) and bone turnover markers (BTM), and associations between SNPs in 24 candidate genes and changes in BMD or BTM were determined. Of the 503 enrolled patients, paired BMD data were available for 123 and 101 patients treated with letrozole and exemestane, respectively, and paired BTM data were available for 175 and 173 patients, respectively. The mean change in lumbar spine BMD was significantly greater for letrozole-treated (-3.2 %) compared to exemestane-treated patients (-1.0 %) (p = 0.0016). Urine N-telopeptide was significantly increased in patients treated with exemestane (p = 0.001) but not letrozole. Two SNPs (rs4870061 and rs9322335) in ESR1 and one SNP (rs10140457) in ESR2 were associated with decreased BMD in letrozole-treated patients. In the exemestane-treated patients, SNPs in ESR1 (Rs2813543) and CYP19A1 (Rs6493497) were associated with decreased bone density. Exemestane had a less negative impact on bone density compared to letrozole, and the effects of AI therapy on bone may be impacted by genetic variants in the ER pathway.

Age changes in the bone density and structure of the lumbar vertebral column.

PubMed Central

Twomey, L; Taylor, J; Furniss, B

1983-01-01

Old age is associated with a decline in bone density in lumbar vertebral bodies in both sexes, although the rate and amount of the decline is greatest in females. The bone translucency index method, described in this study, is a sensitive method of estimating bone density. The primary reason for this decline is the significant decrease in the number of transverse trabeculae of lumbar vertebrae in old age. It is postulated that the increase in vertebral end plate concavity and the increased horizontal dimensions of lumbar vertebral bodies in old age follows as a direct consequence of the selective loss of the transverse trabeculae. Images Fig. 2 PMID:6833115

Finite Element Modelling of the Femur Bone of a Subject Suffering from Motor Neuron Lesion Subjected to Electrical Stimulation.

PubMed

Gislason, Magnus K; Ingvarsson, Páll; Gargiulo, Paolo; Yngvason, Stefán; Guðmundsdóttir, Vilborg; Knútsdóttir, Sigrún; Helgason, Þórður

2014-09-23

Bone loss and a decrease in bone mineral density is frequently seen in patients with motor neuron lesion due to lack of mechanical stimulation. This causes weakening of the bones and a greater risk of fracture. By using functional electrical stimulation it is possible to activate muscles in the body to produce the necessary muscle force to stimulate muscle growth and potentially decrease the rate of bone loss. A longitudinal study was carried out on a single patient undergoing electrical stimulation over a 6 year period. The patient underwent a CT scan each year and a full three dimensional finite element model for each year was created using Mimics (Materialise) and Abaqus (Simulia) to calculate the risk of fracture under physiologically relevant loading conditions. Using empirical formulas connecting the bone mineral density to the stiffness and ultimate tensile stress of the bone, each element was assigned a unique material property, based on its density. The risk of fracture was estimated by calculating the ratio between the predicted stress and the ultimate tensile stress, should it exceed unity, failure was assumed. The results showed that the number of elements that were predicted to be at risk of failure varied between years.

High-fat Diet Decreases Cancellous Bone Mass But Has No Effect on Cortical Bone Mass in the Tibia in Mice

USDA-ARS?s Scientific Manuscript database

Introduction: Body mass has a positive effect on bone mineral density and the strength. Whether mass derived from an obesity condition is beneficial to bone has not been established; neither have the mechanism by which obesity affects bone metabolism. The aim of this study was to examine the effects...

The association between mammographic breast density and bone mineral density in the study of women's health across the nation.

PubMed

Crandall, Carolyn J; Zheng, Yan; Karlamangla, Arun; Sternfeld, Barbara; Habel, Laurel A; Oestreicher, Nina; Johnston, Janet; Cauley, Jane A; Greendale, Gail A

2007-08-01

Bone mineral density and mammographic breast density are each associated with markers of lifetime estrogen exposure. The association between mammographic breast density and bone mineral density in early perimenopausal women is unknown. We analyzed data from a cohort (n = 501) of premenopausal (no change in menstrual regularity) and early perimenopausal (decreased menstrual regularity in past 3 months) participants of African-American, Caucasian, Chinese, and Japanese ethnicity in the Study of Women's Health Across the Nation. Using multivariable linear regression, we examined the cross-sectional association between percent mammographic density and bone mineral density (BMD). Percent mammographic density was statistically significantly inversely associated with hip BMD and lumbar spine BMD after adjustment (body mass index, ethnicity, age, study site, parity, alcohol intake, cigarette smoking, physical activity, age at first childbirth) in early perimenopausal, but not premenopausal, women. In early perimenopausal women, every 0.1g/cm(2) greater hip BMD predicted a 2% lower percent mammographic density (95% confidence interval -37.0 to -0.6%, p = 0.04). Mammographic breast density is inversely associated with BMD in the perimenopausal participants of this community-based cohort. The biological underpinnings of these findings may reflect differential responsiveness of breast and bone mineral density to the steroid milieu.

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.

Difference in Bone Mineral Density between Young versus Midlife Women

ERIC Educational Resources Information Center

Sanderson, Sonya; Anderson, Pamela S.; Benton, Melissa J.

2016-01-01

Background: Older age is a risk factor for low bone mineral density (BMD). Older women have been found to have lower BMD than younger women. Recent trends for decreased calcium consumption and physical activity may place younger women at greater risk than previously anticipated. Purpose: The purpose of this study was to evaluate the effect of age…

Obesity does not aggravate osteoporosis or osteoblastic insulin resistance in orchiectomized rats.

PubMed

Potikanond, Saranyapin; Rattanachote, Pinyada; Pintana, Hiranya; Suntornsaratoon, Panan; Charoenphandhu, Narattaphol; Chattipakorn, Nipon; Chattipakorn, Siriporn

2016-02-01

The present study aimed to test the hypothesis that testosterone deprivation impairs osteoblastic insulin signaling, decreases osteoblast survival, reduces bone density, and that obesity aggravates those deleterious effects in testosterone-deprived rats. Twenty four male Wistar rats underwent either a bilateral orchiectomy (O, n=12) or a sham operation (S, n=12). Then the rats in each group were further divided into two subgroups fed with either a normal diet (ND) or a high-fat diet (HF) for 12 weeks. At the end of the protocol, blood samples were collected to determine metabolic parameters and osteocalcin ratios. The tibiae were collected to determine bone mass using microcomputed tomography and for osteoblast isolation. The results showed that rats fed with HF (sham-operated HF-fed rats (HFS) and ORX HF-fed rats (HFO)) developed peripheral insulin resistance and had decreased trabecular bone density. In ND-fed rats, only the ORX ND-fed rats (NDO) group had decreased trabecular bone density. In addition, osteoblastic insulin resistance, as indicated by a decrease in tyrosine phosphorylation of the insulin receptor and Akt, were observed in all groups except the sham-operated ND-fed rats (NDS) rats. Those groups, again with the exception of the NDS rats, also had decreased osteoblastic survival. No differences in the levels of osteoblastic insulin resistance and osteoblastic survival were found among the NDO, HFS, and HFO groups. These findings suggest that either testosterone deprivation or obesity alone can impair osteoblastic insulin signaling and decrease osteoblastic survival leading to the development of osteoporosis. However, obesity does not aggravate those deleterious effects in the bone of testosterone-deprived rats. © 2016 Society for Endocrinology.

[The value of the Kapandji-Sauvé procedure with considering clinical results and measurement of bone density. A clinical study].

PubMed

Wüstner-Hofmann, M C; Schober, F; Hofmann, A K

2003-05-01

Between 1989 and 1995, 33 patients were treated with a Kapandji-Sauvé procedure for malunited fracture of the distal radius and instabilities of the distal radioulnar joint. Thirty patients were followed up with a mean follow-up time of 91 months. Fourteen patients underwent a measurement of bone density of the distal forearm. Twenty-eight patients showed good ossification of the distal radioulnar arthrodesis. Forearm rotation improved by 17.3 %. Mean grip strength was 72 % of that of the contralateral hand. Evaluation by the Cooney score resulted in 10 % very good, in 65 % good, 22 % fair and in 3 % poor results. The measurement of bone density of the distal radius showed an increase of rotation and flexure firmness. The cortical density remained constant. In the subcortical bone of the distal radius, we found a decrease of the trabecular density in the radial part.

Osteoporosis in men with idiopathic hypogonadotropic hypogonadism

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

Finkelstein, J.S.; Klibanski, A.; Neer, R.M.

To assess the effect of testosterone deficiency on skeletal integrity in men, we determined bone density in 23 hypogonadal men with isolated gonadotropin-releasing hormone deficiency and compared those values with ones from controls. Cortical bone density, as assessed by single-photon absorptiometry of the nondominant radius, ranged from 0.57 to 0.86 g/cm2 (mean +/- SE, 0.71 +/- 0.02) in patients with fused epiphyses and from 0.57 to 0.67 g/cm2 (mean, 0.61 +/- 0.01) in patients with open epiphyses, both of which were significantly (p less than 0.001) lower than normal. Spinal trabecular bone density, as assessed by computed tomography, was similarlymore » decreased (p less than 0.0001) and ranged from 42 to 177 mg K2HPO4/cm3 (mean, 112 +/- 7). Cortical bone density was at least 2 SD below normal in 16 of 23 men, and 8 men had spinal bone densities below the fracture threshold of 80 to 100 mg K2HPO4/cm3. Osteopenia was equally severe in men with immature and mature bone ages, suggesting that abnormal bone development plays an important role in the osteopenia of men with idiopathic hypogonadotropic hypogonadism.« less

Does Otosclerosis Affect Dark and Transitional Cells in the Human Vestibular Labyrinth?

PubMed

Kaya, Serdar; Paparella, Michael M; Cureoglu, Sebahattin

2017-02-01

The density of vestibular dark cells (DCs) and vestibular transitional cells (TCs) can be quantitatively decreased in human temporal bones with otosclerosis. Previous reports have shown that otosclerosis can lead to vestibular symptoms. We examined 61 human temporal bone specimens from 52 deceased donors with otosclerosis group-with and without endosteal involvement (EI), and with and without endolymphatic hydrops (EH)-versus 25 specimens from 18 age-matched controls. Using light microscopy, we evaluated the nonsensory epithelium of the lateral semicircular canal (LSC) and posterior semicircular canal (PSC) of the human vestibular labyrinth, focusing on the density of DCs and TCs. In both the LSC and the PSC, as compared with the control group, the mean density of DCs significantly decreased in the EI (+) group, in the EI (+) and EH (+) subgroup, and in the EI (+) and EH (-) subgroup (p < 0.05). In addition, we found a significant difference in the mean density of DCs between the EI (+) group and the EI (-) group in the LSC and in the PSC (p < 0.05). But we found no significant difference in the mean density of TCs in any of the otosclerosis groups or subgroups as compared with the control group (p > 0.05). We found a decrease in the density of DCs associated with EI in human temporal bone specimens with otosclerosis, regardless of the presence of EH. This decrease might cause damage in ion and water transportation, leading to vestibular symptoms.

Does Otosclerosis Affect Dark and Transitional Cells in the Human Vestibular Labyrinth?

PubMed Central

Kaya, Serdar; Paparella, Michael M.; Cureoglu, Sebahattin

2016-01-01

Hypothesis The density of vestibular dark cells (DCs) and vestibular transitional cells (TCs) can be quantitatively decreased in human temporal bones with otosclerosis. Background Previous reports have shown that otosclerosis can lead to vestibular symptoms. Methods We examined 61 human temporal bone specimens from 52 deceased donors with otosclerosis group—with and without endosteal involvement (EI), and with and without endolymphatic hydrops (EH)—vs. 25 specimens from 18 age-matched controls. Using light microscopy, we evaluated the nonsensory epithelium of the lateral semicircular canal (LSC) and posterior semicircular canal (PSC) of the human vestibular labyrinth, focusing on the density of DCs and TCs. Results In both the LSC and the PSC, as compared with the control group, the mean density of DCs significantly decreased in the EI (+) group, in the EI (+) and EH (+) subgroup, and in the EI (+) and EH (−) subgroup (P < 0.05). In addition, we found a significant difference in the mean density of DCs between the EI (+) group and the EI (−) group in the LSC and in the PSC (P < 0.05). But we found no significant difference in the mean density of TCs in any of the otosclerosis groups or subgroups as compared with the control group (P > 0.05). Conclusion We found a decrease in the density of DCs associated with EI in human temporal bone specimens with otosclerosis, regardless of the presence of EH. This decrease might cause damage in ion and water transportation, leading to vestibular symptoms. PMID:27851656

Endocrine Consequences of Anorexia Nervosa

PubMed Central

Misra, Madhusmita; Klibanski, Anne

2014-01-01

Summary Anorexia nervosa (AN) is prevalent in adolescents and young adults, and endocrine changes include hypothalamic amenorrhea, a nutritionally acquired growth hormone resistance with low insulin like growth factor-1 (IGF-1), relative hypercortisolemia, decreases in leptin, insulin, amylin and incretins, and increases in ghrelin, PYY and adiponectin. These changes in turn have deleterious effects on bone, and may affect neurocognition, anxiety, depression and eating disorder psychopathology. Low bone density is particularly concerning; clinical fractures occur and changes in both bone microarchitecture and strength estimates have been reported. Recovery causes improvement of many, but not all, hormonal changes, and deficits in bone accrual may persist despite recovery. Physiologic, primarily transdermal, estrogen replacement increases bone density in adolescents, although catch-up is incomplete. In adults, oral estrogen co-administered with rhIGF-1 in one study, and bisphosphonates in another increased bone density, though not to normal. More studies are necessary to determine the optimal therapeutic approach in AN. PMID:24731664

Microarchitecture of irradiated bone: comparison with healthy bone

NASA Astrophysics Data System (ADS)

Bléry, Pauline; Amouriq, Yves; Guédon, Jeanpierre; Pilet, Paul; Normand, Nicolas; Durand, Nicolas; Espitalier, Florent; Arlicot, Aurore; Malard, Olivier; Weiss, Pierre

2012-03-01

The squamous cell carcinomas of the upper aero-digestive tract represent about ten percent of cancers. External radiation therapy leads to esthetic and functional consequences, and to a decrease of the bone mechanical abilities. For these patients, the oral prosthetic rehabilitation, including possibilities of dental implant placement, is difficult. The effects of radiotherapy on bone microarchitecture parameters are not well known. Thus, the purpose of this study is to assess the effects of external radiation on bone micro architecture in an experimental model of 25 rats using micro CT. 15 rats were irradiated on the hind limbs by a single dose of 20 Grays, and 10 rats were non irradiated. Images of irradiated and healthy bone were compared. Bone microarchitecture parameters (including trabecular thickness, trabecular number, trabecular separation, connectivity density and tissue and bone volume) between irradiated and non-irradiated bones were calculated and compared using a Mann and Whitney test. After 7 and 12 weeks, images of irradiated and healthy bone are different. Differences on the irradiated and the healthy bone populations exhibit a statistical significance. Trabecular number, connectivity density and closed porosity are less important on irradiated bone. Trabecular thickness and separation increase for irradiated bone. These parameters indicate a decrease of irradiated bone properties. Finally, the external irradiation induces changes on the bone micro architecture. This knowledge is of prime importance for better oral prosthetic rehabilitation, including implant placement.

Bone mineral density in subjects using central nervous system-active medications.

PubMed

Kinjo, Mitsuyo; Setoguchi, Soko; Schneeweiss, Sebastian; Solomon, Daniel H

2005-12-01

Decreased bone mineral density defines osteoporosis according to the World Health Organization and is an important predictor of future fractures. The use of several types of central nervous system-active drugs, including benzodiazepines, anticonvulsants, antidepressants, and opioids, have all been associated with increased risk of fracture. However, it is unclear whether such an increase in risk is related to an effect of bone mineral density or to other factors, such as increased risk of falls. We sought to examine the relationship between bone mineral density and the use of benzodiazepines, anticonvulsants, antidepressants, and opioids in a representative US population-based sample. We analyzed data on adults aged 17 years and older from the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994). Total femoral bone mineral density of 7114 male and 7532 female participants was measured by dual-energy x-ray absorptiometry. Multivariable linear regression models were used to quantify the relation between central nervous system medication exposure and total femoral bone mineral density. Models controlled for relevant covariates, including age, sex, and body mass index. In linear regression models, significantly reduced bone mineral density was found in subjects taking anticonvulsants (0.92 g/cm2; 95% confidence interval [CI]: 0.89 to 0.94) and opioids (0.92 g/cm2; 95% CI: 0.88 to 0.95) compared with nonusers (0.95 g/cm2; 95% CI: 0.95 to 0.95) after adjusting for several potential confounders. The other central nervous system-active drugs--benzodiazepines or antidepressants--were not associated with significantly reduced bone mineral density. In cross-sectional analysis of NHANES III, anticonvulsants and opioids (but not benzodiazepines or antidepressants) were associated with significantly reduced bone mineral density. These findings have implications for fracture-prevention strategies.

Effect of ultra-low doses, ASIR and MBIR on density and noise levels of MDCT images of dental implant sites.

PubMed

Widmann, Gerlig; Al-Shawaf, Reema; Schullian, Peter; Al-Sadhan, Ra'ed; Hörmann, Romed; Al-Ekrish, Asma'a A

2017-05-01

Differences in noise and density values in MDCT images obtained using ultra-low doses with FBP, ASIR, and MBIR may possibly affect implant site density analysis. The aim of this study was to compare density and noise measurements recorded from dental implant sites using ultra-low doses combined with FBP, ASIR, and MBIR. Cadavers were scanned using a standard protocol and four low-dose protocols. Scans were reconstructed using FBP, ASIR-50, ASIR-100, and MBIR, and either a bone or standard reconstruction kernel. Density (mean Hounsfield units [HUs]) of alveolar bone and noise levels (mean standard deviation of HUs) was recorded from all datasets and measurements were compared by paired t tests and two-way ANOVA with repeated measures. Significant differences in density and noise were found between the reference dose/FBP protocol and almost all test combinations. Maximum mean differences in HU were 178.35 (bone kernel) and 273.74 (standard kernel), and in noise, were 243.73 (bone kernel) and 153.88 (standard kernel). Decreasing radiation dose increased density and noise regardless of reconstruction technique and kernel. The effect of reconstruction technique on density and noise depends on the reconstruction kernel used. • Ultra-low-dose MDCT protocols allowed more than 90 % reductions in dose. • Decreasing the dose generally increased density and noise. • Effect of IRT on density and noise varies with reconstruction kernel. • Accuracy of low-dose protocols for interpretation of bony anatomy not known. • Effect of low doses on accuracy of computer-aided design models unknown.

Streptozocin-induced type-1 diabetes mellitus results in decreased density of CGRP sensory and TH sympathetic nerve fibers that are positively correlated with bone loss at the mouse femoral neck.

PubMed

Enríquez-Pérez, Iris A; Galindo-Ordoñez, Karla E; Pantoja-Ortíz, Christian E; Martínez-Martínez, Arisaí; Acosta-González, Rosa I; Muñoz-Islas, Enriqueta; Jiménez-Andrade, Juan M

2017-08-10

Type-1 diabetes mellitus (T1DM) results in loss of innervation in some tissues including epidermis and retina; however, the effect on bone innervation is unknown. Likewise, T1DM results in pathological bone loss and increased risk of fracture. Thus, we quantified the density of calcitonin gene-related peptide (CGRP + ) sensory and tyrosine hydroxylase (TH + ) sympathetic nerve fibers and determined the association between the innervation density and microarchitecture of trabecular bone at the mouse femoral neck. Ten weeks-old female mice received 5 daily administrations of streptozocin (i.p. 50mg/kg) or citrate (control group). Twenty weeks later, femurs were analyzed by microCT and processed for immunohistochemistry. Confocal microscopy analysis revealed that mice with T1DM had a significant loss of both CGRP + and TH + nerve fibers in the bone marrow at the femoral neck. Likewise, microCT analysis revealed a significant decrease in the trabecular bone mineral density (tBMD), bone volume/total volume ratio (BV/TB), trabecular thickness (Tb.Th), trabecular number (Tb.N) and trabecular separation (Tb.Sp) in mice with T1DM as compared to control mice. Analysis of correlation revealed a positive and significant association between density of CGRP + or TH + nerve fibers with tBMD, BV/TV, Tb.Th and Tb.Sp, but not with trabecular number (there was a positive association only for CGRP + ) and degree of anisotropy (DA). This study suggests an interaction between sensory and sympathetic nervous system and T1DM-induced bone loss. Identification of the factors involved in the loss of CGRP + sensory and TH + sympathetic fibers and how they regulate bone loss may result in new avenues to treat T1DM-related osteoporosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of Ibuprofen and Resistance Training on Bone and Muscle: A Randomized Controlled Trial in Older Women.

PubMed

Duff, Whitney R D; Chilibeck, Philip D; Candow, Darren G; Gordon, Julianne J; Mason, Riley S; Taylor-Gjevre, Regina; Nair, Bindu; Szafron, Michael; Baxter-Jones, Adam; Zello, Gordon A; Kontulainen, Saija A

2017-04-01

Resistance training with ibuprofen supplementation may improve musculoskeletal health in postmenopausal women. The study purpose was to determine the efficacy of resistance training and ibuprofen supplementation on bone and muscle properties in postmenopausal women. Participants (n = 90, 65.3 ± 4.9 yr) were randomly assigned to: supervised resistance training or stretching (placebo-exercise) with postexercise ibuprofen (400 mg) or placebo supplementation for 3 d·wk (9 months). Baseline and postintervention measurements included distal and shaft scans of the forearm and lower leg using peripheral quantitative computed tomography. Distal site outcomes included cross-sectional area, content, and density for total and trabecular bone, as well as estimated bone strength in compression. Shaft site outcomes included total bone area; cortical bone area, content, and density; estimated bone strength in torsion; and muscle area and density. Exercise-supplement-time interactions for total bone content at the distal radius (P = 0.009) and cortical density at the radius shaft (P = 0.038) were significant. Resistance training with ibuprofen decreased total bone content (-1.5%) at the distal radius in comparison to the resistance training (0.6%; P = 0.032) and ibuprofen alone (0.5%; P = 0.050). Change in cortical density at the radius shaft differed between the stretching with placebo and ibuprofen supplementation groups (-1.8% vs 1.1%; P = 0.050). Resistance training preserved muscle density in the lower leg more so than stretching (-3.1% vs -5.4%; P = 0.015). Ibuprofen consumed immediately after resistance training had a deleterious effect on bone mineral content at the distal radius, whereas resistance training or ibuprofen supplementation individually prevented bone loss. Resistance training prevented muscle density decline in the lower leg.

Vitamin D supplementation protects against bone loss associated with chronic alcohol administration in female mice

USDA-ARS?s Scientific Manuscript database

Chronic alcohol consumption is detrimental to bone by decreasing bone mineral density (BMD) resulting in increased risk of osteoporosis risk and fracture, particularly in women. In moderation, alcohol is positively associated with increased BMD and reduced fracture risk. Alcohol's toxic effects ha...

Simulated space radiation sensitizes bone but not muscle to the catabolic effects of mechanical unloading.

PubMed

Krause, Andrew R; Speacht, Toni L; Zhang, Yue; Lang, Charles H; Donahue, Henry J

2017-01-01

Deep space travel exposes astronauts to extended periods of space radiation and mechanical unloading, both of which may induce significant muscle and bone loss. Astronauts are exposed to space radiation from solar particle events (SPE) and background radiation referred to as galactic cosmic radiation (GCR). To explore interactions between skeletal muscle and bone under these conditions, we hypothesized that decreased mechanical load, as in the microgravity of space, would lead to increased susceptibility to space radiation-induced bone and muscle loss. We evaluated changes in bone and muscle of mice exposed to hind limb suspension (HLS) unloading alone or in addition to proton and high (H) atomic number (Z) and energy (E) (HZE) (16O) radiation. Adult male C57Bl/6J mice were randomly assigned to six groups: No radiation ± HLS, 50 cGy proton radiation ± HLS, and 50 cGy proton radiation + 10 cGy 16O radiation ± HLS. Radiation alone did not induce bone or muscle loss, whereas HLS alone resulted in both bone and muscle loss. Absolute trabecular and cortical bone volume fraction (BV/TV) was decreased 24% and 6% in HLS-no radiation vs the normally loaded no-radiation group. Trabecular thickness and mineral density also decreased with HLS. For some outcomes, such as BV/TV, trabecular number and tissue mineral density, additional bone loss was observed in the HLS+proton+HZE radiation group compared to HLS alone. In contrast, whereas HLS alone decreased muscle mass (19% gastrocnemius, 35% quadriceps), protein synthesis, and increased proteasome activity, radiation did not exacerbate these catabolic outcomes. Our results suggest that combining simulated space radiation with HLS results in additional bone loss that may not be experienced by muscle.

WNT1-induced Secreted Protein-1 (WISP1), a Novel Regulator of Bone Turnover and Wnt Signaling*

PubMed Central

Maeda, Azusa; Ono, Mitsuaki; Holmbeck, Kenn; Li, Li; Kilts, Tina M.; Kram, Vardit; Noonan, Megan L.; Yoshioka, Yuya; McNerny, Erin M. B.; Tantillo, Margaret A.; Kohn, David H.; Lyons, Karen M.; Robey, Pamela G.; Young, Marian F.

2015-01-01

WISP1/CCN4 (hereafter referred to as WISP1), a member of the CCN family, is found in mineralized tissues and is produced by osteoblasts and their precursors. In this study, Wisp1-deficient (Wisp1−/−) mice were generated. Using dual-energy x-ray absorptiometry, we showed that by 3 months, the total bone mineral density of Wisp1−/− mice was significantly lower than that of WT mice. Further investigation by micro-computed tomography showed that female Wisp1−/− mice had decreased trabecular bone volume/total volume and that both male and female Wisp1−/− mice had decreased cortical bone thickness accompanied by diminished biomechanical strength. The molecular basis for decreased bone mass in Wisp1−/− mice arises from reduced bone formation likely caused by osteogenic progenitors that differentiate poorly compared with WT cells. Osteoclast precursors from Wisp1−/− mice developed more tartrate-resistant acid phosphatase-positive cells in vitro and in transplants, suggesting that WISP1 is also a negative regulator of osteoclast differentiation. When bone turnover (formation and resorption) was induced by ovariectomy, Wisp1−/− mice had lower bone mineral density compared WT mice, confirming the potential for multiple roles for WISP1 in controlling bone homeostasis. Wisp1−/− bone marrow stromal cells had reduced expression of β-catenin and its target genes, potentially caused by WISP1 inhibition of SOST binding to LRP6. Taken together, our data suggest that the decreased bone mass found in Wisp1−/− mice could potentially be caused by an insufficiency in the osteodifferentiation capacity of bone marrow stromal cells arising from diminished Wnt signaling, ultimately leading to altered bone turnover and weaker biomechanically compromised bones. PMID:25864198

The effect of weight training on bone mineral density and bone turnover in postmenopausal breast cancer survivors with bone loss: a 24-month randomized controlled trial.

PubMed

Waltman, N L; Twiss, J J; Ott, C D; Gross, G J; Lindsey, A M; Moore, T E; Berg, K; Kupzyk, K

2010-08-01

This study examined whether 24 months of weight training exercises enhanced the effectiveness of risedronate, calcium, and vitamin D in maintaining or improving bone mineral density (BMD) in 223 postmenopausal breast cancer survivors. Subjects who were > or =50% adherent to exercise had no improvement in BMD but were less likely to lose BMD. This study examined whether (1) postmenopausal breast cancer survivors (BCS) with bone loss taking 24 months of risedronate, calcium, and vitamin D had increased bone mineral density (BMD) at the total hip, femoral neck, L1-L4 spine, total radius and 33% radius, and decreased bone turnover; (2) subjects who also participated in strength/weight training (ST) exercises had greater increases in BMD and greater decreases in bone turnover; and (3) subjects who also exercised were more likely to preserve (at least maintain) BMD. Postmenopausal BCS (223) were randomly assigned to exercise plus medication or medication only groups. Both groups received 24 months of 1,200 mg of calcium and 400 IU of vitamin D daily and 35 mg of risedronate weekly, and the exercise group additionally had ST exercises twice weekly. After 24 months, women who took medications without exercising had significant improvements in BMD at the total hip (+1.81%) and spine (+2.85%) and significant decreases in Alkphase B (-8.7%) and serum NTx (-16.7%). Women who also exercised had additional increases in BMD at the femoral neck (+0.29%), total hip (+0.34%), spine (+0.23%), total radius (+0.30%), and additional decreases in Alkphase B (-2.4%) and Serum NTx (-6.5%). Additional changes in BMD and bone turnover with exercise were not significant. Subjects who were > or =50% adherent to exercise were less likely to lose BMD at the total hip (chi-square [1] = 4.66, p = 0.03) and femoral neck (chi-square [1] = 4.63, p = 0.03). Strength/weight training exercises may prevent loss of BMD in postmenopausal BCS at risk for bone loss.

Bone density and functional results after femoral revision with a cementless press-fit stem.

PubMed

Canovas, F; Roche, O; Girard, J; Bonnomet, F; Goldschild, M; Le Béguec, P

2015-05-01

The influence of radiographic bone density changes in the area surrounding a total hip arthroplasty (THA) revision with a cementless press-fit stem is unknown, notably in terms of functional results. We have therefore conducted a study aiming to (1) propose a radiographic method to assess bone density, (2) measure the functional effects of reduced bone density, and (3) determine the factors contributing to these modifications. A reduction in radiographic bone density has a negative influence on the functional result after revision using a cementless press-fit stem. We retrospectively assessed 150 THA revisions at a mean follow-up of 6.3 ± 3.2 years (range, 2-15 years). The clinical assessment was based on the Harris Hip Score. Bone density modifications were measured radiographically and the method was evaluated. The change in bone density was classified into two groups: (1) bone density not reduced or < 2 Gruen zones (118 cases [79%]); (2) bone density reduced ≥ 2 zones (32 cases [21%]). The variables showing a potential influence were the Cortical Index (CI), the type of primary stability with the press-fit system, and the femoral implant length. Inter- and intraobserver reliability of radiographic bone density measurement was evaluated as moderate or good (Kappa, 0.58; 0.60 and 0.67, respectively). For the Harris Hip Score at follow-up, there was a borderline statistical relation between stages 1 and 2: for the 118 stage 1 patients, this score was 83.62 ± 11.54 (range, 27-99) versus 78.34 ± 15.98 (range, 62-91) for stage 2 patients (P = 0.09). A CI ≤ 0.44 showed mediocre bone quality contributing to decreased bone density (P < 0.02). On the other hand, there was no statistically significant relation with the type of primary fixation (P = 0.34) or the length of the implant (P = 0.23). A cementless revision femoral stem can induce a reduction in bone density with possible functional effects. The negative role played by bone scarcity on the functional score is confirmed, and even though the difference is not statistically significant, we suggest using a short stem when this is possible. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Treatment with eldecalcitol positively affects mineralization, microdamage, and collagen crosslinks in primate bone.

PubMed

Saito, Mitsuru; Grynpas, Marc D; Burr, David B; Allen, Matthew R; Smith, Susan Y; Doyle, Nancy; Amizuka, Norio; Hasegawa, Tomoka; Kida, Yoshikuni; Marumo, Keishi; Saito, Hitoshi

2015-04-01

Eldecalcitol (ELD), an active form of vitamin D analog approved for the treatment of osteoporosis in Japan, increases lumbar spine bone mineral density (BMD), suppresses bone turnover markers, and reduces fracture risk in patients with osteoporosis. We have previously reported that treatment with ELD for 6 months improved the mechanical properties of the lumbar spine in ovariectomized (OVX) cynomolgus monkeys. ELD treatment increased lumbar BMD, suppressed bone turnover markers, and reduced histomorphometric parameters of both bone formation and resorption in vertebral trabecular bone. In this study, we elucidated the effects of ELD on bone quality (namely, mineralization, microarchitecture, microdamage, and bone collagen crosslinks) in OVX cynomolgus monkeys in comparison with OVX-vehicle control monkeys. Density fractionation of bone powder prepared from lumbar vertebrae revealed that ELD treatment shifted the distribution profile of bone mineralization to a higher density, and backscattered electron microscopic imaging showed improved trabecular bone connectivity in the ELD-treated groups. Higher doses of ELD more significantly reduced the amount of microdamage compared to OVX-vehicle controls. The fractionated bone powder samples were divided according to their density, and analyzed for collagen crosslinks. Enzymatic crosslinks were higher in both the high-density (≥2.0 mg/mL) and low-density (<2.0 mg/mL) fractions from the ELD-treated groups than in the corresponding fractions in the OVX-vehicle control groups. On the other hand, non-enzymatic crosslinks were lower in both the high- and low-density fractions. These observations indicated that ELD treatment stimulated the enzymatic reaction of collagen crosslinks and bone mineralization, but prevented non-enzymatic reaction of collagen crosslinks and accumulation of bone microdamage. Bone anti-resorptive agents such as bisphosphonates slow down bone remodeling so that bone mineralization, bone microdamage, and non-enzymatic collagen crosslinks all increase. Bone anabolic agents such as parathyroid hormone decrease bone mineralization and bone microdamage by stimulating bone remodeling. ELD did not fit into either category. Histological analysis indicated that the ELD treatment strongly suppressed bone resorption by reducing the number of osteoclasts, while also stimulating focal bone formation without prior bone resorption (bone minimodeling). These bidirectional activities of ELD may account for its unique effects on bone quality. Copyright © 2014. Published by Elsevier Inc.

Decreases in bone blood flow and bone material properties in aging Fischer-344 rats

NASA Technical Reports Server (NTRS)

Bloomfield, Susan A.; Hogan, Harry A.; Delp, Michael D.

2002-01-01

The purpose of this study was to quantify precisely aging-induced changes in skeletal perfusion and bone mechanical properties in a small rodent model. Blood flow was measured in conscious juvenile (2 months old), adult (6 months old), and aged (24 months old) male Fischer-344 rats using radiolabeled microspheres. There were no significant differences in bone perfusion rate or vascular resistance between juvenile and adult rats. However, blood flow was lower in aged versus adult rats in the forelimb bones, scapulas, and femurs. To test for functional effects of this decline in blood flow, bone mineral density and mechanical properties were measured in rats from these two age groups. Bone mineral density and cross-sectional moment of inertia in femoral and tibial shafts and the femoral neck were significantly larger in the aged versus adult rats, resulting in increased (+14%-53%) breaking strength and stiffness. However, intrinsic material properties at midshaft of the long bones were 12% to 25% lower in the aged rats. Although these data are consistent with a potential link between decreased perfusion and focal alterations in bone remodeling activity related to clinically relevant bone loss, additional studies are required to establish the mechanisms for this putative relationship.

Reported zinc, but not copper, intakes influence whole-body bone density, mineral content and T score responses to zinc and copper supplementation in healthy postmenopausal women.

PubMed

Nielsen, Forrest H; Lukaski, Henry C; Johnson, LuAnn K; Roughead, Z K Fariba

2011-12-01

A supplementation trial starting with 224 postmenopausal women provided with adequate vitamin D and Ca was conducted to determine whether increased Cu and Zn intakes would reduce the risk for bone loss. Healthy women aged 51-80 years were recruited for a double-blind, placebo-controlled study. Women with similar femoral neck T scores and BMI were randomly assigned to two groups of 112 each that were supplemented daily for 2 years with 600 mg Ca plus maize starch placebo or 600 mg Ca plus 2 mg Cu and 12 mg Zn. Whole-body bone mineral contents, densities and T scores were determined biannually by dual-energy X-ray absorptiometry, and 5 d food diaries were obtained annually. Repeated-measures ANCOVA showed that bone mineral contents, densities and T scores decreased from baseline values to year 2. A priori contrasts between baseline and year 2 indicated that the greatest decreases occurred with Cu and Zn supplementation. Based on 5 d food diaries, the negative effect was caused by Zn and mainly occurred with Zn intakes ≥ 8·0 mg/d. With Zn intakes < 8·0 mg/d, Zn supplementation apparently prevented a significant decrease in whole-body bone densities and T scores. Food diaries also indicated that Mg intakes < 237 mg/d, Cu intakes < 0·9 mg/d and Zn intakes < 8·0 mg/d are associated with poorer bone health. The findings indicate that Zn supplementation may be beneficial to bone health in postmenopausal women with usual Zn intakes < 8·0 mg/d but not in women consuming adequate amounts of Zn.

FGF21 decreases body weight without reducing food intake or bone mineral density in high-fat fed obese rhesus macaque monkeys.

PubMed

Andersen, Birgitte; Straarup, Ellen M; Heppner, Kristy M; Takahashi, Diana L; Raffaele, Virginia; Dissen, Gregory A; Lewandowski, Katherine; Bödvarsdottir, Thóra B; Raun, Kirsten; Grove, Kevin L; Kievit, Paul

2018-06-11

Administration of FGF21 and FGF21 analogues reduce body weight; improve insulin sensitivity and dyslipidemia in animal models of obesity and in short term clinical trials. However potential adverse effects identified in mice have raised concerns for the development of FGF21 therapeutics. Therefore, this study was designed to address the actions of FGF21 on body weight, glucose and lipid metabolism and importantly its effects on bone mineral density (BMD), bone markers, and plasma cortisol in high-fat fed obese rhesus macaque monkeys. Obese non-diabetic rhesus macaque monkeys (five males and five ovariectomized (OVX) females) were maintained on a high-fat diet and treated for 12 weeks with escalating doses of FGF21. Food intake was assessed daily and body weight weekly. Bone mineral content (BMC) and BMD were measured by DEXA scanning prior to the study and on several occasions throughout the treatment period as well as during washout. Plasma glucose, glucose tolerance, insulin, lipids, cortisol, and bone markers were likewise measured throughout the study. On average, FGF21 decreased body weight by 17.6 ± 1.6% after 12 weeks of treatment. No significant effect on food intake was observed. No change in BMC or BMD was observed, while a 2-fold increase in CTX-1, a marker of bone resorption, was seen. Overall glucose tolerance was improved with a small but significant decrease in HbA 1C . Furthermore, FGF21 reduced concentrations of plasma triglycerides and very low density lipoprotein cholesterol. No adverse changes in clinical chemistry markers were demonstrated, and no alterations in plasma cortisol were observed during the study. In conclusion, FGF21 reduced body weight in obese rhesus macaque monkeys without reducing food intake. Furthermore, FGF21 had beneficial effects on body composition, insulin sensitivity, and plasma triglycerides. No adverse effects on bone density or plasma cortisol were observed after 12 weeks of treatment.

Bone strength in pure bending: bearing of geometric and material properties.

PubMed

Winter, Werner

2008-01-01

Osteoporosis is characterized by decreasing of bone mass and bone strength with advanced age. For characterization of material properties of dense and cellular bone the volumetric bone mineral density (vBMD) is one of the most important contributing factors to bone strength. Often bending tests of whole bone are used to get information about the state of osteoporosis. In a first step, different types of cellular structures are considered to characterize vBMD and its influence to elastic and plastic material properties. Afterwards, the classical theory of plastic bending is used to describe the non-linear moment-curvature relation of a whole bone. For bending of whole bone with sandwich structure an effective second moment of area can be defined. The shape factor as a pure geometrical value is considered to define bone strength. This factor is discussed for a bone with circular cross section and different thickness of cortical bone. The deduced relations and the decrease of material properties are used to demonstrate the influence of osteoporosis to bone bending strength. It can be shown that the elastic and plastic material properties of bone are related to a relative bone mineral density. Starting from an elastic-plastic bone behavior with an constant yield stress the non-linear moment-curvature relation in bending is related to yielding of the fibres in the cross section. The ultimate moment is characterized by a shape factor depending on the geometry of the cross section and on the change of cortical thickness.

Effects of rosiglitazone on bone mineral density and remodelling parameters in Postmenopausal diabetic women: a 2-year follow-up study.

PubMed

Berberoglu, Zehra; Yazici, Ayse C; Demirag, Nilgun G

2010-09-01

To evaluate the effect of rosiglitazone on bone metabolism and bone density. An open-label, randomized, controlled trial of 24-month duration. Patients and measurements Obese, postmenopausal women with newly diagnosed diabetes were studied. Before and after the intervention, metabolic bone markers and bone density were assessed. Twenty-six patients received rosiglitazone (4 mg/day), and 23 remained on diet alone. Serum bone-specific alkaline phosphatase and osteocalcin levels decreased by 17% (P < 0.001 vs control group) and 26% (P < 0.01 vs control group), respectively, in the rosiglitazone group. There were no significant changes in the deoxypyridinoline levels between the two groups. Annual bone loss at the trochanter and at the lumbar spine associated with each year of rosiglitazone use was 2.56% (P = 0.01 vs control group) and 2.18% (P < 0.01 vs control group), respectively. Femoral neck and total hip bone density declined significantly in both groups (P < 0.01, and P = 0.01, respectively) but was not significantly different between the two groups. Rosiglitazone treatment adversely affects bone formation over a 2-year period. It increases bone loss at the lumbar spine and trochanter in postmenopausal, type 2 diabetic women. However, bone loss at the total hip did not differ with use of this agent.

Prevalence of Osteopenia and Osteoporosis in Patients with Noncystic Fibrosis Bronchiectasis.

PubMed

Diehl, Nathan; Johnson, Margaret M

2016-12-01

The objective of our study was to define the prevalence of osteoporosis and osteopenia in patients with noncystic fibrosis bronchiectasis (NCFB). We conducted a retrospective chart review of all patients with physician-diagnosed NCFB evaluated at Mayo Clinic Florida between January 1, 2011 and June 3, 2013. A total of 113 patients with physician-diagnosed NCFB and confirmatory findings on computed tomography scan were identified. The cohort was overwhelmingly women (90%) with a mean age of 72 ± 10.6 and a body mass index of 24.8 ± 6.8. The medical history indicated that 30% (34) had osteoporosis, 39% (44) had osteopenia, and 9% (10) had normal bone density. In 25 (22%) of the subjects, bone density was unknown or undocumented. Most were never smokers (55.7%) or past smokers (41.6%) and airflow obstruction was present in 58% of the 84 subjects who had undergone pulmonary function tests. In total, 57 patients (50.44%) and 45 patients (39.82%) had been prescribed proton pump inhibitors and inhaled corticosteroids, respectively. Bone mineral density testing was performed during the study period in 70 (62%) of the subjects. Decreased bone density consistent with osteoporosis was present in 19 (27%); 41 (59%) had osteopenia, and bone density was normal in 10 (14%) subjects. Diminished bone density was present in 82.8% (24/29) of patients younger than age 70, with 27.6% (8/29) having osteoporosis. There was a greater incidence of diminished bone density in those with reduced body mass index (100% vs 82%), but this difference did not reach statistical significance ( P = 0.10). Forty-seven and 32% of patients with diminished bone density were using proton pump inhibitor therapy and inhaled corticosteroids, respectively. This study suggested that diminished bone density is common in patients with bronchiectasis, with >85% of this cohort having osteoporosis or osteopenia confirmed by bone density testing. Although the prevalence of both bronchiectasis and diminished bone density increases with advancing age and female sex, these data suggest a greater prevalence than expected based on demographic risks. Medications that may predispose individuals to diminished bone density are not uncommonly prescribed in patients with bronchiectasis. Provider awareness of the substantial prevalence of diminished bone density in patients with bronchiectasis may improve patient care by prompting appropriate screening for and treatment of osteoporosis and osteopenia. In light of these observations, judicious use of medications that may predispose to diminished bone density is warranted.

Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone.

PubMed Central

Weinstein, R S; Jilka, R L; Parfitt, A M; Manolagas, S C

1998-01-01

Glucocorticoid-induced bone disease is characterized by decreased bone formation and in situ death of isolated segments of bone (osteonecrosis) suggesting that glucocorticoid excess, the third most common cause of osteoporosis, may affect the birth or death rate of bone cells, thus reducing their numbers. To test this hypothesis, we administered prednisolone to 7-mo-old mice for 27 d and found decreased bone density, serum osteocalcin, and cancellous bone area along with trabecular narrowing. These changes were accompanied by diminished bone formation and turnover, as determined by histomorphometric analysis of tetracycline-labeled vertebrae, and impaired osteoblastogenesis and osteoclastogenesis, as determined by ex vivo bone marrow cell cultures. In addition, the mice exhibited a threefold increase in osteoblast apoptosis in vertebrae and showed apoptosis in 28% of the osteocytes in metaphyseal cortical bone. As in mice, an increase in osteoblast and osteocyte apoptosis was documented in patients with glucocorticoid-induced osteoporosis. Decreased production of osteoclasts explains the reduction in bone turnover, whereas decreased production and apoptosis of osteoblasts would account for the decline in bone formation and trabecular width. Furthermore, accumulation of apoptotic osteocytes may contribute to osteonecrosis. These findings provide evidence that glucocorticoid-induced bone disease arises from changes in the numbers of bone cells. PMID:9664068

Vitamin D3 supplementation increases spine bone mineral density in adolescents and young adults with HIV infection being treated with tenofovir disoproxil fumarate: a randomized, placebo controlled trial

USDA-ARS?s Scientific Manuscript database

Background: Tenofovir disoproxil fumarate (TDF) decreases bone mineral density (BMD). We hypothesized vitamin D3 (VITD3) would increase BMD in adolescents/young adults receiving TDF. Methods: Randomized double-blind placebo-controlled trial of directly observed VITD3 50,000 IU vs. placebo every 4 ...

DMPA's effect on bone mineral density: A particular concern for adolescents.

PubMed

Schrager, Sarina B

2009-05-01

Discuss the potential for decreased bone mineral density in using depot-medroxyprogesterone acetate (DMPA) with any woman who is thinking of it as a means of contraception. Recommend to women that they take 1300 mg of calcium and 400 IU of vitamin D when using DMPA. Consider prescribing estrogen replacement if DMPA is going to be used for more than 2 years.

Radiation activated CHK1/MEPE pathway may contribute to microgravity-induced bone density loss

NASA Astrophysics Data System (ADS)

Zhang, Xiangming; Wang, Ping; Wang, Ya

2015-11-01

Bone density loss in astronauts on long-term space missions is a chief medical concern. Microgravity in space is the major cause of bone density loss (osteopenia), and it is believed that high linear energy transfer (LET) radiation in space exacerbates microgravity-induced bone density loss; however, the mechanism remains unclear. It is known that acidic serine- and aspartate-rich motif (ASARM) as a small peptide released by matrix extracellular phosphoglycoprotein (MEPE) promotes osteopenia. We previously discovered that MEPE interacted with checkpoint kinase 1 (CHK1) to protect CHK1 from ionizing radiation promoted degradation. In this study, we addressed whether the CHK1-MEPE pathway activated by radiation contributes to the effects of microgravity on bone density loss. We examined the CHK1, MEPE and secreted MEPE/ASARM levels in irradiated (1 Gy of X-ray) and rotated cultured human osteoblast cells. The results showed that radiation activated CHK1, decreased the levels of CHK1 and MEPE in human osteoblast cells and increased the release of MEPE/ASARM. These results suggest that the radiation-activated CHK1/MEPE pathway exacerbates the effects of microgravity on bone density loss, which may provide a novel targeting factor/pathway for a future countermeasure design that could contribute to reducing osteopenia in astronauts.

Relationship Between Bariatric Surgery and Bone Mineral Density: a Meta-analysis.

PubMed

Ko, Byung-Joon; Myung, Seung Kwon; Cho, Kyung-Hwan; Park, Yong Gyu; Kim, Sin Gon; Kim, Do Hoon; Kim, Seon Mee

2016-07-01

A meta-analysis regarding bone loss after bariatric surgery, designed to compare surgical and nonsurgical groups, has not yet been performed. Therefore, we performed a meta-analysis to compare the differences between bariatric surgical groups and nonoperated controls with regard to bone mineral density. In March 2015, we performed a review of the literature using PubMed, EMBASE, and the Cochrane Library. The search focused on retrospective and prospective studies, including but not limited to randomized studies published in English. Among 1299 studies that were initially screened, ten met the selection criteria. For all types of bariatric surgery, bone density at the femoral neck was lower in the surgical group than in the nonsurgical control group (mean difference [MD] -0.05 g/cm(2); 95 % confidence interval [CI], -0.07 to -0.02; p = 0.001); no difference in bone density was found between the two groups at the lumbar spine (MD -0.01 g/cm(2); 95 % CI -0.07 to 0.05; p = 0.661). The analysis of Roux-en-Y gastric bypass showed similar results. Bone density at the femoral neck decreased after bariatric surgery, compared to that in nonsurgical controls, whereas bone density at the lumbar spine did not show a difference between groups. Further larger scale studies with comparative nonsurgical controls are warranted to overcome the heterogeneity among studies in this analysis and to add evidence of possible bone loss subsequent to bariatric surgical procedures.

Influence of weight and body fat distribution on bone density in postmenopausal women.

PubMed

Murillo-Uribe, A; Carranza-Lira, S; Martínez-Trejo, N; Santos-González, J

2000-01-01

To determine whether obesity or body fat distribution induces a greater modification on bone remodeling biochemistry (BRB) and bone density in postmenopausal women. One hundred and thirteen postmenopausal patients were studied. They were initially divided according to body mass index (BMI), and afterwards by waist-hip ratio (WHR) as well as combinations of the two factors. Hormone measurements and assessments of BRB were also done. Dual-emission X-ray absorptiometry from the lumbar column and hip was performed with Lunar DPXL equipment, and the standard deviation in relation to young adult (T) and age-matched subjects (Z) was calculated. Statistical analysis was done by the Mann-Whitney U test. The relation of BMI and WHR with the variables was calculated by simple regression analysis. When divided according to BMI, there was greater bone density in the femoral neck in those with normal weight. After dividing according to WHR, the Z scores had a trend to a lesser decrease in those with upper level body fat distribution. Divided according to BMI and WHR, obese patients with upper-level body fat distribution had greater bone density in the lumbar column than those with normal weight and lower-level body fat distribution. With the same WHR, those with normal weight had greater bone density than those who were obese. A beneficial effect of upper-level body fat distribution on bone density was found. It is greater than that from obesity alone, and obesity and upper-level body fat distribution have an additive effect on bone density.

Pathologic Changes of the Peripheral Vestibular System Secondary to Chronic Otitis Media.

PubMed

da Costa Monsanto, Rafael; Erdil, Mehmet; Pauna, Henrique F; Kwon, Geeyoun; Schachern, Patricia A; Tsuprun, Vladimir; Paparella, Michael M; Cureoglu, Sebahattin

2016-09-01

To evaluate the histopathologic changes of dark, transitional, and hair cells of the vestibular system in human temporal bones from patients with chronic otitis media. Comparative human temporal bone study. Otopathology laboratory. To compare the density of vestibular dark, transitional, and hair cells in temporal bones with and without chronic otitis media, we used differential interference contrast microscopy. In the chronic otitis media group (as compared with the age-matched control group), the density of type I and type II hair cells was significantly decreased in the lateral semicircular canal, saccule, and utricle (P < .05). The density of type I cells was also significantly decreased in the chronic otitis media group in the posterior semicircular canal (P = .005), but that of type II cells was not (P = .168). The mean number of dark cells was significantly decreased in the chronic otitis media group in the lateral semicircular canal (P = .014) and in the posterior semicircular canal (P = .002). We observed no statistically significant difference in the density of transitional cells between the 2 groups (P > .1). The findings of our study suggest that the decrease in the number of vestibular sensory cells and dark cells could be the cause of the clinical symptoms of imbalance of some patients with chronic otitis media. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

An Approach for Determining Quantitative Measures for Bone Volume and Bone Mass in the Pediatric Spina Bifida Population

PubMed Central

Horenstein, Rachel E.; Shefelbine, Sandra J.; Mueske, Nicole M.; Fisher, Carissa L.; Wren, Tishya A.L.

2015-01-01

Background The pediatric spina bifida population suffers from decreased mobility and recurrent fractures. This study aimed to develop a method for quantifying bone mass along the entire tibia in youth with spina bifida. This will provide information about all potential sites of bone deficiencies. Methods Computed tomography images of the tibia for 257 children (n=80 ambulatory spina bifida, n=10 non-ambulatory spina bifida, n=167 typically developing) were analyzed. Bone area was calculated at regular intervals along the entire tibia length and then weighted by calibrated pixel intensity for density weighted bone area. Integrals of density weighted bone area were used to quantify bone mass in the proximal and distal epiphyses and diaphysis. Group differences were evaluated using analysis of variance. Findings Non-ambulatory children suffer from decreased bone mass in the diaphysis and proximal and distal epiphyses compared to ambulatory and control children (P≤0.001). Ambulatory children with spina bifida showed statistically insignificant differences in bone mass in comparison to typically developing children at these sites (P>0.5). Interpretation This method provides insight into tibial bone mass distribution in the pediatric spina bifida population by incorporating information along the whole length of the bone, thereby providing more information than dual-energy x-ray absorptiometry and peripheral quantitative computed tomography. This method can be applied to any population to assess bone mass distribution across the length of any long bone. PMID:26002057

Bone Mineral Density as a Marker of Cumulative Estrogen Exposure in Psychotic Disorder: A 3 Year Follow-Up Study.

PubMed

van der Leeuw, Christine; Peeters, Sanne; Domen, Patrick; van Kroonenburgh, Marinus; van Os, Jim; Marcelis, Machteld

2015-01-01

Altered estrogen-induced neuroprotection has been implicated in the etiology of psychotic disorders. Using bone mineral density as a marker of lifetime estrogen exposure, a longitudinal family study was conducted to discriminate between etiological mechanisms and secondary effects of disease and treatment. Dual X-ray absorptiometry scans were acquired twice, with an interval of 3 years, in 30 patients with psychotic disorder (male (M)/female (F): 24/6, mean age of 32 years at second measurement), 44 non-psychotic siblings of patients with a psychotic disorder (M/F: 26/18, mean age 32) and 27 controls (M/F: 7/20, mean age 35). Total bone mineral density, Z-scores and T-scores were measured in the lumbar spine and proximal femur. Associations between group and bone mineral density changes were investigated with multilevel random regression analyses. The effect of prolactin-raising antipsychotic medication was evaluated. (Increased risk of) psychotic disorder was not associated with disproportionate bone mineral density loss over a three year period. Instead, femoral bone mineral density measures appeared to decrease less in the patient versus control comparison (total BMD: B = 0.026, 95% CI 0.002 to 0.050, p = 0.037; Z-score: B = 0.224, 95% CI 0.035 to 0.412, p = 0.020; and T-score: B = 0.193, 95% CI 0.003 to 0.382, p = 0.046). Current or past use of a prolactin-raising antipsychotic medication was not associated with bone mineral density changes. In this small longitudinal study, there was no evidence of ongoing estrogen deficiency in psychotic disorder as there was no excessive loss of bone mineral density over a 3-year period in patients using antipsychotic medication.

Bone Mineral Density as a Marker of Cumulative Estrogen Exposure in Psychotic Disorder: A 3 Year Follow-Up Study

PubMed Central

van der Leeuw, Christine; Peeters, Sanne; Domen, Patrick; van Kroonenburgh, Marinus; van Os, Jim; Marcelis, Machteld

2015-01-01

Altered estrogen-induced neuroprotection has been implicated in the etiology of psychotic disorders. Using bone mineral density as a marker of lifetime estrogen exposure, a longitudinal family study was conducted to discriminate between etiological mechanisms and secondary effects of disease and treatment. Dual X-ray absorptiometry scans were acquired twice, with an interval of 3 years, in 30 patients with psychotic disorder (male (M)/female (F): 24/6, mean age of 32 years at second measurement), 44 non-psychotic siblings of patients with a psychotic disorder (M/F: 26/18, mean age 32) and 27 controls (M/F: 7/20, mean age 35). Total bone mineral density, Z-scores and T-scores were measured in the lumbar spine and proximal femur. Associations between group and bone mineral density changes were investigated with multilevel random regression analyses. The effect of prolactin-raising antipsychotic medication was evaluated. (Increased risk of) psychotic disorder was not associated with disproportionate bone mineral density loss over a three year period. Instead, femoral bone mineral density measures appeared to decrease less in the patient versus control comparison (total BMD: B = 0.026, 95% CI 0.002 to 0.050, p = 0.037; Z-score: B = 0.224, 95% CI 0.035 to 0.412, p = 0.020; and T-score: B = 0.193, 95% CI 0.003 to 0.382, p = 0.046). Current or past use of a prolactin-raising antipsychotic medication was not associated with bone mineral density changes. In this small longitudinal study, there was no evidence of ongoing estrogen deficiency in psychotic disorder as there was no excessive loss of bone mineral density over a 3-year period in patients using antipsychotic medication. PMID:26309037

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

Neuronal hypothalamic regulation of body metabolism and bone density is galanin dependent.

PubMed

Idelevich, Anna; Sato, Kazusa; Nagano, Kenichi; Rowe, Glenn; Gori, Francesca; Baron, Roland

2018-06-01

In the brain, the ventral hypothalamus (VHT) regulates energy and bone metabolism. Whether this regulation uses the same or different neuronal circuits is unknown. Alteration of AP1 signaling in the VHT increases energy expenditure, glucose utilization, and bone density, yet the specific neurons responsible for each or all of these phenotypes are not identified. Using neuron-specific, genetically targeted AP1 alterations as a tool in adult mice, we found that agouti-related peptide-expressing (AgRP-expressing) or proopiomelanocortin-expressing (POMC-expressing) neurons, predominantly present in the arcuate nucleus (ARC) within the VHT, stimulate whole-body energy expenditure, glucose utilization, and bone formation and density, although their effects on bone resorption differed. In contrast, AP1 alterations in steroidogenic factor 1-expressing (SF1-expressing) neurons, present in the ventromedial hypothalamus (VMH), increase energy but decrease bone density, suggesting that these effects are independent. Altered AP1 signaling also increased the level of the neuromediator galanin in the hypothalamus. Global galanin deletion (VHT galanin silencing using shRNA) or pharmacological galanin receptor blockade counteracted the observed effects on energy and bone. Thus, AP1 antagonism reveals that AgRP- and POMC-expressing neurons can stimulate body metabolism and increase bone density, with galanin acting as a central downstream effector. The results obtained with SF1-expressing neurons, however, indicate that bone homeostasis is not always dictated by the global energy status, and vice versa.

Macroscopic anisotropic bone material properties in children with severe osteogenesis imperfecta.

PubMed

Albert, Carolyne; Jameson, John; Tarima, Sergey; Smith, Peter; Harris, Gerald

2017-11-07

Children with severe osteogenesis imperfecta (OI) typically experience numerous fractures and progressive skeletal deformities over their lifetime. Recent studies proposed finite element models to assess fracture risk and guide clinicians in determining appropriate intervention in children with OI, but lack of appropriate material property inputs remains a challenge. This study aimed to characterize macroscopic anisotropic cortical bone material properties and investigate relationships with bone density measures in children with severe OI. Specimens were obtained from tibial or femoral shafts of nine children with severe OI and five controls. The specimens were cut into beams, characterized in bending, and imaged by synchrotron radiation X-ray micro-computed tomography. Longitudinal modulus of elasticity, yield strength, and bending strength were 32-65% lower in the OI group (p<0.001). Yield strain did not differ between groups (p≥0.197). In both groups, modulus and strength were lower in the transverse direction (p≤0.009), but anisotropy was less pronounced in the OI group. Intracortical vascular porosity was almost six times higher in the OI group (p<0.001), but no differences were observed in osteocyte lacunar porosity between the groups (p=0.086). Volumetric bone mineral density was lower in the OI group (p<0.001), but volumetric tissue mineral density was not (p=0.770). Longitudinal OI bone modulus and strength were correlated with volumetric bone mineral density (p≤0.024) but not volumetric tissue mineral density (p≥0.099). Results indicate that cortical bone in children with severe OI yields at the same strain as normal bone, and that their decreased bone material strength is associated with reduced volumetric bone mineral density. These results will enable the advancement of fracture risk assessment capability in children with severe OI. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dynamic Alterations in Microarchitecture, Mineralization and Mechanical Property of Subchondral Bone in Rat Medial Meniscal Tear Model of Osteoarthritis

PubMed Central

Yu, De-Gang; Nie, Shao-Bo; Liu, Feng-Xiang; Wu, Chuan-Long; Tian, Bo; Wang, Wen-Gang; Wang, Xiao-Qing; Zhu, Zhen-An; Mao, Yuan-Qing

2015-01-01

Background: The properties of subchondral bone influence the integrity of articular cartilage in the pathogenesis of osteoarthritis (OA). However, the characteristics of subchondral bone alterations remain unresolved. The present study aimed to observe the dynamic alterations in the microarchitecture, mineralization, and mechanical properties of subchondral bone during the progression of OA. Methods: A medial meniscal tear (MMT) operation was performed in 128 adult Sprague Dawley rats to induce OA. At 2, 4, 8, and 12 weeks following the MMT operation, cartilage degeneration was evaluated using toluidine blue O staining, whereas changes in the microarchitecture indices and tissue mineral density (TMD), mineral-to-collagen ratio, and intrinsic mechanical properties of subchondral bone plates (BPs) and trabecular bones (Tbs) were measured using micro-computed tomography scanning, confocal Raman microspectroscopy and nanoindentation testing, respectively. Results: Cartilage degeneration occurred and worsened progressively from 2 to 12 weeks after OA induction. Microarchitecture analysis revealed that the subchondral bone shifted from bone resorption early (reduced trabecular BV/TV, trabecular number, connectivity density and trabecular thickness [Tb.Th], and increased trabecular spacing (Tb.Sp) at 2 and 4 weeks) to bone accretion late (increased BV/TV, Tb.Th and thickness of subchondral bone plate, and reduced Tb.Sp at 8 and 12 weeks). The TMD of both the BP and Tb displayed no significant changes at 2 and 4 weeks but decreased at 8 and 12 weeks. The mineral-to-collagen ratio showed a significant decrease from 4 weeks for the Tb and from 8 weeks for the BP after OA induction. Both the elastic modulus and hardness of the Tb showed a significant decrease from 4 weeks after OA induction. The BP showed a significant decrease in its elastic modulus from 8 weeks and its hardness from 4 weeks. Conclusion: The microarchitecture, mineralization and mechanical properties of subchondral bone changed in a time-dependent manner as OA progressed. PMID:26521785

Effects of cast-mediated immobilization on bone mineral mass at various sites in adolescents with lower-extremity fracture.

PubMed

Ceroni, Dimitri; Martin, Xavier; Delhumeau, Cécile; Rizzoli, René; Kaelin, André; Farpour-Lambert, Nathalie

2012-02-01

Leg or ankle fractures occur commonly in the pediatric population and are primarily treated with closed reduction and cast immobilization. The most predictable consequences of immobilization and subsequent weight-bearing restriction are loss of bone mineral mass, substantial muscle atrophy, and functional limitations. The purposes of this study were to determine if lower-limb fractures in adolescents are associated with abnormal bone mineral density or content at the time of fracture, and to quantify bone mineral loss at various sites due to cast-mediated immobilization and limited weight-bearing. We recruited fifty adolescents aged ten to sixteen years who had undergone cast immobilization for a leg or ankle fracture. Dual x-ray absorptiometry scans of the total body, lumbar spine, hip, leg, and calcaneus were performed at the time of fracture and at cast removal. Patients with a fracture were paired with healthy controls according to sex and age. Values at baseline and at cast removal, or at equivalent time intervals in the control group, were compared between groups and between the injured and uninjured legs of the adolescents with the fracture. At the time of fracture, there were no observed differences in the bone mineral density or bone mineral content Z-scores of the total body or the lumbar spine, or in the bone mineral density Z-scores of the calcaneus, between the injured and healthy subjects. At cast removal, bone mineral parameters on the injured side were significantly lower than those on the uninjured side in the injured group. Differences ranged from -5.8% to -31.7% for bone mineral density and from -5.2% to -19.4% for bone mineral content. During the cast period, the injured adolescents had a significant decrease of bone mineral density at the hip, greater trochanter, calcaneus, and total lower limb as compared with the healthy controls. Lower-limb fractures are not related to osteopenia in adolescents at the time of fracture. However, osteopenia does develop in the injured limb during cast immobilization for fracture treatment. Further investigation is required to determine if the bone mineral mass will return to normal or if a permanent decrease is to be expected, which may constitute a hypothetical risk of sustaining a second fracture.

Zoledronic Acid Induces Site-Specific Structural Changes and Decreases Vascular Area in the Alveolar Bone.

PubMed

Soares, Mariana Quirino Silveira; Van Dessel, Jeroen; Jacobs, Reinhilde; da Silva Santos, Paulo Sérgio; Cestari, Tania Mary; Garlet, Gustavo Pompermaier; Duarte, Marco Antonio Hungaro; Imada, Thaís Sumie Nozu; Lambrichts, Ivo; Rubira-Bullen, Izabel Regina Fischer

2018-03-15

The aim was to assess the effect of a relevant regimen of zoledronic acid (ZA) treatment for the study of bisphosphonate-related osteonecrosis of the jaw on alveolar bone microstructure and vasculature. A sub-objective was to use 3-dimensional imaging to describe site-specific changes induced by ZA in the alveolar bone. Five Wistar rats received ZA (0.6 mg/kg) and five (controls) received saline solution in the same volume. The compounds were administered intraperitoneally in 5 doses every 28 days. The rats were euthanized 150 days after therapy onset. The mandibles were scanned using high-resolution (14-μm) micro-computed tomography (micro-CT), decalcified, cut into slices for histologic analysis (5 μm), and stained with hematoxylin-eosin. Bone quality parameters were calculated using CT-Analyser software (Bruker, Kontich, Belgium) in 2 different volumes of interest (VOIs): the region between the first molar roots (VOI-1) and the periapical region under the first and second molars' apex (VOI-2). Blood vessel density and bone histomorphometric parameters were calculated only for the region between the roots of the first molar using AxioVision Imaging software (version 4.8; Carl Zeiss, Gottingen, Germany). ZA-treated rats showed a significant increase in percentage of bone volume and density (P < .05), with thicker and more connected trabeculae. Furthermore, the ZA group showed a significant decrease in the size of the marrow spaces and nutritive canals and in blood vessel density (P < .05). In the micro-CT evaluation, VOI-2 showed better outcomes in measuring the effect of ZA on alveolar bone. ZA treatment induced bone corticalization and decreased alveolar bone vascularization. VOI-2 should be preferred for micro-CT evaluation of the effect of bisphosphonates on alveolar bone. This analysis allowed the effect of ZA on alveolar bone and its vascularization to be characterized. The results of this analysis may add further knowledge to the understanding of the physiopathology of osteonecrosis of the jaw. Copyright © 2018 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Cadmium osteotoxicity in experimental animals: Mechanisms and relationship to human exposures

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

Bhattacharyya, Maryka H.

Extensive epidemiological studies have recently demonstrated increased cadmium exposure correlating significantly with decreased bone mineral density and increased fracture incidence in humans at lower exposure levels than ever before evaluated. Studies in experimental animals have addressed whether very low concentrations of dietary cadmium can negatively impact the skeleton. This overview evaluates results in experimental animals regarding mechanisms of action on bone and the application of these results to humans. Results demonstrate that long-term dietary exposures in rats, at levels corresponding to environmental exposures in humans, result in increased skeletal fragility and decreased mineral density. Cadmium-induced demineralization begins soon after exposure,more » within 24 h of an oral dose to mice. In bone culture systems, cadmium at low concentrations acts directly on bone cells to cause both decreases in bone formation and increases in bone resorption, independent of its effects on kidney, intestine, or circulating hormone concentrations. Results from gene expression microarray and gene knock-out mouse models provide insight into mechanisms by which cadmium may affect bone. Application of the results to humans is considered with respect to cigarette smoke exposure pathways and direct vs. indirect effects of cadmium. Clearly, understanding the mechanism(s) by which cadmium causes bone loss in experimental animals will provide insight into its diverse effects in humans. Preventing bone loss is critical to maintaining an active, independent lifestyle, particularly among elderly persons. Identifying environmental factors such as cadmium that contribute to increased fractures in humans is an important undertaking and a first step to prevention.« less

[Bone structure in rheumatoid arthritis].

PubMed

Ono, Kumiko; Ohashi, Satoru; Tanaka, Sakae; Matsumoto, Takuya

2013-07-01

In rheumatoid arthritis (RA) , the osteoclast pathway is activated by abnormal immune conditions accompanied by chronic inflammation, resulting in periarticular osteoporosis and local bone destruction around joints. In addition, multiple factors, including reduced physical activity and pharmacotherapies such as steroids, lead to systemic osteoporosis. These conditions cause decreasing bone mineral density and deterioration of bone quality, and expose patients to increased risk of fracture. Understanding the bone structures of RA and evaluating fracture risk are central to the treatment of RA.

Mitigating HZE Radiation-Induced Deficits in Marrow-Derived Mesenchymal Progenitor Cells and Skeletal Structure

NASA Technical Reports Server (NTRS)

Globus, Ruth K.; Schreurs, Ann-Sofie; Shirazi-Fard, Yasaman; Terada, Masahiro; Alwood, Joshua; Halloran, Bernard; Tahimic, Candice

2016-01-01

Future long-duration space exploration beyond the earths magnetosphere will increase human exposure to space radiation and associated risks to skeletal health. We hypothesize that oxidative stress resulting from radiation exposure causes progressive bone loss and dysfunction in associated tissue. In animal studies, increased free radical formation is associated with pathological changes in bone structure, enhanced bone resorption, reduced bone formation and decreased bone mineral density, which can lead to skeletal fragility.

Quantifying the degradation of degradable implants and bone formation in the femoral condyle using micro-CT 3D reconstruction

PubMed Central

Xu, Yichi; Meng, Haoye; Yin, Heyong; Sun, Zhen; Peng, Jiang; Xu, Xiaolong; Guo, Quanyi; Xu, Wenjing; Yu, Xiaoming; Yuan, Zhiguo; Xiao, Bo; Wang, Cheng; Wang, Yu; Liu, Shuyun; Lu, Shibi; Wang, Zhaoxu; Wang, Aiyuan

2018-01-01

Degradation limits the application of magnesium alloys, and evaluation methods for non-traumatic in vivo quantification of implant degradation and bone formation are imperfect. In the present study, a micro-arc-oxidized AZ31 magnesium alloy was used to evaluate the degradation of implants and new bone formation in 60 male New Zealand white rabbits. Degradation was monitored by weighing the implants prior to and following implantation, and by performing micro-computed tomography (CT) scans and histological analysis after 1, 4, 12, 24, 36, and 48 weeks of implantation. The results indicated that the implants underwent slow degradation in the first 4 weeks, with negligible degradation in the first week, followed by significantly increased degradation during weeks 12–24 (P<0.05), and continued degradation until the end of the 48-week experimental period. The magnesium content decreased as the implant degraded (P<0.05); however, the density of the material exhibited almost no change. Micro-CT results also demonstrated that pin volume, pin mineral density, mean ‘pin thickness’, bone surface/bone volume and trabecular separation decreased over time (P<0.05), and that the pin surface area/pin volume, bone volume fraction, trabecular thickness, trabecular number and tissue mineral density increased over time (P<0.05), indicating that the number of bones and density of new bone increased as magnesium degraded. These results support the positive effect of magnesium on osteogenesis. However, from the maximum inner diameter of the new bone loop and diameter of the pin in the same position, the magnesium alloy was not capable of creating sufficient bridges between the bones and biomaterials when there were preexisting gaps. Histological analyses indicated that there were no inflammatory responses around the implants. The results of the present study indicate that a micro-arc-oxidized AZ31 magnesium alloy is safe in vivo and efficiently degraded. Furthermore, the novel bone formation increased as the implant degraded. The findings concluded that micro-CT, which is useful for providing non-traumatic, in vivo, quantitative and precise data, has great value for exploring the degradation of implants and novel bone formation. PMID:29375677

Quantifying the degradation of degradable implants and bone formation in the femoral condyle using micro-CT 3D reconstruction.

PubMed

Xu, Yichi; Meng, Haoye; Yin, Heyong; Sun, Zhen; Peng, Jiang; Xu, Xiaolong; Guo, Quanyi; Xu, Wenjing; Yu, Xiaoming; Yuan, Zhiguo; Xiao, Bo; Wang, Cheng; Wang, Yu; Liu, Shuyun; Lu, Shibi; Wang, Zhaoxu; Wang, Aiyuan

2018-01-01

Degradation limits the application of magnesium alloys, and evaluation methods for non-traumatic in vivo quantification of implant degradation and bone formation are imperfect. In the present study, a micro-arc-oxidized AZ31 magnesium alloy was used to evaluate the degradation of implants and new bone formation in 60 male New Zealand white rabbits. Degradation was monitored by weighing the implants prior to and following implantation, and by performing micro-computed tomography (CT) scans and histological analysis after 1, 4, 12, 24, 36, and 48 weeks of implantation. The results indicated that the implants underwent slow degradation in the first 4 weeks, with negligible degradation in the first week, followed by significantly increased degradation during weeks 12-24 (P<0.05), and continued degradation until the end of the 48-week experimental period. The magnesium content decreased as the implant degraded (P<0.05); however, the density of the material exhibited almost no change. Micro-CT results also demonstrated that pin volume, pin mineral density, mean 'pin thickness', bone surface/bone volume and trabecular separation decreased over time (P<0.05), and that the pin surface area/pin volume, bone volume fraction, trabecular thickness, trabecular number and tissue mineral density increased over time (P<0.05), indicating that the number of bones and density of new bone increased as magnesium degraded. These results support the positive effect of magnesium on osteogenesis. However, from the maximum inner diameter of the new bone loop and diameter of the pin in the same position, the magnesium alloy was not capable of creating sufficient bridges between the bones and biomaterials when there were preexisting gaps. Histological analyses indicated that there were no inflammatory responses around the implants. The results of the present study indicate that a micro-arc-oxidized AZ31 magnesium alloy is safe in vivo and efficiently degraded. Furthermore, the novel bone formation increased as the implant degraded. The findings concluded that micro-CT, which is useful for providing non-traumatic, in vivo , quantitative and precise data, has great value for exploring the degradation of implants and novel bone formation.

[Insights into cystic fibrosis-related bone disease].

PubMed

Braun, C; Bacchetta, J; Reix, P

2016-08-01

With the increasing life expectancy of patients with cystic fibrosis (CF), prevalence of late complications such as CF-related bone disease (CFBD) has increased. It was initially described in 24% of the adult population with CF and has also been reported in the pediatric population. CFBD is multifactorial and progresses in different steps. Both decreased bone formation and increased bone resorption (in different amounts) are observed. CFBD is likely primitive (directly related to the CFTR defect itself), but is also worsened by acquired secondary factors such as lung infections, chronic inflammation, denutrition, vitamin deficiency, and decreased physical activity. CFBD may be clinically apparent (i.e., mainly vertebral and costal fractures), or clinically asymptomatic (therefore corresponding to abnormalities in bone density and architecture). CFBD management mainly aims to prevent the occurrence of fractures. Prevention and regular monitoring of bone disease as early as 8 years of age is of the utmost importance, as is the control of possible secondary deleterious CFBD factors. New radiological tools, such as high-resolution peripheral quantitative computed tomography, allow an accurate evaluation of cortical and trabecular bone micro-architecture in addition to compartmental density; as such, they will likely improve the assessment of the bone fracture threat in CF patients in the near future. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

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.

[The burden of disease attributed to low bone mineral density among population aged ≥40 years old in China, 1990 and 2013].

PubMed

Zhao, Z P; Ai, H H; Li, Y C; Wang, L M; Yin, P; Zhang, M; Deng, Q; Huang, Z J; Liu, J M; Liu, Y N; Gao, Y J; Zhou, M G

2016-09-06

Objective: To identify cause-specific death and attributed burden of low bone mineral density in China among population aged ≥40 years old , 1990 and 2013. Methods: By using data from Global Burden of Disease(GBD)2013, this study analyzed death caused by low mineral density, and disability-adjusted life years(DALY)among population aged 40 and above in China(not including Taiwan, China). This study also analyzed DALY by composition of injury which due to low bone mineral density. It also analyzed changes in DALY by provinces in China, 1990 and 2013. An average world population age-structure for the period 2000- 2025 was adopted to calculate the age standardized rates. Results: In 2013, there were 38.1 thousands male and 30.7 thousands female who aged 40 and above dead due to low bone mineral density in China. The burden of injury caused by low bone mineral density was more sever in male than female, which accounted for 1.525 million DALY in male and 0.873 million DALY in female. In 1990, low bone mineral density attributed transportation and accidental injury caused 0.794 million and 0.567 million DALY losses, respectively. In 2013, low bone mineral density attributed transportation and accidental injury caused 1.421 million and 0.951 million DALY losses, respectively. Compared to 1990, DALY losses caused by transportation and accidental injury, increased by 79.1% and 67.6%, respectively. In 1990, DALY rate losses due to low bone mineral density attributed transportation and accidental injury were 68.1 per 100 000 and 48.7 per 100 000, respectively. In 2013, DALY rate losses due to low bone mineral density attributed transportation and accidental injury were 102.0 per 100 000 and 68.2 per 100 000, respectively. Compared to 1990, DALY rates which caused by transportation and accidental injury, increased by 49.8% and 40.2%, respectively. According to the ranking of standardized DALY rate in 2013 by provinces, the top 3 provinces, which standardized DALYs attributed to low bone mineral density lost the most, were Zhejiang Province(2.6 per 100 000), Jiangsu Province(2.4 per 100 000), and Fujian Province(2.2 per 100 000). Compared to 1990, the standardized rate of DALY decreased in 27 provinces, while the DALY rate increased in only 6 provinces which included Ningxia Hui Autonomous Region, Qinghai Province, Hebei Province, Guangxi Zhuang Autonomous Region, and Henan Province and Xinjiang Uygur Autonomous Region. Conclusion: This study found that the burden of health losses attributed to it was higher in men than in women. Compared to 1990, DALY rates decreased in most of the provinces, however, the rates of losses of DALY which caused by transportation and accidental injury were still increasing.

Bone mineral density is decreased in fibromyalgia syndrome: a systematic review and meta-analysis.

PubMed

Upala, Sikarin; Yong, Wai Chung; Sanguankeo, Anawin

2017-04-01

Previous studies have shown that fibromyalgia syndrome (FMS) is associated with low level of physical activity and exercise, which may lead to an increased risk of osteoporosis. However, studies of bone mineral density (BMD) in fibromyalgia have shown conflicting results. Thus, we conducted a systematic review and meta-analysis to better characterize the association between FMS and BMD. A comprehensive search of the databases MEDLINE and EMBASE was performed from inception through May 2016. The inclusion criterion was the observational studies' assessment of the association between fibromyalgia and bone mineral density in adult subjects. Fibromyalgia was diagnosed in accordance with the American College of Rheumatology criteria for the diagnosis of fibromyalgia syndrome. BMD was measured at the lumbar spine and femoral neck by dual-energy X-ray absorptiometry. Pooled mean difference (MD) of BMD at each site and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. The between-study heterogeneity of effect size was quantified using the Q statistic and I 2 . Data were extracted from four observational studies involving 680 subjects. At lumbar spine (L2-L4), BMD is significantly decreased in patients with FMS compared with controls with pooled MD of -0.02 (95% CI -0.03 to -0.01, P value = 0.003, I 2  = 0%) (Fig. 1). At femoral neck, BMD is not significantly decreased in patients with FMS compared with controls with pooled MD of 0.01 (95% CI -0.02 to 0.01, P value = 0.23, I 2  = 0%) (Fig. 2). In this meta-analysis, we observe that BMD at lumbar spine is decreased in FMS compared with normal individuals. Patients with FMS should be assessed for risk of osteoporosis. Fig. 1 Forest plot of bone mineral density at the lumbar spine, for patients with and without fibromyalgia syndrome. CI-confidence interval Fig. 2 Forest plot of bone mineral density at the femoral neck, for patients with and without fibromyalgia syndrome. CI-confidence interval.

Muscle-Bone Interactions in Pediatric Bone Diseases.

PubMed

Veilleux, Louis-Nicolas; Rauch, Frank

2017-10-01

Here, we review the skeletal effects of pediatric muscle disorders as well as muscle impairment in pediatric bone disorders. When starting in utero, muscle disorders can lead to congenital multiple contractures. Pediatric-onset muscle weakness such as cerebral palsy, Duchenne muscular dystrophy, spinal muscular atrophy, or spina bifida typically are associated with small diameter of long-bone shafts, low density of metaphyseal bone, and increased fracture incidence in the lower extremities, in particular, the distal femur. Primary bone diseases can affect muscles through generic mechanisms, such as decreased physical activity or in disease-specific ways. For example, the collagen defect underlying the bone fragility of osteogenesis imperfecta may also affect muscle force generation or transmission. Transforming growth factor beta released from bone in Camurati Engelman disease may decrease muscle function. Considering muscle-bone interactions does not only contribute to the understanding of musculoskeletal disorders but also can identify new targets for therapeutic interventions.

Longitudinal study of bone loss in pre- and perimenopausal women: evidence for bone loss in perimenopausal women.

PubMed

Chapurlat, R D; Garnero, P; Sornay-Rendu, E; Arlot, M E; Claustrat, B; Delmas, P D

2000-01-01

Bone loss before and around the time of menopause is not well characterized by longitudinal studies. We measured bone mineral density at various skeletal sites--total body, femoral neck, trochanter, anteroposterior (AP) and lateral spine, and forearm--with dual-energy X-ray absorptiometry in a large prospective cohort of 272 untreated pre- and perimenopausal women aged 31-59 years, at 1 year intervals for 3 years. Sex steroids and the following markers of bone remodeling were measured: serum osteocalcin (OC), procollagen I carboxyterminal extension peptide, bone alkaline phosphatase (BAP) and urinary crosslinks (CTX and NTX). Seventy-six women were classified as perimenopausal and 196 as premenopausal. Over the 3 years, premenopausal women had no significant bone loss at any site and a small but significant increase in bone mineral density at the trochanter, total hip, AP spine and radius. Perimenopausal women significantly lost bone from cancellous and cortical sites, i.e., the femoral neck, trochanter and lumbar spine. In perimenopausal women with increased follicle stimulating hormone, the rate of bone loss at the femoral neck correlated negatively with OC and BAP. In perimenopausal women, serum estradiol levels decreased during the 3 years of follow-up and bone loss from the trochanter and the AP spine was correlated with serum estradiol after 3 years. In conclusion, among premenopausal women there is no bone loss. In contrast, there is a rapid and diffuse bone loss in perimenopausal women, related to decreased estrogen secretion. Bone markers may be useful to identify these women losing bone.

Effects of dexamethasone, celecoxib, and methotrexate on the histology and metabolism of bone tissue in healthy Sprague Dawley rats.

PubMed

Liu, Yanzhi; Cui, Yang; Chen, Yan; Gao, Xiang; Su, Yanjie; Cui, Liao

2015-01-01

To investigate the long-term effects of three antiarthritics, namely dexamethasone, celecoxib, and methotrexate on the histology and metabolism of intact bone tissue in rats. Thirty-two 12-week-old healthy female Sprague Dawley rats were randomly allocated into four groups: 1) control (saline, daily); 2) dexamethasone (2 mg/kg, twice weekly); 3) celecoxib (50 mg/kg, daily); and 4) methotrexate (0.5 mg/kg, twice weekly). The drugs were administered to the rats for 12 weeks and the animals were weighed on a weekly basis. The femurs and lumbar vertebrae were harvested for bone mineral density and bone mechanical properties analyses. The proximal tibiae were processed for bone histomorphometry and micro-computed tomography analyses. The following results were obtained: 1) dexamethasone strongly inhibited bone formation rate accompanied with a decrease in bone mineral density and bone biomechanical properties; 2) celecoxib stimulated bone resorption, leading to a decrease of bone mass and femur biomechanic properties; and 3) methotrexate caused bone loss and bone quality deterioration to a lesser extent due to the increase of the bone turnover rate on the proximal tibial metaphysis of the rats. This study provides a comparative profile of the long-term effects of clinical doses of celecoxib, methotrexate, and dexamethasone on intact skeletons of the rats. The results indicate that the three antiarthritics have varying degrees of side effects on bone metabolism, and these findings will help physicians to learn more about the potential effects of antiarthritics on bone metabolism.

Effect on bone density of postoperative calcium and vitamin-D supplementation in patients with primary hyperparathyroidism: A retrospective study.

PubMed

Nordenström, Erik; Westerdahl, Johan; Bergenfelz, Anders

2009-05-01

Primary hyperparathyroidism (pHPT) is associated with decreased bone density and increased fracture risk. A significant number of pHPT patients have low calcium intake and suffer from vitamin deficiency. Thus, we adopted a policy of postoperative supplements with calcium and vitamin D after parathyroid surgery. In this study, we investigated if this policy enhanced the postoperative increase in bone density. Forty-two consecutive patients (83% female) were studied. The first 21 patients received no supplements, whereas the following 21 patients received 1,000 g calcium and 800 IU hydroxy D: -vitamin daily (Ca-D group) for 1 year postoperatively. The patients were monitored with bone density and biochemistry pre- and at 1 year postoperatively. Preoperatively, the patients without vitamin D supplementation (non-Ca-D group) did neither differ in biochemistry, clinical features, nor in bone density from patients in Ca-D group. Postoperatively, there was a tendency that patients in Ca-D group increased their bone density, at all sites measured, in a greater extent than patients that did not receive calcium and vitamin D supplementation. In conclusion, based on our results, it is difficult to give a recommendation of vitamin D supplementation in routine use following surgery for primary hyperparathyroidism. Based on the present data, a calculation of sample size for a future randomized controlled trial is presented.

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

The consequences of modern military deployment on calcium status and bone health.

PubMed

McCarthy, Mary S; Loan, Lori A; Azuero, Andres; Hobbs, Curtis

2010-06-01

This article highlights the potential negative effect of the current combat environment on bone health of young military men and women who may be at risk for stress fractures and future bone disease because of alterations primarily in diet and physical activity level during deployment. A combination of physiologic biomarkers, including bone turnover and bone mineral density, and nutrition and exercise surveys can provide meaningful data on potential health risks related to deployment. Soldiers participating in an investigation into bone health before and after deployment did not have decreased bone density but the study did raise awareness about an issue that might otherwise go unnoticed because preventive care is typically focused on older adults. Several risk factors may be modifiable and nurses have the necessary skills for counseling and monitoring behaviors that can minimize disabling musculoskeletal injuries that affect quality of life for the individual and unit readiness for the commander. Published by Elsevier Inc.

Fractures in geriatric mice show decreased callus expansion and bone volume.

PubMed

Lopas, Luke A; Belkin, Nicole S; Mutyaba, Patricia L; Gray, Chancellor F; Hankenson, Kurt D; Ahn, Jaimo

2014-11-01

Poor fracture healing in geriatric populations is a significant source of morbidity, mortality, and cost to individuals and society; however, a fundamental biologic understanding of age-dependent healing remains elusive. The development of an aged-based fracture model system would allow for a mechanistic understanding that could guide future biologic treatments. Using a small animal model of long-bone fracture healing based on chronologic age, we asked how aging affected (1) the amount, density, and proportion of bone formed during healing; (2) the amount of cartilage produced and the progression to bone during healing; (3) the callus structure and timing of the fracture healing; and (4) the behavior of progenitor cells relative to the observed deficiencies of geriatric fracture healing. Transverse, traumatic tibial diaphyseal fractures were created in 5-month-old (n=104; young adult) and 25-month-old (n=107; which we defined as geriatric, and are approximately equivalent to 70-85 year-old humans) C57BL/6 mice. Fracture calluses were harvested at seven times from 0 to 40 days postfracture for micro-CT analysis (total volume, bone volume, bone volume fraction, connectivity density, structure model index, trabecular number, trabecular thickness, trabecular spacing, total mineral content, bone mineral content, tissue mineral density, bone mineral density, degree of anisotropy, and polar moment of inertia), histomorphometry (total callus area, cartilage area, percent of cartilage, hypertrophic cartilage area, percent of hypertrophic cartilage area, bone and osteoid area, percent of bone and osteoid area), and gene expression quantification (fold change). The geriatric mice produced a less robust healing response characterized by a pronounced decrease in callus amount (mean total volume at 20 days postfracture, 30.08±11.53 mm3 versus 43.19±18.39 mm3; p=0.009), density (mean bone mineral density at 20 days postfracture, 171.14±64.20 mg hydroxyapatite [HA]/cm3 versus 210.79±37.60 mg HA/cm3; p=0.016), and less total cartilage (mean cartilage area at 10 days postfracture, 101,279±46,755 square pixels versus 302,167±137,806 square pixels; p=0.013) and bone content (mean bone volume at 20 days postfracture, 11.68±3.18 mm3 versus 22.34±10.59 mm3; p<0.001) compared with the young adult mice. However, the amount of cartilage and bone relative to the total callus size was similar between the adult and geriatric mice (mean bone volume fraction at 25 days postfracture, 0.48±0.10 versus 0.50±0.13; p=0.793), and the relative expression of chondrogenic (mean fold change in SOX9 at 10 days postfracture, 135+25 versus 90±52; p=0.221) and osteogenic genes (mean fold change in osterix at 20 days postfracture, 22.2±5.3 versus 18.7±5.2; p=0.324) was similar. Analysis of mesenchymal cell proliferation in the geriatric mice relative to adult mice showed a decrease in proliferation (mean percent of undifferentiated mesenchymal cells staining proliferating cell nuclear antigen [PCNA] positive at 10 days postfracture, 25%±6.8% versus 42%±14.5%; p=0.047). Our findings suggest that the molecular program of fracture healing is intact in geriatric mice, as it is in geriatric humans, but callus expansion is reduced in magnitude. Our study showed altered healing capacity in a relevant animal model of geriatric fracture healing. The understanding that callus expansion and bone volume are decreased with aging can help guide the development of targeted therapeutics for these difficult to heal fractures.

Changes in bone density and bone markers in rhythmic gymnasts and ballet dancers: implications for puberty and leptin levels.

PubMed

Muñoz, María Teresa; de la Piedra, Concepción; Barrios, Vicente; Garrido, Guadalupe; Argente, Jesús

2004-10-01

Our aim was to compare physical activity and biochemical markers with bone mineral acquisition in rhythmic gymnasts and ballet dancers. Weight, height, body mass index, nutritional intake, bone age and menstrual histories were analyzed in nine rhythmic gymnasts, twelve ballet dancers and fourteen controls. Bone mineral density (BMD) was assessed by X-ray absorptiometry at the lumbar spine, hip and radius. Bone alkaline phosphatase (bAP) and amino-terminal propeptide of procollagen I (PNIP) in serum and urinary alpha-isomer of the carboxy-terminal telopeptide of collagen I (alpha-CTX) were measured. Bone age was delayed 2 years and mean age at menarche was 15+/-0.9 years in rhythmic gymnasts and 13.7+/-1 years in ballet dancers, compared with 12.5+/-1 years in controls. Trocanteric and femoral neck BMD was significantly higher in rhythmic gymnasts compared with ballet dancers and controls. Right forearm (non-loaded zone) BMD was significantly decreased in rhythmic gymnasts and ballet dancers compared with controls. All subjects had normal bAP and PNIP levels, but the alpha-CTX/creatinine (Cr) ratio was increased in rhythmic gymnasts (P<0.001) with an inverse correlation between right forearm BMD and the alpha-CTX/Cr ratio (r=-0.74, P<0.001). Serum leptin levels were decreased in rhythmic gymnasts and ballet dancers. Rhythmic gymnasts had a positive correlation between right forearm BMD and leptin levels (r=0.85, P<0.001). Decreased bone mass in rhythmic gymnasts could be partially explained by an increase in bone resorption. Serum leptin levels could be implicated in the pubertal delay and be a good marker of bone mass in these subjects.

Impact of Weight Loss With Intragastric Balloon on Bone Density and Microstructure in Obese Adults.

PubMed

Madeira, Eduardo; Madeira, Miguel; Guedes, Erika Paniago; Mafort, Thiago Thomaz; Moreira, Rodrigo Oliveira; de Mendonça, Laura Maria Carvalho; Lima, Inayá Correa Barbosa; Neto, Leonardo Vieira; de Pinho, Paulo Roberto Alves; Lopes, Agnaldo José; Farias, Maria Lucia Fleiuss

2018-03-21

The historical concept that obesity protects against bone fractures has been questioned. Weight loss appears to reduce bone mineral density (BMD); however, the results in young adults are inconsistent, and data on the effects of weight loss on bone microstructure are limited. This study aimed to evaluate the impact of weight loss using an intragastric balloon (IGB) on bone density and microstructure. Forty obese patients with metabolic syndrome (mean age 35.1 ± 7.3 yr) used an IGB continuously for 6 mo. Laboratory tests, areal BMD, and body composition measurements via dual-energy X-ray absorptiometry, and volumetric BMD and bone microstructure measurements via high-resolution peripheral quantitative computed tomography were conducted before IGB placement and after IGB removal. The mean weight loss was 11.5%. After 6 mo, there were significant increases in vitamin D and carboxyterminal telopeptide of type 1 collagen levels. After IGB use, areal BMD increased in the spine but decreased in the total femur and the 33% radius. Cortical BMD increased in the distal radius but tended to decrease in the distal tibia. The observed trabecular bone loss in the distal tibia contributed to the decline in the total volumetric BMD at this site. There was a negative correlation between the changes in leptin levels and the measures of trabecular quality in the tibia on high-resolution peripheral quantitative computed tomography. Weight loss may negatively impact bone microstructure in young patients, especially for weight-bearing bones, in which obesity has a more prominent effect. Copyright © 2018 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

The effect of pregnancy and lactation on bone mineral density in fluoride-exposed rats.

PubMed

Yildiz, Mustafa; Oral, Baha

2006-06-01

Fluoride increases metabolic turnover of the bone in favour of bone formation. Excessive intake of fluoride may lead to pathological changes in teeth and bones: dental and skeletal fluorosis. In this study, we investigated the effect of pregnancy and lactation on bone mineral density (BMD) in fluoride-exposed rats. Female Wistar rats were given commercially available spring water with 100 ppm fluoride (N = 8), or without addition (N = 8) for 18 weeks. At 16 weeks of age, four female rats and one male rat were kept in a cage for 5 days; all females were successfully impregnated. BMD was measured at 16 weeks of age, on the first day postpartum, and at the end of lactation. Spinal BMD was significantly higher in fluoride-exposed rats than control (P < 0.05), but there were no differences in femoral BMD (P = 0.670). During pregnancy, spinal BMD and femoral BMD were not significantly changed in fluoride-exposed rats, whereas BMD of the spine was significantly decreased in the control rats (P = 0.013), but not in the femur. During lactation, BMD was significantly decreased at the two regions compared to initial values (P < 0.05) in both groups. This study shows that pregnancy has no effect on bone, but lactation has a decreasing effect on BMD in fluoride-exposed rats.

Skeletal Health After Continuation, Withdrawal, or Delay of Alendronate in Men With Prostate Cancer Undergoing Androgen-Deprivation Therapy

PubMed Central

Greenspan, Susan L.; Nelson, Joel B.; Trump, Donald L.; Wagner, Julie M.; Miller, Megan E.; Perera, Subashan; Resnick, Neil M.

2008-01-01

Purpose Androgen-deprivation therapy (ADT) for prostate cancer is associated with bone loss and osteoporotic fractures. Our objective was to examine changes in bone density and turnover with sustained, discontinued, or delayed oral bisphosphonate therapy in men receiving ADT. Patients and Methods A total of 112 men with nonmetastatic prostate cancer receiving ADT were randomly assigned to alendronate 70 mg once weekly or placebo in a double-blind, partial-crossover trial with a second random assignment at year 2 for those who initially received active therapy. Outcomes included bone mineral density and bone turnover markers. Results Men initially randomly assigned to alendronate and randomly reassigned at year 2 to continue had additional bone density gains at the spine (mean, 2.3% ± 0.7) and hip (mean, 1.3% ± 0.5%; both P < .01); those randomly assigned to placebo in year 2 maintained density at the spine and hip but lost (mean, −1.9% ± 0.6%; P < .01) at the forearm. Patients randomly assigned to begin alendronate in year 2 experienced improvements in bone mass at the spine and hip, but experienced less of an increase compared with those who initiated alendronate at baseline. Men receiving alendronate for 2 years experienced a mean 6.7% (± 1.2%) increase at the spine and a 3.2% (± 1.5%) at the hip (both P < .05). Bone turnover remained suppressed. Conclusion Among men with nonmetastatic prostate cancer receiving ADT, once-weekly alendronate improves bone density and decreases turnover. A second year of alendronate provides additional skeletal benefit, whereas discontinuation results in bone loss and increased bone turnover. Delay in bisphosphonate therapy appears detrimental to bone health. PMID:18802155

Effects of vitamin K2 on cortical and cancellous bone mass, cortical osteocyte and lacunar system, and porosity in sciatic neurectomized rats.

PubMed

Iwamoto, Jun; Matsumoto, Hideo; Takeda, Tsuyoshi; Sato, Yoshihiro; Yeh, James K

2010-09-01

The purpose of the present study was to examine the effects of vitamin K2 on cortical and cancellous bone mass, cortical osteocyte and lacunar system, and porosity in sciatic neurectomized rats. Thirty-four female Sprague-Dawley retired breeder rats were randomized into three groups: age-matched control, sciatic neurectomy (NX), and NX + vitamin K2 administration (menatetrenone, 30 mg/kg/day p.o., three times a week). At the end of the 8-week experiment, bone histomorphometric analysis was performed on cortical and cancellous bone of the tibial diaphysis and proximal metaphysis, respectively, and osteocyte lacunar system and porosity were evaluated on cortical bone of the tibial diaphysis. NX decreased cortical and cancellous bone mass compared with age-matched controls as a result of increased endocortical and trabecular bone erosion and decreased trabecular mineral apposition rate (MAR). Vitamin K2 ameliorated the NX-induced increase in bone erosion, prevented the NX-induced decrease in MAR, and increased bone formation rate (BFR/bone surface) in cancellous bone, resulting in an attenuation of NX-induced cancellous bone loss. However, vitamin K2 did not significantly influence cortical bone mass. NX also decreased osteocyte density and lacunar occupancy and increased porosity in cortical bone compared with age-matched controls. Vitamin K2 ameliorated the NX-induced decrease in lacunar occupancy by viable osteocytes and the NX-induced increase in porosity. The present study showed the efficacy of vitamin K2 for cancellous bone mass and cortical lacunar occupancy by viable osteocytes and porosity in sciatic NX rats.

Preservation of volumetric bone density and geometry in trans women during cross-sex hormonal therapy: a prospective observational study.

PubMed

Van Caenegem, E; Wierckx, K; Taes, Y; Schreiner, T; Vandewalle, S; Toye, K; Kaufman, J-M; T'Sjoen, G

2015-01-01

Although trans women before the start of hormonal therapy have a less bone and muscle mass compared with control men, their bone mass and geometry are preserved during the first 2 years of hormonal therapy, despite of substantial muscle loss, illustrating the major role of estrogen in the male skeleton. The aim of this study is to examine the evolution of areal and volumetric bone density, geometry, and turnover in trans women undergoing sex steroid changes, during the first 2 years of hormonal therapy. In a prospective observational study, we examined 49 trans women (male-to-female) before and after 1 and 2 years of cross-sex hormonal therapy (CSH) in comparison with 49 age-matched control men measuring grip strength (hand dynamometer), areal bone mineral density (aBMD), and total body fat and lean mass using dual X-ray absorptiometry (DXA), bone geometry and volumetric bone mineral density, regional fat, and muscle area at the forearm and calf using peripheral quantitative computed tomography. Standardized treatment regimens were used with oral estradiol valerate, 4 mg daily (or transdermal 17-β estradiol 100 μg/24 h for patients >45 years old), both combined with oral cyproterone acetate 50 mg daily. Prior to CSH, trans women had lower aBMD at all measured sites (all p < 0.001), smaller cortical bone size (all p < 0.05), and lower muscle mass and strength and lean body mass (all p < 0.05) compared with control men. During CSH, muscle mass and strength decreased and all measures of fat mass increased (all p < 0.001). The aBMD increased at the femoral neck, radius, lumbar spine, and total body; cortical and trabecular bone remained stable and bone turnover markers decreased (all p < 0.05). Although trans women, before CSH, have a lower aBMD and cortical bone size compared with control men, their skeletal status is well preserved during CSH treatment, despite of substantial muscle loss.

Idiopathic toe-walking in children, adolescents and young adults: a matter of local or generalised stiffness?

PubMed Central

2011-01-01

Background Idiopathic Toe Walking (ITW) is present in children older than 3 years of age still walking on their toes without signs of neurological, orthopaedic or psychiatric diseases. ITW has been estimated to occur in 7% to 24% of the childhood population. To study associations between Idiopathic Toe Walking (ITW) and decrease in range of joint motion of the ankle joint. To study associations between ITW (with stiff ankles) and stiffness in other joints, muscle strength and bone density. Methods In a cross-sectional study, 362 healthy children, adolescents and young adults (mean age (sd): 14.2 (3.9) years) participated. Range of joint motion (ROM), muscle strength, anthropometrics sport activities and bone density were measured. Results A prevalence of 12% of ITW was found. Nine percent had ITW and severely restricted ROM of the ankle joint. Children with ITW had three times higher chance of severe ROM restriction of the ankle joint. Participants with ITW and stiff ankle joints had a decreased ROM in other joints, whereas bone density and muscle strength were comparable. Conclusion ITW and a decrease in ankle joint ROM might be due to local stiffness. Differential etiological diagnosis should be considered. PMID:21418634

Idiopathic toe-walking in children, adolescents and young adults: a matter of local or generalised stiffness?

PubMed

Engelbert, Raoul; Gorter, Jan Willem; Uiterwaal, Cuno; van de Putte, Elise; Helders, Paul

2011-03-21

Idiopathic Toe Walking (ITW) is present in children older than 3 years of age still walking on their toes without signs of neurological, orthopaedic or psychiatric diseases. ITW has been estimated to occur in 7% to 24% of the childhood population. To study associations between Idiopathic Toe Walking (ITW) and decrease in range of joint motion of the ankle joint. To study associations between ITW (with stiff ankles) and stiffness in other joints, muscle strength and bone density. In a cross-sectional study, 362 healthy children, adolescents and young adults (mean age (sd): 14.2 (3.9) years) participated. Range of joint motion (ROM), muscle strength, anthropometrics sport activities and bone density were measured. A prevalence of 12% of ITW was found. Nine percent had ITW and severely restricted ROM of the ankle joint. Children with ITW had three times higher chance of severe ROM restriction of the ankle joint. Participants with ITW and stiff ankle joints had a decreased ROM in other joints, whereas bone density and muscle strength were comparable. ITW and a decrease in ankle joint ROM might be due to local stiffness. Differential etiological diagnosis should be considered.

Characterization of bone microstructure using photoacoustic spectrum analysis

NASA Astrophysics Data System (ADS)

Feng, Ting; Kozloff, Kenneth M.; Xu, Guan; Du, Sidan; Yuan, Jie; Deng, Cheri X.; Wang, Xueding

2015-03-01

Osteoporosis is a progressive bone disease that is characterized by a decrease in bone mass and deterioration in microarchitecture. This study investigates the feasibility of characterizing bone microstructure by analyzing the frequency spectrum of the photoacoustic signals from the bone. Modeling and numerical simulation of photoacoustic signals and their frequency-domain analysis were performed on trabecular bones with different mineral densities. The resulting quasilinear photoacoustic spectra were fit by linear regression, from which spectral parameter slope can be quantified. The modeling demonstrates that, at an optical wavelength of 685 nm, bone specimens with lower mineral densities have higher slope. Preliminary experiment on osteoporosis rat tibia bones with different mineral contents has also been conducted. The finding from the experiment has a good agreement with the modeling, both demonstrating that the frequency-domain analysis of photoacoustic signals can provide objective assessment of bone microstructure and deterioration. Considering that photoacoustic measurement is non-ionizing, non-invasive, and has sufficient penetration in both calcified and noncalcified tissues, this new technology holds unique potential for clinical translation.

Vitamin K2 improves femoral bone strength without altering bone mineral density in gastrectomized rats.

PubMed

Iwamoto, Jun; Sato, Yoshihiro; Matsumoto, Hideo

2014-01-01

Gastrectomy (GX) induces osteopenia in rats. The present study examined the skeletal effects of vitamin K2 in GX rats. Thirty male Sprague-Dawley rats (12 wk old) were randomized by the stratified weight method into the following three groups of 10 animals each: sham operation (control) group; GX group; and GX+oral vitamin K2 (menatetrenone, 30 mg/kg, 5 d/wk) group. Treatment was initiated at 1 wk after surgery. After 6 wk of treatment, the bone mineral content (BMC), bone mineral density (BMD), and mechanical strength of the femoral diaphysis and distal metaphysis were determined by peripheral quantitative computed tomography and mechanical strength tests, respectively. GX induced decreases in the BMC, BMD, and ultimate force of the femoral diaphysis and distal metaphysis. Vitamin K2 did not significantly influence the BMC or BMD of the femoral diaphysis or distal metaphysis in GX rats, but attenuated the decrease in the ultimate force and increased the stiffness of the femoral diaphysis. The present study showed that administration of vitamin K2 to GX rats improved the bone strength of the femoral diaphysis without altering the BMC or BMD, suggesting effects of vitamin K2 on the cortical bone quality.

Cortical and Trabecular Bone Microstructure Did Not Recover at Weight-Bearing Skeletal Sites and Progressively Deteriorated at Non-Weight-Bearing Sites During the Year Following International Space Station Missions.

PubMed

Vico, Laurence; van Rietbergen, Bert; Vilayphiou, Nicolas; Linossier, Marie-Thérèse; Locrelle, Hervé; Normand, Myriam; Zouch, Mohamed; Gerbaix, Maude; Bonnet, Nicolas; Novikov, Valery; Thomas, Thierry; Vassilieva, Galina

2017-10-01

Risk for premature osteoporosis is a major health concern in astronauts and cosmonauts; the reversibility of the bone lost at the weight-bearing bone sites is not established, although it is suspected to take longer than the mission length. The bone three-dimensional structure and strength that could be uniquely affected by weightlessness is currently unknown. Our objective is to evaluate bone mass, microarchitecture, and strength of weight-bearing and non-weight-bearing bone in 13 cosmonauts before and for 12 months after a 4-month to 6-month sojourn in the International Space Station (ISS). Standard and advanced evaluations of trabecular and cortical parameters were performed using high-resolution peripheral quantitative computed tomography. In particular, cortical analyses involved determination of the largest common volume of each successive individual scan to improve the precision of cortical porosity and density measurements. Bone resorption and formation serum markers, and markers reflecting osteocyte activity or periosteal metabolism (sclerostin, periostin) were evaluated. At the tibia, in addition to decreased bone mineral densities at cortical and trabecular compartments, a 4% decrease in cortical thickness and a 15% increase in cortical porosity were observed at landing. Cortical size and density subsequently recovered and serum periostin changes were associated with cortical recovery during the year after landing. However, tibial cortical porosity or trabecular bone failed to recover, resulting in compromised strength. The radius, preserved at landing, unexpectedly developed postflight fragility, from 3 months post-landing onward, particularly in its cortical structure. Remodeling markers, uncoupled in favor of bone resorption at landing, returned to preflight values within 6 months, then declined farther to lower than preflight values. Our findings highlight the need for specific protective measures not only during, but also after spaceflight, because of continuing uncertainties regarding skeletal recovery long after landing. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

Grizzly bears (Ursus arctos horribilis) and black bears (Ursus americanus) prevent trabecular bone loss during disuse (hibernation).

PubMed

McGee-Lawrence, Meghan E; Wojda, Samantha J; Barlow, Lindsay N; Drummer, Thomas D; Castillo, Alesha B; Kennedy, Oran; Condon, Keith W; Auger, Janene; Black, Hal L; Nelson, O Lynne; Robbins, Charles T; Donahue, Seth W

2009-12-01

Disuse typically causes an imbalance in bone formation and bone resorption, leading to losses of cortical and trabecular bone. In contrast, bears maintain balanced intracortical remodeling and prevent cortical bone loss during disuse (hibernation). Trabecular bone, however, is more detrimentally affected than cortical bone in other animal models of disuse. Here we investigated the effects of hibernation on bone remodeling, architectural properties, and mineral density of grizzly bear (Ursus arctos horribilis) and black bear (Ursus americanus) trabecular bone in several skeletal locations. There were no differences in bone volume fraction or tissue mineral density between hibernating and active bears or between pre- and post-hibernation bears in the ilium, distal femur, or calcaneus. Though indices of cellular activity level (mineral apposition rate, osteoid thickness) decreased, trabecular bone resorption and formation indices remained balanced in hibernating grizzly bears. These data suggest that bears prevent bone loss during disuse by maintaining a balance between bone formation and bone resorption, which consequently preserves bone structure and strength. Further investigation of bone metabolism in hibernating bears may lead to the translation of mechanisms preventing disuse-induced bone loss in bears into novel treatments for osteoporosis.

Grizzly bears (Ursus arctos horribilis) and black bears (Ursus americanus) prevent trabecular bone loss during disuse (hibernation)

PubMed Central

McGee-Lawrence, Meghan E.; Wojda, Samantha J.; Barlow, Lindsay N.; Drummer, Thomas D.; Castillo, Alesha B.; Kennedy, Oran; Condon, Keith W.; Auger, Janene; Black, Hal L.; Nelson, O. Lynne; Robbins, Charles T.; Donahue, Seth W.

2009-01-01

Disuse typically causes an imbalance in bone formation and bone resorption, leading to losses of cortical and trabecular bone. In contrast, bears maintain balanced intracortical remodeling and prevent cortical bone loss during disuse (hibernation). Trabecular bone, however, is more detrimentally affected than cortical bone in other animal models of disuse. Here we investigated the effects of hibernation on bone remodeling, architectural properties, and mineral density of grizzly bear (Ursus arctos horribilis) and black bear (Ursus americanus) trabecular bone in several skeletal locations. There were no differences in bone volume fraction or tissue mineral density between hibernating and active bears or between pre- and post-hibernation bears in the ilium, distal femur, or calcaneus. Though indices of cellular activity level (mineral apposition rate, osteoid thickness) decreased, trabecular bone resorption and formation indices remained balanced in hibernating grizzly bears. These data suggest that bears prevent bone loss during disuse by maintaining a balance between bone formation and bone resorption, which consequently preserves bone structure and strength. Further investigation of bone metabolism in hibernating bears may lead to the translation of mechanisms preventing disuse induced bone loss in bears into novel treatments for osteoporosis. PMID:19703606

Loss of bone strength in HLA-B27 transgenic rats is characterized by a high bone turnover and is mainly osteoclast-driven.

PubMed

Rauner, Martina; Thiele, Sylvia; Fert, Ingrid; Araujo, Luiza M; Layh-Schmitt, Gerlinde; Colbert, Robert A; Hofbauer, Christine; Bernhardt, Ricardo; Bürki, Alexander; Schwiedrzik, Jakob; Zysset, Philippe K; Pietschmann, Peter; Taurog, Joel D; Breban, Maxime; Hofbauer, Lorenz C

2015-06-01

Although osteopenia is frequent in spondyloarthritis (SpA), the underlying cellular mechanisms and association with other symptoms are poorly understood. This study aimed to characterize bone loss during disease progression, determine cellular alterations, and assess the contribution of inflammatory bowel disease (IBD) to bone loss in HLA-B27 transgenic rats. Bones of 2-, 6-, and 12-month-old non-transgenic, disease-free HLA-B7 and disease-associated HLA-B27 transgenic rats were examined using peripheral quantitative computed tomography, μCT, and nanoindentation. Cellular characteristics were determined by histomorphometry and ex vivo cultures. The impact of IBD was determined using [21-3 x 283-2]F1 rats, which develop arthritis and spondylitis, but not IBD. HLA-B27 transgenic rats continuously lost bone mass with increasing age and had impaired bone material properties, leading to a 3-fold decrease in bone strength at 12 months of age. Bone turnover was increased in HLA-B27 transgenic rats, as evidenced by a 3-fold increase in bone formation and a 6-fold increase in bone resorption parameters. Enhanced osteoclastic markers were associated with a larger number of precursors in the bone marrow and a stronger osteoclastogenic response to RANKL or TNFα. Further, IBD-free [21-3 x 283-2]F1 rats also displayed decreased total and trabecular bone density. HLA-B27 transgenic rats lose an increasing amount of bone density and strength with progressing age, which is primarily mediated via increased bone remodeling in favor of bone resorption. Moreover, IBD and bone loss seem to be independent features of SpA in HLA-B27 transgenic rats. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

Impact of intra- and extra-osseous soft tissue composition on changes in bone mineral density with weight loss and regain.

PubMed

Bosy-Westphal, Anja; Later, Wiebke; Schautz, Britta; Lagerpusch, Merit; Goele, Kristin; Heller, Martin; Glüer, Claus-C; Müller, Manfred J

2011-07-01

Recent studies report a significant gain in bone mineral density (BMD) after diet-induced weight loss. This might be explained by a measurement artefact. We therefore investigated the impact of intra- and extra-osseous soft tissue composition on bone measurements by dual X-ray absorptiometry (DXA) in a longitudinal study of diet-induced weight loss and regain in 55 women and 17 men (19-46 years, BMI 28.2-46.8 kg/m(2)). Total and regional BMD were measured before and after 12.7 ± 2.2 week diet-induced weight loss and 6 months after significant weight regain (≥30%). Hydration of fat free mass (FFM) was assessed by a 3-compartment model. Skeletal muscle (SM) mass, extra-osseous adipose tissue, and bone marrow were measured by whole body magnetic resonance imaging (MRI). Mean weight loss was -9.2 ± 4.4 kg (P < 0.001) and was followed by weight regain in a subgroup of 24 subjects (+6.3 ± 2.9 kg; P < 0.001). With weight loss, bone marrow and extra-osseous adipose tissue decreased whereas BMD increased at the total body, lumbar spine, and the legs (women only) but decreased at the pelvis (men only, all P < 0.05). The decrease in BMD(pelvis) correlated with the loss in visceral adipose tissue (VAT) (P < 0.05). Increases in BMD(legs) were reversed after weight regain and inversely correlated with BMD(legs) decreases. No other associations between changes in BMD and intra- or extra-osseous soft tissue composition were found. In conclusion, changes in extra-osseous soft tissue composition had a minor contribution to changes in BMD with weight loss and decreases in bone marrow adipose tissue (BMAT) were not related to changes in BMD.

Reloading partly recovers bone mineral density and mechanical properties in hind limb unloaded rats

NASA Astrophysics Data System (ADS)

Zhao, Fan; Li, Dijie; Arfat, Yasir; Chen, Zhihao; Liu, Zonglin; Lin, Yu; Ding, Chong; Sun, Yulong; Hu, Lifang; Shang, Peng; Qian, Airong

2014-12-01

Skeletal unloading results in decreased bone formation and bone mass. During long-term space flight, the decreased bone mass is impossible to fully recover. Therefore, it is necessary to develop the effective countermeasures to prevent spaceflight-induced bone loss. Hindlimb Unloading (HLU) simulates effects of weightlessness and is utilized extensively to examine the response of musculoskeletal systems to certain aspects of space flight. The purpose of this study is to investigate the effects of a 4-week HLU in rats and subsequent reloading on the bone mineral density (BMD) and mechanical properties of load-bearing bones. After HLU for 4 weeks, the rats were then subjected to reloading for 1 week, 2 weeks and 3 weeks, and then the BMD of the femur, tibia and lumbar spine in rats were assessed by dual energy X-ray absorptiometry (DXA) every week. The mechanical properties of the femur were determined by three-point bending test. Dry bone and bone ash of femur were obtained through Oven-Drying method and were weighed respectively. Serum alkaline phosphatase (ALP) and serum calcium were examined through ELISA and Atomic Absorption Spectrometry. The results showed that 4 weeks of HLU significantly decreased body weight of rats and reloading for 1 week, 2 weeks or 3 weeks did not recover the weight loss induced by HLU. However, after 2 weeks of reloading, BMD of femur and tibia of HLU rats partly recovered (+10.4%, +2.3%). After 3 weeks of reloading, the reduction of BMD, energy absorption, bone mass and mechanical properties of bone induced by HLU recovered to some extent. The changes in serum ALP and serum calcium induced by HLU were also recovered after reloading. Our results indicate that a short period of reloading could not completely recover bone after a period of unloading, thus some interventions such as mechanical vibration or pharmaceuticals are necessary to help bone recovery.

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.

Reactive oxygen species on bone mineral density and mechanics in Cu,Zn superoxide dismutase (Sod1) knockout mice

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

Smietana, Michael J.; Arruda, Ellen M.; Mechanical Engineering, University of Michigan, 2250 GG Brown, 2350 Hayward, Ann Arbor, MI 48109

Research highlights: {yields} Reactive oxygen species (ROS) are considered to be a factor in the onset of a number of age-associated conditions, including loss of BMD. {yields} Cu,Zn-superoxide dismutase (Sod1) deficient mice have increased ROS, reduced bone mineral density, decreased bending stiffness, and decreased strength compared to WT controls. {yields} Increased ROS caused by the deficiency of Sod1, may be responsible for the changes in BMD and bone mechanics and therefore represent an appropriate model for studying mechanisms of age-associated bone loss. -- Abstract: Reactive oxygen species (ROS) play a role in a number of degenerative conditions including osteoporosis. Micemore » deficient in Cu,Zn-superoxide dismutase (Sod1) (Sod1{sup -/-} mice) have elevated oxidative stress and decreased muscle mass and strength compared to wild-type mice (WT) and appear to have an accelerated muscular aging phenotype. Thus, Sod1{sup -/-} mice may be a good model for evaluating the effects of free radical generation on diseases associated with aging. In this experiment, we tested the hypothesis that the structural integrity of bone as measured by bending stiffness (EI; N/mm{sup 2}) and strength (MPa) is diminished in Sod1{sup -/-} compared to WT mice. Femurs were obtained from male and female WT and Sod1{sup -/-} mice at 8 months of age and three-point bending tests were used to determine bending stiffness and strength. Bones were also analyzed for bone mineral density (BMD; mg/cc) using micro-computed tomography. Femurs were approximately equal in length across all groups, and there were no significant differences in BMD or EI with respect to gender in either genotype. Although male and female mice demonstrated similar properties within each genotype, Sod1{sup -/-} mice exhibited lower BMD and EI of femurs from both males and females compared with gender matched WT mice. Strength of femurs was also lower in Sod1{sup -/-} mice compared to WT as well as between genders. These data indicate that increased oxidative stress, due to the deficiency of Sod1 is associated with decreased bone stiffness and strength and Sod1{sup -/-} mice may represent an appropriate model for studying disease processes in aging bone.« less

Biomechanical study of the tibia in knee replacement revision.

PubMed

Quílez, M P; Pérez, M A; Seral-García, B

2015-01-01

The best management of severe bone defects following total knee replacement is still controversial. Metal augments, tantalum cones and porous tibial sleeves could help the surgeon to manage any type of bone loss, providing a stable and durable knee joint reconstruction. Five different types of prostheses have been analysed: one prosthesis with straight stem; two prostheses with offset stem, with and without supplement, and two prostheses with sleeves, with and without stem. The purpose of this study is to report a finite element study of revision knee tibial implants. The main objective was to analyse the tibial bone density changes and Von Misses tension changes following different tibial implant designs. In all cases, the bone density decreases in the proximal epiphysis and medullary channels, with a bone density increase also being predicted in the diaphysis and at the bone around the stems tips. The highest value of Von Misses stress has been obtained for the straight tibial stem, and the lowest for the stemless metaphyseal sleeves prosthesis. Copyright © 2014 SECOT. Published by Elsevier Espana. All rights reserved.

Coffee-associated osteoporosis offset by daily milk consumption. The Rancho Bernardo Study.

PubMed

Barrett-Connor, E; Chang, J C; Edelstein, S L

1994-01-26

To describe the association of lifetime intake of caffeinated coffee, in cup-years, to bone mineral density (BMD) of the hip and spine in postmenopausal women; and to determine the effect of regular milk intake on this association. Women from an established epidemiologic cohort had measures of BMD and gave a medical and behavioral history that included caffeinated coffee and daily milk intake between the ages of 12 and 18 years, 20 and 50 years, and 50 years of age and older. A community-based population of older women, Rancho Bernardo, Calif. All 980 postmenopausal women aged 50 to 98 years (mean age, 72.7 years) who participated between 1988 and 1991. Bone density at the hip and lumbar spine measured by dual energy x-ray absorptiometry. There was a statistically significant graded association between increasing lifetime intake of caffeinated coffee and decreasing BMD at both the hip and spine, independent of age, obesity, parity, years since menopause, and the use of tobacco, alcohol, estrogen, thiazides, and calcium supplements. Bone density did not vary by lifetime coffee intake in women who reported drinking at least one glass of milk per day during most of their adult lives. Lifetime caffeinated coffee intake equivalent to two cups per day is associated with decreased bone density in older women who do not drink milk on a daily basis.

IGF-1 and IGF-binding proteins and bone mass, geometry, and strength: relation to metabolic control in adolescent girls with type 1 diabetes.

PubMed

Moyer-Mileur, Laurie J; Slater, Hillarie; Jordan, Kristine C; Murray, Mary A

2008-12-01

Children and adolescents with poorly controlled type 1 diabetes mellitus (T1DM) are at risk for decreased bone mass. Growth hormone (GH) and its mediator, IGF-1, promote skeletal growth. Recent observations have suggested that children and adolescents with T1DM are at risk for decreased bone mineral acquisition. We examined the relationships between metabolic control, IGF-1 and its binding proteins (IGFBP-1, -3, -5), and bone mass in T1DM in adolescent girls 12-15 yr of age with T1DM (n = 11) and matched controls (n = 10). Subjects were admitted overnight and given a standardized diet. Periodic blood samples were obtained, and bone measurements were performed. Serum GH, IGFBP-1 and -5, glycosylated hemoglobin (HbA(1c)), glucose, and urine magnesium levels were higher and IGF-1 values were lower in T1DM compared with controls (p < 0.05). Whole body BMC/bone area (BA), femoral neck areal BMD (aBMD) and bone mineral apparent density (BMAD), and tibia cortical BMC were lower in T1DM (p < 0.05). Poor diabetes control predicted lower IGF-1 (r(2) = 0.21) and greater IGFBP-1 (r(2) = 0.39), IGFBP-5 (r(2) = 0.38), and bone-specific alkaline phosphatase (BALP; r(2) = 0.41, p < 0.05). Higher urine magnesium excretion predicted an overall shorter, lighter skeleton, and lower tibia cortical bone size, mineral, and density (r(2) = 0.44-0.75, p < 0.05). In the T1DM cohort, earlier age at diagnosis was predictive of lower IGF-1, higher urine magnesium excretion, and lighter, thinner cortical bone (r(2) >or=0.45, p < 0.01). We conclude that poor metabolic control alters the GH/IGF-1 axis, whereas greater urine magnesium excretion may reflect subtle changes in renal function and/or glucosuria leading to altered bone size and density in adolescent girls with T1DM.

Effects of growth hormone therapy on bone density and fracture risk in age-related osteoporosis in the absence of growth hormone deficiency: a systematic review and meta-analysis.

PubMed

Barake, Maya; Arabi, Asma; Nakhoul, Nancy; El-Hajj Fuleihan, Ghada; El Ghandour, Sarah; Klibanski, Anne; Tritos, Nicholas A

2018-01-01

In adults, growth hormone deficiency (GHD) has been associated with low bone mineral density (BMD), an effect counteracted by growth hormone (GH) replacement. Whether GH is beneficial in adults with age-related bone loss and without hypopituitarism is unclear. We conducted a systematic literature search using Medline, Embase and the Cochrane Register of Controlled Trials. We extracted and analyzed data according to the bone outcome included [bone mineral content (BMC), BMD, and bone biomarker, fracture risk]. We performed a meta-analysis when possible. We included eight studies. Seven randomized 272 post-menopausal women, 61-69 years, to GH or control, for 6-24 months, and the eighth was an extension trial. Except for one study, all women received concurrent osteoporosis therapies. There was no significant effect of GH, as compared to control, on BMD at the lumbar spine (Weighted mean difference WMD = -0.01 [-0.04, 0.02]), total hip (WMD = 0 [-0.05, 0.06]) or femoral neck (WMD = 0 [-0.03, 0.04]). Similarly, no effect was seen on BMC. GH significantly increased the bone formation marker procollagen type-I carboxy-terminal propeptide (PICP) (WMD = 14.03 [2.68, 25.38]). GH resulted in a trend for increase in osteocalcin and in bone resorption markers. Patients who received GH had a significant decrease in fracture risk as compared to control (RR = 0.63 [0.46, 0.87]). Reported adverse events were not major, mostly related to fluid retention. GH may not improve bone density in women with age-related bone loss but may decrease fracture risk. Larger studies of longer duration are needed to further explore these findings in both genders, and to investigate the effect of GH on bone quality.

Cyst-Like Osteolytic Formations in Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2) Augmented Sheep Spinal Fusion.

PubMed

Pan, Hsin Chuan; Lee, Soonchul; Ting, Kang; Shen, Jia; Wang, Chenchao; Nguyen, Alan; Berthiaume, Emily A; Zara, Janette N; Turner, A Simon; Seim, Howard B; Kwak, Jin Hee; Zhang, Xinli; Soo, Chia

2017-07-01

Multiple case reports using recombinant human bone morphogenetic protein-2 (rhBMP-2) have reported complications. However, the local adverse effects of rhBMP-2 application are not well documented. In this report we show that, in addition to promoting lumbar spinal fusion through potent osteogenic effects, rhBMP-2 augmentation promotes local cyst-like osteolytic formations in sheep trabecular bones that have undergone anterior lumbar interbody fusion. Three months after operation, conventional computed tomography showed that the trabecular bones of the rhBMP-2 application groups could fuse, whereas no fusion was observed in the control group. Micro-computed tomography analysis revealed that the core implant area's bone volume fraction and bone mineral density increased proportionately with rhBMP-2 dose. Multiple cyst-like bone voids were observed in peri-implant areas when using rhBMP-2 applications, and these sites showed significant bone mineral density decreases in relation to the unaffected regions. Biomechanically, these areas decreased in strength by 32% in comparison with noncystic areas. Histologically, rhBMP-2-affected void sites had an increased amount of fatty marrow, thinner trabecular bones, and significantly more adiponectin- and cathepsin K-positive cells. Despite promoting successful fusion, rhBMP-2 use in clinical applications may result in local adverse structural alterations and compromised biomechanical changes to the bone. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Role of Pitavastatin in Prevention of Osteopenic Changes in Ovariectomized Rats.

PubMed

Qadir, Farida; Alam, Syed Mahboob; Zehra, Tabassum; Mehmood, Ahmar; Siddiqi, Abeer Qamar

2016-01-01

To determine the effect of pitavastatin, a third generation statin, on development of osteopenia in ovariectomized rats. Experimental study. Department of Pharmacology, Basic Medical Sciences Institute, Jinnah Postgraduate Medical Center, Karachi, from January to July 2013. Forty female Sprague Dawley rats were divided into ovariectomized (OVX), Sham OVX and OVX given pitavastatin 0.4 mg/kg/day, 0.8 mg/kg/day, for 8 weeks. Bone density measurements using CT scan and Archimedes’ principle were made on femora and tibiae. Blood samples were analyzed for acid phosphatase (ACP) and alkaline phosphatase (ALP) levels. Ovariectomy-induced osteopenic changes were indicated by significant decrease in bone densities and Hounsfield (HU) index of distal femoral and proximal tibial metaphyses and elevation of ACP and ALP levels. 0.4 mg/kg pitavastatin did not significantly alter the evaluated parameters. 0.8 mg/kg produced a restoration of HU of lower femur and femoral density comparable to Sham. HU of upper tibia and tibial density following 0.8 mg/kg was significantly higher than OVX but was not approximate to Sham. ALP and ACP with 0.8 mg/kg were comparable to Sham. Supra-therapeutic dose of pitavastatin was effective in preventing estrogen deficiency-induced decrease in bone density of ovariectomized rates, over an 8-week period.

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

Disrupted Bone Metabolism in Long-Term Bedridden Patients

PubMed Central

Endo, Naoto; Uchiyama, Seiji; Takahashi, Yoshinori; Kawashima, Hiroyuki; Watanabe, Kei

2016-01-01

Background Bedridden patients are at risk of osteoporosis and fractures, although the long-term bone metabolic processes in these patients are poorly understood. Therefore, we aimed to determine how long-term bed confinement affects bone metabolism. Methods This study included 36 patients who had been bedridden from birth due to severe immobility. Bone mineral density and bone metabolism markers were compared to the bedridden period in all study patients. Changes in the bone metabolism markers during a follow-up of 12 years were studied in 17 patients aged <30 years at baseline. Results The bone mineral density was reduced (0.58±0.19 g/cm3), and the osteocalcin (13.9±12.4 ng/mL) and urine N-terminal telopeptide (NTX) levels (146.9±134.0 mM BCE/mM creatinine) were greater than the cutoff value for predicting fracture. Among the bone metabolism markers studied, osteocalcin and NTX were negatively associated with the bedridden period. During the follow-up, osteocalcin and parathyroid hormone were decreased, and the 25(OH) vitamin D was increased. NTX at baseline was negatively associated with bone mineral density after 12 years. Conclusions Unique bone metabolic abnormalities were found in patients who had been bedridden for long periods, and these metabolic abnormalities were altered by further bed confinement. Appropriate treatment based on the unique bone metabolic changes may be important in long-term bedridden patients. PMID:27275738

Disrupted Bone Metabolism in Long-Term Bedridden Patients.

PubMed

Eimori, Keiko; Endo, Naoto; Uchiyama, Seiji; Takahashi, Yoshinori; Kawashima, Hiroyuki; Watanabe, Kei

2016-01-01

Bedridden patients are at risk of osteoporosis and fractures, although the long-term bone metabolic processes in these patients are poorly understood. Therefore, we aimed to determine how long-term bed confinement affects bone metabolism. This study included 36 patients who had been bedridden from birth due to severe immobility. Bone mineral density and bone metabolism markers were compared to the bedridden period in all study patients. Changes in the bone metabolism markers during a follow-up of 12 years were studied in 17 patients aged <30 years at baseline. The bone mineral density was reduced (0.58±0.19 g/cm3), and the osteocalcin (13.9±12.4 ng/mL) and urine N-terminal telopeptide (NTX) levels (146.9±134.0 mM BCE/mM creatinine) were greater than the cutoff value for predicting fracture. Among the bone metabolism markers studied, osteocalcin and NTX were negatively associated with the bedridden period. During the follow-up, osteocalcin and parathyroid hormone were decreased, and the 25(OH) vitamin D was increased. NTX at baseline was negatively associated with bone mineral density after 12 years. Unique bone metabolic abnormalities were found in patients who had been bedridden for long periods, and these metabolic abnormalities were altered by further bed confinement. Appropriate treatment based on the unique bone metabolic changes may be important in long-term bedridden patients.

Low-dosage micronized 17 beta-estradiol prevents bone loss in postmenopausal women

NASA Technical Reports Server (NTRS)

Ettinger, B.; Genant, H. K.; Steiger, P.; Madvig, P.

1992-01-01

With the use of a double-blind, randomized, dose-ranging design, we tested during an 18-month period the degree of protection against postmenopausal bone loss afforded by micronized 17 beta-estradiol in dosages of 0.5, 1.0, and 2.0 mg. All subjects received supplementation to ensure a minimum of 1500 mg calcium daily. Fifty-one subjects completed at least 1 year of follow-up bone density measurements by quantitative computed tomography and by single- and dual-photon absorptiometry. In the placebo group spinal trabecular bone density decreased 4.9% annually (p less than 0.001), whereas in those taking micronized 17 beta-estradiol bone density tended to increase (annual increases of 0.3% in the 0.5 mg micronized 17 beta-estradiol group, 1.8% in the 1.0 mg micronized 17 beta-estradiol group, and 2.5% in the 2.0 mg micronized 17 beta-estradiol group). After completing the double-blind phase, 41 subjects completed an additional 18 months of follow-up while taking 1.0 mg micronized 17 beta-estradiol. During this time one third of the subjects were randomly assigned to discontinue calcium supplements. Among those who previously received placebo, trabecular bone density increased 4.3% annually, whereas among those who had used micronized 17 beta-estradiol, trabecular bone density response was inversely related to the dosage previously used. Additionally and independently, the level of calcium intake showed a statistically significant correlation with the change in spinal trabecular bone density (r = 0.37, p = 0.02). We conclude that micronized 17 beta-estradiol has a continuous skeletal dose-response effect in the range of 0.5 to 2.0 mg and that calcium intake positively modifies the skeletal response to 1.0 mg micronized 17 beta-estradiol.

Is cortical bone hip? What determines cortical bone properties?

PubMed

Epstein, Sol

2007-07-01

Increased bone turnover may produce a disturbance in bone structure which may result in fracture. In cortical bone, both reduction in turnover and increase in hip bone mineral density (BMD) may be necessary to decrease hip fracture risk and may require relatively greater proportionate changes than for trabecular bone. It should also be noted that increased porosity produces disproportionate reduction in bone strength, and studies have shown that increased cortical porosity and decreased cortical thickness are associated with hip fracture. Continued studies for determining the causes of bone strength and deterioration show distinct promise. Osteocyte viability has been observed to be an indicator of bone strength, with viability as the result of maintaining physiological levels of loading and osteocyte apoptosis as the result of a decrease in loading. Osteocyte apoptosis and decrease are major factors in the bone loss and fracture associated with aging. Both the osteocyte and periosteal cell layer are assuming greater importance in the process of maintaining skeletal integrity as our knowledge of these cells expand, as well being a target for pharmacological agents to reduce fracture especially in cortical bone. The bisphosphonate alendronate has been seen to have a positive effect on cortical bone by allowing customary periosteal growth, while reducing the rate of endocortical bone remodeling and slowing bone loss from the endocortical surface. Risedronate treatment effects were attributed to decrease in bone resorption and thus a decrease in fracture risk. Ibandronate has been seen to increase BMD as the spine and femur as well as a reduced incidence of new vertebral fractures and non vertebral on subset post hoc analysis. And treatment with the anabolic agent PTH(1-34) documented modeling and remodelling of quiescent and active bone surfaces. Receptor activator of nuclear factor kappa B ligand (RANKL) plays a key role in bone destruction, and the human monoclonal antibody denosumab binds to RANKL, inhibiting its action and thus improving BMD significantly.

Noninvasive markers of bone metabolism in the rhesus monkey: normal effects of age and gender

NASA Technical Reports Server (NTRS)

Cahoon, S.; Boden, S. D.; Gould, K. G.; Vailas, A. C.

1996-01-01

Measurement of bone turnover in conditions such as osteoporosis has been limited by the need for invasive iliac bone biopsy to reliably determine parameters of bone metabolism. Recent advances in the area of serum and urinary markers of bone metabolism have raised the possibility for noninvasive measurements; however, little nonhuman primate data exist for these parameters. The purpose of this experiment was to define the normal range and variability of several of the newer noninvasive bone markers which are currently under investigation in humans. The primary intent was to determine age and gender variability, as well as provide some normative data for future experiments in nonhuman primates. Twenty-four rhesus macaques were divided into equal groups of male and female according to the following age groupings: 3 years, 5-10 years, 15-20 years, and > 25 years. Urine was collected three times daily for a four-day period and measured for several markers of bone turnoverm including pyridinoline (PYD), deoxypyrodinoline (DPD), hydroxyproline, and creatinine. Bone mineral density measurements of the lumbar spine were performed at the beginning and end of the study period. Serum was also obtained at the time of bone densitometry for measurement of osteocalcin levels by radioimmunoassay. There were no significant differences in bone mineral density, urine PYD, or urine DPD based on gender. Bone density was lowest in the youngest animals, peaked in the 15-20-year group, but again decreased in the oldest animals. The osteocalcin, PYD, and DPD levels followed an inversely related pattern to bone density. The most important result was the relative age insensitivity of the ratio of PYD:DPD in monkeys up to age 20 years. Since bone density changes take months or years to become measurable and iliac biopsies are invasive, the PYD/DPD marker ratio may have important implications for rapid noninvasive measurement of the effects of potential treatments for osteoporosis in the non-human primate model.

Low Bone Density

MedlinePlus

... Bone Density Exam/Testing › Low Bone Density Low Bone Density Low bone density is when your bone ... to people with normal bone density. Detecting Low Bone Density A bone density test will determine whether ...

Bone mineral density at the hip predicts mortality in elderly men.

PubMed

Trivedi, D P; Khaw, K T

2001-01-01

Low bone density as assessed by calcaneal ultrasound has been associated with mortality in elderly men and women. We examined the relationship between bone density measured at the hip and all cause and cardiovascular mortality in elderly men. Men aged 65-76 years from the general community were recruited from general practices in Cambridge between 1991 and 1995. At baseline survey, data collection included health questionnaires, measures of anthropometry and cardiovascular risk factors, as well as bone mineral density (BMD) measured using dual energy X-ray absorptiometry. All men have been followed up for vital status up to December 1999. BMD was significantly inversely related to mortality from all causes and cardiovascular disease, with decreasing rates with increasing bone density quartile, and an approximate halving of risk between the bottom and top quartile (p < 0.002, test for trend all causes and p < 0.025, test for trend for cardiovascular deaths). In multivariate analyses using the Cox proportional hazards model, an increase of 1 standard deviation (0.144 g/cm2) in total hip bone density was significantly associated with an age-adjusted 0.77 relative risk (95% CI 0.66-0.91) for all-cause mortality and 0.76 relative risk (95% CI 0.62-0.93) for cardiovascular disease mortality. The association remained significant after adjusting for age, body mass index, cigarette smoking status, serum cholesterol, systolic blood pressure, past history of heart attack, stroke or cancer and other lifestyle factors which included use of alcohol, physical activity and general health status. Low bone density at the hip is thus a strong and independent predictor of all-cause and cardiovascular mortality in older men.

Comparison of bone density in amenorrheic women due to athletics, weight loss, and premature menopause.

PubMed

Jones, K P; Ravnikar, V A; Tulchinsky, D; Schiff, I

1985-07-01

Studied was the peripheral bone density of 39 women (ages 18 to 43) with the diagnosis of secondary amenorrhea in an effort to define the population of amenorrheic women at risk for osteoporosis. Eight women had exercise-induced amenorrhea (athletes), 20 women had amenorrhea associated with weight loss, and 11 women had premature menopause. These diagnoses were made on the basis of history, physical examination, and luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin levels, and failure to have withdrawal bleeding after the administration of progestin. Twenty-five nonathletic, normally menstruating women served as control subjects. The peripheral bone density of the amenorrheic athletes (0.738 g/cm2 +/- 0.047) was not significantly different from that of the controls (0.726 g/cm2 +/- 0.044). The average bone density of the group with weight loss-associated amenorrhea (0.672 g/cm2 +/- 0.066) was significantly less than controls (P less than .005) as was that of the women with premature menopause (0.616 g/cm2 +/- 0.048, P less than .001). There was a significant correlation between months of amenorrhea and decrease in bone density (r = 0.506, P less than .001). From this study it was concluded that women with exercise-associated amenorrhea are not at significant risk for cortical bone loss as measured by direct photon absorptiometry. Women with weight loss-associated amenorrhea and women with premature menopause are at significant risk for bone loss when compared with normal controls.

The effects of soy isoflavone on bone density in north region of climacteric Chinese women

PubMed Central

Chi, Xiao-Xing; Zhang, Tao

2013-01-01

Only a few investigations were based on limb bone density. This study evaluated the efficacy of soy isoflavone in the treatment of the principal menopausal disorders, limb bone density and the role of pathway. The research protocol involved the random subdivision of the enrolled sample into two groups of 40 women, who were to receive treatment for 6 months with isoflavone (90 mg/day) and with placebo. All of the patients were asked to fill in a questionnaire concerning their complaints. BMD of the radius and tibia were measured using quantitative ultrasound. Bone metabolism indexes calcium, phosphorus and alkaline phosphatase (ALP) were examined regularly. Serum cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) examined by ELISA. The results of the score of Kupperman table showed that the isoflavone can lead to a significant reduction in some of the disorders. Compared with placebo, the tibia bone density in isoflavone group increased obviously against the base value before trail. Isoflavone led to a stronger descent of the concentration of ALP and a decrease of IL-6 and TNF-α level than placebo. For climacteric women, soy isoflavone in the dose of 90 mg/day could improve some menopausal syndromes and was effective on increasing limb bone density, which maybe had the relationship with the levels of IL-6, TNF-α and ALP in serum. PMID:24062607

Glycinol Enhances Osteogenic Differentiation and Attenuates the Effects of Aging on Bone Marrow-derived Mesenchymal Stem Cells

USDA-ARS?s Scientific Manuscript database

Osteoporosis is characterized by decreased bone mineral density and increased risk of fractures. It is most prevalent in the elderly population, leading to significant morbidity and mortality. Recently, phytoestrogens have gained significant attention as an alternative therapy due to their structura...

Bone Fractures with Sodium-Glucose Co-transporter-2 Inhibitors: How Real is the Risk?

PubMed

Mannucci, Edoardo; Monami, Matteo

2017-02-01

This article succinctly summarizes the available evidence on the risk of bone fractures with sodium-glucose co-transporter-2 inhibitors. The US Food and Drug Administration has strengthened the warning for canagliflozin related to the increased risk of bone fractures, and added new information about decreased bone mineral density. The agency has also said that it will evaluate the risk of bone fractures with other drugs in the sodium-glucose co-transporter-2 inhibitor class. Increases in parathyroid hormone levels and decreases in 1,25-dihydroxyvitamin D levels have been postulated as possible mechanisms. In contrast, some studies with dapagliflozin have shown no effects on bone health. Because a consensus has not been reached, we believe that an expert opinion on how to interpret the available evidence would be of great benefit for clinicians.

Decline in bone mineral density with stress fractures in a woman on depot medroxyprogesterone acetate. A case report.

PubMed

Harkins, G J; Davis, G D; Dettori, J; Hibbert, M L; Hoyt, R A

1999-03-01

Depot medroxyprogesterone acetate is a popular contraceptive among young, physically active women. However, its administration has been linked to a relative decrease in estrogen levels. Since bone resorption is accelerated during hypoestrogenic states, there has been growing concern about the potential development of osteoporosis and fractures with the use of this contraceptive method. A physically active, 33-year-old woman demonstrated a 12.4% drop in femoral neck bone mineral density (BMD), 6.4% drop in lumbar BMD and 0.8% drop in total BMD with the subsequent development of a tibial stress fracture while on depot medroxyprogesterone acetate. Bone mineralization rapidly improved, and the stress fracture resolved with discontinuation of the medication. The long-term effects of depot medroxyprogesterone acetate on bone mineralization in physically active women should be evaluated more thoroughly.

Bone mineral density trends in Indian patients with hyperthyroidism--effect of antithyroid therapy.

PubMed

Dhanwal, Dinesh Kumar; Gupta, Nandita

2011-09-01

Hyperthyroidism is associated with bone loss, which is reversible after treatment. The extent of reversibility of loss of bone mass density (BMD) in hyperthyroid patients after treatment especially at forearm is not clear. Therefore, the present study was conducted to assess degree of reversibility in bone mineral density following one-year medical treatment in Indian patients with hyperthyroidism. A total of 30 consecutive patients with hyperthyroidism were included in this one year study at All India Institute of Medical Sciences, New Delhi, India. All the patients were assessed for parameters of bone mineral homeostasis such as calcium, phosphorous, alkaline phosphatase, 25-hydroxy vitamin D [25 (OH) D], parathyroid hormone (PTH) at the time of diagnosis and after one year medical treatment. Bone mineral density was measured using Hologic DXA scan at hip, spine and forearm. All the patients received medical therapy with carbimazole. The parameters of bone homeostasis and bone mineral density at base line and after one year medical treatment was compared. All patients attained euthyroid status after eight weeks of carbimazole therapy. Parameters of bone homeostasis such as calcium, phosphorous, 25 (OH) D and PTH did not show any significant change from base line. Bone mineral density expressed as bone mineral content in gm/cm2 at left hip neck, trochanteric and intertrochanteric region was significantly higher after carbimazole therapy (745.2 +/- 127.6 gm/cm2 vs. 688.2 +/- 123.5 gm/cm2; p = 0.02, 573.4 +/- 109.9 gm/cm2 vs. 641.0 +/- 138.0 gm/cm2, p = 0.005 and 1008.6 +/- 185.5 gm/cm2 vs. 938.0 +/- 145.3 gm/cm2 p = 0.0131 respectively). Bone mineral density at lumbar spine expressed as either T and Z score was significantly higher after treatment (10 months of euthyroid state) (-0.6 +/- 1.3 vs. -1.7 +/- 1.2, p = 0.013 and -0.4 +/- 1.2 vs. -1.4 +/- 1.2, p = 0.012 respectively). However Bone mineral measures as T and Z score at left forearm decreased significantly after one year of medical therapy. In Indian patients with hyperthyroidism, the pattern of recovery of bone loss after one year of antithyroid therapy suggests early recovery at hip and lumbar spine and deterioration at forearm.

SECONDARY OSTEOPOROSIS: PATHOPHYSIOLOGY AND MANAGEMENT

PubMed Central

Mirza, Faryal; Canalis, Ernesto

2015-01-01

Osteoporosis is a skeletal disorder characterized by decreased bone mineral density and compromised bone strength predisposing to an increased risk of fractures. Although idiopathic osteoporosis is the most common form of osteoporosis, secondary factors may contribute to the bone loss and increased fracture risk in patients presenting with fragility fractures or osteoporosis. Several medical conditions and medications significantly increase the risk for bone loss and skeletal fragility. This review focuses on some of the common causes of osteoporosis, addressing the underlying mechanisms, diagnostic approach and treatment of low bone mass in the presence of these conditions. PMID:25971649

Ghrelin plasma levels, gastric ghrelin cell density and bone mineral density in women with rheumatoid arthritis

PubMed Central

Maksud, F.A.N.; Kakehasi, A.M.; Guimarães, M.F.B.R.; Machado, C.J.; Barbosa, A.J.A.

2017-01-01

Generalized bone loss can be considered an extra-articular manifestation of rheumatoid arthritis (RA) that may lead to the occurrence of fractures, resulting in decreased quality of life and increased healthcare costs. The peptide ghrelin has demonstrated to positively affect osteoblasts in vitro and has anti-inflammatory actions, but the studies that correlate ghrelin plasma levels and RA have contradictory results. We aimed to evaluate the correlation between total ghrelin plasma levels, density of ghrelin-immunoreactive cells in the gastric mucosa, and bone mineral density (BMD) in twenty adult women with established RA with 6 months or more of symptoms (mean age of 52.70±11.40 years). Patients with RA presented higher ghrelin-immunoreactive cells density in gastric mucosa (P=0.008) compared with healthy females. There was a positive relationship between femoral neck BMD and gastric ghrelin cell density (P=0.007). However, these same patients presented a negative correlation between plasma ghrelin levels and total femoral BMD (P=0.03). The present results indicate that ghrelin may be involved in bone metabolism of patients with RA. However, the higher density of ghrelin-producing cells in the gastric mucosa of these patients does not seem to induce a corresponding elevation in the plasma levels of this peptide. PMID:28538835

Ghrelin plasma levels, gastric ghrelin cell density and bone mineral density in women with rheumatoid arthritis.

PubMed

Maksud, F A N; Kakehasi, A M; Guimarães, M F B R; Machado, C J; Barbosa, A J A

2017-05-18

Generalized bone loss can be considered an extra-articular manifestation of rheumatoid arthritis (RA) that may lead to the occurrence of fractures, resulting in decreased quality of life and increased healthcare costs. The peptide ghrelin has demonstrated to positively affect osteoblasts in vitro and has anti-inflammatory actions, but the studies that correlate ghrelin plasma levels and RA have contradictory results. We aimed to evaluate the correlation between total ghrelin plasma levels, density of ghrelin-immunoreactive cells in the gastric mucosa, and bone mineral density (BMD) in twenty adult women with established RA with 6 months or more of symptoms (mean age of 52.70±11.40 years). Patients with RA presented higher ghrelin-immunoreactive cells density in gastric mucosa (P=0.008) compared with healthy females. There was a positive relationship between femoral neck BMD and gastric ghrelin cell density (P=0.007). However, these same patients presented a negative correlation between plasma ghrelin levels and total femoral BMD (P=0.03). The present results indicate that ghrelin may be involved in bone metabolism of patients with RA. However, the higher density of ghrelin-producing cells in the gastric mucosa of these patients does not seem to induce a corresponding elevation in the plasma levels of this peptide.

Gain-of-function mutation in FGFR3 in mice leads to decreased bone mass by affecting both osteoblastogenesis and osteoclastogenesis

PubMed Central

Su, Nan; Sun, Qidi; Li, Can; Lu, Xiumin; Qi, Huabing; Chen, Siyu; Yang, Jing; Du, Xiaolan; Zhao, Ling; He, Qifen; Jin, Min; Shen, Yue; Chen, Di; Chen, Lin

2010-01-01

Achondroplasia (ACH) is a short-limbed dwarfism resulting from gain-of-function mutations in fibroblast growth factor receptor 3 (FGFR3). Previous studies have shown that ACH patients have impaired chondrogenesis, but the effects of FGFR3 on bone formation and bone remodeling at adult stages of ACH have not been fully investigated. Using micro-computed tomography and histomorphometric analyses, we found that 2-month-old Fgfr3G369C/+ mice (mouse model mimicking human ACH) showed decreased bone mass due to reduced trabecular bone volume and bone mineral density, defect in bone mineralization and increased osteoclast numbers and activity. Compared with primary cultures of bone marrow stromal cells (BMSCs) from wild-type mice, Fgfr3G369C/+ cultures showed decreased cell proliferation, increased osteogenic differentiation including up-regulation of alkaline phosphatase activity and expressions of osteoblast marker genes, and reduced bone matrix mineralization. Furthermore, our studies also suggest that decreased cell proliferation and enhanced osteogenic differentiation observed in Fgfr3G369C/+ BMSCs are caused by up-regulation of p38 phosphorylation and that enhanced Erk1/2 activity is responsible for the impaired bone matrix mineralization. In addition, in vitro osteoclast formation and bone resorption assays demonstrated that osteoclast numbers and bone resorption area were increased in cultured bone marrow cells derived from Fgfr3G369C/+ mice. These findings demonstrate that gain-of-function mutation in FGFR3 leads to decreased bone mass by regulating both osteoblast and osteoclast activities. Our studies provide new insight into the mechanism underlying the development of ACH. PMID:20053668

Environmental exposure to cadmium at a level insufficient to induce renal tubular dysfunction does not affect bone density among female Japanese farmers.

PubMed

Horiguchi, Hyogo; Oguma, Etsuko; Sasaki, Satoshi; Miyamoto, Kayoko; Ikeda, Yoko; Machida, Munehito; Kayama, Fujio

2005-01-01

Some recent research suggests that environmental exposure to cadmium, even at low levels, may increase the risk of osteoporosis, and that the bone demineralization is not just a secondary effect of renal dysfunction induced by high doses of cadmium as previously reported. To investigate the effect of exposure to cadmium at a level insufficient to induce kidney damage on bone mineral density (BMD) and bone metabolism, we conducted health examinations on 1380 female farmers from five districts in Japan who consumed rice contaminated by low-to-moderate levels of cadmium. We collected peripheral blood and urine samples and medical and nutritional information, and measured forearm BMD. Analysis of the data for subjects grouped by urinary cadmium level and age-related menstrual status suggested that cadmium accelerates both the increase of urinary calcium excretion around the time of menopause and the subsequent decrease in bone density after menopause. However, multivariate analyses showed no significant contribution of cadmium to bone density or urinary calcium excretion, indicating that the results mentioned above were confounded by other factors. These results indicate that environmental exposure to cadmium at levels insufficient to induce renal dysfunction does not increase the risk of osteoporosis, strongly supporting the established explanation for bone injury induced by cadmium as a secondary effect.

Biomechanical evaluation of tibial bone adaptation after revision total knee arthroplasty: A comparison of different implant systems

PubMed Central

Quilez, María Paz; Seral, Belen; Pérez, María Angeles

2017-01-01

The best methods to manage tibial bone defects following total knee arthroplasty remain under debate. Different fixation systems exist to help surgeons reconstruct knee osseous bone loss (such as tantalum cones, cement, modular metal augments, autografts, allografts and porous metaphyseal sleeves) However, the effects of the various solutions on the long-term outcome remain unknown. In the present work, a bone remodeling mathematical model was used to predict bone remodeling after total knee arthroplasty (TKA) revision. Five different types of prostheses were analyzed: one with a straight stem; two with offset stems, with and without supplements; and two with sleeves, with and without stems. Alterations in tibia bone density distribution and implant Von Mises stresses were quantified. In all cases, the bone density decreased in the proximal epiphysis and medullary channels, and an increase in bone density was predicted in the diaphysis and around stem tips. The highest bone resorption was predicted for the offset prosthesis without the supplement, and the highest bone formation was computed for the straight stem. The highest Von Mises stress was obtained for the straight tibial stem, and the lowest was observed for the stemless metaphyseal sleeves prosthesis. The computational model predicted different behaviors among the five systems. We were able to demonstrate the importance of choosing an adequate revision system and that in silico models may help surgeons choose patient-specific treatments. PMID:28886100

An essential role for the association of CD47 to SHPS-1 in skeletal remodeling.

PubMed

Maile, Laura A; DeMambro, Victoria E; Wai, Christine; Lotinun, Sutada; Aday, Ariel W; Capps, Byron E; Beamer, Wesley G; Rosen, Clifford J; Clemmons, David R

2011-09-01

Integrin-associated protein (IAP/CD47) has been implicated in macrophage-macrophage fusion. To understand the actions of CD47 on skeletal remodeling, we compared Cd47(-/-) mice with Cd47(+/+) controls. Cd47(-/-) mice weighed less and had decreased areal bone mineral density compared with controls. Cd47(-/-) femurs were shorter in length with thinner cortices and exhibited lower trabecular bone volume owing to decreased trabecular number and thickness. Histomorphometry revealed reduced bone-formation and mineral apposition rates, accompanied by decreased osteoblast numbers. No differences in osteoclast number were observed despite a nonsignificant but 40% decrease in eroded surface/bone surface in Cd47(-/-) mice. In vitro, the number of functional osteoclasts formed by differentiating Cd47(-/-) bone marrow cells was significantly decreased compared with wild-type cultures and was associated with a decrease in bone-resorption capacity. Furthermore, by disrupting the CD47-SHPS-1 association, we found that osteoclastogenesis was markedly impaired. Assays for markers of osteoclast maturation suggested that the defect was at the point of fusion and not differentiation and was associated with a lack of SHPS-1 phosphorylation, SHP-1 phosphatase recruitment, and subsequent dephosphorylation of non-muscle cell myosin IIA. We also demonstrated a significant decrease in osteoblastogenesis in bone marrow stromal cells derived from Cd47(-/-) mice. Our finding of cell-autonomous defects in Cd47(-/-) osteoblast and osteoclast differentiation coupled with the pronounced skeletal phenotype of Cd47(-/-) mice support the conclusion that CD47 plays an important role in regulating skeletal acquisition and maintenance through its actions on both bone formation and bone resorption. Copyright © 2011 American Society for Bone and Mineral Research.

The conclusiveness of less-invasive imaging techniques (computer tomography, X-ray) with regard to their identification of bone diseases in a primate model (Callithrix jacchus).

PubMed

Grohmann, J; Taetzner, S; Theuss, T; Kuehnel, F; Buchwald, U; Einspanier, A

2012-04-01

Although common marmosets seem to be appropriate animal models to examine bone diseases, no data about the conclusiveness of less-invasive techniques are available. Therefore, the aim was to combine different techniques to analyse changes in bone metabolism of common marmosets with bone diseases. Five monkeys were examined by X-ray, computer tomography (CT), histology and immunohistochemistry (IHC). Monkeys with lowest bone mineral density (BMD) showed increased bone marrow, decreased cancellous bone and decreased contrast in X-ray. Highest alkaline phosphatase (AP)-levels were detected in bones with low elastic modulus. Expression of osteopontin (OPN), osteocalcin (OC) and runt-related transcriptions factor 2 (RUNX 2) was detected in bones with high modulus. No expression was present in bones with lower modulus. Collagen type I and V were found in every bone. In conclusion, CT, X-ray and AP are useful techniques to detect bone diseases in common marmosets. These observations could be confirmed by IHC. © 2012 John Wiley & Sons A/S.

Hyperthyroidism and Hypothyroidism in Male Mice and Their Effects on Bone Mass, Bone Turnover, and the Wnt Inhibitors Sclerostin and Dickkopf-1.

PubMed

Tsourdi, Elena; Rijntjes, Eddy; Köhrle, Josef; Hofbauer, Lorenz C; Rauner, Martina

2015-10-01

Thyroid hormones are key regulators of bone homeostasis, and Wnt signaling has been implicated in thyroid hormone-associated bone loss. Here we tested whether hyperthyroidism and hypothyroidism interfere with dickkopf-1 (DKK1) and sclerostin, two inhibitors of Wnt signaling. Twelve-week-old male C57BL/6 mice were rendered either hyperthyroid or hypothyroid. Hyperthyroid mice displayed decreased trabecular (-54%, P < .001) and cortical bone density (-5%, P < .05) and reduced cortical thickness (-15%, P < .001), whereas hypothyroid mice showed a higher trabecular bone density (+26%, P < .001) with unchanged cortical bone parameters. Histomorphometry and biochemical markers of bone remodeling indicated high bone turnover in hyperthyroid mice and low bone turnover in hypothyroid mice. In vivo, serum DKK1 concentrations were decreased in hyperthyroid mice (-24%, P < .001) and increased in hypothyroid mice (+18%, P < .01). The increase of the number of DKK1-positive cells in hypothyroid mice was confirmed at the tissue level. Interestingly, sclerostin was increased in both disease models, although to a higher extent in hyperthyroid mice (+50%, P < .001, and +24%, P < .05). Serum sclerostin concentrations adjusted for bone mass were increased by 3.3-fold in hyperthyroid (P < .001) but not in hypothyroid mice. Consistently, sclerostin mRNA expression and the number of sclerostin-positive cells were increased in hyperthyroid but not in hypothyroid mice. Our data show that thyroid hormone-induced changes in bone remodeling are associated with a divergent regulation of DKK1 and sclerostin. Thus, the modulation of Wnt signaling by thyroid hormones may contribute to thyroid hormone-associated bone disease and altered expression of Wnt inhibitors may emerge as potential therapeutic targets.

Risedronate and ergocalciferol prevent hip fracture in elderly men with Parkinson disease.

PubMed

Sato, Yoshihiro; Honda, Yoshiaki; Iwamoto, Jun

2007-03-20

There is a high incidence of hip fractures in patients with Parkinson disease (PD). Bone mineral density (BMD) is decreased in patients with PD, correlating with the immobilization-induced bone resorption and hypovitaminosis D with compensatory hyperparathyroidism. To evaluate the effectiveness of risedronate, an inhibitor of bone resorption, on osteoporosis and the risk of hip fractures in elderly men with PD. This was a 2-year, randomized, double-blind, placebo-controlled trial. In a prospective study of patients with PD, 121 patients received a daily dose of 2.5 mg risedronate and vitamin D2 1,000 IU for 2 years, and the remaining 121 received placebo and vitamin D2 1,000 IU. Incidence of hip fractures was compared between the two groups. Nine patients sustained hip fractures in the placebo group, and three hip fractures occurred in the risedronate group. The relative risk of a hip fracture in the risedronate group vs the placebo group was 0.33 (95% CI, 0.09 to 1.20). BMD increased by 2.2% in the risedronate group and decreased by 2.9% in the placebo group (p < 0.0001). Urinary deoxypyridinoline, a bone resorption marker, decreased by 46.7% in the risedronate group and by 33.0% in the placebo group. Treatment with risedronate and vitamin D2 increases bone mineral density in elderly men with Parkinson disease and reduces the risk of hip fractures.

Associations between bone-alkaline phosphatase and bone mineral density in adults with and without diabetes

PubMed Central

Chen, Hailing; Li, Jufen; Wang, Qian

2018-01-01

Abstract Insufficient evidence is available to reliably compare the roles of bone alkaline phosphatase (BAP) and bone mineral density (BMD) in diabetes. This study aimed to compare associations between BAP and BMD in adults with and without diabetes to elucidate fracture risk in diabetes. Data were extracted from the National Health and Nutrition Examination Survey (NHANES), 2001–2004, including 4197 adults aged 20 to 49 years, 143 with diabetes (DM group), and 4054 without (non-DM group). Main outcome measure was BMD and regression analyses were performed to identify serum BAP and other covariates associated with total BMD. BMD decreased significantly in DM patients when BAP was increased. In the non-DM group, all BMD results were significantly decreased when BAP was increased. Factors associated with total BMD varied with DM status. Lifestyle measures such as smoking and physical activity were also associated with BMD in the non-DM group. BAP and BMD are inversely associated in DM and non-DM patients. BAP is significantly associated with BMD after controlling for other variables, suggesting that BAP may interact with other factors altering bone metabolism in DM patients. PMID:29702995

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.

Vertebral fractures assessed with dual-energy X-ray absorptiometry in patients with Addison's disease on glucocorticoid and mineralocorticoid replacement therapy.

PubMed

Camozzi, Valentina; Betterle, Corrado; Frigo, Anna Chiara; Zaccariotto, Veronica; Zaninotto, Martina; De Caneva, Erica; Lucato, Paola; Gomiero, Walter; Garelli, Silvia; Sabbadin, Chiara; Salvà, Monica; Costa, Miriam Dalla; Boscaro, Marco; Luisetto, Giovanni

2018-02-01

to assess bone damage and metabolic abnormalities in patients with Addison's disease given replacement doses of glucocorticoids and mineralocorticoids. A total of 87 patients and 81 age-matched and sex-matched healthy controls were studied. The following parameters were measured: urinary cortisol, serum calcium, phosphorus, creatinine, 24-h urinary calcium excretion, bone alkaline phosphatase, parathyroid hormone, serum CrossLaps, 25 hydroxyvitamin D, and 1,25 dihydroxyvitamin D. Clear vertebral images were obtained with dual-energy X-ray absorptiometry in 61 Addison's disease patients and 47 controls and assessed using Genant's classification. Nineteen Addison's disease patients (31.1%) had at least one morphometric vertebral fracture, as opposed to six controls (12.8%, odds ratio 3.09, 95% confidence interval 1.12-8.52). There were no significant differences in bone mineral density parameters at any site between patients and controls. In Addison's disease patients, there was a positive correlation between urinary cortisol and urinary calcium excretion. Patients with fractures had a longer history of disease than those without fractures. Patients taking fludrocortisone had a higher bone mineral density than untreated patients at all sites except the lumbar spine. Addison's disease patients have more fragile bones irrespective of any decrease in bone mineral density. Supra-physiological doses of glucocorticoids and longer-standing disease (with a consequently higher glucocorticoid intake) might be the main causes behind patients' increased bone fragility. Associated mineralocorticoid treatment seems to have a protective effect on bone mineral density.

Repeated superovulation increases the risk of osteoporosis and cardiovascular diseases by accelerating ovarian aging in mice.

PubMed

Zhang, Jinjin; Lai, Zhiwen; Shi, Liangyan; Tian, Yong; Luo, Aiyue; Xu, Zheyuan; Ma, Xiangyi; Wang, Shixuan

2018-05-22

Superovulation procedures and assisted reproductive technologies have been widely used to treat couples who have infertility problems. Although generally safe, the superovulation procedures are associated with a series of complications, such as ovarian hyper-stimulation syndrome, thromboembolism, and adnexal torsion. The role of long-term repeated superovulation in ovarian aging and especially in associated disorders such as osteoporosis and cardiovascular diseases is still unclear. In this study, we sought to determine if repeated superovulation by ten cycles of treatment with pregnant mare serum gonadotropin/human chorionic gonadotropin could affect ovarian reserve, ovarian function, bone density and heart function. Ovarian reserve and function were reflected by the size of the primordial follicle pool, anti-Mullerian hormone expressions, hormone levels and fertility status. Furthermore, we examined bone density and heart function by microCT and cardiovascular ultrasonography, respectively. After repeated superovulation, the size of the primordial follicle pool and the expression of anti-mullerian hormone decreased, along with the concentrations of estrogen and progesterone. Mice exposed to repeated superovulation showed an obvious decrease in fertility and fecundity. Furthermore, both bone density and heart ejection fraction significantly decreased. These results suggest that repeated superovulation may increase the risk of osteoporosis and cardiovascular diseases by accelerating ovarian aging.

Citrus juice modulates bone strength in male senescent rat model of osteoporosis.

PubMed

Deyhim, Farzad; Garica, Kristy; Lopez, Erica; Gonzalez, Julia; Ino, Sumiyo; Garcia, Michelle; Patil, Bhimanagouda S

2006-05-01

An experiment evaluated the effect of citrus juice on enhancing serum antioxidant status and on osteoporosis prevention in orchidectomized rats. Thirty-six 1-y-old male rats were randomized to two groups: a sham-control group (n = 9) and an orchidectomized group (n = 27). The orchidectomized group was divided into three groups of nine and assigned to one of the following treatments: orchidectomy, orchidectomy plus orange juice, and orchidectomy plus grapefruit juice. Sixty days after initiation of the study, all rats were killed, blood was collected, and serum was harvested for total antioxidant status and indices of bone formation and resorption. Femoral density and biomechanical properties were monitored. Orchidectomy decreased (P < 0.05) total antioxidant capacity, femoral density, and biomechanical properties and increased (P < 0.05) alkaline phosphatase, acid phosphatase, and urinary excretion of hydroxyproline compared with the sham-control group. In contrast to orchidectomy, orchidectomy plus orange juice and orchidectomy plus grapefruit juice reversed (P < 0.05) orchidectomy-induced antioxidant suppression, decreased (P < 0.05) alkaline phosphatase and acid phosphatase activities, moderately restored (P = 0.07) femoral density, increased (P < 0.05) femoral strength, significantly delayed time-induced femoral fracture, and decreased (P < 0.05) urinary excretion of hydroxyproline. The present study supports the supposition in that drinking citrus juice positively affects serum antioxidant status and bone strength.

Correlation Between Bone Density and Instantaneous Torque at Implant Site Preparation: A Validation on Polyurethane Foam Blocks of a Device Assessing Density of Jawbones.

PubMed

Di Stefano, Danilo Alessio; Arosio, Paolo

2016-01-01

Bone density at implant placement sites is one of the key factors affecting implant primary stability, which is a determinant for implant osseointegration and rehabilitation success. Site-specific bone density assessment is, therefore, of paramount importance. Recently, an implant micromotor endowed with an instantaneous torque-measuring system has been introduced. The aim of this study was to assess the reliability of this system. Five blocks with different densities (0.16, 0.26, 0.33, 0.49, and 0.65 g/cm(3)) were used. A single trained operator measured the density of one of them (0.33 g/cm(3)), by means of five different devices (20 measurements/device). The five resulting datasets were analyzed through the analysis of variance (ANOVA) model to investigate interdevice variability. As differences were not significant (P = .41), the five devices were each assigned to a different operator, who collected 20 density measurements for each block, both under irrigation (I) and without irrigation (NI). Measurements were pooled and averaged for each block, and their correlation with the actual block-density values was investigated using linear regression analysis. The possible effect of irrigation on density measurement was additionally assessed. Different devices provided reproducible, homogenous results. No significant interoperator variability was observed. Within the physiologic range of densities (> 0.30 g/cm(3)), the linear regression analysis showed a significant linear correlation between the mean torque measurements and the actual bone densities under both drilling conditions (r = 0.990 [I], r = 0.999 [NI]). Calibration lines were drawn under both conditions. Values collected under irrigation were lower than those collected without irrigation at all densities. The NI/I mean torque ratio was shown to decrease linearly with density (r = 0.998). The mean error introduced by the device-operator system was less than 10% in the range of normal jawbone density. Measurements performed with the device were linearly correlated with the blocks' bone densities. The results validate the device as an objective intraoperative tool for bone-density assessment that may contribute to proper jawbone-density evaluation and implant-insertion planning.

Prior ankle fractures in postmenopausal women are associated with low areal bone mineral density and bone microstructure alterations.

PubMed

Biver, E; Durosier, C; Chevalley, T; Herrmann, F R; Ferrari, S; Rizzoli, R

2015-08-01

In a cross-sectional analysis in postmenopausal women, prior ankle fractures were associated with lower areal bone mineral density (BMD) and trabecular bone alterations compared to no fracture history. Compared to women with forearm fractures, microstructure alterations were of lower magnitude. These data suggest that ankle fractures are another manifestation of bone fragility. Whether ankle fractures represent fragility fractures associated with low areal bone mineral density (aBMD) and volumetric bone mineral density (vBMD) and/or bone microstructure alterations remains unclear, in contrast to the well-recognised association between forearm fractures and osteoporosis. The objective of this study was to investigate aBMD, vBMD and bone microstructure in postmenopausal women with prior ankle fracture in adulthood, compared with women without prior fracture or with women with prior forearm fractures, considered as typically of osteoporotic origin. In a cross-sectional analysis in the Geneva Retirees Cohort study, 63 women with ankle fracture and 59 with forearm fracture were compared to 433 women without fracture (mean age, 65 ± 1 years). aBMD was measured by dual-energy X-ray absorptiometry; distal radius and tibia vBMD and bone microstructure were measured by high-resolution peripheral quantitative computed tomography. Compared with women without fracture, those with ankle fractures had lower aBMD, radius vBMD (-7.9%), trabecular density (-10.7%), number (-7.3%) and thickness (-4.6%) and higher trabecular spacing (+14.5%) (P < 0.05 for all). Tibia trabecular variables were also altered. For 1 standard deviation decrease in total hip aBMD or radius trabecular density, odds ratios for ankle fractures were 2.2 and 1.6, respectively, vs 2.2 and 2.7 for forearm fracture, respectively (P ≤ 0.001 for all). Compared to women with forearm fractures, those with ankle fractures had similar spine and hip aBMD, but microstructure alterations of lower magnitude. Women with ankle fractures have lower aBMD and vBMD and trabecular bone alterations, suggesting that ankle fractures are another manifestation of bone fragility.

Possible therapeutic potential of berberine in diabetic osteopathy.

PubMed

Rahigude, A B; Kaulaskar, S V; Bhutada, P S

2012-10-01

Diabetic osteopathy is a complication that leads to decreased bone mineral density, bone formation and having high risk of fractures that heals slowly. Diabetic osteopathy is a result of increase in osteoclastogenesis and decrease in osteoblastogenesis. Various factors viz., oxidative stress, increased inflammatory markers, PPAR-γ activation in osteoblast, activation of apoptotic pathway, increased glucose levels and inhibitory effect on parathyroid hormone etc. are mainly responsible for decreased bone mineral density. Berberine is an isoquinoline alkaloid widely used in Asian countries as a traditional medicine. Berberine is extensively reported to be an antioxidant, anti-inflammatory, antidiabetic, and having potential to treat diabetic complications and glucocorticoid induced osteoporosis. The osteoclastogenesis decreasing property of berberine can be hypothesized for inhibiting diabetic osteopathy. In addition, chronic treatment of berberine will be helpful for increasing the osteoblastic activity and expression of the modulators that affect osteoblastic differentiation. The apoptotic pathways stimulated due to increased inflammatory markers and nucleic acid damages could be reduced due to berberine. Another important consideration that berberine is having stimulatory effect on glucagon like peptide release and insulin sensitization that will be helpful for decreasing glucose levels and therefore, may exerts osteogenesis. Thiazolidinediones show bone loss due to activation of PPAR-γ in osteoblasts, whereas berberine stimulates PPAR-γ only in adipocytes and not in osteoblasts, and therefore the decreased bone loss due to use of thiazolidinediones may not be observed in berberine treatment conditions. Berberine decreases the advanced glycation end-products (AGE) formation in diabetic condition which will be ultimately helpful to decrease the stiffness of collagen fibers due to AGE-induced cross linking. Lastly, it is also reported that berberine has inhibitory effect on parathyroid hormone and enhances marker genes like osteocalcin, which are responsible for the osteoblastic activity. From these evidences, we hypothesized that berberine may have potential in the treatment of diabetic osteopathy. Copyright © 2012 Elsevier Ltd. All rights reserved.

Black bears with longer disuse (hibernation) periods have lower femoral osteon population density and greater mineralization and intracortical porosity.

PubMed

Wojda, Samantha J; Weyland, David R; Gray, Sarah K; McGee-Lawrence, Meghan E; Drummer, Thomas D; Donahue, Seth W

2013-08-01

Intracortical bone remodeling is persistent throughout life, leading to age related increases in osteon population density (OPD). Intracortical porosity also increases with age in many mammals including humans, contributing to bone fragility and fracture risk. Unbalanced bone resorption and formation during disuse (e.g., physical inactivity) also increases intracortical porosity. In contrast, hibernating bears are a naturally occurring model for the prevention of both age-related and disuse osteoporoses. Intracortical bone remodeling is decreased during hibernation, but resorption and formation remain balanced. Black bears spend 0.25-7 months in hibernation annually depending on climate and food availability. We found longer hibernating bears demonstrate lower OPD and higher cortical bone mineralization than bears with shorter hibernation durations, but we surprisingly found longer hibernating bears had higher intracortical porosity. However, bears from three different latitudes showed age-related decreases in intracortical porosity, indicating that regardless of hibernation duration, black bears do not show the disuse- or age-related increases in intracortical porosity which is typical of other animals. This ability to prevent increases in intracortical porosity likely contributes to their ability to maintain bone strength during prolonged periods of physical inactivity and throughout life. Improving our understanding of the unique bone metabolism in hibernating bears will potentially increase our ability to develop treatments for age- and disuse-related osteoporoses in humans. Copyright © 2013 Wiley Periodicals, Inc.

Effects of cadmium, calcium, age and parity on bone mineral, density and strength in female rats

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

Hammond, B.F.

Weanling female rats were fed diets containing one of three levels of calcium and one of four levels of cadmium in the drinking water. Approximately 10 animals from each group were sacrificed after the first pregnancy and the remaining animals after the fourth pregnancy. Reproductive performance, plasma and bone Ca and P and bone density and strength were measured. After the first pregnancy, offspring of dams treated with 5 or 10 ppM Cd were smaller at birth than offspring of dams treated with 0 or 1 ppM Cd. Offspring of dams fed 5 or 10 ppM Cd or the 0.3%more » Ca diet had decreased weaning weight regardless of parity. Cadmium treatment had no effect on the plasma Ca or the Ca-P ratio. At Cd levels of 5 or 10 ppM the plasma P was increased. The 0.3% Ca diet depressed the plasma Ca and the 0.9% Ca diet elevated the plasma Ca and depressed the plasma P when compared to the 0.6% diet. Parity did not affect plasma Ca but, after four pregnancies, plasma P was decreased. Plasma Ca of mature dams was higher than that of adolescent dams but plasma P was unaffected. Bone mineral, density and strength were decreased by the 0.3% Ca diet especially when Cd levels reached 10 ppM. Increasing dietary Ca above normal increased femur Ca of dams fed 1 ppM Cd but did not increase the Ca of the femur of dams given higher levels of Cd. After the first pregnancy, femur Ca of mature dams was greater than that of adolescent dams. After the fourth pregnancy, femurs of mature dams were less strong than those of adolescent dams; however, the density was the same. Increasing dietary Ca above 0.6% lessened the detrimental effects of 5 ppM Cd ingestion on bone density. Mature dams were less affected by the 0.3% Ca 10 ppM Cd treatment than were adolescent dams. 60 refs., 3 figs., 26 tabs.« less

Effects of electromagnetic radiation exposure on bone mineral density, thyroid, and oxidative stress index in electrical workers

PubMed Central

Kunt, Halil; Şentürk, İhsan; Gönül, Yücel; Korkmaz, Mehmet; Ahsen, Ahmet; Hazman, Ömer; Bal, Ahmet; Genç, Abdurrahman; Songur, Ahmet

2016-01-01

Background In the literature, some articles report that the incidence of numerous diseases increases among the individuals who live around high-voltage electric transmission lines (HVETL) or are exposed vocationally. However, it was not investigated whether HVETL affect bone metabolism, oxidative stress, and the prevalence of thyroid nodule. Methods Dual-energy X-ray absorptiometry (DEXA) bone density measurements, serum free triiodothyronine (FT3), free thyroxine (FT4), RANK, RANKL, osteoprotegerin (OPG), alkaline phosphatase (ALP), phosphor, total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) levels were analyzed to investigate this effect. Results Bone mineral density levels of L1–L4 vertebrae and femur were observed significantly lower in the electrical workers. ALP, phosphor, RANK, RANKL, TOS, OSI, and anteroposterior diameter of the left thyroid lobe levels were significantly higher, and OPG, TAS, and FT4 levels were detected significantly lower in the study group when compared with the control group. Conclusion Consequently, it was observed that the balance between construction and destruction in the bone metabolism of the electrical workers who were employed in HVETL replaced toward destruction and led to a decrease in OPG levels and an increase in RANK and RANKL levels. In line with the previous studies, long-term exposure to an electromagnetic field causes disorders in many organs and systems. Thus, it is considered that long-term exposure to an electromagnetic field affects bone and thyroid metabolism and also increases OSI by increasing the TOS and decreasing the antioxidant status. PMID:26929645

Thermal evaluation by infrared measurement of implant site preparation between single and gradual drilling in artificial bone blocks of different densities.

PubMed

Möhlhenrich, S C; Abouridouane, M; Heussen, N; Hölzle, F; Klocke, F; Modabber, A

2016-11-01

The aim of this study was to investigate the influence of bone density and drilling protocol on heat generation during implant bed preparation. Ten single and 10 gradual implant sites with diameters of 2.8, 3.5, and 4.2mm were prepared in four artificial bone blocks (density types I-IV; D1-D4). Drilling was done at constant speed (1500rpm) and with external irrigation (50ml/min); vertical speed was set at 2mm/s. An infrared camera was used for temperature measurements. Significantly higher temperatures for single drilling were found between 2.8-mm drills in D1 (P=0.0014) and D4 (P<0.0001) and between 3.5-mm drills in D3 (P=0.0087) and D4 (P<0.0001), as well as between 4.2-mm drills in D1 (P<0.0001) and D4 (P=0.0014). Low bone density led to a thermal decrease after single drilling and a thermal increase after gradual drilling. Burs with a large diameter always showed a higher temperature generation. In comparisons between 2.8- and 4.2-mm diameters for both single and gradual drills, significant differences (P<0.001) were noted for bone types II, III, and IV. Single drilling could generate more heat than traditional sequential drilling, and bone density, as well as drill diameter, influenced thermal increases. Particularly in lower-density bone, conventional sequential drilling seems to raise the temperature less. Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

BMI, hypertension and low bone mineral density in adult men and women.

PubMed

Szklarska, Alicja; Lipowicz, Anna

2012-08-01

The aim of this work was to estimate the body mass index (BMI) at which risk of hypertension is lowest in men and women, while concurrently considering the protective role of adipose tissue in osteoporosis. Healthy, occupationally active inhabitants of the city of Wrocław, Poland, 1218 women and 434 men were studied. BMI, systolic and diastolic blood pressures, bone mineral density (BMD) of the trabecular compartment and distal radius of the non-dominant hand were recorded. Overweight in young women (≤45 years) was associated with increased risk of hypertension, whereas the risk of low bone mineral was decreased for the same BMI. In older women (>45 years), a BMI>27 was the threshold for increased risk of hypertension. In this age group, extremely slim women (BMI<21) had the highest risk of low bone mineral density. In younger males (≤45 years), risk of hypertension was lowest among the thinnest subjects (BMI<21). Increase in BMI over 21 kg/m(2) increased the risk of hypertension. The probability of low bone mineral density was the same in all BMI categories of men. In older men (>45 years), the thinnest (BMI<21) had higher risk of hypertension. To begin from BMI=25 kg/m(2), there was a monotonous increase in risk of hypertension in men. Higher risk for low bone mineral density was observed in older men with the BMI<23. Among younger adults, risk of hypertension and low bone mineral density increase at BMI≥21 kg/m(2) in men and BMI≥23 kg/m(2) in women. Among older men and women, the BMI threshold was 27 kg/m(2). Copyright © 2012 Elsevier GmbH. All rights reserved.

The effects of bone on proton NMR relaxation times of surrounding liquids

NASA Technical Reports Server (NTRS)

Davis, C. A.; Genant, H. K.; Dunham, J. S.

1986-01-01

Preliminary attempts by our group at UCSF to assess fat content of vertebral marrow in the lumbar spine using relaxation time information demonstrated that the presence of trabecular bone affects relaxation times. The objective of this work was a thorough study of the effects of bone on NMR relaxation characteristics of surrounding liquids. Trabecular bone from autopsy specimens was ground up and sifted into a series of powders with graded densities ranging from 0.3 gm/cc to 0.8 gm/cc. Each powder was placed first in n-saline and then in cottonseed oil. With spectroscopy, spin-lattice relaxation times (T1) and effective spin-spin relaxation times (T2*) were measured for each liquid in each bone powder. As bone density and surface to volume ratio increased, T1 decreased faster for saline than for oil. T2* decreased significantly for both water and oil as the surface to volume ratio increased. It was concluded that effects of water on T1 could be explained by a surface interaction at the bone/liquid interface, which restricted rotational and translational motion of nearby molecules. The T1s of oil were not affected since oil molecules are nonpolar, do not participate in significant intermolecular hydrogen bonding, and therefore would not be expected to interact strongly with the bone surface. Effects on T2* could be explained by local magnetic field inhomogeneities created by discontinuous magnetic susceptibility near the bone surface. These preliminary results suggest that water in contact with trabecular bone in vivo will exhibit shortened relaxation times.

Men and Women in Space: Bone Loss and Kidney Stone Risk after Long-Duration Space Flight

NASA Technical Reports Server (NTRS)

Smith, Scott M.; Zwart, Sara R.; Heer, Martina; Hudson, Edgar, K.; Shackelford, Linda; Morgan, Jennifer L. L.

2014-01-01

Bone loss on Earth is more prevalent in women than men, leading to the assumption that women may be at greater risk from bone loss during flight. Until recently, the number of women having flown long-duration missions was too small to allow any type of statistical analysis. We report here data from 42 astronauts on long-duration missions to the International Space Station, 33 men and 9 women. Bone mineral density (dual-energy X-ray absorptiometry), bone biochemistry (from blood and urine samples), and renal stone risk factors were evaluated before and after flight. Data were analyzed in two groups, based on available resistance exercise equipment. The response of bone mineral density to flight was the same for men and women, and the typical decrease in bone mineral density (whole body and/or regional) after flight was not observed for either sex for those using an Advanced Resistive Exercise Device. Bone biochemistry, specifically markers of formation and resorption, generally responded similarly in male and female astronauts. The response of urinary supersaturation risk to space flight was not significantly different between men and women, although risks were typically increased after flight in both groups and risks were generally greater in men than in women before and after flight. Overall, the bone and renal stone responses of men and women to space flight were not different.

Radiological features of the skull in Klinefelter's syndrome and male hypogonadism.

PubMed

Kosowicz, J; Rzymski, K

1975-07-01

Skull radiographs were performed in 21 cases of Klinefelter's syndrome and in 30 cases of eunuchoidism. The radiographic changes of the skull in Klinefelter's syndrome are: temporal flattening, decreased width of the vault, narrowing of the mandible, decreased length of the skull, shortening of the anterior fossa cranii, decrease in the angle of the base, thinning of the vault bones at the major fontanelle, premature and excessive calcification of the coronal suture, deepening of the posterior fossa and shortening of the mandibular rami. In hypogonadotropic eunuchoidism the skull radiographs show: small mastoid processes, fine bones of the vault, small sella turcica, club-shaped clinoid processes, excessive development of sphenoidal sinuses and in the fourth and later decades of life a diminished bone density (osteoporosis).

A 14-day ground-based hypokinesia study in nonhuman primates: A compilation of results

NASA Technical Reports Server (NTRS)

Kazarian, L.; Cann, C. E.; Parfitt, M.; Simmons, D.; Morey-Holton, E.

1981-01-01

A 14 day ground based hypokinesia study with rhesus monkeys was conducted to determine if a spaceflight of similar duration might affect bone remodeling and calcium homeostatis. The monkeys were placed in total body casts and sacrificed either immediately upon decasting or 14 days after decasting. Changes in vertebral strength were noted and further deterioration of bone strength continued during the recovery phase. Resorption in the vertebrae increased dramatically while formation decreased. Cortical bone formation was impaired in the long bones. The immobilized animals showed a progressive decrease in total serum calcium which rebounded upon remobilization. Most mandibular parameters remained unchanged during casting except for retardation of osteon birth or maturation rate and density distribution of matrix and mineral moieties.

Supplementing with Opuntia ficus-indica Mill and Dioscorea nipponica Makino extracts synergistically attenuates menopausal symptoms in estrogen-deficient rats.

PubMed

Ko, Byoung-Seob; Lee, Hye Won; Kim, Da Sol; Kang, Suna; Ryuk, Jin Ah; Park, Sunmin

2014-08-08

Prickly pear cactus grown in Korea (Opuntia ficus-indica Mill, KC) and Buchema (Dioscorea nipponica Makino, B) have been traditionally used in East Asia and South America to treat various metabolic diseases. The aim of the present study was to determine whether the extracts of KC, B, and KC+B can prevent the impairments of energy, glucose, lipid and bone homeostasis in estrogen-deficient ovariectomized (OVX) rats and to explore their mechanisms. OVX rats were divided into 4 groups and fed high fat diets supplemented with either 3% dextrin (control), 3% KC, 3% B or 1.5% KC+1.5% B. Sham rats were fed 3% dextrin. After 12 weeks of diet consumption, energy, lipid, glucose and bone metabolisms were analyzed and Wnt signaling in the femur and hepatic signaling were determined. OVX impaired energy, glucose and lipid metabolism and decreased uterine and bone masses. B and KC+B prevented the decrease in energy expenditure, especially from fat oxidation, in OVX rats, but did not affect food intake. KC+B and B reduced body weight and visceral fat levels, as compared to the OVX-control, by decreasing fat synthesis and inhibiting FAS and SREBP-1c expression. KC+B and B prevented the increases in serum lipid levels and insulin resistance by improving hepatic insulin signaling (pIRS→pAkt→pGSK-3β). KC and KC+B also prevented decreases in bone mineral density (BMD) in the femur and lumbar spine in OVX rats. This was related to decreased expressions of bone turnover markers such as serum osteocalcin, alkaline phosphatase (ALP) and bone-specific ALP levels, and increased serum P levels. KC and KC+B upregulated low-density lipoprotein receptor-related protein 5 and β-catenin in OVX rats, but suppressed the expression of dickkopf-related protein 1. B alone improved energy, lipid and glucose homeostasis, but not bone loss, whereas KC alone enhanced BMD, but not energy, lipid or glucose homeostasis. KC+B synergistically attenuated impairments of bone, energy, lipid and glucose metabolism by OVX, suggesting potential efficacy of the combination for alleviating menopausal symptoms. Copyright © 2014. Published by Elsevier Ireland Ltd.

Bone and mineral metabolism in adult celiac disease

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

Caraceni, M.P.; Molteni, N.; Bardella, M.T.

1988-03-01

Bone mineral density (/sup 125/I photon absorptiometry) was lower in 20 untreated adult celiac patients than in sex- and age-matched controls (p less than 0.001), and plasma alkaline phosphatase, parathyroid hormone, urinary hydroxyproline/creatinine levels were higher than normal (p less than 0.05, less than 0.001, less than 0.05, respectively). Gluten-free diet was started, and the patients were divided randomly into two treatment groups, one which received oral 25-hydroxyvitamin D 50 micrograms/day and one which did not. After 12 months' treatment, bone turnover markers showed a decrease, which did not reach statistical significance, and bone mineral density did not show significantmore » modifications compared with base line in either group. It was found that a gluten-free diet followed for 1 yr can prevent further bone loss, but no significant differences were detected between the two groups.« less

Evaluation of cortical bone mass, thickness and density by z-scores in osteopenic conditions and in relation to menopause and estrogen treatment

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

Meema, S.; Meema, H.E.

1982-08-01

Z-scores express, differences from normals in standard deviation units, and are particularly useful for comparison of changes where normal values are age- and sex-dependent. We determined z-scores for bone mineral mass, cortical thickness, and bone mineral density in the radius in various conditions and diseases in both sexes. In the males, z-scores were calculated for age, but in the females z-scores for menopausal status (years postmenopausal exclusive of years on estrogen treatment) were found to be more appropriate. With few exceptions, changes in a disease were of a similar order in both sexes. For bone minerals mass few mean z-scoresmore » were significantly increased, but diseases with significantly decreased mean z-scores were numerous. The usefulness of z-scores in diagnosis and study of metabolic bone disease is discussed.« less

Bone mineral content and bone mineral density in adolescent girls with anorexia nervosa--a longitudinal study.

PubMed

Jagielska, G; Wolańczyk, T; Komender, J; Tomaszewicz-Libudzic, C; Przedlacki, J; Ostrowski, K

2001-08-01

Total body and lumbar spine bone mineral density (BMD-TB, BMD-L) and total body bone mineral content (BMC-TB) were measured to establish the course of bone demineralization in anorexia nervosa and the clinical factors influencing BMC-TB and BMD changes during treatment. Forty-two girls with DSM III-R anorexia nervosa, age 14.7+/-2.4 years. BMC-TB, BMD-TB and BMD-L were measured in approximately 7-month intervals for 27.8+/-4.1 months using DXA. Despite nutritional improvement, there was an initial decrease of BMD-L, and no change in BMC-TB and BMD-TB. an increase in BMC-TB and BMD was observed after approx. 21 months from the beginning of the study. The improvement in BMC-TB and BMD was related to changes in nutritional status and was significantly marked in younger patients, with earlier anorexia onset and before menarche.

Resistance training is medicine: effects of strength training on health.

PubMed

Westcott, Wayne L

2012-01-01

Inactive adults experience a 3% to 8% loss of muscle mass per decade, accompanied by resting metabolic rate reduction and fat accumulation. Ten weeks of resistance training may increase lean weight by 1.4 kg, increase resting metabolic rate by 7%, and reduce fat weight by 1.8 kg. Benefits of resistance training include improved physical performance, movement control, walking speed, functional independence, cognitive abilities, and self-esteem. Resistance training may assist prevention and management of type 2 diabetes by decreasing visceral fat, reducing HbA1c, increasing the density of glucose transporter type 4, and improving insulin sensitivity. Resistance training may enhance cardiovascular health, by reducing resting blood pressure, decreasing low-density lipoprotein cholesterol and triglycerides, and increasing high-density lipoprotein cholesterol. Resistance training may promote bone development, with studies showing 1% to 3% increase in bone mineral density. Resistance training may be effective for reducing low back pain and easing discomfort associated with arthritis and fibromyalgia and has been shown to reverse specific aging factors in skeletal muscle.

Mandibular bone remodeling under a choline-deficient diet: a histomorphometric study in rats.

PubMed

Gorustovich, Alejandro A; Espósito, María A; Guglielmotti, María B; Giglio, Máximo J

2003-06-01

A deficiency of lipotropic factors in the rat induces renal, hepatic, and/or hematic damage. The aim of the present study was to evaluate the effect of a choline-deficient diet and refeeding on mandibular bone remodeling. Fifty Wistar rats were divided into 5 groups: group 1 (G1): control diet for 15 days; group 2 (G2): choline-deficient diet for 15 days; group 3 (G3): control diet for 30 days; group 4 (G4): choline-deficient diet for 30 days; and group 5 (G5): choline-deficient diet for 15 days and control diet for 15 days. All animals were sacrificed by ether overdose. The mandibles were resected, radiographed, decalcified, processed, and embedded in paraffin. Bucco-lingually oriented sections were obtained at the level of the interradicular bone of the medial roots of the left first molar, and stained with hematoxylin and eosin (H & E). Bone tissue density and bone remodeling were determined histomorphometrically. Body weight, food intake, hematocrit, and hemoglobinemia were also recorded. Microscopic observation revealed that osteogenesis was lower in rats fed a choline-deficient diet, at both 15 and 30 days, and that this decrease did not revert with a control diet. Histomorphometric evaluation showed 37% and 27% reduction in bone tissue density at 15 and 30 days, respectively, and a 30% decrease in bone formation at 30 days, compared to controls. In this experimental model, a choline-deficient diet led to altered bone remodeling as observed by a marked reduction in osteogenesis.

Efficacy and Safety of Bisphosphonate Therapy in Children with Osteogenesis Imperfecta: A Systematic Review.

PubMed

Rijks, Ester B G; Bongers, Bart C; Vlemmix, Marloes J G; Boot, Annemieke M; van Dijk, Atty T H; Sakkers, Ralph J B; van Brussel, Marco

2015-01-01

To systematically assess contemporary knowledge regarding the effectiveness and safety of bisphosphonates (BPs) in children with osteogenesis imperfecta (OI). PubMed/MEDLINE, Embase, and Cochrane were searched for eligible articles up to June 2014. Studies eligible for inclusion were (randomized) controlled trials assessing the effects of BPs in children with OI. Methodological quality was assessed independently by 4 reviewers using the Cochrane Collaboration's tool for risk of bias. Ten studies (519 children) were included. Four studies (40%) showed a low risk of bias. All studies investigating lumbar spine areal bone mineral density indicated a significant increase as a result of BP treatment. Most studies observed a significant decrease in fracture incidence. The most frequently reported adverse events were gastrointestinal complaints, fever, and muscle soreness. A significant decrease in (bone) pain due to BP treatment was observed in more than half of the studies. Most studies measuring urinary markers of bone resorption reported a significant decrease. The majority of studies with intravenous treatment showed a significant increase in lumbar projection area, whereas studies with oral treatment did not. Treatment with oral or intravenous BPs in children with OI results in an increase in bone mineral density and seems to be safe and well tolerated. © 2015 S. Karger AG, Basel.

Effects of aging and dietary antler supplementation on the calcium-regulating hormones and bone status in ovariectomized SAMP8 mice.

PubMed

Chen, Chun-Chi; Liu, Mei-Hui; Wang, Ming-Fu; Chen, Cheng-Chin

2007-12-31

This study was conducted to investigate the effects of aging and long-term dietary antler supplementation on the calcium-regulating hormones and bone status in ovariectomized (Ovx) SAMP8 mice. The female SAMP8 mice were divided into four groups (in each group n = 6), Ovx or sham operated at the age of 2 months, and fed with 0.2% antler containing diet or control diet from the age of 2.5 months. The samples were collected at the age of 3, 6, 9, 12, and 15 months, respectively, for physicochemical analyses, biochemical analyses, and the determination of hormones by radioimmunoassay. The results showed that plasma calcium (Ca) concentrations were maintained in a narrow range in all groups throughout the whole experimental period. With aging and/or ovariectomy, plasma parathyroid hormone (PTH) and 1,25-dihydroxycholecalciferol (1,25-(OH)2-D3) levels increased, and plasma phosphorus (P) and calcitonin (CT) levels decreased, and the femoral bone densities and Ca contents increased during the earlier stage, and then decreased gradually in all groups. Plasma PTH and 1,25-(OH)2-D3 levels in the Ovx mice were significantly higher than those in the intact mice, and plasma P concentrations, plasma CT levels, femoral bone densities, and femoral Ca contents in the Ovx mice were significantly lower than those in the intact mice. In addition, the decreases of plasma P levels, plasma CT levels, femoral bone densities, and femoral Ca contents, and the increases of plasma PTH levels were moderated by antler administration in both Ovx and intact mice. However, there was no effect of the dietary antler supplementation on the plasma 1,25-(OH)2-D3 levels in the female mice. It is concluded that prolonged dietary antler supplementation has important positive effects on bone loss with age and/ or ovarian function deficiency.

Bone Density, Microarchitecture, and Tissue Quality Long-term After Kidney Transplant.

PubMed

Pérez-Sáez, María José; Herrera, Sabina; Prieto-Alhambra, Daniel; Nogués, Xavier; Vera, María; Redondo-Pachón, Dolores; Mir, Marisa; Güerri, Roberto; Crespo, Marta; Díez-Pérez, Adolfo; Pascual, Julio

2017-06-01

Bone mineral density (BMD) measured by dual-energy x-ray absorptiometry is used to assess bone health in kidney transplant recipients (KTR). Trabecular bone score and in vivo microindentation are novel techniques that directly measure trabecular microarchitecture and mechanical properties of bone at a tissue level and independently predict fracture risk. We tested the bone status of long-term KTR using all 3 techniques. Cross-sectional study including 40 KTR with more than 10 years of follow-up and 94 healthy nontransplanted subjects as controls. Bone mineral density was measured at lumbar spine and the hip. Trabecular bone score was measured by specific software on the dual-energy x-ray absorptiometry scans of lumbar spine in 39 KTR and 77 controls. Microindentation was performed at the anterior tibial face with a reference-point indenter device. Bone measurements were standardized as percentage of a reference value, expressed as bone material strength index (BMSi) units. Multivariable (age, sex, and body mass index-adjusted) linear regression models were fitted to study the association between KTR and BMD/BMSi/trabecular bone score. Bone mineral density was lower at lumbar spine (0.925 ± 0.15 vs 0.982 ± 0.14; P = 0.025), total hip (0.792 ± 0.14 vs 0.902 ± 0.13; P < 0.001), and femoral neck (0.667 ± 0.13 vs 0.775 ± 0.12; P < 0.001) in KTR than in controls. BMSi was also lower in KTR (79.1 ± 7.7 vs 82.9 ± 7.8; P = 0.012) although this difference disappeared after adjusted model (P = 0.145). Trabecular bone score was borderline lower (1.21 ± 0.14 vs 1.3 ± 0.15; adjusted P = 0.072) in KTR. Despite persistent decrease in BMD, trabecular microarchitecture and tissue quality remain normal in long-term KTR, suggesting important recovery of bone health.

Antiosteoporotic Effect of Combined Extract of Morus alba and Polygonum odoratum

PubMed Central

Sungkamanee, Sudarat; Thukham-mee, Wipawee

2014-01-01

Due to the limitation of osteoporosis therapy, the alternative therapies from natural sources have been considered. In this study, we aimed to determine the antiosteoporotic effect of the combined extract of Morus alba and Polygonum odoratum leaves. Ovariectomized rats, weighing 200–220 g, were orally given the combined extract at doses of 5, 150, and 300 mg·kg−1 BW for 3 months. At the end of study, blood was collected to determine serum osteocalcin, calcium, and alkaline phosphatase level. In addition, tibia bone was isolated to determine bone oxidative stress markers, cortical bone thickness, and density of osteoblast. The combined extract decreased oxidative stress and osteoclast density but increased osteoblast density and cortical thickness. The elevation of serum calcium, alkaline phosphatase, and osteocalcin was also observed. These results suggested the antiosteoporotic effect of the combined extract via the increased growth formation together with the suppression of bone resorption. However, further studies concerning chronic toxicity and the underlying mechanism are required. PMID:25478061

[The effects of oxygen partial pressure changes on the osteometric markers of the bone tissue in rats].

PubMed

Berezovs'kyĭ, V Ia; Zamors'ka, T M; Ianko, R V

2013-01-01

Our purpose was to investigate the oxygen partial pressure changes on the osteometric and biochemical markers of bone tissue in rats. It was shown that breathing of altered gas mixture did not change the mass, general length, sagittal diameter and density thigh-bones in 12-month Wistar male-rats. The dosed normobaric hypoxia increased the activity of alkaline phosphatase and decreased the activity of tartrate-resistant acid phosphatase. At the same time normobaric hyperoxia with 40 and 90% oxygen conversely decreased the activity of alkaline phosphatase and increased the activity of tartrate-resistant acid phosphatase.

Genetic predisposition to low bone mass is paralleled by an enhanced sensitivity to signals anabolic to the skeleton

NASA Technical Reports Server (NTRS)

Judex, Stefan; Donahue, Leah-Rae; Rubin, Clinton

2002-01-01

The structure of the adult skeleton is determined, in large part, by its genome. Whether genetic variations may influence the effectiveness of interventions to combat skeletal diseases remains unknown. The differential response of trabecular bone to an anabolic (low-level mechanical vibration) and a catabolic (disuse) mechanical stimulus were evaluated in three strains of adult mice. In low bone-mineral-density C57BL/6J mice, the low-level mechanical signal caused significantly larger bone formation rates (BFR) in the proximal tibia, but the removal of functional weight bearing did not significantly alter BFR. In mid-density BALB/cByJ mice, mechanical stimulation also increased BFR, whereas disuse significantly decreased BFR. In contrast, neither anabolic nor catabolic mechanical signals influenced any index of bone formation in high-density C3H/HeJ mice. Together, data from this study indicate that the sensitivity of trabecular tissue to both anabolic and catabolic stimuli is influenced by the genome. Extrapolated to humans, these results may explain in part why prophylaxes for low bone mass are not universally effective, yet also indicate that there may be a genotypic indication of people who are at reduced risk of suffering from bone loss.

Genetic background of osteoporosis.

PubMed

Obermayer-Pietsch, B; Chararas, C; Kotschan, S; Walter, D; Leb, G

2000-01-01

Osteoporosis is a systemic disorder of decreased skeletal mass as measured by bone mineral density (BMD), and disturbed skeletal architecture and function which results in an increased risk for bone fractures with consecutively increased morbidity and mortality. Twin and family studies have shown an important genetic component of BMD of about 40-60%. This exceeds other well known factors influencing BMD such as environmental factors like dietary calcium, physical activity or several drugs and diseases. Therefore, interest increased in the genetic background of bone mineral density. Polymorphisms of the Vitamin D receptor gene were the first to be published in this area. Studies on other loci or candidate genes such as the estrogen receptor gene or the collagen type I alpha1 gene also showed associations with bone mineral density that could explain at least a part of the genetic background of osteoporosis. Recently published data suggest that these genetic markers of bone metabolism are important in interaction with each other or in certain bone-affecting diseases. In the future, genetic studies on osteoporosis will have to screen further relevant genes and markers for bone metabolism as well as to evaluate the complex interactions of genetic influences, so that it would be possible to calculate a patient's individual risk for osteoporosis in the context of environmental influences.

The effect of exemestane and tamoxifen on bone health within the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial: a meta-analysis of the US, German, Netherlands, and Belgium sub-studies.

PubMed

Hadji, Peyman; Asmar, Lina; van Nes, Johanna G H; Menschik, Thomas; Hasenburg, Annette; Kuck, Joachim; Nortier, Johan W R; van de Velde, Cornelis J H; Jones, Stephen E; Ziller, May

2011-06-01

We performed a meta-analysis of three sub-studies of the randomized Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial to determine the effects of exemestane and tamoxifen on bone health. Patients received exemestane or tamoxifen as adjuvant therapy for hormone receptor-positive breast cancer. Bone mineral density (BMD) was assessed at baseline and after 12 and 24 months of treatment. Bone turnover markers were also measured. Patients receiving tamoxifen showed a mean increase from baseline in lumbar spine BMD of 1.2% at month 12 and 0.2% at month 24. Patients receiving exemestane showed a mean decrease from baseline of 2.6% after 12 months and 3.5% after 24 months. There were significant differences in the changes in lumbar spine BMD between treatment groups (P < 0.0001 at both time points). Changes in BMD from baseline at the total hip were also significantly different between exemestane and tamoxifen (P < 0.05 at both time points). Bone turnover markers decreased from baseline with tamoxifen and increased with exemestane. Exemestane resulted in decreases in BMD and increases in bone turnover markers. BMD increased and bone turnover markers decreased with tamoxifen.

Spontaneous mutation of Dock7 results in lower trabecular bone mass and impaired periosteal expansion in aged female Misty mice.

PubMed

Le, Phuong T; Bishop, Kathleen A; Maridas, David E; Motyl, Katherine J; Brooks, Daniel J; Nagano, Kenichi; Baron, Roland; Bouxsein, Mary L; Rosen, Clifford J

2017-12-01

Misty mice (m/m) have a loss of function mutation in Dock7 gene, a guanine nucleotide exchange factor, resulting in low bone mineral density, uncoupled bone remodeling and reduced bone formation. Dock7 has been identified as a modulator of osteoblast number and in vitro osteogenic differentiation in calvarial osteoblast culture. In addition, m/m exhibit reduced preformed brown adipose tissue innervation and temperature as well as compensatory increase in beige adipocyte markers. While the low bone mineral density phenotype is in part due to higher sympathetic nervous system (SNS) drive in young mice, it is unclear what effect aging would have in mice homozygous for the mutation in the Dock7 gene. We hypothesized that age-related trabecular bone loss and periosteal envelope expansion would be altered in m/m. To test this hypothesis, we comprehensively characterized the skeletal phenotype of m/m at 16, 32, 52, and 78wks of age. When compared to age-matched wild-type control mice (+/+), m/m had lower areal bone mineral density (aBMD) and areal bone mineral content (aBMC). Similarly, both femoral and vertebral BV/TV, Tb.N, and Conn.D were decreased in m/m while there was also an increase in Tb.Sp. As low bone mineral density and decreased trabecular bone were already present at 16wks of age in m/m and persisted throughout life, changes in age-related trabecular bone loss were not observed highlighting the role of Dock7 in controlling trabecular bone acquisition or bone loss prior to 16wks of age. Cortical thickness was also lower in the m/m across all ages. Periosteal and endosteal circumferences were higher in m/m compared to +/+ at 16wks. However, endosteal and periosteal expansion were attenuated in m/m, resulting in m/m having lower periosteal and endosteal circumferences by 78wks of age compared to +/+, highlighting the critical role of Dock7 in appositional bone expansion. Histomorphometry revealed that osteoblasts were nearly undetectable in m/m and marrow adipocytes were elevated 3.5 fold over +/+ (p=0.014). Consistent with reduced bone formation, osteoblast gene expression of Alp, Col1a1, Runx-2, Sp7, and Bglap was significantly decreased in m/m whole bone. Furthermore, markers of osteoclasts were either unchanged or suppressed. Bone marrow stromal cell migration and motility were inhibited in culture and changes in senescence markers suggest that osteoblast function may also be inhibited with loss of Dock7 expression in m/m. Finally, increased Oil Red O staining in m/m ear mesenchymal stem cells during adipogenesis highlights a potential shift of cells from the osteogenic to adipogenic lineages. In summary, loss of Dock7 in the aging m/m resulted in an impairment of periosteal and endocortical envelope expansion, but did not alter age-related trabecular bone loss. These studies establish Dock7 as a critical regulator of both cortical and trabecular bone mass, and demonstrate for the first time a novel role of Dock7 in modulating compensatory changes in the periosteum with aging. Copyright © 2017 Elsevier Inc. All rights reserved.

Bones and Crohn's: estradiol deficiency in men with Crohn's disease is not associated with reduced bone mineral density.

PubMed

Klaus, J; Reinshagen, M; Adler, G; Boehm, Bo; von Tirpitz, C

2008-10-23

Reduced bone mineral density (BMD) and osteoporosis are frequent in Crohn's disease (CD), but the underlying mechanisms are still not fully understood. Deficiency of sex steroids, especially estradiol (E2), is an established risk factor in postmenopausal osteoporosis. To assess if hormonal deficiencies in male CD patients are frequent we investigated both, sex steroids, bone density and bone metabolism markers. 111 male CD patients underwent osteodensitometry (DXA) of the spine (L1-L4). Disease related data were recorded. Disease activity was estimated using Crohn's disease activity index (CDAI). Testosterone (T), dihydrotestosterone (DHT), estradiol (E2), sex hormone binding globulin (SHBG), Osteocalcin and carboxyterminal cross-linked telopeptids (ICTP) were measured in 111 patients and 99 age-matched controls. Patients had lower T, E2 and SHBG serum levels (p < 0.001) compared to age-matched controls. E2 deficiency was seen in 30 (27.0%) and T deficiency in 3 (2.7%) patients but only in 5 (5.1%) and 1 (1%) controls. Patients with E2 deficiency had significantly decreased T and DHT serum levels. Use of corticosteroids for 3 of 12 months was associated with lower E2 levels (p < 0.05). Patients with life-time steroids >10 g had lower BMD. 32 (28.8%) patients showed osteoporosis, 55 (49.5%) osteopenia and 24 (21.6%) had normal BMD. Patients with normal or decreased BMD showed no significant difference in their hormonal status. No correlation between markers of bone turnover and sex steroids could be found. ICTP was increased in CD patients (p < 0.001), and patients with osteoporosis had higher ICTP levels than those with normal BMD. We found an altered hormonal status--i.e. E2 and, to a lesser extent T deficiency--in male CD patients but failed to show an association to bone density or markers of bone turnover. The role of E2 in the negative skeletal balance in males with CD, analogous to E2 deficiency in postmenopausal females, deserves further attention.

EFFECTS OF LONG-TERM ALENDRONATE TREATMENT ON A LARGE SAMPLE OF PEDIATRIC PATIENTS WITH OSTEOGENESIS IMPERFECTA.

PubMed

Lv, Fang; Liu, Yi; Xu, Xiaojie; Wang, Jianyi; Ma, Doudou; Jiang, Yan; Wang, Ou; Xia, Weibo; Xing, Xiaoping; Yu, Wei; Li, Mei

2016-12-01

Osteogenesis imperfecta (OI) is a group of inherited diseases characterized by reduced bone mass, recurrent bone fractures, and progressive bone deformities. Here, we evaluate the efficacy and safety of long-term treatment with alendronate in a large sample of Chinese children and adolescents with OI. In this prospective study, a total of 91 children and adolescents with OI were included. The patients received 3 years' treatment with 70 mg alendronate weekly and 500 mg calcium daily. During the treatment, fracture incidence, bone mineral density (BMD), and serum levels of the bone turnover biomarkers (alkaline phosphatase [ALP] and cross-linked C-telopeptide of type I collagen [β-CTX]) were evaluated. Linear growth speed and parameters of safety were also measured. After 3 years of treatment, the mean annual fracture incidence decreased from 1.2 ± 0.8 to 0.2 ± 0.3 (P<.01). BMD at the lumbar spine and femoral neck significantly increased by 74.6% and 39.5%, with their BMD Z-score increasing from -3.0 to 0.1 and from -4.2 to -1.3, respectively (both P<.01 vs. baseline). In addition, serum ALP and β-CTX levels decreased by 35.6% and 44.3%, respectively (both P<.05 vs. baseline). Height significantly increased, but without an obvious increase in its Z-score. Patient tolerance of alendronate was good. Three years' treatment with alendronate was demonstrated for the first time to significantly reduce fracture incidence, increase lumbar spine and femoral neck BMD, and decrease bone turnover biomarkers in Chinese children and adolescents with OI. ALP = alkaline phosphatase β-CTX = cross-linked C-telopeptide of type I collagen BMD = bone mineral density BP = bisphosphonate DXA = dual-energy X-ray absorptiometry 25OHD = 25-hydroxyvitamin D OI = osteogenesis imperfecta PTH = parathyroid hormone.

High fat diet promotes achievement of peak bone mass in young rats.

PubMed

Malvi, Parmanand; Piprode, Vikrant; Chaube, Balkrishna; Pote, Satish T; Mittal, Monika; Chattopadhyay, Naibedya; Wani, Mohan R; Bhat, Manoj Kumar

2014-12-05

The relationship between obesity and bone is complex. Epidemiological studies demonstrate positive as well as negative correlation between obesity and bone health. In the present study, we investigated the impact of high fat diet-induced obesity on peak bone mass. After 9 months of feeding young rats with high fat diet, we observed obesity phenotype in rats with increased body weight, fat mass, serum triglycerides and cholesterol. There were significant increases in serum total alkaline phosphatase, bone mineral density and bone mineral content. By micro-computed tomography (μ-CT), we observed a trend of better trabecular bones with respect to their microarchitecture and geometry. This indicated that high fat diet helps in achieving peak bone mass and microstructure at younger age. We subsequently shifted rats from high fat diet to normal diet for 6 months and evaluated bone/obesity parameters. It was observed that after shifting rats from high fat diet to normal diet, fat mass, serum triglycerides and cholesterol were significantly decreased. Interestingly, the gain in bone mineral density, bone mineral content and trabecular bone parameters by HFD was retained even after body weight and obesity were normalized. These results suggest that fat rich diet during growth could accelerate achievement of peak bone mass that is sustainable even after withdrawal of high fat diet.

Correlation between longitudinal, circumferential, and radial moduli in cortical bone: effect of mineral content.

PubMed

Macione, J; Depaula, C A; Guzelsu, N; Kotha, S P

2010-07-01

Previous studies indicate that changes in the longitudinal elastic properties of bone due to changes in mineral content are related to the longitudinal strength of bone tissue. Changes in mineral content are expected to affect bone tissue mechanical properties along all directions, albeit to different extents. However, changes in tissue mechanical properties along the different directions are expected to be correlated to one another. In this study, we investigate if radial, circumferential, and longitudinal moduli are related in bone tissue with varying mineral content. Plexiform bovine femoral bone samples were treated in fluoride ion solutions for a period of 3 and 12 days to obtain bones with 20% and 32% lower effective mineral contents. Transmission ultrasound velocities were obtained in the radial, circumferential, and longitudinal axes of bone and combined with measured densities to obtain corresponding tensorial moduli. Results indicate that moduli decreased with fluoride ion treatments and were significantly correlated to one another (r(2) radial vs. longitudinal = 0.80, r(2) circumferential vs. longitudinal = 0.90, r(2) radial vs. circumferential = 0.85). Densities calculated from using ultrasound parameters, acoustic impedance and transmission velocities, were moderately correlated to those measured by the Archimedes principle (r(2)=0.54, p<0.01). These results suggest that radial and circumferential ultrasound measurements could be used to determine the longitudinal properties of bone and that ultrasound may not be able to predict in vitro densities of bones containing unbonded mineral. Published by Elsevier Ltd.

A high-fat diet can affect bone healing in growing rats.

PubMed

Yamanaka, Jéssica Suzuki; Yanagihara, Gabriela Rezende; Carlos, Bruna Leonel; Ramos, Júnia; Brancaleon, Brígida Batista; Macedo, Ana Paula; Issa, João Paulo Mardegan; Shimano, Antônio Carlos

2018-05-01

A high-fat diet (HFD) can have a negative effect on bone quality in young and old people. Although bone healing in children is normally efficient, there is no evidence that children who have a diet rich in fat have compromised bone fracture regeneration compared with children with recommended dietary fat levels. The purpose of the present study was to evaluate the effects of an HFD on bone healing in growing female rats. Twenty-six postweaning female Wistar rats were divided into two groups (13 animals per group): a standard diet (SD) group and an HFD (with 60% of energy from fat) group. The rats received the assigned diets for 5 weeks, and in the third week they were submitted to an osteotomy procedure of the left tibia. Body mass and feed intake were recorded during the experiment. One day before euthanasia, an insulin tolerance test was performed. After euthanasia, the tibiae were removed and analyzed by densitometry, mechanical testing, histomorphometry, stereology and immunohistochemistry. An HFD caused an adaptive response to maintain energetic balance by decreasing feed intake and causing insulin insensitivity. There was no change in bone mineral density, collagen amount and immunostaining for bone formation, but maximal load and stiffness were decreased in the HFD group. In addition, bone volume had a tendency to be higher in the SD group than in the HFD group. Compared with rats receiving an SD, growing rats receiving an HFD for 5 weeks had similar bone mineral density but altered mechanical properties at the osteotomy defect site.

Greater milk intake is associated with lower bone turnover, higher bone density, and higher bone microarchitecture index in a population of elderly Japanese men with relatively low dietary calcium intake: Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) Study.

PubMed

Sato, Y; Iki, M; Fujita, Y; Tamaki, J; Kouda, K; Yura, A; Moon, J-S; Winzenrieth, R; Iwaki, H; Ishizuka, R; Amano, N; Tomioka, K; Okamoto, N; Kurumatani, N

2015-05-01

The effects of milk intake on bone health are not clear in elderly Asian men with low dietary calcium intake. This study showed that greater milk intake is associated with lower bone turnover, higher bone density, and higher bone microarchitecture index in community-dwelling elderly Japanese men. The consumption of milk or dairy products is widely recommended for maintaining bone health regardless of gender or age. However, little evidence exists on the beneficial effects of milk intake on bone health in elderly Japanese men characterized with relatively low dietary calcium intake. Here we examined whether or not greater milk intake was associated with lower bone turnover, higher bone density, and stronger bone microarchitecture in community-dwelling elderly Japanese men. Interviews were conducted to obtain information on medical history and lifestyle, including the amount of habitual milk intake, nutrient intake calculations based on a 1-week food diary, and measurements of areal bone mineral density (aBMD) at the lumbar spine (LS), total hip (TH), and femoral neck (FN) by dual-energy x-ray absorptiometry (DXA), trabecular bone score (TBS) using DXA images at LS, and biochemical markers of bone turnover in sera. Participants with a history of diseases or medications that affect bone metabolism, or with missing data, were excluded from the analysis. The median intake of milk in the 1479 participants (mean age, 73.0 ± 5.1 years) was one glass of milk per day. Bone turnover markers showed a decreasing trend (p < 0.05) and aBMD at TH (p = 0.0019) and FN (p = 0.0057) and TBS (p = 0.0017) showed increasing trends with greater milk intake after adjusting for demographic and behavioral confounding factors. This association was attenuated after further adjusting for nutrient intake, in particular, calcium intake. Greater milk intake was associated with lower bone turnover, higher aBMD, and higher TBS in community-dwelling elderly Japanese men.

Cigarette smoking and alveolar bone in young adults: a study using digitized radiographs.

PubMed

Rosa, Guillermo M; Lucas, Gabriela Q; Lucas, Oscar N

2008-02-01

Evidence indicates that cigarette smoking is one of the most significant risk factors for periodontal diseases; however, there have been few radiographic prospective studies of alveolar bone in young populations. The purpose of this study was to evaluate the effect of smoking on alveolar bone in young adults. Eighty-one dental students (mean age: 20.5 years), considered not to have periodontitis according to clinical criteria, participated in this study. Forty-two subjects were smokers (mean consumption was 14.1 cigarettes/day for > or =2 years), and 39 subjects had never smoked. A parallel-arm prospective design was used. All subjects took part in a dental hygiene program (DHP) that included oral hygiene instructions, mechanical debridement, and polishing. The following clinical variables were measured before and after the DHP: plaque index (PI), gingival crevicular fluid (GCF) flow rate, gingival index (GI), probing depth, and clinical attachment level (CAL). Standardized posterior vertical bitewing radiographs were taken and digitized preexperimentally and on days 180, 365, and 545. The following analyses were performed: bone height measurement (BHM), computer-assisted densitometric image analysis (CADIA), and qualitative analysis of digital subtraction radiography (DSR). Repeated-measures multiple-way analysis of variance (ANOVA) was performed between the groups, and one-way ANOVA was performed within the groups. The mean PI and GI were significantly greater in the smokers (P <0.01). The mean GCF flow rate was significantly lower in the smokers (P <0.01). CAL and the number of sites with recession were significantly greater in the smokers (P <0.001). The BHM indicated a significantly lower mean alveolar bone height in the smokers (P <0.01). The smokers showed significantly lower CADIA values, which indicated a lower bone density on days 0 (P <0.05), 180, 365, and 545 (P <0.01). CADIA values decreased during the study in the smokers, with significant differences on day 545 (P <0.05). The smokers had a significantly higher mean percentage of sites that had decreased density, as assessed by DSR (P <0.001). In the smokers, the mean percentage of sites with decreased density, as assessed by DSR, had increased significantly by days 365 (P <0.05) and 545 (P <0.01). Smoking produces an adverse effect on clinical periodontal variables and alveolar bone height and density, acting as a potential risk factor for alveolar bone loss, even at an early age with low tobacco consumption. It is very important to inform young smokers about the risk of this habit in relation to periodontal health.

Low serum and bone vitamin K status in patients with longstanding Crohn's disease: another pathogenetic factor of osteoporosis in Crohn's disease?

PubMed Central

Schoon, E; Muller, M; Vermeer, C; Schurgers, L; Brummer, R; Stockbrugger, R

2001-01-01

BACKGROUND—A high prevalence of osteoporosis is reported in Crohn's disease. The pathogenesis is not completely understood but is probably multifactorial. Longstanding Crohn's disease is associated with a deficiency of fat soluble vitamins, among them vitamin K. Vitamin K is a cofactor in the carboxylation of osteocalcin, a protein essential for calcium binding to bone. A high level of circulating uncarboxylated osteocalcin is a sensitive marker of vitamin K deficiency.
AIMS—To determine serum and bone vitamin K status in patients with Crohn's disease and to elucidate its relationship with bone mineral density.
METHODS—Bone mineral density was measured in 32 patients with longstanding Crohn's disease and small bowel involvement, currently in remission, and receiving less than 5 mg of prednisolone daily. Serum levels of vitamins D and K, triglycerides, and total immunoreactive osteocalcin, as well as uncarboxylated osteocalcin ("free" osteocalcin) were determined. The hydroxyapatite binding capacity of osteocalcin was calculated. Data were compared with an age and sex matched control population.
RESULTS—Serum vitamin K levels of CD patients were significantly decreased compared with normal controls (p<0.01). "Free" osteocalcin was higher and hydroxyapatite binding capacity of circulating osteocalcin was lower than in matched controls (p<0.05 and p<0.001, respectively), indicating a low bone vitamin K status in Crohn's disease. In patients, an inverse correlation was found between "free" osteocalcin and lumbar spine bone mineral density (r=−0.375, p<0.05) and between "free" osteocalcin and the z score of the lumbar spine (r=−0.381, p<0.05). Multiple linear regression analysis showed that "free" osteocalcin was an independent risk factor for low bone mineral density of the lumbar spine whereas serum vitamin D was not.
CONCLUSIONS—The finding that a poor vitamin K status is associated with low bone mineral density in longstanding Crohn's disease may have implications for the prevention and treatment of osteoporosis in this disorder.


Keywords: Crohn's disease; bone mineral density; vitamin K; osteocalcin PMID:11247890

The Effect of Local Delivery Doxycycline and Alendronate on Bone Repair.

PubMed

Limirio, Pedro Henrique Justino Oliveira; Rocha, Flaviana Soares; Batista, Jonas Dantas; Guimarães-Henriques, João César; de Melo, Geraldo Batista; Dechichi, Paula

2016-08-01

The aim of the present study was to investigate the local effect of 10% doxycycline and 1% alendronate combined with poly(lactic-co-glycolic acid) (PLGA) on bone repair. Thirty rats were divided into three groups, as follows: control group (CG), drug group (DG), and vehicle-PLGA group (VG). Bone defect was created in the right femur and filled with the following: blood clot (CG); PLGA gel, 10% doxycycline and 1% alendronate (DG); or vehicle-PLGA (VG). The animals were euthanized 7 or 15 days after surgery. Bone density, bone matrix and number of osteoclasts were quantified. At 7 days, the findings showed increased density in DG (177.75 ± 76.5) compared with CG (80.37 ± 27.4), but no difference compared with VG (147.1 ± 41.5); no statistical difference in bone neoformation CG (25.6 ± 4.8), VG (27.8 ± 4), and DG (18.9 ± 7.8); and decrease osteoclasts in DG (4.6 ± 1.9) compared with CG (26.7 ± 7.4) and VG (17.3 ± 2.7). At 15 days, DG (405.1 ± 63.1) presented higher density than CG (213.2 ± 60.9) and VG (283.4 ± 85.8); there was a significant increase in percentage of bone neoformation in DG (31.5 ± 4.2) compared with CG (23 ± 4), but no difference compared with VG (25.1 ± 2.9). There was a decreased number of osteoclasts in DG (20.7 ± 4.7) and VG (29.5 ± 5.4) compared with CG (40 ± 9.4). The results suggest that the association of 10% doxycycline and 1% alendronate with PLGA-accelerated bone repair.

Fatigue of immature baboon cortical bone.

PubMed

Keller, T S; Lovin, J D; Spengler, D M; Carter, D R

1985-01-01

Strain-controlled uniaxial fatigue and monotonic tensile tests were conducted on turned femoral cortical bone specimens obtained from baboons at various ages of maturity. Fatigue loading produced a progressive loss in stiffness and an increase in hysteresis prior to failure, indicating that immature primate cortical bone responds to repeated loading in a fashion similar to that previously observed for adult human cortical bone. Bone fatigue resistance under this strain controlled testing decreased during maturation. Maturation was also associated with an increase in bone dry density, ash fraction and elastic modulus. The higher elastic modulus of more mature bone meant that these specimens were subjected to higher stress levels during testing than more immature bone specimens. Anatomical regions along the femoral shaft exhibited differences in strength and fatigue resistance.

Short-Term Effects of Kefir-Fermented Milk Consumption on Bone Mineral Density and Bone Metabolism in a Randomized Clinical Trial of Osteoporotic Patients

PubMed Central

Tung, Yu-Tang; Kao, Chao-Chih; Hu, Fu-Chang; Chen, Chuan-Mu

2015-01-01

Milk products are good sources of calcium that may reduce bone resorption and help prevent bone loss as well as promote bone remodeling and increase bone formation. Kefir is a product made by kefir grains that degrade milk proteins into various peptides with health-promoting effects, including antithrombotic, antimicrobial and calcium-absorption enhancing bioactivities. In a controlled, parallel, double-blind intervention study over 6 months, we investigated the effects of kefir-fermented milk (1,600 mg) supplemented with calcium bicarbonate (CaCO3, 1,500 mg) and bone metabolism in 40 osteoporosis patients, and compared them with CaCO3 alone without kefir supplements. Bone turnover markers were measured in fasting blood samples collected before therapy and at 1, 3, and 6 months. Bone mineral density (BMD) values at the spine, total hip, and hip femoral neck were assessed by dual-energy x-ray absorptiometry (DXA) at baseline and at 6 months. Among patients treated with kefir-fermented milk, the relationships between baseline turnover and 6 months changes in DXA-determined BMD were significantly improved. The serum β C-terminal telopeptide of type I collagen (β-CTX) in those with T-scores > -1 patients significantly decreased after three months treatment. The formation marker serum osteocalcin (OC) turned from negative to positive after 6 months, representing the effect of kefir treatment. Serum parathyroid hormone (PTH) increased significantly after treatment with kefir, but decreased significantly in the control group. PTH may promote bone remodeling after treatment with kefir for 6 months. In this pilot study, we concluded that kefir-fermented milk therapy was associated with short-term changes in turnover and greater 6-month increases in hip BMD among osteoporotic patients. Trial Registration: ClinicalTrials.gov NCT02361372 PMID:26655888

Short-Term Effects of Kefir-Fermented Milk Consumption on Bone Mineral Density and Bone Metabolism in a Randomized Clinical Trial of Osteoporotic Patients.

PubMed

Tu, Min-Yu; Chen, Hsiao-Ling; Tung, Yu-Tang; Kao, Chao-Chih; Hu, Fu-Chang; Chen, Chuan-Mu

2015-01-01

Milk products are good sources of calcium that may reduce bone resorption and help prevent bone loss as well as promote bone remodeling and increase bone formation. Kefir is a product made by kefir grains that degrade milk proteins into various peptides with health-promoting effects, including antithrombotic, antimicrobial and calcium-absorption enhancing bioactivities. In a controlled, parallel, double-blind intervention study over 6 months, we investigated the effects of kefir-fermented milk (1,600 mg) supplemented with calcium bicarbonate (CaCO3, 1,500 mg) and bone metabolism in 40 osteoporosis patients, and compared them with CaCO3 alone without kefir supplements. Bone turnover markers were measured in fasting blood samples collected before therapy and at 1, 3, and 6 months. Bone mineral density (BMD) values at the spine, total hip, and hip femoral neck were assessed by dual-energy x-ray absorptiometry (DXA) at baseline and at 6 months. Among patients treated with kefir-fermented milk, the relationships between baseline turnover and 6 months changes in DXA-determined BMD were significantly improved. The serum β C-terminal telopeptide of type I collagen (β-CTX) in those with T-scores > -1 patients significantly decreased after three months treatment. The formation marker serum osteocalcin (OC) turned from negative to positive after 6 months, representing the effect of kefir treatment. Serum parathyroid hormone (PTH) increased significantly after treatment with kefir, but decreased significantly in the control group. PTH may promote bone remodeling after treatment with kefir for 6 months. In this pilot study, we concluded that kefir-fermented milk therapy was associated with short-term changes in turnover and greater 6-month increases in hip BMD among osteoporotic patients. ClinicalTrials.gov NCT02361372.

Assessment of bone metabolism in premenopausal females with hyperthyroidism and hypothyroidism.

PubMed

Tuchendler, Dominika; Bolanowski, Marek

2013-01-01

Osteoporosis is one of the commonest metabolic diseases of bone. Its possible causes may include thyroid hormonal dysfunction. The objective of this study was to evaluate the effects of hyperthyroidism and hypothyroidism on osseous tissue metabolism in premenopausal women. 38 women with hyperthyroidism, 40 with hypothyroidism and 41 healthy women participated in this study. Initially after 6 and 12 months, each patient underwent selected hormonal, immunological and biochemical tests, measurement of concentrations of bone turnover markers and densitometry were also performed. On initial evaluation, lower cortical bone density was found in patients with hyperthyroidism (femoral neck). After 12 months, an increase in BMD was seen, but it was still lower than in the control group. Statistically significantly higher concentrations of bone turnover markers, decreasing from the sixth month of treatment, were noted only in the group with hyperthyroidism. Statistically significant differences were not noted in the femoral neck nor in the lumbar spine BMD in patients with hypothyroidism. Hyperthyroidism poses a negative effect on bone metabolism. Hypothyroidism in premenopausal females does not have any influence on bone density.

Sex differences in parameters of bone strength in new recruits: beyond bone density.

PubMed

Evans, Rachel K; Negus, Charles; Antczak, Amanda J; Yanovich, Ran; Israeli, Eran; Moran, Daniel S

2008-11-01

Stress fracture (SF) injuries in new recruits have long been attributed to low bone mineral density (BMD). Low areal BMD assessed using two-dimensional dual-energy x-ray absorptiometry imaging, however, reflects structural density and is affected by smaller measures of bone geometry. Recent studies support a relationship between bone size and SF and indicate that slender bones are more susceptible to damage under identical loading conditions. Peripheral quantitative computed tomography (pQCT) is a three-dimensional imaging tool that provides measures of tissue density and geometry parameters of the tibia, a common site of SF. To evaluate sex differences in parameters of volumetric BMD (vBMD), geometry, and strength of the tibia in new recruits using a novel pQCT image analysis procedure. pQCT images were obtained from 128 healthy men and women (20 male, 108 female, aged 18-21 yr) entering a 4-month gender-integrated combat training program in the Israeli Defense Forces. Tibial scans taken at sites 4% (trabecular bone), 38%, and 66% (cortical bone) from the distal end plate were analyzed using MATLAB to assess whole-bone and regional parameters. Measures included vBMD, geometry (diameter, area, cortical thickness, and canal radius), and strength (moments of inertia and bone strength and slenderness indices). With the exception of normalized canal radius, which did not differ between sexes, all measures of bone geometry (P < 0.0001) and strength (P < 0.0001 to P = 0.07) were greater in men. Women exhibited 2.7% to 3.0% greater cortical vBMD than men, whereas trabecular vBMD was 8.4% lower in women (P < 0.001). These differences remained significant after adjusting for body size. Sex differences in bone geometry and mineralization of the tibia may contribute to a decreased ability to withstand the demands imposed by novel, repetitive exercise in untrained individuals entering recruit training.

Fan-beam densitometry of the growing skeleton: are we measuring what we think we are?

PubMed

Cole, Jacqueline H; Scerpella, Tamara A; van der Meulen, Marjolein C H

2005-01-01

Magnification error in fan-beam densitometers varies with distance from the X-ray source to the bone measured and might obscure bone mineral changes in the growing skeleton. Magnification was examined by scanning aluminum rods of different shapes (square, rectangular, solid round, and hollow round) at four distances above the X-ray source in two orientations, with rods aligned parallel (SI) and perpendicular (ML) to the longitudinal axis of the scanning table. Measured area (cm(2)) decreased linearly with distance above the X-ray source for all rods in the SI orientation (p < 0.005). Measured mineral content (g) decreased linearly with distance but only for SI round rods (p < 0.0001) and for ML hollow round rods (p < 0.005). Area and mineral content decreased 1.6-1.8% per centimeter above the source for round rods. Measured mineral density (g/cm(2)) decreased linearly with distance from the source only for ML hollow round rods (p < 0.005). Variation in area, mineral content, and mineral density measurements was 6.6-6.9%, 6.9-7.5%, and 1.9-2.3%, respectively, for SI round rods. Magnification errors of this magnitude are problematic for clinical studies using fan-beam densitometry. Particularly in pediatric subjects, increases in soft tissue during normal growth could increase a bone's distance from the fan-beam source and result in apparent reductions in area and bone mineral content.

Internal rib structure can be predicted using mathematical models: An anatomic study comparing the chest to a shell dome with application to understanding fractures.

PubMed

Casha, Aaron R; Camilleri, Liberato; Manché, Alexander; Gatt, Ruben; Attard, Daphne; Gauci, Marilyn; Camilleri-Podesta, Marie-Therese; Mcdonald, Stuart; Grima, Joseph N

2015-11-01

The human rib cage resembles a masonry dome in shape. Masonry domes have a particular construction that mimics stress distribution. Rib cortical thickness and bone density were analyzed to determine whether the morphology of the rib cage is sufficiently similar to a shell dome for internal rib structure to be predicted mathematically. A finite element analysis (FEA) simulation was used to measure stresses on the internal and external surfaces of a chest-shaped dome. Inner and outer rib cortical thickness and bone density were measured in the mid-axillary lines of seven cadaveric rib cages using computerized tomography scanning. Paired t tests and Pearson correlation were used to relate cortical thickness and bone density to stress. FEA modeling showed that the stress was 82% higher on the internal than the external surface, with a gradual decrease in internal and external wall stresses from the base to the apex. The inner cortex was more radio-dense, P < 0.001, and thicker, P < 0.001, than the outer cortex. Inner cortical thickness was related to internal stress, r = 0.94, P < 0.001, inner cortical bone density to internal stress, r = 0.87, P = 0.003, and outer cortical thickness to external stress, r = 0.65, P = 0.035. Mathematical models were developed relating internal and external cortical thicknesses and bone densities to rib level. The internal anatomical features of ribs, including the inner and outer cortical thicknesses and bone densities, are similar to the stress distribution in dome-shaped structures modeled using FEA computer simulations of a thick-walled dome pressure vessel. Fixation of rib fractures should include the stronger internal cortex. © 2015 Wiley Periodicals, Inc.

Associations of Parity, Breastfeeding, and Fractures in the Women's Health Observational Study.

PubMed

Crandall, Carolyn J; Liu, Jingmin; Cauley, Jane; Newcomb, Polly A; Manson, JoAnn E; Vitolins, Mara Z; Jacobson, Lisette T; Rykman, Kelli K; Stefanick, Marcia L

2017-07-01

To examine associations of several aspects of parity and history of lactation with incident hip fractures and clinical fractures and, in a subset of women, with bone mineral density. In this observational study, we analyzed data from 93,676 postmenopausal women participating in the Women's Health Initiative Observational Study and all bone density data from the subset of participants who underwent bone density testing at three clinical centers. At baseline, participants were aged 50-79 years. Using Cox proportional hazards regression analysis, we examined associations of fracture incidence and bone density with several aspects of parity (number of pregnancies, age at first pregnancy lasting 6 months or greater, and number of pregnancies lasting 6 months or greater) and breastfeeding (number of episodes of breastfeeding for at least 1 month, number of children breastfed, age when first breastfed, age when last breastfed, total number of months breastfed). The mean baseline age (standard deviation) of participants was 64 (±7.4) years (mean follow-up 7.9 years). During follow-up, the incident rate of hip fracture was 1.27%. Ten percent of participants were nulligravid. In fully adjusted models, number of pregnancies, parity, age at first birth, number of children breastfed, age at first breastfeeding, age at last breastfeeding, and total duration of breastfeeding were not statistically significantly associated with hip fracture incidence. There were no consistent associations of parity or lactation characteristics with overall clinical fracture risk or bone density. However, compared with never breastfeeding, a history of breastfeeding for at least 1 month was associated with a decreased risk of hip fracture (yes compared with no, hazard ratio 0.84, 95% confidence interval 0.73-0.98). Patterns of parity and history of lactation were largely unrelated to fracture risk or bone density.

Femur Neck Fracture in a Young Marfan Syndrome Patient.

PubMed

Kwon, Yong-Uk; Kong, Gyu-Min; Park, Jun-Ho

2016-12-01

Marfan syndrome is an autosomal dominant and could decrease bone mineral density. So patients with Marfan syndrome could vulnerable to trauma in old ages. We present the first report, to the best of our knowledge, of a rare fracture of the femoral neck with a minor traumatic history in a juvenile Marfan syndrome patient whose physis is still open. Although the patient is young, her bone mineral density was low and the geometry of femur is changed like old ages. The femur neck fracture in children is very rare and only caused by high energy trauma, we concluded that the Marfan syndrome makes the bone weaker in young age and preventative medications to avoid fractures in younger Marfan syndrome patients are necessary in early ages.

Dietary boron does not affect tooth strength, micro-hardness, and density, but affects tooth mineral composition and alveolar bone mineral density in rabbits fed a high-energy diet.

PubMed

Hakki, Sema S; SiddikMalkoc; Dundar, Niyazi; Kayis, Seyit Ali; Hakki, Erdogan E; Hamurcu, Mehmet; Baspinar, Nuri; Basoglu, Abdullah; Nielsen, Forrest H; Götz, Werner

2015-01-01

The objective of this study was to determine whether dietary boron (B) affects the strength, density and mineral composition of teeth and mineral density of alveolar bone in rabbits with apparent obesity induced by a high-energy diet. Sixty female, 8-month-old, New Zealand rabbits were randomly assigned for 7 months into five groups as follows: (1) control 1, fed alfalfa hay only (5.91 MJ/kg and 57.5 mg B/kg); (2) control 2, high energy diet (11.76 MJ and 3.88 mg B/kg); (3) B10, high energy diet + 10 mg B gavage/kg body weight/96 h; (4) B30, high energy diet + 30 mg B gavage/kg body weight/96 h; (5) B50, high energy diet + 50 mg B gavage/kg body weight/96 h. Maxillary incisor teeth of the rabbits were evaluated for compression strength, mineral composition, and micro-hardness. Enamel, dentin, cementum and pulp tissue were examined histologically. Mineral densities of the incisor teeth and surrounding alveolar bone were determined by using micro-CT. When compared to controls, the different boron treatments did not significantly affect compression strength, and micro-hardness of the teeth, although the B content of teeth increased in a dose-dependent manner. Compared to control 1, B50 teeth had decreased phosphorus (P) concentrations. Histological examination revealed that teeth structure (shape and thickness of the enamel, dentin, cementum and pulp) was similar in the B-treated and control rabbits. Micro CT evaluation revealed greater alveolar bone mineral density in B10 and B30 groups than in controls. Alveolar bone density of the B50 group was not different than the controls. Although the B treatments did not affect teeth structure, strength, mineral density and micro-hardness, increasing B intake altered the mineral composition of teeth, and, in moderate amounts, had beneficial effects on surrounding alveolar bone.

Melatonin-micronutrients Osteopenia Treatment Study (MOTS): a translational study assessing melatonin, strontium (citrate), vitamin D3 and vitamin K2 (MK7) on bone density, bone marker turnover and health related quality of life in postmenopausal osteopenic women following a one-year double-blind RCT and on osteoblast-osteoclast co-cultures

PubMed Central

Maria, Sifat; Swanson, Mark H.; Enderby, Larry T.; D'Amico, Frank; Enderby, Brianna; Samsonraj, Rebekah M.; Dudakovic, Amel; van Wijnen, Andre J.; Witt-Enderby, Paula A.

2017-01-01

This one-year double blind randomized control trial assessed the effects of nightly melatonin, strontium (citrate), vitamin D3 and vitamin K2 (MK7; MSDK) on bone mineral density (BMD) and quality of life (QOL) in postmenopausal osteopenic women (ages 49-75). Compared to placebo, MSDK treatment increased BMD in lumbar spine (4.3%) and left femoral neck (2.2%), with an upward trend for total left hip (p=0.069). MSDK increased serum P1NP levels and reduced bone turnover (CTx:P1NP). Psychometric analyses indicated that mood and sleep quality improved for the MSDK group. MSDK-exposed human mesenchymal stem cells (hMSCs) and human peripheral blood monocytes (hPBMCs) plated in transwells or layered demonstrated increases in osteoblastogenesis, decreases in osteoclastogenesis, increases in OPG (TNFRSF11B) and decreases in RANKL (TNFSF11) levels. In transwell osteoblasts, MSDK increased pERK1/2 (MAPK1/MAPK3) and RUNX2 levels; decreased ERK5 (MAPK7); and did not affect the expression of NFκB (NFKB1) and β1integrin (ITGB1). In layered osteoblasts, MSDK also decreased expression of the metabolic proteins PPARγ (PPARG) and GLUT4 (SLC2A4). In adipose-derived human MSCs, MSDK induced osteoblastogenesis. These findings provide both clinical and mechanistic support for the use of MSDK for the prevention or treatment of osteopenia, osteoporosis or other bone-related diseases. PMID:28130552

Melatonin-micronutrients Osteopenia Treatment Study (MOTS): a translational study assessing melatonin, strontium (citrate), vitamin D3 and vitamin K2 (MK7) on bone density, bone marker turnover and health related quality of life in postmenopausal osteopenic women following a one-year double-blind RCT and on osteoblast-osteoclast co-cultures.

PubMed

Maria, Sifat; Swanson, Mark H; Enderby, Larry T; D'Amico, Frank; Enderby, Brianna; Samsonraj, Rebekah M; Dudakovic, Amel; van Wijnen, Andre J; Witt-Enderby, Paula A

2017-01-26

This one-year double blind randomized control trial assessed the effects of nightly melatonin, strontium (citrate), vitamin D3 and vitamin K2 (MK7; MSDK) on bone mineral density (BMD) and quality of life (QOL) in postmenopausal osteopenic women (ages 49-75). Compared to placebo, MSDK treatment increased BMD in lumbar spine (4.3%) and left femoral neck (2.2%), with an upward trend for total left hip (p=0.069). MSDK increased serum P1NP levels and reduced bone turnover (CTx:P1NP). Psychometric analyses indicated that mood and sleep quality improved for the MSDK group. MSDK-exposed human mesenchymal stem cells (hMSCs) and human peripheral blood monocytes (hPBMCs) plated in transwells or layered demonstrated increases in osteoblastogenesis, decreases in osteoclastogenesis, increases in OPG (TNFRSF11B) and decreases in RANKL (TNFSF11) levels. In transwell osteoblasts, MSDK increased pERK1/2 (MAPK1/MAPK3) and RUNX2 levels; decreased ERK5 (MAPK7); and did not affect the expression of NFκB (NFKB1) and β1integrin (ITGB1). In layered osteoblasts, MSDK also decreased expression of the metabolic proteins PPARγ (PPARG) and GLUT4 (SLC2A4). In adipose-derived human MSCs, MSDK induced osteoblastogenesis. These findings provide both clinical and mechanistic support for the use of MSDK for the prevention or treatment of osteopenia, osteoporosis or other bone-related diseases.

Protection against ethanol-induced osteopenia in female mice by dietary antioxidants

USDA-ARS?s Scientific Manuscript database

Chronic alcohol consumption leads to increased fracture risk and an elevated risk of osteoporosis by decreasing bone mineral density through increasing osteoclast activity and decreasing osteoblast activity. Our lab has shown this mechanism to be mediated by reactive oxygen species (ROS) produced by...

Combination of micellar casein with calcium and vitamins D2 and K2 improves bone status of ovariectomized mice.

PubMed

Boulier, A; Schwarz, J; Lespesailles, E; Baniel, A; Tomé, D; Blais, A

2016-10-01

Nutritional approaches may help to preserve bone quality. The purpose of our study was to demonstrate the efficiency of an innovative bone health product (BHP) including micellar casein rich in calcium, vitamin D2 and vitamin K2, to improve bone mineral density. The aim of postmenopausal osteoporosis treatment is to decrease bone resorption and/or increase bone formation. Because of the slow bone turnover, osteoporosis prevention and therapies are long-lasting, implying great costs and poor compliance. Even if the effects of nutrition on bone are not as marked as that of pharmaceutical agents, it can be of great help. The purpose of our study was to demonstrate the efficiency of an innovative bone health product (BHP) containing micellar casein rich in calcium, vitamin D2 and vitamin K2, for the improvement of bone mineral density (BMD). An ovariectomized mice model was used to study the effect of different concentrations of the ingredient on BMD and microarchitectural parameters. Blood concentrations of C-terminal telopeptide of type I collagen (CTX), N-terminal propeptide of type 1 procollagene (PINP), alkaline phosphatase (ALP), osteocalcin (OC) and RANKL were also measured to evaluate bone remodelling, To evaluate the efficiency of the product to modulate osteoblast and osteoclast growth and differentiation, primary murine bone cells were used. In vivo studies showed that BMD and microarchitectural parameters were dose-dependently improved after ingestion of the supplement for 3 months. We also report increased osteoblast activity as shown by increased OC activity and decreased osteoclastogenesis as shown by reduced CTX activity. In vitro studies support that BHPs stimulate osteoblast differentiation and mineralization and inhibit osteoclast resorption activity. Our results show that, when chronically ingested, BHPs improve BMD of ovariectomized mice. This work supports that providing an ingredient including micellar casein rich in calcium, vitamin D2 and vitamin K2 is more efficient than the control diet to maintain bone quality.

Efficacy of Vitamin K2 for Glucocorticoid-induced Osteoporosis in Patients with Systemic Autoimmune Diseases.

PubMed

Shikano, Kotaro; Kaneko, Kaichi; Kawazoe, Mai; Kaburaki, Makoto; Hasunuma, Tomoko; Kawai, Shinichi

2016-01-01

Objective Vitamin K2 (menatetrenone) is an effective treatment for patients with postmenopausal osteoporosis. We herein performed a subanalysis of patients with systemic autoimmune diseases undergoing glucocorticoid therapy in our previous prospective study. Methods Sixty patients were categorized into a group with vitamin K2 treatment (n=20, Group A) and a group without vitamin K2 treatment (n=40, Group B). All patients were treated with bisphosphonates. Results Serum levels of osteocalcin and undercarboxylated osteocalcin decreased significantly after the start of glucocorticoid therapy in both groups, while the serum osteocalcin level was significantly higher in Group A than Group B during the third (p=0.0250) and fourth weeks (p=0.0155). The serum level of the N-terminal peptide of type I procollagen, a bone formation marker, decreased during glucocorticoid therapy, but was significantly higher in Group A than Group B during the fourth week (p=0.0400). The bone mineral density and fracture rate showed no significant differences between the two groups. Conclusion Although vitamin K2 improves bone turnover markers in patients with osteoporosis on glucocorticoid therapy, it has no significant effect on the bone mineral density and fracture rate after 1.5 years of treatment.

Home-based resistance training improves femoral bone mineral density in women on hormone therapy.

PubMed

Judge, James Oat; Kleppinger, Alison; Kenny, Anne; Smith, Jo-Anne; Biskup, Brad; Marcella, Glenn

2005-09-01

This study tested whether moderate resistance training would improve femoral bone mineral density (BMD) in long-term users of hormone therapy with low BMD. The study was a 2-year randomized, controlled, trial (RCT) of moderate resistance training of either the lower extremity or the upper extremity. Eighty-five women participated in a 6-month observation period. The setting was center-based and home-based training. The participants were 189 women aged 59-78 years, with total femur T-scores from -0.8 to -2.8 and on hormone therapy (HT) for a minimum of 2 years (mean 11.8 years); 153 completed the trial. Lower extremity training used weight belts (mean 7.8 kg) in step-ups and chair rises; upper extremity training used elastic bands and dumbbells. Measurements were BMD and body composition [dual-energy X-ray absorptiometry (DXA)], bone turnover markers. Total femoral BMD showed a downward trend during the observation period: 0.35%+/-0.18% (P=0.14). The response to training was similar in the upper and lower groups in the primary outcomes. At 2 years, total femoral BMD increased 1.5% (95% CI 0.8%-2.2%) in the lower group and 1.8% (95% CI 1.1%-2.5%) in the upper group. Trochanter BMD increased 2.4% (95% CI 1.3%-3.5%) in the lower group and 2.5% (95% CI 1.4%-3.6%) in the upper group (for both analyses time effect P<0.001). At 1 year, a bone resorption marker (C-telopeptide) decreased 9% (P=0.04). Bone formation markers, bone-specific alkaline phosphatase, decreased 5% (P<0.001), and N-terminal type I procollagen peptide decreased 7% (P=0.01). Body composition (percent lean and percent body fat) was maintained in both groups. We concluded that long-term moderate resistance training reversed bone loss, decreased bone turnover, increased femur BMD, and maintained body composition. The similarity of response in upper and lower groups supports a systemic response rather than a site-specific response to moderate resistance training.

Targeted disruption of BMP signaling through type IA receptor (BMPR1A) in osteocyte suppresses SOST and RANKL, leading to dramatic increase in bone mass, bone mineral density and mechanical strength.

PubMed

Kamiya, Nobuhiro; Shuxian, Lin; Yamaguchi, Ryosuke; Phipps, Matthew; Aruwajoye, Olumide; Adapala, Naga Suresh; Yuan, Hui; Kim, Harry K W; Feng, Jian Q

2016-10-01

Recent studies suggest a critical role of osteocytes in controlling skeletal development and bone remodeling although the molecular mechanism is largely unknown. This study investigated BMP signaling in osteocytes by disrupting Bmpr1a under the Dmp1-promoter. The conditional knockout (cKO) mice displayed a striking osteosclerotic phenotype with increased trabecular bone volume, thickness, number, and mineral density as assessed by X-ray and micro-CT. The bone histomorphometry, H&E, and TRAP staining revealed a dramatic increase in trabecular and cortical bone masses but a sharp reduction in osteoclast number. Moreover, there was an increase in BrdU positive osteocytes (2-5-fold) and osteoid volume (~4-fold) but a decrease in the bone formation rate (~85%) in the cKO bones, indicating a defective mineralization. The SEM analysis revealed poorly formed osteocytes: a sharp increase in cell numbers, a great reduction in cell dendrites, and a remarkable change in the cell distribution pattern. Molecular studies demonstrated a significant decrease in the Sost mRNA levels in bone (>95%), and the SOST protein levels in serum (~85%) and bone matrices. There was a significant increase in the β-catenin (>3-fold) mRNA levels as well as its target genes Tcf1 (>6-fold) and Tcf3 (~2-fold) in the cKO bones. We also showed a significant decrease in the RANKL levels of serum proteins (~65%) and bone mRNA (~57%), and a significant increase in the Opg mRNA levels (>20-fold) together with a significant reduction in the Rankl/Opg ratio (>95%), which are responsible for a sharp reduction in the cKO osteoclasts. The values of mechanical strength were higher in cKO femora (i.e. max force, displacement, and work failure). These results suggest that loss of BMP signaling specifically in osteocytes dramatically increases bone mass presumably through simultaneous inhibition of RANKL and SOST, leading to osteoclast inhibition and Wnt activation together. Finally, a working hypothesis is proposed to explain how BMPR1A controls bone remodeling by inhibiting cell proliferation and stimulating differentiation. It is reported that RANKL and SOST are abundantly expressed by osteocytes. Thus, BMP signaling through BMPR1A plays important roles in osteocytes. Copyright © 2016 Elsevier Inc. All rights reserved.

Bone pain and extremely low bone mineral density due to severe vitamin D deficiency in celiac disease.

PubMed

Rabelink, Noortje M; Westgeest, Hans M; Bravenboer, Nathalie; Jacobs, Maarten A J M; Lips, Paul

2011-01-01

A 29-year-old wheelchair-bound woman was presented to us by the gastroenterologist with suspected osteomalacia. She had lived in the Netherlands all her life and was born of Moroccan parents. Her medical history revealed iron deficiency, growth retardation, and celiac disease, for which she was put on a gluten-free diet. She had progressive bone pain since 2 years, difficulty with walking, and about 15 kg weight loss. She had a short stature, scoliosis, and pronounced kyphosis of the spine and poor condition of her teeth. Laboratory results showed hypocalcemia, an immeasurable serum 25-hydroxyvitamin D level, and elevated parathyroid hormone and alkaline phosphatase levels. Spinal radiographs showed unsharp, low contrast vertebrae. Bone mineral density measurement at the lumbar spine and hip showed a T-score of -6.0 and -6.5, respectively. A bone scintigraphy showed multiple hotspots in ribs, sternum, mandible, and long bones. A duodenal biopsy revealed villous atrophy (Marsh 3C) and positive antibodies against endomysium, transglutaminase, and gliadin, compatible with active celiac disease. A bone biopsy showed severe osteomalacia but normal bone volume. She was treated with calcium intravenously and later orally. Furthermore, she was treated with high oral doses of vitamin D and a gluten-free diet. After a few weeks of treatment, her bone pain decreased, and her muscle strength improved. In this article, the pathophysiology and occurrence of osteomalacia as a complication of celiac disease are discussed. Low bone mineral density can point to osteomalacia as well as osteoporosis.

A hospital based study of biochemical markers of bone turnovers & bone mineral density in north Indian women

PubMed Central

Kumar, Ashok; Devi, Salam Gyaneshwori; Mittal, Soniya; Shukla, Deepak Kumar; Sharma, Shashi

2013-01-01

Background & objectives: The osteoporotic risk for women increases soon after menopause. Bone turnover markers are known to be associated with bone loss and fracture risk. This study was aimed to assess bone turnover using bone markers and their correlation with bone mineral density (BMD) in pre- and post-menopausal women. Methods: A total of 255 healthy women (160 pre- and 95 post-menopausal) were enrolled. Serum bone alkaline phosphatase (sBAP) and serum N-terminal telopeptide of type I collagen (NTX) were measured to evaluate the bone formation and resorption, respectively. Bone mineral density was determined at lumbar spine (L2-L4) anteroposteriorly, femoral neck and Ward's triangle using Prodigy dual-energy X-ray absorptiometry (DXA) system. The comparison of years since menopause with respect to BMD and bone markers was also evaluated. Results: NTX and sBAP showed significant negative correlation with BMD of femur neck and Ward's triangle in postmenopausal women. BMD of all three sides were significant variables for NTX and BMD of femur neck and Ward's triangle for sBAP in postmenopausal women. BMD lumbar spine was a significant variable for sBAP in premenopausal women. The mean values of NTX increased significantly with increase in the duration of years since menopause. The BMD of all three sides decreased significantly with increase in the duration of years since menopause. Interpretation & conclusions: Serum NTX and sBAP were inversely correlated to BMD of femur neck and Ward's triangle in post-menopausal women. Simultaneous measurements of NTX and BMD in the north Indian women, suggest that bone resorption in women with low BMD remains high after menopause. PMID:23481051

Risk factors for decreased bone mineral density in inflammatory bowel disease: A cross-sectional study.

PubMed

Wada, Yasuyo; Hisamatsu, Tadakazu; Naganuma, Makoto; Matsuoka, Katsuyoshi; Okamoto, Susumu; Inoue, Nagamu; Yajima, Tomoharu; Kouyama, Keisuke; Iwao, Yasushi; Ogata, Haruhiko; Hibi, Toshifumi; Abe, Takayuki; Kanai, Takanori

2015-12-01

Although inflammatory bowel disease (IBD) patients are at risk for metabolic bone disease, studies analyzing this correlation have identified various risk factors, including disease phenotype, age, sex and steroid therapy. Furthermore, few studies have assessed risk factors for bone loss in Japanese IBD patients. This study analyzed risk factors for metabolic bone disease in Japanese IBD patients. This cross-sectional study assessed 388 patients with IBD aged 20-50 years, including 232 with ulcerative colitis (UC) and 156 with Crohn's disease (CD). Bone mineral density of the femoral neck, total femur and lumbar spine was quantified by dual-energy X-ray absorptiometry. The blood concentrations of bone metabolism markers were measured. History of smoking and bone fracture, and nutritional intake were assessed using questionnaires. Of the 388 patients with IBD, 78 (20.1%; UC, 17.2%; CD, 24.4%) had osteopenia and 17 (4.4%; UC, 3.4%; CD, 5.8%) had osteoporosis, as assessed by T-score. Bone mineral density of the lumbar vertebrae was lower in males than in females. Multivariate regression analysis showed that risk factors for bone loss in UC patients were male sex, low body mass index (BMI), high steroid dose and disease location. Risk factors for bone loss in CD patients were male sex and low BMI. Among Japanese patients with IBD, male sex and low BMI were associated with increased risk for metabolic bone disease. In addition, Steroid therapy shouldn't be indiscriminate in UC patients. These findings may help identify patients at particularly high risk of metabolic bone disease and may help implement appropriate therapies in a timely manner and improve long-term quality of life. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

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.

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.

Hypercalciuric Bone Disease

NASA Astrophysics Data System (ADS)

Favus, Murray J.

2008-09-01

Hypercalciuria plays an important causal role in many patients with calcium oxalate (CaOx) stones. The source of the hypercalciuria includes increased intestinal Ca absorption and decreased renal tubule Ca reabsorption. In CaOx stone formers with idiopathic hypercalciuria (IH), Ca metabolic balance studies have revealed negative Ca balance and persistent hypercalciuria in the fasting state and during low dietary Ca intake. Bone resorption may also contribute to the high urine Ca excretion and increase the risk of bone loss. Indeed, low bone mass by DEXA scanning has been discovered in many IH patients. Thiazide diuretic agents reduce urine Ca excretion and may increase bone mineral density (BMD), thereby reducing fracture risk. Dietary Ca restriction that has been used unsuccessfully in the treatment of CaOx nephrolithiasis in the past may enhance negative Ca balance and accelerate bone loss. DEXA scans may demonstrate low BMD at the spine, hip, or forearm, with no predictable pattern. The unique pattern of bone histologic changes in IH differs from other causes of low DEXA bone density including postmenopausal osteoporosis, male hypogonadal osteoporosis, and glucocorticoid-induced osteoporosis. Hypercalciuria appears to play an important pathologic role in the development of low bone mass, and therefore correction of urine Ca losses should be a primary target for treatment of the bone disease accompanying IH.

Effects of Radiation and a High Iron Load on Bone Mineral Density

NASA Technical Reports Server (NTRS)

Yuen, E.; Morgan, J. L. L.; Zwart, S. R.; Gonzales, E.; Camp, K.; Smith, S. M.; Bloomfield, S. A.

2012-01-01

Astronauts on long duration space flight missions to the moon or mars are exposed to radiation and have increase iron (Fe) stores, both of which can independently induce oxidative stress and may exacerbate bone mass loss and strength. We hypothesize a high Fe diet and a fractionated gamma radiation exposure would increase oxidative stress and lower bone mass. Three mo-old, SD rats (n=32) were randomized to receive an adequate Fe diet (45 mg Fe/kg diet) or a high Fe diet (650 mg Fe/kg diet) for 4 wks and either a cumulative 3 Gy dose (fractionated 8 x 0.375 Gy) of gamma radiation (Cs-137) or sham exposure starting on day 14. Elisa kit assessed serum catalase, clinical analyzer assessed serum Fe status and ex vivo pQCT scans measured bone parameters in the proximal/midshaft tibia and femoral neck. Mechanical strength was assessed by 3-pt bending and femoral neck test. There is a significant decrease in trabecular bone mineral density (BMD) from radiation (p less than 0.05) and a trend in diet (p=0.05) at the proximal tibia. There is a significant interaction in cortical BMD from the combined treatments at the midshaft tibia (p less than 0.05). There is a trending decrease in total BMD from diet (p=0.07) at the femoral neck. In addition, high serum Fe was correlated to low trabecular BMD (p less than 0.05) and high serum catalase was correlated to low BMD at all 3 bone sites (p less than 0.05). There was no difference in the max load of the tibia or femoral neck. Radiation and a high iron diet increases iron status and catalase in the serum and decreases BMD.

The variation of cancellous bones at lumbar vertebra, femoral neck, mandibular angle and rib in ovariectomized sheep.

PubMed

Zhang, Yongqiang; Li, Yongfeng; Gao, Qi; Shao, Bo; Xiao, Jianrui; Zhou, Hong; Niu, Qiang; Shen, Mingming; Liu, Baolin; Hu, Kaijin; Kong, Liang

2014-07-01

This study aimed to compare the variation of cancellous bones at four skeletal sites: lumbar vertebra, femoral neck, mandibular angle and rib in ovariectomized sheep. Sixteen adult sheep were randomly divided into two groups: eight sheep were ovariectomized served as experimental group; the other eight untreated sheep were served as control group. Bone mineral density was assessed by dual-energy X-ray absorptiometry on lumbar vertebrae at baseline and twelve months after ovariectomy. After 12 months, lumbar vertebrae L3 and L4, femoral necks, mandibular angles and the fourth ribs were harvested for micro-CT scanning, histological analysis and biomechanical test. The results showed that bone mineral density of lumbar vertebra decreased significantly in twelfth month (p<0.05). The results of micro-CT showed that the bone volume/total volume decreased by 45.6%, 36.1% 21.3% and 18.7% in lumbar vertebrae, femoral necks, mandibular angles and ribs in experimental group (p<0.05) respectively. The trabecular number showed the same downtrend (p<0.05). Histological analysis showed trabecular area/tissue area decreased by 32.1%, 23.2% and 20.7% in lumbar vertebrae, femoral necks and mandibular angles respectively (p<0.05), but no significant difference in ribs. Specimens elastic modulus from lumbar vertebra, femoral neck and mandibular angle were 952±76MPa (628±70MPa), 961±173MPa (610±72MPa) and 595±60MPa (444±31MPa) in control group (experimental group) respectively. These datum indicated that the sensibility of cancellous bones to oestrogen deficiency in ovariectomized sheep was site-specific on a pattern as follows: lumbar vertebra, femoral neck, mandibular angle and rib. Copyright © 2014 Elsevier Ltd. All rights reserved.

Statistical analysis of biomechanical properties of the adult skull and age-related structural changes by sex in a Japanese forensic sample.

PubMed

Torimitsu, Suguru; Nishida, Yoshifumi; Takano, Tachio; Koizumi, Yoshinori; Makino, Yohsuke; Yajima, Daisuke; Hayakawa, Mutsumi; Inokuchi, Go; Motomura, Ayumi; Chiba, Fumiko; Otsuka, Katsura; Kobayashi, Kazuhiro; Odo, Yuriko; Iwase, Hirotaro

2014-01-01

The purpose of this research was to investigate the biomechanical properties of the adult human skull and the structural changes that occur with age in both sexes. The heads of 94 Japanese cadavers (54 male cadavers, 40 female cadavers) autopsied in our department were used in this research. A total of 376 cranial samples, four from each skull, were collected. Sample fracture load was measured by a bending test. A statistically significant negative correlation between the sample fracture load and cadaver age was found. This indicates that the stiffness of cranial bones in Japanese individuals decreases with age, and the risk of skull fracture thus probably increases with age. Prior to the bending test, the sample mass, the sample thickness, the ratio of the sample thickness to cadaver stature (ST/CS), and the sample density were measured and calculated. Significant negative correlations between cadaver age and sample thickness, ST/CS, and the sample density were observed only among the female samples. Computerized tomographic (CT) images of 358 cranial samples were available. The computed tomography value (CT value) of cancellous bone which refers to a quantitative scale for describing radiodensity, cancellous bone thickness and cortical bone thickness were measured and calculated. Significant negative correlation between cadaver age and the CT value or cortical bone thickness was observed only among the female samples. These findings suggest that the skull is substantially affected by decreased bone metabolism resulting from osteoporosis. Therefore, osteoporosis prevention and treatment may increase cranial stiffness and reinforce the skull structure, leading to a decrease in the risk of skull fractures. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Bone Resorption and Environmental Exposure to Cadmium in Women: A Population Study

PubMed Central

Schutte, Rudolph; Nawrot, Tim S.; Richart, Tom; Thijs, Lutgarde; Vanderschueren, Dirk; Kuznetsova, Tatiana; Van Hecke, Etienne; Roels, Harry A.; Staessen, Jan A.

2008-01-01

Background Environmental exposure to cadmium decreases bone density indirectly through hypercalciuria resulting from renal tubular dysfunction. Objective We sought evidence for a direct osteotoxic effect of cadmium in women. Methods We randomly recruited 294 women (mean age, 49.2 years) from a Flemish population with environmental cadmium exposure. We measured 24-hr urinary cadmium and blood cadmium as indexes of lifetime and recent exposure, respectively. We assessed the multivariate-adjusted association of exposure with specific markers of bone resorption, urinary hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP), as well as with calcium excretion, various calciotropic hormones, and forearm bone density. Results In all women, the effect sizes associated with a doubling of lifetime exposure were 8.4% (p = 0.009) for HP, 6.9% (p = 0.10) for LP, 0.77 mmol/day (p = 0.003) for urinary calcium, –0.009 g/cm2 (p = 0.055) for proximal forearm bone density, and –16.8% (p = 0.065) for serum parathyroid hormone. In 144 postmenopausal women, the corresponding effect sizes were –0.01223 g/cm2 (p = 0.008) for distal forearm bone density, 4.7% (p = 0.064) for serum calcitonin, and 10.2% for bone-specific alkaline phosphatase. In all women, the effect sizes associated with a doubling of recent exposure were 7.2% (p = 0.001) for urinary HP, 7.2% (p = 0.021) for urinary LP, –9.0% (p = 0.097) for serum parathyroid hormone, and 5.5% (p = 0.008) for serum calcitonin. Only one woman had renal tubular dysfunction (urinary retinol-binding protein > 338 μg/day). Conclusions In the absence of renal tubular dysfunction, environmental exposure to cadmium increases bone resorption in women, suggesting a direct osteotoxic effect with increased calciuria and reactive changes in calciotropic hormones. PMID:18560534

Effect of dimethyl sulfoxide on inhibition of post-ovariectomy osteopenia in rats.

PubMed

Tamjidipoor, Ahmad; Tavafi, Majid; Ahmadvand, Hasan

2013-01-01

There is increasing evidence that oxidative stress, due to estrogen deficiency, leads to osteopenia. In this study, dimethyl sulfoxide (DMSO), an antioxidant solvent, was used against post-ovariectomy osteopenia (PO) in rats. Forty female rats were divided into 5 groups randomly as follows: Sham, control group; OVX, ovariectomized group; DMSO1, ovariectomized injected DMSO (0.5 ml/kg/d ip); DMSO2, ovariectomized injected DMSO (1 ml/kg/day ip) and DMSO3, ovariectomized injected DMSO (2 ml/kg/d ip). DMSO therapy started 1 week after ovariectomy and continued for 13 weeks. After 13th weeks, sera were prepared, and then L4 vertebrae and right tibial bones rinsed in fixative. Serum bone alkaline phosphatase (BALP), osteocalcin, pyridinoline, malondialdehyde (MDA) and glutathione (GSH) were measured. Trabecular volume density, trabecular and cortex thickness were estimated. Osteoclast and osteoblast numbers were counted morphometrically. The data were analyzed by ANOVA and then post hoc Tukey test at p < 0.05. The increase of pyridinoline and decrease of BALP in DMSO injected groups were inhibited compared with OVX group (p < 0.05). In DMSO injected groups, decrease of bone density, trabecular volume density, thickness of trabecular and tibial cortex were inhibited compared with OVX group (p < 0.05). MDA decreased significantly in DMSO injected groups compared with OVX group. Osteoclast number decreased in DMSO injected groups compared with OVX group (p < 0.05). Osteoblast number did not show significant change in DMSO groups compared with OVX group. In conclusion, DMSO ameliorates PO through decrease of osteoclast number, osteoclast inhibition and osteoblast activation. These effects may probably be mediated via antioxidant property of DMSO.

Circulating gonadotropins and ovarian adiponectin system are modulated by acupuncture independently of sex steroid or β-adrenergic action in a female hyperandrogenic rat model of polycystic ovary syndrome.

PubMed

Maliqueo, Manuel; Benrick, Anna; Alvi, Asif; Johansson, Julia; Sun, Miao; Labrie, Fernand; Ohlsson, Claes; Stener-Victorin, Elisabet

2015-09-05

Acupuncture with combined manual and low-frequency electrical stimulation, or electroacupuncture (EA), reduces endocrine and reproductive dysfunction in women with polycystic ovary syndrome (PCOS), likely by modulating sympathetic nerve activity or sex steroid synthesis. To test this hypothesis, we induced PCOS in rats by prepubertal implantation of continuous-release letrozole pellets (200 µg/day) or vehicle. Six weeks later, rats were treated for 5-6 weeks with low-frequency EA 5 days/week, subcutaneous injection of 17β-estradiol (2.0 µg) every fourth day, or a β-adrenergic blocker (propranolol hydrochloride, 0.1 mg/kg) 5 days/week. Letrozole controls were handled without needle insertion or injected with sesame oil every fourth day. Estrous cyclicity, ovarian morphology, sex steroids, gonadotropins, insulin-like growth factor I, bone mineral density, and gene and protein expression in ovarian tissue were measured. Low-frequency EA induced estrous-cycle changes, decreased high levels of circulating luteinizing hormone (LH) and the LH/follicle-stimulating hormone (FSH) ratio, decreased high ovarian gene expression of adiponectin receptor 2, and increased expression of adiponectin receptor 2 protein and phosphorylation of ERK1/2. EA also increased cortical bone mineral density. Propranolol decreased ovarian expression of Foxo3, Srd5a1, and Hif1a. Estradiol decreased circulating LH, induced estrous cycle changes, and decreased ovarian expression of Adipor1, Foxo3, and Pik3r1. Further, total bone mineral density was higher in the letrozole-estradiol group. Thus, EA modulates the circulating gonadotropin levels independently of sex steroids or β-adrenergic action and affects the expression of ovarian adiponectin system. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

POTASSIUM CITRATE DECREASES BONE RESORPTION IN POSTMENOPAUSAL WOMEN WITH OSTEOPENIA: A RANDOMIZED, DOUBLE-BLIND CLINICAL TRIAL.

PubMed

Gregory, Naina Sinha; Kumar, Rekha; Stein, Emily M; Alexander, Ellen; Christos, Paul; Bockman, Richard S; Rodman, John S

2015-12-01

Diets rich in animal protein, such as the typical American diet, are thought to create a high acid load. An association between acid load and bone loss has led to the idea that providing positive alkaline salt therapy could have beneficial effects on bone metabolism. The objective of this study was to investigate the effects of potassium citrate (K-citrate), 40 mEq daily, over 1 year on bone resorption and formation. A randomized, double-blind, placebo-controlled trial of 83 women with postmenopausal osteopenia. Levels of bone turnover markers, specifically urinary N-telopeptide of collagen type 1 (u-NTX), amino-terminal propeptide of type 1 procollagen (P1NP), bone-specific alkaline phosphatase (BSAP), and osteocalcin (OC) were compared. Changes in bone mineral density (BMD) were also examined. K-citrate decreased both u-NTX (P = .005) and serum P1NP (P<.001) starting at month 1 and continuing through month 12. No significant change was seen in BSAP or OC. No significant change was seen in lumbar or hip BMD between the 2 groups. In women with postmenopausal osteopenia, treatment with K-citrate for 1 year resulted in a significant decrease in markers of turnover. The effect on markers of bone formation was not consistent. K-citrate may serve as a potential treatment for bone loss that is well tolerated and without any significant known long-term consequences.

Degeneration of the osteocyte network in the C57BL/6 mouse model of aging.

PubMed

Tiede-Lewis, LeAnn M; Xie, Yixia; Hulbert, Molly A; Campos, Richard; Dallas, Mark R; Dusevich, Vladimir; Bonewald, Lynda F; Dallas, Sarah L

2017-10-26

Age-related bone loss and associated fracture risk are major problems in musculoskeletal health. Osteocytes have emerged as key regulators of bone mass and as a therapeutic target for preventing bone loss. As aging is associated with changes in the osteocyte lacunocanalicular system, we focused on the responsible cellular mechanisms in osteocytes. Bone phenotypic analysis was performed in young-(5mo) and aged-(22mo) C57BL/6 mice and changes in bone structure/geometry correlated with alterations in osteocyte parameters determined using novel multiplexed-3D-confocal imaging techniques. Age-related bone changes analogous to those in humans were observed, including increased cortical diameter, decreased cortical thickness, reduced trabecular BV/TV and cortical porosities. This was associated with a dramatic reduction in osteocyte dendrite number and cell density, particularly in females, where osteocyte dendricity decreased linearly from 5, 12, 18 to 22mo and correlated significantly with cortical bone parameters. Reduced dendricity preceded decreased osteocyte number, suggesting dendrite loss may trigger loss of viability. Age-related degeneration of osteocyte networks may impair bone anabolic responses to loading and gender differences in osteocyte cell body and lacunar fluid volumes we observed in aged mice may lead to gender-related differences in mechanosensitivity. Therapies to preserve osteocyte dendricity and viability may be beneficial for bone health in aging.

Regional distribution of mineral and matrix in the femurs of rats flown on Cosmos 1887 biosatellite

NASA Technical Reports Server (NTRS)

Mechanic, Gerald L.; Arnaud, Sara B.; Boyde, Alan; Bromage, Timothy G.; Buckendahl, Patricia

1990-01-01

The location and nature of the defect in mineralization known to occur in growing animals after spaceflight are studied. The distribution of bone mineral density in situ is mapped, and these images are correlated with the chemical composition of the diaphyseal bone. Concentrations of mineral and osteocalcin are found to be low in the distal half of the diaphysis and concentrations of collagen to be low with evidence of increased synthesis in the proximal half of the diaphysis of the flight bones. X-ray microtomography indicates a longitudinal gradient of decreasing mineralization toward the distal diaphysis. Analysis of embedded sections by backscattered electrons reveals patterns of mineral distribution in the proximal, central, and distal regions of the diaphysis and also shows a net reduction in mineral levels toward the distal shaft. Increases in mineral density to higher fractions in controls are less in the flight bones at all three levels.

Efficacy and safety of bisphosphonates in management of low bone density in inflammatory bowel disease

PubMed Central

Yao, Liwei; Wang, Haiqing; Dong, Wenwei; Liu, Zhenxin; Mao, Haijiao

2017-01-01

Abstract This study aims to determine whether bisphosphonates are safe, as well as effective against bone mineral loss in inflammatory bowel disease (IBD). A computerized search of electronic databases from 1966 to 2016 was performed. Randomized controlled trials (RCTs) were included in this review to evaluate the role of bisphosphonates in the management of osteoporosis in IBD patients. A revised 7-point Jadad scale was used to evaluate the quality of each study. Overall, 13 RCTs and 923 patients met the inclusion criteria of this meta-analysis. The result showed that bisphosphonates decreased bone mass density (BMD) loss at the lumbar spine (P = 0.0002), reduced the risk of new fractures (P = 0.01), and retained the similar adverse events (P = 0.86). Bisphosphonates may provide protection and safety against bone mineral loss in IBD patients. PMID:28099343

Efficacy and safety of bisphosphonates in management of low bone density in inflammatory bowel disease: A meta-analysis.

PubMed

Yao, Liwei; Wang, Haiqing; Dong, Wenwei; Liu, Zhenxin; Mao, Haijiao

2017-01-01

This study aims to determine whether bisphosphonates are safe, as well as effective against bone mineral loss in inflammatory bowel disease (IBD). A computerized search of electronic databases from 1966 to 2016 was performed. Randomized controlled trials (RCTs) were included in this review to evaluate the role of bisphosphonates in the management of osteoporosis in IBD patients. A revised 7-point Jadad scale was used to evaluate the quality of each study. Overall, 13 RCTs and 923 patients met the inclusion criteria of this meta-analysis. The result showed that bisphosphonates decreased bone mass density (BMD) loss at the lumbar spine (P = 0.0002), reduced the risk of new fractures (P = 0.01), and retained the similar adverse events (P = 0.86). Bisphosphonates may provide protection and safety against bone mineral loss in IBD patients.

Bone disease in thyrotoxicosis.

PubMed

Reddy, P Amaresh; Harinarayan, C V; Sachan, Alok; Suresh, V; Rajagopal, G

2012-03-01

Thyrotoxicosis, a clinical syndrome characterized by manifestations of excess thyroid hormone, is one of the commonly-recognised conditions of the thyroid gland. Thyrotoxicosis causes acceleration of bone remodelling and though it is one of the known risk factors for osteoporosis, the metabolic effects of thyroxine on bone are not well discussed. Studies show that thyroid hormones have effects on bone, both in vitro and in vivo. Treatment of thyrotoxicosis leads to reversal of bone loss and metabolic alterations, and decreases the fracture risk. There are limited studies in India as to whether these changes are fully reversible. In this review we discuss about the effects of thyrotoxicosis (endogenous and exogenous) on bone and mineral metabolism, effects of subclinical thyrotoxicosis on bone and mineral metabolism and effects of various forms of treatment in improving the bone mineral density in thyrotoxicosis.

Growth-Associated Changes in the Periodontal Bone and Molar Teeth of Male Rats

PubMed Central

García, María F; Moreno, Hilda; Rigalli, Alfredo; Puche, Rodolfo C

2009-01-01

Here we report quantitative data associating periodontal bone variables of young conventional rats with the growth process. The hemimandibles of male rats (IIM/Fm stock, 2 to 15 wk of age.) were excised and submitted to conventional morphologic, radiologic, and histologic evaluation. The length, area, or X-ray absorbance of various regions or structures was measured on digital images of radiographs by using an image-analysis program. The sum of periodontal bone areas undergoing resorption (interproximal + intraradicular) increased until 9 or 10 wk of age and decreased thereafter. Mineral accretion rates and mineral density asymptotes were not significantly different among molars. The mineral density of resorption areas in alveolar bone fitted sinusoidal kinetics, indicative of the ‘instability’ of the tissue due to its high metabolic activity. Mineral accretion rates and mineral density asymptotes were not significantly different among molars. The proportion of root length within alveolar bone exhibited a biphasic curve (minimum at 5 wk of age), due to differences in the growth rates of variables involved in its calculation (distance between the cementoenamel junction to the apex and height of the resorption areas). The distance between the cementoenamel junction and alveolar bone crest over time fitted a sigmoidal function with a point of inflection that did not differ significantly from that of body or mandible dry weight. In summary, the growth process appears to affect periodontal bone support and the distance between the cementoenamel junction and alveolar bone crest in male rats. PMID:19807966

Effects of anticonvulsants and inactivity on bone disease in epileptics

PubMed Central

Murchison, Lilian E.; Bewsher, P. D.; Chesters, Marion; Gilbert, J.; Catto, G.; Law, Elizabeth; McKay, E.; Ross, H. S.

1975-01-01

No significant biochemical or radiological features of vitamin D deficiency were found in groups of juvenile and adult epileptics and control groups of non-epileptic patients in hospitals for the mentally retarded. There was evidence of hepatic enzyme induction in patients on anticonvulsants, in that urinary D-glucaric acid concentration and excretion were raised. No effect was found of prolonged anticonvulsant therapy on bone densitometry, but in children immobility was closely associated with decreased bone density. The evidence suggests that disuse osteoporosis is the major bone disease in these mentally retarded children. PMID:1161672

[Characteristics of bone tissue of rats after flight aboard biosputnik Kosmos-1129].

PubMed

Rogacheva, I V; Stupakov, G P; Volozhin, A I; Pavlova, M N; Poliakov, A N

1984-01-01

Bones of rats flown for 19 days onboard Cosmos-1129 were examined. The examination included bone mass, density, mineral composition, reconstruction parameters, and elemental composition at R + 1, R + 6, and R + 29. After flight the rats developed osteoporosis in the spongy structures of tubular bones and a smaller thickness of the cortical layer of the diaphysis; they showed no mineralization of the microstructures, a slight decrease of the Ca concentration, and a normal content of P. At R + 6 these changes progressively developed and at R + 29 they returned to normal.

Melatonin improves bone mineral density at the femoral neck in postmenopausal women with osteopenia: a randomized controlled trial.

PubMed

Amstrup, Anne Kristine; Sikjaer, Tanja; Heickendorff, Lene; Mosekilde, Leif; Rejnmark, Lars

2015-09-01

Melatonin is known for its regulation of circadian rhythm. Recently, studies have shown that melatonin may have a positive effect on the skeleton. By increasing age, the melatonin levels decrease, which may lead to a further imbalanced bone remodeling. We aimed to investigate whether treatment with melatonin could improve bone mass and integrity in humans. In a double-blind RCT, we randomized 81 postmenopausal osteopenic women to 1-yr nightly treatment with melatonin 1 mg (N = 20), 3 mg (N = 20), or placebo (N = 41). At baseline and after 1-yr treatment, we measured bone mineral density (BMD) by dual X-ray absorptiometry, quantitative computed tomography (QCT), and high-resolution peripheral QCT (HR-pQCT) and determined calciotropic hormones and bone markers. Mean age of the study subjects was 63 (range 56-73) yr. Compared to placebo, femoral neck BMD increased by 1.4% in response to melatonin (P < 0.05) in a dose-dependent manner (P < 0.01), as BMD increased by 0.5% in the 1 mg/day group (P = 0.55) and by 2.3% (P < 0.01) in the 3 mg/day group. In the melatonin group, trabecular thickness in tibia increased by 2.2% (P = 0.04), and volumetric bone mineral density (vBMD) in the spine, by 3.6% (P = 0.04) in the 3 mg/day. Treatment did not significantly affect BMD at other sites or levels of bone turnover markers; however, 24-hr urinary calcium was decreased in response to melatonin by 12.2% (P = 0.02). In conclusion, 1-yr treatment with melatonin increased BMD at femoral neck in a dose-dependent manner, while high-dose melatonin increased vBMD in the spine. Further studies are needed to assess the mechanisms of action and whether the positive effect of nighttime melatonin will protect against fractures. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Is Bone Tissue Really Affected by Swimming? A Systematic Review

PubMed Central

Gómez-Bruton, Alejandro; Gónzalez-Agüero, Alejandro; Gómez-Cabello, Alba; Casajús, José A.; Vicente-Rodríguez, Germán

2013-01-01

Background Swimming, a sport practiced in hypogravity, has sometimes been associated with decreased bone mass. Aim This systematic review aims to summarize and update present knowledge about the effects of swimming on bone mass, structure and metabolism in order to ascertain the effects of this sport on bone tissue. Methods A literature search was conducted up to April 2013. A total of 64 studies focusing on swimmers bone mass, structure and metabolism met the inclusion criteria and were included in the review. Results It has been generally observed that swimmers present lower bone mineral density than athletes who practise high impact sports and similar values when compared to sedentary controls. However, swimmers have a higher bone turnover than controls resulting in a different structure which in turn results in higher resistance to fracture indexes. Nevertheless, swimming may become highly beneficial regarding bone mass in later stages of life. Conclusion Swimming does not seem to negatively affect bone mass, although it may not be one of the best sports to be practised in order to increase this parameter, due to the hypogravity and lack of impact characteristic of this sport. Most of the studies included in this review showed similar bone mineral density values in swimmers and sedentary controls. However, swimmers present a higher bone turnover than sedentary controls that may result in a stronger structure and consequently in a stronger bone. PMID:23950908

The relationships of irisin with bone mineral density and body composition in PCOS patients.

PubMed

Gao, Shanshan; Cheng, Yan; Zhao, Lingling; Chen, Yuxin; Liu, Yu

2016-05-01

Our study aims to assay the irisin level and investigate the relationships of irisin level with body mass index (BMI), body composition and bone metabolism in the polycystic ovary syndrome (PCOS) and control women. Fifty two PCOS and 39 control women were recruited. Serum sex hormone, fasting insulin and C-peptide were tested. Fasting serum irisin and adiponectin were measured with enzyme-linked immunosorbent assay. Body composition and bone mineral density were assayed by dual energy X-ray absorptiometry. Polycystic ovary syndrome women showed different body compositions compared with controls. Serum irisin level of PCOS did not show significant difference compared with controls although it was decreased. The level of adiponectin in PCOS patients was significantly reduced. BMI had no correlation with irisin level. It indicated a positive correlation between serum irisin levels and bone mineral density in the control group and a negative correlation in the PCOS group after BMI and age adjusted. Furthermore, total lean mass has a significant effect on irisin concentration in the PCOS group. There are no correlations between adiponection and body compositions and bone mineral density in both groups. The abnormal body composition in PCOS may contribute to the circulation irisin. The crosstalk of irisin in different organs was found and may be related to disease development in PCOS. Copyright © 2015 John Wiley & Sons, Ltd.

First principles study of biomineral hydroxyapatite

NASA Astrophysics Data System (ADS)

Slepko, Alexander

2010-03-01

Hydroxyapatite (HA) [Ca10(PO4)6(OH)2] is one of the most abundant materials in mammal bone. It crystallizes within the spaces between the tropocollagen chains and strengthens the bone tissue. The mineral content of human bone increases with age reaching a maximum value from which it starts to decrease leading to diseases such as osteomalacia. Therefore, an emergent application of this study is bone repair and the production of synthetic bone. Despite its importance, little is known about the growth of HA crystallites in bones. Nor is it well understood how the HA attaches to protein chains and interacts with the surrounding aqueous solution. Using density functional theory (DFT) we calculate the theoretical ground state structure, electronic and vibration properties of hexagonal HA. We find several low energy structures and analyze the energy barriers for spontaneous phase transitions. We calculate the phonon density of states and study the surface energetics for different orientations. We identify the surfaces with highest reactivity using the frontier orbital approach and analyze interactions between these surfaces and water molecules/amino acids.

Acute Exposure to High Dose γ-Radiation Results in Transient Activation of Bone Lining Cells

PubMed Central

Turner, Russell T.; Iwaniec, Urszula T.; Wong, Carmen P.; Lindenmaier, Laurence B.; Wagner, Lindsay A.; Branscum, Adam J.; Menn, Scott A.; Taylor, James; Zhang, Ye; Wu, Honglu; Sibonga, Jean D.

2014-01-01

The present studies investigated the cellular mechanisms for the detrimental effects of high dose whole body γ-irradiation on bone. In addition, radioadaptation and bone marrow transplantation were assessed as interventions to mitigate the skeletal complications of irradiation. Increased trabecular thickness and separation and reduced fractional cancellous bone volume, connectivity density, and trabecular number were detected in proximal tibia and lumbar vertebra 14 days following γ-irradiation with 6 Gy. To establish the cellular mechanism for the architectural changes, vertebrae were analyzed by histomorphometry 1, 3, and 14 days following irradiation. Marrow cell density decreased within 1 day (67% reduction, p<0.0001), reached a minimum value after 3 days (86% reduction, p<0.0001), and partially rebounded by 14 days (30% reduction, p=0.0025) following irradiation. In contrast, osteoblast-lined bone perimeter was increased by 290% (1 day, p=0.04), 1230% (3 days, p<0.0001), and 530% (14 days, p=0.003), respectively. There was a strong association between radiation-induced marrow cell death and activation of bone lining cells to express the osteoblast phenotype (Pearson correlation −0.85, p<0.0001). An increase (p=0.004) in osteoclast-lined bone perimeter was also detected with irradiation. A priming dose of γ-radiation (0.5 mGy), previously shown to reduce mortality, had minimal effect on the cellular responses to radiation and did not prevent detrimental changes in bone architecture. Bone marrow transplantation normalized marrow cell density, bone turnover, and most indices of bone architecture following irradiation. In summary, radiation-induced death of marrow cells is associated with 1) a transient increase in bone formation due, at least in part, to activation of bone lining cells, and 2) an increase in bone resorption due to increased osteoclast perimeter. Bone marrow transplantation is effective in mitigating the detrimental effects of acute exposure to high dose whole body γ-radiation on bone turnover. PMID:23954507

Effects of a short-term whole body vibration intervention on bone mass and structure in elderly people.

PubMed

Gómez-Cabello, Alba; González-Agüero, Alejandro; Morales, Silvia; Ara, Ignacio; Casajús, José A; Vicente-Rodríguez, Germán

2014-03-01

We aimed to clarify whether a short-term whole body vibration training has a beneficial effect on bone mass and structure in elderly men and women. Randomised controlled trial. A total of 49 non-institutionalised elderly (20 men and 29 women) volunteered to participate in the study. Participants who met the inclusion criteria were randomly assigned to one of the study groups (whole body vibration or control). A total of 24 elderly trained squat positioned on a vibration platform 3 times per week for 11 weeks. Bone-related variables were assessed by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. Two-way repeated measures one-way analysis of variance (group by time) was used to determine the effects of the intervention on the bone-related variables and also to determinate the changes within group throughout the intervention period. Analysis of covariance was used to test the differences between groups for bone-related variables in pre- and post-training assessments and in the percentage of change between groups. All analysis were carried out including age, height, subtotal lean mass and daily calcium intake as covariates. 11 weeks of whole body vibration training led to no changes in none of the bone mineral content and bone mineral density parameters measured by dual-energy X-ray absorptiometry through the skeleton. At the tibia, total, trabecular and cortical volumetric bone mineral density decreased significantly in the whole body vibration group (all P<0.05). A short-term whole body vibration therapy is not enough to cause any changes on bone mineral content or bone mineral density and it only produces a slight variation on bone structure among elderly people. Copyright © 2013 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

[Long-term effects of 7-year growth hormone substitution on bone metabolism, bone density, and bone quality in growth hormone-deficient adults].

PubMed

Wilhelm, Birgit; Kann, Peter Herbert

2004-10-15

Subnormal bone mineral density (BMD) and increased fracture risk are described in patients with growth hormone deficiency (GHD). Growth hormone (GH) has been reported to have beneficial effects on bone in GHD. The aim of this study was to investigate the long-term effects of GH replacement therapy on bone metabolism, BMD, and bone quality in patients with GHD. 20 adult patients with GHD (eleven male, nine female, mean age 42.5 years) were included in the study and randomized to either GH or placebo in a dose of 0.25 U/kg body weight/week. After 6 months all patients received GH. After a 1-year double-blind, placebo-controlled study the patients were followed for another 72 months in an open study. The patients were compared to 20 age- und sex-matched healthy controls. Bone turnover was determined by ICTP (type I collagen carboxyterminal cross-linked telopeptide) as parameter of bone resorption and PICP (carboxyterminal propeptide of type I procollagen) as marker of bone formation. BMD was measured at the lumbar spine by dual-photon absorptiometry (DPA) and at the forearm by single-photon absorptiometry (SPA). Apparent phalangeal ultrasound transmission velocity (APU) was assessed as parameter of bone quality independent of BMD. At the beginning of the study BMD at both measuring sites was lower in patients with GHD than in healthy controls. During the 1st year of GH replacement therapy BMD decreased, followed by a continuous increase in BMD (about 12%) up to 60 months which remained unchanged thereafter, building up a plateau. After 72 months no significant difference between the patients and the healthy controls could be detected. Concerning parameters of bone turnover, first ICTP as marker of bone resorption showed a significant increase, later on the marker of bone formation increased as well. APU decreased during the first 6 months of treatment, but had returned to its baseline value after 24 months and remained unchanged throughout the rest of the study. BMD is subnormal in adults with GHD. GH replacement therapy stimulates bone turnover in patients with GHD and in the long term such stimulation results in an increased BMD. Thereby, GH shows a triphasic action on BMD: an initial decrease in BMD during the 1st year, followed by a continuous increase in BMD with buildup of a stable plateau after 60 months. The newly formed bone seems to have normal bone elasticity.

Administration of growth hormone in selectively protein-deprived rats decreases BMD and bone strength.

PubMed

Ammann, Patrick; Brennan, Tara C; Mekraldi, Samia; Aubert, Michel L; Rizzoli, René

2010-06-01

Isocaloric protein undernutrition is associated with decreased bone mass and decreased bone strength, together with lower IGF-I levels. It remains unclear whether administration of growth hormone (GH) corrects these alterations in bone metabolism. Six-month-old female rats were fed isocaloric diets containing either 2.5% or 15% casein for 2 weeks. Bovine growth hormone (bGH, 0.5 or 2.5mg/kg of body weight) or vehicle was then administered as subcutaneous injections, twice daily, to rats on either diet for 4 weeks. At the proximal tibia, analysis of bone mineral density (BMD), maximal load and histomorphometry were performed. In addition, urinary deoxypyridinoline, plasma osteocalcin and IGF-I concentrations were measured. Weight was monitored weekly. bGH caused a dose-dependent increase in plasma IGF-I regardless of the dietary protein content. However, bGH dose-dependently decreased BMD and bone strength in rats fed the low-protein diet. There was no significant effect of bGH on BMD in rats fed the normal protein diet within this short-term treatment period, however bone formation as detected by histomorphometry was improved in this group but not the low-protein group. Osteoclast surface was increased in the low-protein bGH-treated animals only. Changes in bone turnover markers were detectable under both normal and low-protein diets. These results emphasize the major importance of dietary protein intake in the bone response to short-term GH administration, and highlight the need for further investigation into the effects of GH treatment in patients with reduced protein intake. Copyright 2010 Elsevier Inc. All rights reserved.

Reciprocal regulation of adipocyte and osteoblast differentiation of mesenchymal stem cells by Eupatorium japonicum prevents bone loss and adiposity increase in osteoporotic rats.

PubMed

Kim, Min-Ji; Jang, Woo-Seok; Lee, In-Kyoung; Kim, Jong-Keun; Seong, Ki-Seung; Seo, Cho-Rong; Song, No-Joon; Bang, Min-Hyuk; Lee, Young Min; Kim, Haeng Ran; Park, Ki-Moon; Park, Kye Won

2014-07-01

Pathological increases in adipogenic potential with decreases in osteogenic differentiation occur in osteoporotic bone marrow cells. Previous studies have shown that bioactive materials isolated from natural products can reciprocally regulate adipogenic and osteogenic fates of bone marrow cells. In this study, we showed that Eupatorium japonicum stem extracts (EJE) suppressed lipid accumulation and inhibited the expression of adipocyte markers in multipotent C3H10T1/2 and primary bone marrow cells. Conversely, EJE stimulated alkaline phosphatase activity and induced the expression of osteoblast markers in C3H10T1/2 and primary bone marrow cells. Daily oral administration of 50 mg/kg of EJE for 6 weeks to ovariectomized rats prevented body weight increase and bone mineral density decrease. Finally, activity-guided fractionation led to the identification of coumaric acid and coumaric acid methyl ester as bioactive anti-adipogenic and pro-osteogenic components in EJE. Taken together, our data indicate a promising possibility of E. japonicum as a functional food and as a therapeutic intervention for preventing osteoporosis and bone fractures.

Olives and Bone: A Green Osteoporosis Prevention Option

PubMed Central

Chin, Kok-Yong; Ima-Nirwana, Soelaiman

2016-01-01

Skeletal degeneration due to aging, also known as osteoporosis, is a major health problem worldwide. Certain dietary components confer protection to our skeletal system against osteoporosis. Consumption of olives, olive oil and olive polyphenols has been shown to improve bone health. This review aims to summarize the current evidence from cellular, animal and human studies on the skeletal protective effects of olives, olive oil and olive polyphenols. Animal studies showed that supplementation of olives, olive oil or olive polyphenols could improve skeletal health assessed via bone mineral density, bone biomechanical strength and bone turnover markers in ovariectomized rats, especially those with inflammation. The beneficial effects of olive oil and olive polyphenols could be attributed to their ability to reduce oxidative stress and inflammation. However, variations in the bone protective, antioxidant and anti-inflammatory effects between studies were noted. Cellular studies demonstrated that olive polyphenols enhanced proliferation of pre-osteoblasts, differentiation of osteoblasts and decreased the formation of osteoclast-like cells. However, the exact molecular pathways for its bone health promoting effects are yet to be clearly elucidated. Human studies revealed that daily consumption of olive oil could prevent the decline in bone mineral density and improve bone turnover markers. As a conclusion, olives, olive oil and its polyphenols are potential dietary interventions to prevent osteoporosis among the elderly. PMID:27472350

Therapeutic effect of icariin combined with stem cells on postmenopausal osteoporosis in rats.

PubMed

Tang, Dao; Ju, Cuiling; Liu, Yanjie; Xu, Fei; Wang, Zhengguang; Wang, Dongbo

2018-03-01

Osteoporosis is characterized by skeletal fragility and microarchitectural deterioration. The side effects of drugs to treat osteoporosis will negatively affect the health of patients. This study aimed to investigate the therapeutic effects of icariin combined with adipose-derived stem cells on osteoporosis in a postmenopausal osteoporosis model after ovariectomy in rats. After ovariectomy the rats were treated with icariin combined with adipose-derived stem cell transplantation. The levels of alkaline phosphatase, tartrate-resistant acid phosphatase, osteoprotegerin, and bone γ-carboxyglutamate protein in serum were determined by ELISA. The bone mineral density was measured by dual-energy X-ray absorptiometry. The mechanical properties were determined by a three-point bending test. The kidney functions were evaluated by an automatic analyzer and a diagnostic kit. Icariin combined with stem cells significantly reduced body weight gain caused by ovariectomy, significantly decreased alkaline phosphatase, tartrate-resistant acid phosphatase, and bone γ-carboxyglutamate protein content in serum, significantly increased osteoprotegerin content, significantly elevated bone mineral density of the lumbar spine, left femur, and right femur, and enhanced bone biomechanical properties of the femur, including maximum bending load, bending rigidity, and fracture energy, in osteoporotic rats. In addition, icariin combined with stem cells substantially decreased the damage to the liver and kidney in osteoporotic rats. Icariin combined with stem cells can not only ameliorate reduction of bone mass and disruption of the microarchitectural structure of bone tissue caused by osteoporosis in a rat model but can also have a beneficial effect on organ functions, such as those of the liver and kidney.

Numerical analysis of standard and modified osteosynthesis in long bone fractures treatment.

PubMed

Sisljagić, Vladimir; Jovanović, Savo; Mrcela, Tomislav; Radić, Radivoje; Selthofer, Robert; Mrcela, Milanka

2010-03-01

The fundamental problem in osteoporotic fracture treatment is significant decrease in bone mass and bone tissue density resulting in decreased firmness and elasticity of osteoporotic bone. Application of standard implants and standard surgical techniques in osteoporotic bone fracture treatment makes it almost impossible to achieve stable osteosynthesis sufficient for early mobility, verticalization and load. Taking into account the form and the size of the contact surface as well as distribution of forces between the osteosynthetic materials and the bone tissue numerical analysis showed advantages of modified osteosynthesis with bone cement filling in the screw bed. The applied numerical model consisted of three sub-models: 3D model from solid elements, 3D cross section of the contact between the plate and the bone and the part of 3D cross section of the screw head and body. We have reached the conclusion that modified osteosynthesis with bone cement resulted in weaker strain in the part of the plate above the fracture fissure, more even strain on the screws, plate and bone, more even strain distribution along all the screws' bodies, significantly greater strain in the part of the screw head opposite to the fracture fissure, firm connection of the screw head and neck and the plate hole with the whole plate and more even bone strain around the screw.

Mathematical modeling of postmenopausal osteoporosis and its treatment by the anti-catabolic drug denosumab

PubMed Central

Scheiner, S; Pivonka, P; Smith, D W; Dunstan, C R; Hellmich, C

2014-01-01

Denosumab, a fully human monoclonal antibody, has been approved for the treatment of postmenopausal osteoporosis. The therapeutic effect of denosumab rests on its ability to inhibit osteoclast differentiation. Here, we present a computational approach on the basis of coupling a pharmacokinetics model of denosumab with a pharmacodynamics model for quantifying the effect of denosumab on bone remodeling. The pharmacodynamics model comprises an integrated systems biology-continuum micromechanics approach, including a bone cell population model, considering the governing biochemical factors of bone remodeling (including the action of denosumab), and a multiscale micromechanics-based bone mechanics model, for implementing the mechanobiology of bone remodeling in our model. Numerical studies of postmenopausal osteoporosis show that denosumab suppresses osteoclast differentiation, thus strongly curtailing bone resorption. Simulation results also suggest that denosumab may trigger a short-term bone volume gain, which is, however, followed by constant or decreasing bone volume. This evolution is accompanied by a dramatic decrease of the bone turnover rate by more than one order of magnitude. The latter proposes dominant occurrence of secondary mineralization (which is not anymore impeded through cellular activity), leading to higher mineral concentration per bone volume. This explains the overall higher bone mineral density observed in denosumab-related clinical studies. Copyright © 2013 John Wiley & Sons, Ltd. PMID:24039120

Acute Ketamine Administration Corrects Abnormal Inflammatory Bone Markers in Major Depressive Disorder

PubMed Central

Kadriu, Bashkim; Gold, Philip W; Luckenbaugh, David A; Lener, Marc S; Ballard, Elizabeth D; Niciu, Mark J; Henter, Ioline D; Park, Lawrence T; De Sousa, Rafael Teixeira; Yuan, Peixiong; Machado-Vieira, Rodrigo; Zarate, Carlos A

2017-01-01

Patients with major depressive disorder (MDD) have clinically relevant, significant decreases in bone mineral density (BMD). We sought to determine if predictive markers of bone inflammation—the osteoprotegerin (OPG)-RANK-RANKL system or osteopontin (OPN)—play a role in the bone abnormalities associated with MDD and, if so, whether ketamine treatment corrected the abnormalities. The OPG-RANK-RANKL system plays the principal role in determining the balance between bone resorption and bone formation. RANKL is the osteoclast differentiating factor and diminishes BMD. OPG is a decoy receptor for RANKL, thereby increasing BMD. OPN is the bone glue that acts as a scaffold between bone tissues matrix composition to bind them together and is an important component of bone strength and fracture resistance. Twenty-eight medication-free inpatients with treatment-resistant MDD and 16 healthy controls (HCs) participated in the study. Peripheral bone marker levels and their responses to IV ketamine infusion in MDD patients and HCs were measured at four time points: at baseline, and post-infusion at 230 minutes, Day 1, and Day 3. Patients with MDD had significant decreases in baseline OPG/RANKL ratio and in plasma OPN levels. Ketamine significantly increased both the OPG/RANKL ratio and plasma OPN levels and significantly decreased RANKL levels. Bone marker levels in HCs remained unaltered. We conclude that the OPG-RANK-RANKL system and the OPN system play important roles in the serious bone abnormalities associated with MDD. These data suggest that in addition to its antidepressant effects, ketamine also has a salutary effect on a major medical complication of depressive illness. PMID:28555075

Age-Related Changes in Bone Morphology Are Accelerated in Group VIA Phospholipase A2 (iPLA2β)-Null Mice

PubMed Central

Ramanadham, Sasanka; Yarasheski, Kevin E.; Silva, Matthew J.; Wohltmann, Mary; Novack, Deborah Veis; Christiansen, Blaine; Tu, Xiaolin; Zhang, Sheng; Lei, Xiaoyong; Turk, John

2008-01-01

Phospholipases A2 (PLA2) hydrolyze the sn−2 fatty acid substituent, such as arachidonic acid, from phospholipids, and arachidonate metabolites are recognized mediators of bone modeling. We have previously generated knockout (KO) mice lacking the group VIA PLA2 (iPLA2β), which participates in a variety of signaling events; iPLA2β mRNA is expressed in bones of wild-type (WT) but not KO mice. Cortical bone size, trabecular bone volume, bone mineralizing surfaces, and bone strength are similar in WT and KO mice at 3 months and decline with age in both groups, but the decreases are more pronounced in KO mice. The lower bone mass phenotype observed in KO mice is not associated with an increase in osteoclast abundance/activity or a decrease in osteoblast density, but is accompanied by an increase in bone marrow fat. Relative to WT mice, undifferentiated bone marrow stromal cells (BMSCs) from KO mice express higher levels of PPAR-γ and lower levels of Runx2 mRNA, and this correlates with increased adipogenesis and decreased osteogenesis in BMSCs from these mice. In summary, our studies indicate that age-related losses in bone mass and strength are accelerated in iPLA2β-null mice. Because adipocytes and osteoblasts share a common mesenchymal stem cell origin, our findings suggest that absence of iPLA2β causes abnormalities in osteoblast function and BMSC differentiation and identify a previously unrecognized role of iPLA2β in bone formation. PMID:18349124

Deficiency of ATP6V1H Causes Bone Loss by Inhibiting Bone Resorption and Bone Formation through the TGF-β1 Pathway

PubMed Central

Duan, Xiaohong; Liu, Jin; Zheng, Xueni; Wang, Zhe; Zhang, Yanli; Hao, Ying; Yang, Tielin; Deng, Hongwen

2016-01-01

Vacuolar-type H +-ATPase (V-ATPase) is a highly conserved, ancient enzyme that couples the energy of ATP hydrolysis to proton transport across vesicular and plasma membranes of eukaryotic cells. Previously reported mutations of various V-ATPase subunits are associated with increased bone density. We now show that haploinsufficiency for the H subunit of the V1 domain (ATP6V1H) is associated with osteoporosis in humans and mice. A genome-wide SNP array analysis of 1625 Han Chinese found that 4 of 15 tag SNPs (26.7%) within ATP6V1H were significantly associated with low spine bone mineral density. Atp6v1h+/- knockout mice generated by the CRISPR/Cas9 technique had decreased bone remodeling and a net bone matrix loss. Atp6v1h+/- osteoclasts showed impaired bone formation and increased bone resorption. The increased intracellular pH of Atp6v1h+/- osteoclasts downregulated TGF-β1 activation, thereby reducing induction of osteoblast formation but the bone mineralization was not altered. However, bone formation was reduced more than bone resorption. Our data provide evidence that partial loss of ATP6V1H function results in osteoporosis/osteopenia. We propose that defective osteoclast formation triggers impaired bone formation by altering bone remodeling. In the future, ATP6V1H might, therefore, serve as a target for the therapy of osteoporosis. PMID:27924156

Decreased bone mineral density in young adults treated with SCT in childhood: the role of 25-hydroxyvitamin D.

PubMed

Frisk, P; Arvidson, J; Ljunggren, O; Gustafsson, J

2012-05-01

We measured bone mineral density (BMD) with dual-energy X-ray absorptiometry in the total body, at the lumbar spine, at the femoral neck and in the total hip, in 18 young adults with a median of 18.2 years after SCT. Fifteen patients had undergone auto-SCT and all patients had received TBI. The patients had significantly lower BMD in the total body, at the femoral neck, and in the total hip compared with age- and sex-matched controls. Six of 18 patients (33%) had low bone mass (z-score <-1) at one or more measurement sites, as opposed to two of the controls (11%, P=0.29). We found no significant influence of growth hormone levels or of untreated hypogonadism on BMD variables. Levels of 25-hydroxy (25(OH)) vitamin D were lower among the patients (35.2 vs 48.8 nmol/L, P=0.044) and were significantly correlated with total body BMD in the patient group (r=0.55, P=0.021). All six patients with low bone mass had hypovitaminosis D (≤37 nmol/L as opposed to 4 of the 11 (36%) patients without low bone mass (P=0.035). In conclusion, we found decreased BMD in SCT survivors, which may in part be caused by 25(OH) vitamin D deficiency.

The prevention of fragility fractures in patients with non-metastatic prostate cancer: a position statement by the international osteoporosis foundation

PubMed Central

Cianferotti, Luisella; Bertoldo, Francesco; Carini, Marco; Kanis, John A.; Lapini, Alberto; Longo, Nicola; Martorana, Giuseppe; Mirone, Vincenzo; Reginster, Jean-Yves; Rizzoli, Rene; Brandi, Maria Luisa

2017-01-01

Androgen deprivation therapy is commonly employed for the treatment of non-metastatic prostate cancer as primary or adjuvant treatment. The skeleton is greatly compromised in men with prostate cancer during androgen deprivation therapy because of the lack of androgens and estrogens, which are trophic factors for bone. Men receiving androgen deprivation therapy sustain variable degrees of bone loss with an increased risk of fragility fractures. Several bone antiresorptive agents have been tested in randomized controlled trials in these patients. Oral bisphosphonates, such as alendronate and risedronate, and intravenous bisphosphonates, such as pamidronate and zoledronic acid, have been shown to increase bone density and decrease the risk of fractures in men receiving androgen deprivation therapy. Denosumab, a fully monoclonal antibody that inhibits osteoclastic-mediated bone resorption, is also effective in increasing bone mineral density and reducing fracture rates in these patients. The assessment of fracture risk, T-score and/or the evaluation of prevalent fragility fractures are mandatory for the selection of patients who will benefit from antiresorptive therapy. In the future, new agents modulating bone turnover and skeletal muscle metabolism will be available for testing in these subjects. PMID:29088899

The prevention of fragility fractures in patients with non-metastatic prostate cancer: a position statement by the international osteoporosis foundation.

PubMed

Cianferotti, Luisella; Bertoldo, Francesco; Carini, Marco; Kanis, John A; Lapini, Alberto; Longo, Nicola; Martorana, Giuseppe; Mirone, Vincenzo; Reginster, Jean-Yves; Rizzoli, Rene; Brandi, Maria Luisa

2017-09-26

Androgen deprivation therapy is commonly employed for the treatment of non-metastatic prostate cancer as primary or adjuvant treatment. The skeleton is greatly compromised in men with prostate cancer during androgen deprivation therapy because of the lack of androgens and estrogens, which are trophic factors for bone. Men receiving androgen deprivation therapy sustain variable degrees of bone loss with an increased risk of fragility fractures. Several bone antiresorptive agents have been tested in randomized controlled trials in these patients. Oral bisphosphonates, such as alendronate and risedronate, and intravenous bisphosphonates, such as pamidronate and zoledronic acid, have been shown to increase bone density and decrease the risk of fractures in men receiving androgen deprivation therapy. Denosumab, a fully monoclonal antibody that inhibits osteoclastic-mediated bone resorption, is also effective in increasing bone mineral density and reducing fracture rates in these patients. The assessment of fracture risk, T-score and/or the evaluation of prevalent fragility fractures are mandatory for the selection of patients who will benefit from antiresorptive therapy. In the future, new agents modulating bone turnover and skeletal muscle metabolism will be available for testing in these subjects.

Differential skeletal responses of hindlimb unloaded rats on a vitamin D-deficient diet to 1,25-dihydroxyvitamin D3 and its analog, seocalcitol (EB1089)

NASA Technical Reports Server (NTRS)

Narayanan, Ramesh; Allen, Matthew R.; Gaddy, Dana; Bloomfield, Susan A.; Smith, Carolyn L.; Weigel, Nancy L.

2004-01-01

Conditions of disuse in bed rest patients, as well as microgravity experienced by astronauts are accompanied by reduced mechanical loading, reduced calcium absorption, and lower serum levels of 1,25(OH)2D3 (1,25-D), the active metabolite of vitamin D, all contributing to bone loss. To determine whether 1,25-D or a less calcemic analog, Seocalcitol or EB1089 (1 alpha,25-dihydroxy-22,24-diene-24,26,27-trihomovitamin D3) can alleviate bone loss in a rat hindlimb unloading model of disuse osteopenia, mature male rats originally on a vitamin D replete diet containing 1.01% calcium were transferred to a vitamin D-deficient diet containing 0.48% calcium and then tail suspended and treated for 28 days with vehicle, 0.05 microg/kg 1,25-D, or 0.05 microg/kg EB1089. The vitamin D-deficient diet caused a substantial decrease in bone mineral density (-8%), which may be compounded by hindlimb unloading (-10%). Exogenous 1,25-D not only prevented the bone loss but also increased the bone mineral density to greater than the baseline level (+7%). EB1089 was less effective in preventing bone loss. Analysis of site and cell-specific effects of 1,25-D and EB1089 revealed that 1,25-D was more active than EB1089 in the intestine, the site of calcium absorption, and in inducing osteoclastogenesis and bone resorption whereas EB1089 was more effective in inducing osteoblast differentiation. These studies suggest that elevating circulating 1,25-D levels presumably increasing calcium absorption can counteract bone loss induced by disuse or microgravity with its associated reductions in circulating 1,25-D and decreased calcium absorption.

Perioperative alendronate, risedronate, calcitonin and indomethacin treatment alters femoral stem fixation and periprosthetic bone mineral density in ovariectomized rats.

PubMed

Cankaya, Deniz; Tabak, Yalcin; Ozturk, Akif Muhtar; Gunay, Muhammed Cuneyd

2015-07-01

Many factors affect implant stability and periprosthetic bone mineral density (BMD) following total joint arthroplasty. We asked whether perioperative alendronate, risedronate, calcitonin and indomethacine administration altered (1) femoral stem shear strength and periprosthetic bone mineral density BMD in ovariectomized rats and (2) whether there were differences in the effect of these drugs. Thirty overiectomized rats were divided into five groups and implanted with intramedullary mini-cortical screws in the femur. Four groups were treated with alendronate, risedronate, salmon calcitonin and indomethacin for 4 weeks preoperatively and 8 weeks postoperatively. Although alendronate and risedronate increased the periprosthetic BMD more than calcitonin, they did not alter implant fixation compared to calcitonin. Indomethacin significantly decreased the BMD around the stem and implant stability compared to all other groups. This study showed that perioperative treatment with bisphosphonates and calcitonin improved the BMD around the stems and implant stability. Although bisphosphonates increased the BMD more than calcitonin, there was no difference in implant stability. Indomethacin markedly decreased the periprosthetic BMD and implant stability. The main clinical significance of our study was the finding about the need to strictly avoid long-term use of high-dose nonsteroidal antiinflammatory drugs for patients who have major joint arthritis and a previous history of arthroplasty.

Correlation of quantitative computed tomographic subchondral bone density and ash density in horses.

PubMed

Drum, M G; Les, C M; Park, R D; Norrdin, R W; McIlwraith, C W; Kawcak, C E

2009-02-01

The purpose of this study was to compare subchondral bone density obtained using quantitative computed tomography with ash density values from intact equine joints, and to determine if there are measurable anatomic variations in mean subchondral bone density. Five adult equine metacarpophalangeal joints were scanned with computed tomography (CT), disarticulated, and four 1-cm(3) regions of interest (ROI) cut from the distal third metacarpal bone. Bone cubes were ashed, and percent mineralization and ash density were recorded. Three-dimensional models were created of the distal third metacarpal bone from CT images. Four ROIs were measured on the distal aspect of the third metacarpal bone at axial and abaxial sites of the medial and lateral condyles for correlation with ash samples. Overall correlations of mean quantitative CT (QCT) density with ash density (r=0.82) and percent mineralization (r=0.93) were strong. There were significant differences between abaxial and axial ROIs for mean QCT density, percent bone mineralization and ash density (p<0.05). QCT appears to be a good measure of bone density in equine subchondral bone. Additionally, differences existed between axial and abaxial subchondral bone density in the equine distal third metacarpal bone.

Primary Hyperparathyroidism is Associated with Abnormal Cortical and Trabecular Microstructure and Reduced Bone Stiffness in Postmenopausal Women

PubMed Central

Stein, Emily M; Silva, Barbara C; Boutroy, Stephanie; Zhou, Bin; Wang, Ji; Udesky, Julia; Zhang, Chiyuan; McMahon, Donald J; Romano, Megan; Dworakowski, Elzbieta; Costa, Aline G.; Cusano, Natalie; Irani, Dinaz; Cremers, Serge; Shane, Elizabeth; Guo, X Edward; Bilezikian, John P

2013-01-01

Typically, in the milder form of primary hyperparathyroidism (PHPT), seen in most countries now, bone density by DXA and detailed analyses of iliac crest bone biopsies by histomorphometry and µCT show detrimental effects in cortical bone, whereas the trabecular site (lumbar spine by DXA) and the trabecular compartment (by bone biopsy) appear to be relatively well preserved. Despite these findings, fracture risk at both vertebral and non-vertebral sites is increased in PHPT. Emerging technologies, such as high-resolution peripheral quantitative computed tomography (HRpQCT), may provide additional insight into microstructural features at sites such as the forearm and tibia that have heretofore not been easily accessible. Using HRpQCT, we determined cortical and trabecular microstructure at the radius and tibia in 51 postmenopausal women with PHPT and 120 controls. Individual trabecula segmentation (ITS) and micro finite element (µFE) analyses of the HRpQCT images were also performed to further understand how the abnormalities seen by HRpQCT might translate into effects on bone strength. Women with PHPT showed, at both sites, decreased volumetric densities at trabecular and cortical compartments, thinner cortices, and more widely spaced and heterogeneously distributed trabeculae. At the radius, trabeculae were thinner and fewer in PHPT. The radius was affected to a greater extent in the trabecular compartment than the tibia. ITS analyses revealed, at both sites, that plate-like trabeculae were depleted, with a resultant reduction in the plate/rod ratio. Microarchitectural abnormalities were evident by decreased plate-rod and plate-plate junctions at the radius and tibia, and rod-rod junctions at the radius. These trabecular and cortical abnormalities resulted in decreased whole bone stiffness and trabecular stiffness. These results provide evidence that in PHPT, microstructural abnormalities are pervasive and not limited to the cortical compartment. They may help to account for increased global fracture risk in PHPT. PMID:23225022

Sclerostin Antibody Treatment Enhances Rotator Cuff Tendon-to-Bone Healing in an Animal Model.

PubMed

Shah, Shivam A; Kormpakis, Ioannis; Havlioglu, Necat; Ominsky, Michael S; Galatz, Leesa M; Thomopoulos, Stavros

2017-05-17

Rotator cuff tears are a common source of pain and disability, and poor healing after repair leads to high retear rates. Bone loss in the humeral head before and after repair has been associated with poor healing. The purpose of the current study was to mitigate bone loss near the repaired cuff and improve healing outcomes. Sclerostin antibody (Scl-Ab) treatment, previously shown to increase bone formation and strength in the setting of osteoporosis, was used in the current study to address bone loss and enhance rotator cuff healing in an animal model. Scl-Ab was administered subcutaneously at the time of rotator cuff repair and every 2 weeks until the animals were sacrificed. The effect of Scl-Ab treatment was evaluated after 2, 4, and 8 weeks of healing, using bone morphometric analysis, biomechanical evaluation, histological analysis, and gene expression outcomes. Injury and repair led to a reduction in bone mineral density after 2 and 4 weeks of healing in the control and Scl-Ab treatment groups. After 8 weeks of healing, animals receiving Scl-Ab treatment had 30% greater bone mineral density than the controls. A decrease in biomechanical properties was observed in both groups after 4 weeks of healing compared with healthy tendon-to-bone attachments. After 8 weeks of healing, Scl-Ab-treated animals had improved strength (38%) and stiffness (43%) compared with control animals. Histological assessment showed that Scl-Ab promoted better integration of tendon and bone by 8 weeks of healing. Scl-Ab had significant effects on gene expression in bone, indicative of enhanced bone formation, and no effect on the expression of genes in tendon. This study provides evidence that Scl-Ab treatment improves tendon-to-bone healing at the rotator cuff by increasing attachment-site bone mineral density, leading to improved biomechanical properties. Scl-Ab treatment may improve outcomes after rotator cuff repair.

Bone disease in thyrotoxicosis

PubMed Central

Reddy, P. Amaresh; Harinarayan, C. V.; Sachan, Alok; Suresh, V.; Rajagopal, G.

2012-01-01

Thyrotoxicosis, a clinical syndrome characterized by manifestations of excess thyroid hormone, is one of the commonly-recognised conditions of the thyroid gland. Thyrotoxicosis causes acceleration of bone remodelling and though it is one of the known risk factors for osteoporosis, the metabolic effects of thyroxine on bone are not well discussed. Studies show that thyroid hormones have effects on bone, both in vitro and in vivo. Treatment of thyrotoxicosis leads to reversal of bone loss and metabolic alterations, and decreases the fracture risk. There are limited studies in India as to whether these changes are fully reversible. In this review we discuss about the effects of thyrotoxicosis (endogenous and exogenous) on bone and mineral metabolism, effects of subclinical thyrotoxicosis on bone and mineral metabolism and effects of various forms of treatment in improving the bone mineral density in thyrotoxicosis. PMID:22561612

Factors affecting bone mineral mass loss after lower-limb fractures in a pediatric population.

PubMed

Ceroni, Dimitri; Martin, Xavier; Kherad, Omar; Salvo, Davide; Dubois-Ferrière, Victor

2015-06-01

The purpose of this study was to assess the effects of the durations of cast immobilization and non-weight-bearing periods, and decreases in vigorous physical activity (VPA) on bone mineral parameters in a pediatric population treated for a lower-limb fracture. Fifty children and teenagers who had undergone a cast-mediated immobilization for a leg or ankle fracture were prospectively recruited. The durations of cast immobilization and non-weight-bearing periods were recorded for each participant. Dual-energy x-ray absorptiometry scans were performed at the time of fracture treatment (baseline) and at cast removal. Physical activity during cast immobilization was assessed using accelerometers. A strong negative correlation was found between the total duration of cast immobilization and decreases in both calcaneal bone mineral density (BMD) (r=-0.497) and total lower-limb bone mineral content (BMC) (r=-0.405). A strong negative correlation was also noted between the durations of the non-weight-bearing periods and alterations in calcaneal BMD (r=-0.420). No apparent correlations were found between lower BMD and BMC and decreased VPA. Bone mineral loss was correlated to the total duration of cast immobilization for all measurement sites on the affected leg, whereas it was only correlated to the durations of non-weight-bearing periods for calcaneal BMD and total lower-limb BMC. However, no correlations were noted between bone mineral loss and decreased VPA.

Bone Densitometry (Bone Density Scan)

MedlinePlus

... News Physician Resources Professions Site Index A-Z Bone Densitometry (DEXA) Bone densitometry, also called dual-energy ... limitations of DEXA Bone Densitometry? What is a Bone Density Scan (DEXA)? Bone density scanning, also called ...

Cellular and Matrix Response of the Mandibular Condylar Cartilage to Botulinum Toxin

PubMed Central

Dutra, Eliane H.; O’ Brien, Mara H.; Lima, Alexandro; Kalajzic, Zana; Tadinada, Aditya; Nanda, Ravindra; Yadav, Sumit

2016-01-01

Objectives To evaluate the cellular and matrix effects of botulinum toxin type A (Botox) on mandibular condylar cartilage (MCC) and subchondral bone. Materials and Methods Botox (0.3 unit) was injected into the right masseter of 5-week-old transgenic mice (Col10a1-RFPcherry) at day 1. Left side masseter was used as intra-animal control. The following bone labels were intraperitoneally injected: calcein at day 7, alizarin red at day 14 and calcein at day 21. In addition, EdU was injected 48 and 24 hours before sacrifice. Mice were sacrificed 30 days after Botox injection. Experimental and control side mandibles were dissected and examined by x-ray imaging and micro-CT. Subsequently, MCC along with the subchondral bone was sectioned and stained with tartrate resistant acid phosphatase (TRAP), EdU, TUNEL, alkaline phosphatase, toluidine blue and safranin O. In addition, we performed immunohistochemistry for pSMAD and VEGF. Results Bone volume fraction, tissue density and trabecular thickness were significantly decreased on the right side of the subchondral bone and mineralized cartilage (Botox was injected) when compared to the left side. There was no significant difference in the mandibular length and condylar head length; however, the condylar width was significantly decreased after Botox injection. Our histology showed decreased numbers of Col10a1 expressing cells, decreased cell proliferation and increased cell apoptosis in the subchondral bone and mandibular condylar cartilage, decreased TRAP activity and mineralization of Botox injected side cartilage and subchondral bone. Furthermore, we observed reduced proteoglycan and glycosaminoglycan distribution and decreased expression of pSMAD 1/5/8 and VEGF in the MCC of the Botox injected side in comparison to control side. Conclusion Injection of Botox in masseter muscle leads to decreased mineralization and matrix deposition, reduced chondrocyte proliferation and differentiation and increased cell apoptosis in the MCC and subchondral bone. PMID:27723812

Socket preservation using freeze-dried bone allograft with and without plasma rich in growth factors in dogs

PubMed Central

Samandari, Mohammad Hasan; Haghighat, Abbas; Torabinia, Nakisa; Taghian, Mehdi; Sadri, Leyli; Naemy, Vahid

2016-01-01

Background: Plasma rich in growth factors (PRGF) and freeze-dried bone allograft (FDBA) are shown to promote bone healing. This study was aimed to histologically and histomorphometrically investigate the effect of combined use of PRGF and FDBA on bone formation, and compare it to FDBA alone and control group. Materials and Methods: The distal roots of the lower premolars were extracted bilaterally in four female dogs. Sockets were randomly divided into FDBA + PRGF, FDBA, and control groups. Two dogs were sacrificed after 2 weeks and two dogs were sacrificed after 4 weeks. Sockets were assessed histologically and histomorphometrically. Data were analyzed by Kruskal–Wallis test followed by Mann–Whitney U-tests utilizing the SPSS software version 20. P < 0.05 was considered statistically significant. Results: While the difference in density of fibrous tissue in three groups was not statistically significant (P = 0.343), the bone density in grafted groups was significantly higher than the control group (P = 0.021). The least decrease in all socket dimensions was observed in the FDBA group. However, these differences were only significant in coronal portion at week 4. Regarding socket dimensions and bone density, the difference between FDBA and FDBA+PRGF groups was not significant in middle and apical portions. Conclusion: The superiority of PRGF+FDBA overFDBA in socket preservation cannot be concluded from this experiment. PMID:27857769

Chronic administration of anticonvulsants but not antidepressants impairs bone strength: clinical implications.

PubMed

Gold, P W; Pavlatou, M G; Michelson, D; Mouro, C M; Kling, M A; Wong, M-L; Licinio, J; Goldstein, S A

2015-06-02

Major depression and bipolar disorder are associated with decreased bone mineral density (BMD). Antidepressants such as imipramine (IMIP) and specific serotonin reuptake inhibitors (SSRIs) have been implicated in reduced BMD and/or fracture in older depressed patients. Moreover, anticonvulsants such as valproate (VAL) and carbamazepine (CBZ) are also known to increase fracture rates. Although BMD is a predictor of susceptibility to fracture, bone strength is a more sensitive predictor. We measured mechanical and geometrical properties of bone in 68 male Sprague Dawley rats on IMIP, fluoxetine (FLX), VAL, CBZ, CBZ vehicle and saline (SAL), given intraperitoneally daily for 8 weeks. Distinct regions were tested to failure by four-point bending, whereas load displacement was used to determine stiffness. The left femurs were scanned in a MicroCT system to calculate mid-diaphyseal moments of inertia. None of these parameters were affected by antidepressants. However, VAL resulted in a significant decrease in stiffness and a reduction in yield, and CBZ induced a decrease in stiffness. Only CBZ induced alterations in mechanical properties that were accompanied by significant geometrical changes. These data reveal that chronic antidepressant treatment does not reduce bone strength, in contrast to chronic anticonvulsant treatment. Thus, decreased BMD and increased fracture rates in older patients on antidepressants are more likely to represent factors intrinsic to depression that weaken bone rather than antidepressants per se. Patients with affective illness on anticonvulsants may be at particularly high risk for fracture, especially as they grow older, as bone strength falls progressively with age.

Behavior of POP-calcium carbonate hydrogel as bone substitute with controlled release capability: a study in rat.

PubMed

Dewi, Anne Handrini; Ana, Ika Dewi; Wolke, Joop; Jansen, John

2015-10-01

Gypsum or calcium sulfate (CS) or plaster of Paris (POP) is considered as a fast degradable material that usually resorbs before the bone defect area is completely filled by new bone. In this study, the incorporation of CaCO3 hydrogel into POP in different compositions was proposed to enhance the bone biological activity of POP and to decrease its degradability. The mechanical and degradation properties of the various materials were characterized by in vitro analysis. Subsequently, the materials were inserted into cylindrically sized bone defects as created into the femoral condyle of rats and left in situ for 1, 4, and 8 weeks. Histological analysis of the retrieved specimens indicated that the addition of CaCO3 hydrogel into POP increased bone formation, angiogenesis and collagen density and resulted into faster bone formation and maturation. It was also confirmed that the degradation rate of the POP decreased by the addition of CaCO3 hydrogel. The in vivo findings did corroborate with the in vitro analysis. In conclusion, the incorporation of CaCO3 hydrogel provides a promising technology to improve the properties of POP, the oldest biomaterial used for bone grafting. © 2015 Wiley Periodicals, Inc.

Site-Specific Variations in Bone Mineral Density under Systemic Conditions Inducing Osteoporosis in Minipigs.

PubMed

Schulz, Matthias C; Kowald, Jan; Estenfelder, Sven; Jung, Roland; Kuhlisch, Eberhard; Eckelt, Uwe; Mai, Ronald; Hofbauer, Lorenz C; Stroszczynski, Christian; Stadlinger, Bernd

2017-01-01

Osteoporosis is a systemic bone disease with an increasing prevalence in the elderly population. There is conflicting opinion about whether osteoporosis affects the alveolar bone of the jaws and whether it poses a risk to the osseointegration of dental implants. The aim of the present study was to evaluate the effects of systemic glucocorticoid administration on the jaw bone density of minipigs. Thirty-seven adult female minipigs were randomly divided into two groups. Quantitative computed tomography (QCT) was used to assess bone mineral density BMD of the lumbar spine as well as the mandible and maxilla, and blood was drawn. One group of minipigs initially received 1.0 mg prednisolone per kg body weight daily for 2 months. The dose was tapered to 0.5 mg per kg body weight per day thereafter. The animals in the other group served as controls and received placebo. QCT and blood analysis were repeated after 6 and 9 months. BMD was compared between the two groups by measuring Hounsfield units, and serum levels of several bone metabolic markers were also assessed. A decrease in BMD was observed in the jaws from baseline to 9 months. This was more pronounced in the prednisolone group. Statistically significant differences were reached for the mandible ( p < 0.001) and the maxilla ( p < 0.001). The administration of glucocorticoids reduced the BMD in the jaws of minipigs. The described model shows promise in the evaluation of osseointegration of dental implants in bone that is compromised by osteoporosis.

Testosterone supplementation, glucocorticoid milieu and bone homeostasis in the ageing male.

PubMed

Ajdžanović, Vladimir Z; Filipović, Branko R; Šošić Jurjević, Branka T; Milošević, Verica Lj

2017-08-01

Male ageing is entwined with a continuous fall in free testosterone levels, which contributes to the pathogenesis of bone loss. Glucocorticoid excess, either dependent on the ageing process or iatrogenically induced, was found to additionally impair the bone structure and metabolism. Cautious testosterone supplementation in this respect may positively affect the glucocorticoid milieu and bone homeostasis, while testosterone-induced changes in the glucocorticoid output could serve as a determinant of bone-related therapeutic outcome. Namely, bone mineral content/density, the parameters of trabecular bone structure as well as bone strength are enhanced, serum calcitonin levels tend to increase, while serum osteocalcin, serum parathyroid hormone and urinary calcium decrease, all upon testosterone administration to the ageing male. In parallel, testosterone application decreases glucocorticoid secretion in the animal models of male ageing, while clinical data in this field are still inconsistent. Importantly, a physiological link exists between testosterone-induced changes in glucocorticoid levels and the tendency of bone status improvement in the ageing male. We believe that the assessment of circulating adrenocorticotropic hormone concentrations together with glucocorticoid levels, reflecting the hypothalamic-pituitary-adrenal axis feedback loop operativeness during testosterone supplementation, represents a well-balanced bone-related therapeutic update. © 2017 Société Française de Pharmacologie et de Thérapeutique.

Global deletion of tetraspanin CD82 attenuates bone growth and enhances bone marrow adipogenesis.

PubMed

Bergsma, Alexis; Ganguly, Sourik S; Dick, Daniel; Williams, Bart O; Miranti, Cindy K

2018-05-18

CD82 is a widely expressed member of the tetraspanin family of transmembrane proteins known to control cell signaling, adhesion, and migration. Tetraspanin CD82 is induced over 9-fold during osteoclast differentiation in vitro; however, its role in bone homeostasis is unknown. A globally deleted CD82 mouse model was used to assess the bone phenotype. Based on microCT and 4-point bending tests, CD82-deficient bones are smaller in diameter and weaker, but display no changes in bone density. Histomorphometry shows a decrease in size, erosion perimeter, and number of osteoclasts in situ, with a corresponding increase in trabecular surface area, specifically in male mice. Male-specific alterations are observed in trabecular structure by microCT and in vitro differentiated osteoclasts are morphologically abnormal. Histomorphometry did not reveal a significant reduction in osteoblast number; however, dynamic labeling reveals a significant decrease in bone growth. Consistent with defects in OB function, OB differentiation and mineralization are defective in vitro, whereas adipogenesis is enhanced. There is a corresponding increase in bone marrow adipocytes in situ. Thus, combined defects in both osteoclasts and osteoblasts can account for the observed bone phenotypes, and suggests a role for CD82 in both bone mesenchyme and myeloid cells. Copyright © 2018 Elsevier Inc. All rights reserved.

Prenatal stress changes courtship vocalizations and bone mineral density in mice.

PubMed

Schmidt, Michaela; Lapert, Florian; Brandwein, Christiane; Deuschle, Michael; Kasperk, Christian; Grimsley, Jasmine M; Gass, Peter

2017-01-01

Stress during the prenatal period has various effects on social and sexual behavior in both human and animal offspring. The present study examines the effects of chronic restraint stress in the second vs third trimester in pregnancy and glucocorticoid receptor (GR) heterozygous mutation on C57BL/6N male offspring's vocal courtship behavior in adulthood by applying a novel analyzing method. Finally, corticosterone and testosterone levels as well as bone mineral density were measured. Prenatal stress in the third, but not in the second trimester caused a significant qualitative change in males' courtship vocalizations, independent of their GR genotype. Bone mineral density was decreased also by prenatal stress exclusively in the third trimester in GR mutant and wildtype mice and - in contrast to corticosterone and testosterone - highly correlated with courtship vocalizations. In Gr +/- males corticosterone serum levels were significantly increased in animals that had experienced prenatal stress in the third trimester. Testosterone serum levels were overall increased in Gr +/- males in comparison to wildtypes as a tendency - whereas prenatal stress had no influence. Prenatal stress alters adult males' courtship vocalizations exclusively when applied in the third trimester, with closely related changes in bone mineral density. Bone mineral density seems to reflect best the complex neuroendocrine mechanisms underlying the production of courtship vocalizations. Besides, we demonstrated for the first time elevated basal corticosterone levels in Gr +/- males after prenatal stress which suggests that the Gr +/- mouse model of depression might also serve as a model of prenatal stress in male offspring. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of fructose-induced metabolic syndrome on rat skeletal cells and tissue, and their responses to metformin treatment.

PubMed

Felice, Juan Ignacio; Schurman, León; McCarthy, Antonio Desmond; Sedlinsky, Claudia; Aguirre, José Ignacio; Cortizo, Ana María

2017-04-01

Deleterious effects of metabolic syndrome (MS) on bone are still controversial. In this study we evaluated the effects of a fructose-induced MS, and/or an oral treatment with metformin on the osteogenic potential of bone marrow mesenchymal stromal cells (MSC), as well as on bone formation and architecture. 32 male 8week-old Wistar rats were assigned to four groups: control (C), control plus oral metformin (CM), rats receiving 10% fructose in drinking water (FRD), and FRD plus metformin (FRDM). Samples were collected to measure blood parameters, and to perform pQCT analysis and static and dynamic histomorphometry. MSC were isolated to determine their osteogenic potential. Metformin improved blood parameters in FRDM rats. pQCT and static and dynamic histomorphometry showed no significant differences in trabecular and cortical bone parameters among groups. FRD reduced TRAP expression and osteocyte density in trabecular bone and metformin only normalized osteocyte density. FRD decreased the osteogenic potential of MSC and metformin administration could revert some of these parameters. FRD-induced MS shows reduction in MSC osteogenic potential, in osteocyte density and in TRAP activity. Oral metformin treatment was able to prevent trabecular osteocyte loss and the reduction in extracellular mineralization induced by FRD-induced MS. Copyright © 2017 Elsevier B.V. All rights reserved.

Duck gait: Relationship to hip angle, bone ash, bone density, and morphology.

PubMed

Robison, Cara I; Rice, Meredith; Makagon, Maja M; Karcher, Darrin M

2015-05-01

The rapid growth meat birds, including ducks, undergo requires skeletal integrity; however, fast growth may not be conducive to adequate bone structure. A relationship likely exists between skeletal changes and duck mobility. Reduced mobility in meat ducks may have impacts on welfare and production. This study examined the relationships among gait score, bone parameters, and hip angle. Commercial Pekin ducks, ages 14 d (n = 100), 21 d (n = 100), and 32 d (n = 100) were weighed and gait scored with a 3-point gait score system by an observer as they walked over a Tekscan gait analysis system. Gait was scored as GS0, GS1, or GS2 with a score of GS0 defined as good walking ability and a score of GS2 as poorest walking ability. Ducks were humanely euthanized, full body scanned using quantitative computed tomography (QCT), and the right femur and tibia were extracted. Leg bones were cleaned, measured, fat extracted, and ashed. QCT scans were rendered to create computerized 3D models where pelvic hip angles and bone density were measured. Statistical analysis was conducted using PROC MIXED with age and gait score in the model. Body weight increased with age, but within an age, body weight decreased as walking ability became worse (P < 0.01). As expected, linear increases in tibia and femur bone width and length were observed as the ducks aged (P < 0.01). Right and left hip angle increased with duck age (P < 0.01). Additionally, ducks with a GS2 had wider hip angles opposed to ducks with a GS0 (P < 0.01). Bone density increased linearly with both age and gait score (P < 0.05). Femur ash content was lowest in 32-day-old ducks and ducks with GS1 and GS2 (P < 0.0001). Tibia ash content increased with age, but decreased as gait score increased (P < 0.001). The observation that right hip angle changed with gait scores merits further investigation into the relationship between duck mobility and skeletal changes during growth. © 2015 Poultry Science Association Inc.

Vps35 loss promotes hyperresorptive osteoclastogenesis and osteoporosis via sustained RANKL signaling

PubMed Central

Xia, Wen-Fang; Tang, Fu-Lei; Xiong, Lei; Xiong, Shan; Jung, Ji-Ung; Lee, Dae-Hoon; Li, Xing-Sheng; Feng, Xu; Mei, Lin

2013-01-01

Receptor activator of NF-κB (RANK) plays a critical role in osteoclastogenesis, an essential process for the initiation of bone remodeling to maintain healthy bone mass and structure. Although the signaling and function of RANK have been investigated extensively, much less is known about the negative regulatory mechanisms of its signaling. We demonstrate in this paper that RANK trafficking, signaling, and function are regulated by VPS35, a major component of the retromer essential for selective endosome to Golgi retrieval of membrane proteins. VPS35 loss of function altered RANK ligand (RANKL)–induced RANK distribution, enhanced RANKL sensitivity, sustained RANKL signaling, and increased hyperresorptive osteoclast (OC) formation. Hemizygous deletion of the Vps35 gene in mice promoted hyperresorptive osteoclastogenesis, decreased bone formation, and caused a subsequent osteoporotic deficit, including decreased trabecular bone volumes and reduced trabecular thickness and density in long bones. These results indicate that VPS35 critically deregulates RANK signaling, thus restraining increased formation of hyperresorptive OCs and preventing osteoporotic deficits. PMID:23509071

Bone mineral density in children with acute leukemia and its associated factors in Iran: a case-control study.

PubMed

Bordbar, Mohammad Reza; Haghpanah, Sezaneh; Dabbaghmanesh, Mohammad Hossein; Omrani, Gholamhossein Ranjbar; Saki, Forough

2016-12-01

Acute leukemia is the most common malignancy in children. We showed that low bone mass is prevalent among children with leukemia, especially in femur. Serum calcium, exercise, chemotherapy protocol, and radiotherapy are the main contributing factors. We suggest that early diagnosis and treatment of this problem could improve bone health in them. Acute leukemia is the most common malignancy in children and has been reported to be associated with low bone mass. Due to lack of sufficient data about the bone mineral density of children with leukemia in the Middle East, and inconsistencies between possible associated factors contributing to decreasing bone density in these children, we aimed to conduct a case-control study in Iran. This case-control study was conducted on 60 children with acute leukemia and 60 age- and sex-matched healthy controls. Anthropometric data, sun exposure, puberty, physical activity, and mineral biochemical parameters were assessed. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DEXA). Data analysis was done by SPSS software v. 21. Serum calcium was higher in the control group (P = 0.012) while serum phosphorous, alkaline phosphatase, and serum 25(OH)D 3 were higher in children with leukemia with P values of 0.04, 0.002, and 0.036, respectively. Sun exposure and physical activity were more in healthy controls (P values <0.001 and 0.003, respectively). Prevalence of vitamin D deficiency in case and control groups was 57.8 and 79.4 %, respectively. This prevalence was higher in healthy controls (P value = 0.007). Both lumbar and femoral neck bone mineral apparent density (BMAD) were higher in the control group (P value <0.001). Serum calcium, physical activity, and radiotherapy were the most relevant factors associated with lumbar BMAD. Femoral neck BMAD was associated with chemotherapy protocol. Low bone mass for chronological age is prevalent among children with leukemia, especially in the femoral neck. Serum calcium, physical activity, chemotherapy protocol, and radiotherapy are the main contributing factors.

The Effects of Combined Treatment with Naringin and Treadmill Exercise on Osteoporosis in Ovariectomized Rats

PubMed Central

SUN, Xiaolei; Fengbo, LI; Xinlong, MA; Jianxiong, MA; ZHAO, Bin; ZHANG, Yang; Yanjun, LI; Jianwei, LV; MENG, Xinmin

2015-01-01

Osteoporosis is a disease characterized by low bone mass and progressive destruction of bone microstructure, resulting in increased the risk of fracture. Previous studies have demonstrated the effect of naringin (NG) or treadmill exercise (EX) on osteoporosis, however, reports about effects of NG plus EX on osteoporosis are limited. This study was designed to investigate the impact of combined treatment with naringin and treadmill exercise on osteoporosis in ovariectomized (OVX) rats. Three months after bilateral ovariectomy, Seventy-five rats were randomly assigned to the following treatment groups: OVX, sham-operated (SHAM), NG, EX, or NG plus EX treatment. Treatments were administered for 60 days. Bone metabolism, bone mineral density, trabecular bone parameters, immunohistochemistry, and the bone strength were evaluated. Compared to the OVX groups, all treatments increased bone volume (BV/TV), trabecula number (Tb.N), trabecula thickness (Tb.Th), bone mineral density (BMD), and mechanical strength. NG + EX showed the strongest effects on BV/TV, Tb.Th, and biomechanical strength. Additionally, decreased C-terminal telopeptides of type I collagen (CTX-1) and enhanced osteocalcin (OCN) expression were observed in the NG + EX group. The present study demonstrates that the NG + EX may have a therapeutic advantage over each monotherapy for the treatment of osteoporosis. PMID:26260240

Low bone mineral density and fragility fractures in permanent vegetative state patients.

PubMed

Oppl, Bastian; Michitsch, Gabriele; Misof, Barbara; Kudlacek, Stefan; Donis, Johann; Klaushofer, Klaus; Zwerina, Jochen; Zwettler, Elisabeth

2014-01-01

Disuse of the musculoskeletal system causes bone loss. Whether patients in vegetative state, a dramatic example of immobilization after severe brain injury, suffer from bone loss and fractures is currently unknown. Serum markers of bone turnover, bone mineral density (BMD) measurements, and clinical data were cross-sectionally analyzed in 30 consecutive vegetative state patients of a dedicated apallic care unit between 2003 and 2007 and compared with age- and sex-matched healthy individuals. Vegetative state patients showed low calcium levels and vitamin D deficiency compared with healthy controls. Serum bone turnover markers revealed high turnover as evidenced by markedly elevated carboxy-terminal telopeptide of type I collagen (β-crosslaps) and increased levels of alkaline phosphatase. BMD measured by dual-energy X-ray absorptiometry (DXA) scanning showed strongly decreased T- and Z-scores for hip and spine. Over a period of 5 years, 8 fragility fractures occurred at peripheral sites in 6 of 30 patients (n = 3 femur, n = 2 tibia, n = 2 fibula, n = 1 humerus). In conclusion, high bone turnover and low BMD is highly prevalent in vegetative state patients, translating into a clinically relevant problem as shown by fragility fractures in 20% of patients over a time period of 5 years. . © 2014 American Society for Bone and Mineral Research.

Bone mineral density in human immunodeficiency virus-1 infected men with hypogonadism prior to highly-active-antiretroviral-therapy (HAART)

PubMed Central

2009-01-01

Alterations of bone metabolism have been observed in numerous studies of HIV-infected patients. Sex steroids are known to profoundly influence bone mass and bone turnover. Hypogonadism is common in HIV-infection. Therefore, we performed a cross sectional study of 80 male HIV-infected patients without wasting syndrome, and 20 healthy male controls, in whom we analyzed urine and serum samples for both calciotropic hormones and markers of bone metabolism and of endocrine testicular function. Bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry both in the lumbar spine and Ward's triangle of the left hip. None of the patients received highly-active-antiretroviral-therapy (HAART). Compared to eugonadal HIV-infected patients, subjects with hypogonadism (n = 32; 40%) showed statistically significant decrease of serum osteocalcin (p < 0.05) and elevated urinary excretion of crosslinks (p < 0.05). However, we found 13 and 15, respectively, patients with osteopenia (t-score -1.0 to -2.5 SD below normal) of the lumbar spine. The dissociation between bone formation and resorption and the reduction of of BMD (p < 0.05) is stronger expressed in patients with hypogonadism. Habitual hypogonadism appears to be of additional relevance for bone metabolism of male HIV-positive patients prior to HAART. PMID:19258214

Processing of hydroxylapatite coatings on titanium alloy bone prostheses

DOEpatents

Nastasi, M.A.; Levine, T.E.; Mayer, J.W.; Pizziconi, V.B.

1998-10-06

Processing of hydroxylapatite sol-gel films on titanium alloy bone prostheses. A method utilizing non-line-of-sight ion beam implantation and/or rapid thermal processing to provide improved bonding of layers of hydroxylapatite to titanium alloy substrates while encouraging bone ingrowth into the hydroxylapatite layers located away from the substrate, is described for the fabrication of prostheses. The first layer of hydroxylapatite is mixed into the substrate by the ions or rapidly thermally annealed, while subsequent layers are heat treated or densified using ion implantation to form layers of decreasing density and larger crystallization, with the outermost layers being suitable for bone ingrowth.

Processing of hydroxylapatite coatings on titanium alloy bone prostheses

DOEpatents

Nastasi, Michael A.; Levine, Timothy E.; Mayer, James W.; Pizziconi, Vincent B.

1998-01-01

Processing of hydroxylapatite sol-gel films on titanium alloy bone prostheses. A method utilizing non-line-of-sight ion beam implantation and/or rapid thermal processing to provide improved bonding of layers of hydroxylapatite to titanium alloy substrates while encouraging bone ingrowth into the hydroxylapatite layers located away from the substrate, is described for the fabrication of prostheses. The first layer of hydroxylapatite is mixed into the substrate by the ions or rapidly thermally annealed, while subsequent layers are heat treated or densified using ion implantation to form layers of decreasing density and larger crystallization, with the outermost layers being suitable for bone ingrowth.

Whole-body vibration therapy in children with severe motor disabilities.

PubMed

Kilebrant, Sophie; Braathen, Gunnar; Emilsson, Roger; Glansén, Ulla; Söderpalm, Ann-Charlott; Zetterlund, Bo; Westerberg, Barbro; Magnusson, Per; Swolin-Eide, Diana

2015-03-01

To study the effect of whole-body vibration therapy on bone mass, bone turnover and body composition in severely disabled children. Nineteen non-ambulatory children aged 5.1-16.3 years (6 males, 13 females) with severe motor disabilities participated in an intervention programme with standing exercise on a self-controlled dynamic platform, which included whole-body vibration therapy (vibration, jump and rotation movements). Whole-body vibration therapy was performed at 40-42 Hz, with an oscillation amplitude of 0.2 mm, 5-15 min/treatment, twice/week for 6 months. Bone mass parameters and bone markers were measured at the study start, and after 6 and 12 months. Whole-body vibration therapy was appreciated by the children. Total-body bone mineral density increased during the study period (p < 0.05). Z-scores for total-body bone mineral density ranged from -5.10 to -0.60 at study start and remained unchanged throughout. Approximately 50% of the subjects had increased levels of carboxy-terminal telopeptides of type I collagen and decreased levels of osteocalcin at the start. Body mass index did not change during the intervention period, but had increased by the 12-month follow-up (p < 0.05). Whole-body vibration therapy appeared to be well tolerated by children with severe motor disabilities. Total-body bone mineral density increased after 6 months of whole-body vibration therapy. Higher carboxy-terminal telopeptides of type I collagen and lower osteocalcin values indicated that severely disabled children have a reduced capacity for bone acquisition.

Bone density and size in ambulatory children with cerebral palsy.

PubMed

Al Wren, Tishya; Lee, David C; Kay, Robert M; Dorey, Frederick J; Gilsanz, Vicente

2011-02-01

To examine the relation of axial and appendicular bone properties in ambulatory children with cerebral palsy (CP) to functional (Gross Motor Function Classification System [GMFCS]) level. Quantitative computed tomography measurements were compared among 37 children with CP (12 children in GMFCS level I, five in level II, 18 in level III, two in level IV; five with hemiplegia, 23 with diplegia, two with triplegia, seven with quadriplegia; mean age 9y 4mo, SD 1y 6mo; 18 males, 19 females) and 37 children in a comparison group (same age and sex distributions). Linear regression was used to evaluate differences in volumetric cancellous bone density (vBMD) and geometric properties of the L3 vertebra and tibia, adjusting for height, weight, and sex as covariates. The comparison group had larger vertebrae than the children with CP (p = 0.02) owing to smaller vertebral size in GMFCS levels III and IV, but there was no difference in vertebral vBMD (p = 0.49). In the tibia, bone volumetric density (p = 0.09) and size (p = 0.02) decreased with increasing GMFCS level. GMFCS level had a greater effect on bone size in females than in males (p<0.07). Children with CP of all levels may have less bone in their tibias, whereas spine deficits differentially affect more involved children. Because even small bone deficits may manifest as osteoporosis later in life, it is important to study bone acquisition in all children with CP. © The Authors. Journal compilation © Mac Keith Press 2010.

Inner ear changes in mucopolysaccharidosis type I/Hurler syndrome.

PubMed

Kariya, Shin; Schachern, Patricia A; Nishizaki, Kazunori; Paparella, Michael M; Cureoglu, Sebahattin

2012-10-01

Mucopolysaccharidosis type I/Hurler syndrome is an autosomal recessive disease caused by a deficiency of α-L-iduronidase activity. Recurrent middle ear infections and hearing loss are common complications in Hurler syndrome. Although sensorineural and conductive components occur, the mechanism of sensorineural hearing loss has not been determined. The purpose of this study is to evaluate the quantitative inner ear histopathology of the temporal bones of patients with Hurler syndrome. Eleven temporal bones from 6 patients with Hurler syndrome were examined. Age-matched healthy control samples consisted of 14 temporal bones from 7 cases. Temporal bones were serially sectioned in the horizontal plane and stained with hematoxylin and eosin. The number of spiral ganglion cells, loss of cochlear hair cells, area of stria vascularis, and cell density of spiral ligament were evaluated using light microscopy. There was no significant difference between Hurler syndrome and healthy controls in the number of spiral ganglion cells, area of stria vascularis, or cell density of spiral ligament. The number of cochlear hair cells in Hurler syndrome was significantly decreased compared with healthy controls. Auditory pathophysiology in the central nerve system in Hurler syndrome remains unknown; however, decreased cochlear hair cells may be one of the important factors for the sensorineural component of hearing loss.

Influence of bone mineral density measurement on fracture risk assessment tool® scores in postmenopausal Indian women.

PubMed

Daswani, Bhavna; Desai, Meena; Mitra, Sumegha; Gavali, Shubhangi; Patil, Anushree; Kukreja, Subhash; Khatkhatay, M Ikram

2016-03-01

Fracture risk assessment tool® calculations can be performed with or without addition of bone mineral density; however, the impact of this addition on fracture risk assessment tool® scores has not been studied in Indian women. Given the limited availability and high cost of bone mineral density testing in India, it is important to know the influence of bone mineral density on fracture risk assessment tool® scores in Indian women. Therefore, our aim was to assess the contribution of bone mineral density in fracture risk assessment tool® outcome in Indian women. Apparently healthy postmenopausal Indian women (n = 506), aged 40-72 years, without clinical risk factors for bone disease, were retrospectively selected, and their fracture risk assessment tool® scores calculated with and without bone mineral density were compared. Based on WHO criteria, 30% women were osteoporotic, 42.9% were osteopenic and 27.1% had normal bone mineral density. Fracture risk assessment tool® scores for risk of both major osteoporotic fracture and hip fracture significantly increased on including bone mineral density (P < 0.0001). When criteria of National Osteoporosis Foundation, US was applied number of participants eligible for medical therapy increased upon inclusion of bone mineral density, (for major osteoporotic fracture risk number of women eligible without bone mineral density was 0 and with bone mineral density was 1, P > 0.05, whereas, for hip fracture risk number of women eligible without bone mineral density was 2 and with bone mineral density was 17, P < 0.0001). Until the establishment of country-specific medication intervention thresholds, bone mineral density should be included while calculating fracture risk assessment tool® scores in Indian women. © The Author(s) 2016.

Effect of epimedium pubescen flavonoid on bone mineral status and bone turnover in male rats chronically exposed to cigarette smoke

PubMed Central

2012-01-01

Background Epimedii herba is one of the most frequently used herbs in formulas that are prescribed for the treatment of osteoporosis in China and its main constituent is Epimedium pubescen flavonoid (EPF). However, it is unclear whether EPF during chronic exposure to cigarette smoke may have a protective influence on the skeleton. The present study investigated the effect of EPF on bone mineral status and bone turnover in a rat model of human relatively high exposure to cigarette smoke. Methods Fifty male Wistar rats were randomized into five groups: controls, passive smoking groups and passive smoking rats administered EPF at three dosage levels (75, 150 or 300 mg/kg/day) in drinking water for 4 months. A rat model of passive smoking was prepared by breeding male rats in a cigarette-smoking box. Bone mineral content (BMC), bone mineral density (BMD), bone turnover markers, bone histomorphometric parameters and biomechanical properties were examined. Results Smoke exposure decreased BMC and BMD, increased bone turnover (inhibited bone formation and stimulated its resorption), affected bone histomorphometry (increased trabecular separation and osteoclast surface per bone surface; decreased trabecular bone volume, trabecular thickness, trabecular number, cortical thickness, bone formation rate and osteoblast surface per bone surface), and reduced mechanical properties. EPF supplementation during cigarette smoke exposure prevented smoke-induced changes in bone mineral status and bone turnover. Conclusion The results suggest that EPF can prevent the adverse effects of smoke exposure on bone by stimulating bone formation and inhibiting bone turnover and bone resorption. PMID:22713117

Effect of epimedium pubescen flavonoid on bone mineral status and bone turnover in male rats chronically exposed to cigarette smoke.

PubMed

Gao, Shu-guang; Cheng, Ling; Li, Kang-hua; Liu, Wen-He; Xu, Mai; Jiang, Wei; Wei, Li-Cheng; Zhang, Fang-jie; Xiao, Wen-feng; Xiong, Yi-lin; Tian, Jian; Zeng, Chao; Sun, Jin-peng; Xie, Qiang; Lei, Guang-hua

2012-06-19

Epimedii herba is one of the most frequently used herbs in formulas that are prescribed for the treatment of osteoporosis in China and its main constituent is Epimedium pubescen flavonoid (EPF). However, it is unclear whether EPF during chronic exposure to cigarette smoke may have a protective influence on the skeleton. The present study investigated the effect of EPF on bone mineral status and bone turnover in a rat model of human relatively high exposure to cigarette smoke. Fifty male Wistar rats were randomized into five groups: controls, passive smoking groups and passive smoking rats administered EPF at three dosage levels (75, 150 or 300 mg/kg/day) in drinking water for 4 months. A rat model of passive smoking was prepared by breeding male rats in a cigarette-smoking box. Bone mineral content (BMC), bone mineral density (BMD), bone turnover markers, bone histomorphometric parameters and biomechanical properties were examined. Smoke exposure decreased BMC and BMD, increased bone turnover (inhibited bone formation and stimulated its resorption), affected bone histomorphometry (increased trabecular separation and osteoclast surface per bone surface; decreased trabecular bone volume, trabecular thickness, trabecular number, cortical thickness, bone formation rate and osteoblast surface per bone surface), and reduced mechanical properties. EPF supplementation during cigarette smoke exposure prevented smoke-induced changes in bone mineral status and bone turnover. The results suggest that EPF can prevent the adverse effects of smoke exposure on bone by stimulating bone formation and inhibiting bone turnover and bone resorption.

Stability of Spinal Bone Lesions in Patients With Multiple Myeloma After Radiotherapy-A Retrospective Analysis of 130 Cases.

PubMed

Lang, Kristin; König, Laila; Bruckner, Thomas; Förster, Robert; Sprave, Tanja; Schlampp, Ingmar; Bostel, Tilman; Welte, Stefan; Nicolay, Nils H; Debus, Jürgen; Rief, Harald

2017-12-01

The objective of the present retrospective analysis was the response evaluation regarding bone density and stability of patients with osteolytic spinal bone lesions due to multiple myeloma after palliative radiotherapy (RT). Patients with multiple myeloma who had undergone spinal RT from March 2003 to May 2016 were analyzed before and 3 and 6 months after RT. Assessment of spinal stability and bone density was performed using the internationally recognized Taneichi scoring system and measurement of bone density using computed tomography imaging-based Hounsfield units. For statistical analysis, we used the Bowker test, McNemar test, and κ statistics to detect possible asymmetries in the distribution of the Taneichi score over time. We used the Student t test for comparison of the density values (Hounsfield units) before and after treatment. Toxicity was evaluated using the Common Terminology Criteria for Adverse Events, version 4.0. Additionally, overall survival was calculated using the Kaplan-Meier method. We evaluated 130 patients (69% male; 31% female) with multiple myeloma and a median age of 58 years. The median follow-up period was 41 months. Before treatment, 51% of the lesions were classified as unstable. At 3 and 6 months after RT, this rate had decreased to 41% (P = .0047) and 24% (P = .2393), respectively. The computed tomography measurements showed a significant increase in bone density at 3 and 6 months after RT. Acute RT-related grade 1 and 2 complications were detected in 34% of patients. Late side effects (grade 1-2) were detected in 23% of the patients. No severe grade 3 or 4 acute or late toxicities were identified. The median overall survival was 19.7 months for all patients and 6.6 months for patients with a Karnofsky performance score of ≤ 70%. To the best of our knowledge, ours is the first report to analyze the bone density and stability in patients with multiple myeloma after RT using a validated scoring system and computed tomography imaging. Palliative RT is an effective method resulting in a significant increase in bone density for local response and stability without severe RT-related toxicity. Furthermore, recalcification could already be detected at 3 months after treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Clopidogrel (Plavix), a P2Y12 receptor antagonist, inhibits bone cell function in vitro and decreases trabecular bone in vivo.

PubMed

Syberg, Susanne; Brandao-Burch, Andrea; Patel, Jessal J; Hajjawi, Mark; Arnett, Timothy R; Schwarz, Peter; Jorgensen, Niklas R; Orriss, Isabel R

2012-11-01

Clopidogrel (Plavix), a selective P2Y(12) receptor antagonist, is widely prescribed to reduce the risk of heart attack and stroke and acts via the inhibition of platelet aggregation. Accumulating evidence now suggests that extracellular nucleotides, signaling through P2 receptors, play a significant role in bone, modulating both osteoblast and osteoclast function. In this study, we investigated the effects of clopidogrel treatment on (1) bone cell formation, differentiation, and activity in vitro; and (2) trabecular and cortical bone parameters in vivo. P2Y(12) receptor expression by osteoblasts and osteoclasts was confirmed using qPCR and Western blotting. Clopidogrel at 10 µM and 25 µM inhibited mineralized bone nodule formation by 50% and >85%, respectively. Clopidogrel slowed osteoblast proliferation with dose-dependent decreases in cell number (25% to 40%) evident in differentiating osteoblasts (day 7). A single dose of 10 to 25 µM clopidogrel to mature osteoblasts also reduced cell viability. At 14 days, ≥10 µM clopidogrel decreased alkaline phosphatase (ALP) activity by ≤70% and collagen formation by 40%, while increasing adipocyte formation. In osteoclasts, ≥1 µM clopidogrel inhibited formation, viability and resorptive activity. Twenty-week-old mice (n = 10-12) were ovariectomized or sham treated and dosed orally with clopidogrel (1 mg/kg) or vehicle (NaCl) daily for 4 weeks. Dual-energy X-ray absorptiometry (DXA) analysis showed clopidogrel-treated animals had decreases of 2% and 4% in whole-body and femoral bone mineral density (BMD), respectively. Detailed analysis of trabecular and cortical bone using micro-computed tomography (microCT) showed decreased trabecular bone volume in the tibia (24%) and femur (18%) of clopidogrel-treated mice. Trabecular number was reduced 20%, while trabecular separation was increased up to 15%. Trabecular thickness and cortical bone parameters were unaffected. Combined, these findings indicate that long-term exposure of bone cells to clopidogrel in vivo could negatively impact bone health. Copyright © 2012 American Society for Bone and Mineral Research.

Anti-climacterium effects of pomegranate concentrated solutions in ovariectomized ddY mice

PubMed Central

Kang, Su Jin; Choi, Beom Rak; Kim, Seung Hee; Yi, Hae Yeon; Park, Hye Rim; Song, Chang Hyun; Ku, Sae Kwang; Lee, Young Joon

2017-01-01

In the present study, the complex anti-climacterium potential of standardized pomegranate concentrated solution (PCS) was investigated using bilateral ovariectomy (OVX) female ddY mice. Changes in body weight and gain during experimental periods, food consumption, serum estradiol levels, total body and abdominal fat densities, abdominal fat pads, and uterus weights were observed, along with the histopathology of abdominal fat pads and uterus for anti-obesity and estrogenic effects. In addition, liver weights, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels, and histopathological inspections were performed to explore the hepato-protective effects. Serum total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein, and triglyceride (TG) levels were monitored for hypolipidemic effects with total body and femur mean bone mineral density (BMD), right femur wet, dry and ash weights, strength, serum osteocalcin, bone-specific alkaline phosphatase (bALP) contents, and histological and histomorphometrical analyses for anti-osteoporosis activity. As a result of OVX, notable increases in body weight and gains, food consumption, abdominal fat mass densities, weights of abdominal fat pads deposited in the abdominal cavity, and serum AST, ALT, TC, LDL, TG, and osteocalcin levels were observed, along with decreases in the uterus, liver, and femur weights, mean total body and femur BMD, femur strength, serum bALP, and estradiol levels. In addition, marked hypertrophic alterations in adipocytes located in the deposited abdominal fat pads, liver steatosis, uterine disused atrophic changes, and decreases in bone mass and structures of the femur were also observed in OVX control mice with significant increases in bone resorption markers based on histopathological and histomorphometrical analysis. However, these estrogen-deficient climacterium symptoms were significantly (P<0.05 or P<0.01) inhibited after 84 days of continuous treatment with estradiol and PCS (1, 2 and 4 ml/kg), respectively. The present results suggested that PCS was able to effectively inhibit or refine the climacterium symptoms, including obesity, hyperlipidemia, hepatic steatosis, and osteoporosis, induced by OVX in ddY mice. PMID:28413464

Effects of Trigonelline, an Alkaloid Present in Coffee, on Diabetes-Induced Disorders in the Rat Skeletal System.

PubMed

Folwarczna, Joanna; Janas, Aleksandra; Pytlik, Maria; Cegieła, Urszula; Śliwiński, Leszek; Krivošíková, Zora; Štefíková, Kornélia; Gajdoš, Martin

2016-03-02

Diabetes increases bone fracture risk. Trigonelline, an alkaloid with potential antidiabetic activity, is present in considerable amounts in coffee. The aim of the study was to investigate the effects of trigonelline on experimental diabetes-induced disorders in the rat skeletal system. Effects of trigonelline (50 mg/kg p.o. daily for four weeks) were investigated in three-month-old female Wistar rats, which, two weeks before the start of trigonelline administration, received streptozotocin (60 mg/kg i.p.) or streptozotocin after nicotinamide (230 mg/kg i.p.). Serum bone turnover markers, bone mineralization, and mechanical properties were studied. Streptozotocin induced diabetes, with significant worsening of bone mineralization and bone mechanical properties. Streptozotocin after nicotinamide induced slight glycemia increases in first days of experiment only, however worsening of cancellous bone mechanical properties and decreased vertebral bone mineral density (BMD) were demonstrated. Trigonelline decreased bone mineralization and tended to worsen bone mechanical properties in streptozotocin-induced diabetic rats. In nicotinamide/streptozotocin-treated rats, trigonelline significantly increased BMD and tended to improve cancellous bone strength. Trigonelline differentially affected the skeletal system of rats with streptozotocin-induced metabolic disorders, intensifying the osteoporotic changes in streptozotocin-treated rats and favorably affecting bones in the non-hyperglycemic (nicotinamide/streptozotocin-treated) rats. The results indicate that, in certain conditions, trigonelline may damage bone.

Effect of angiotensin II receptor blocker, olmesartan, on turnover of bone metabolism in bedridden elderly hypertensive women with disuse syndrome.

PubMed

Aoki, Motokuni; Kawahata, Hirohisa; Sotobayashi, Daisuke; Yu, Hisahiro; Moriguchi, Atsushi; Nakagami, Hironori; Ogihara, Toshio; Morishita, Ryuichi

2015-08-01

Although recent studies suggest that several antihypertensive drugs could reduce the risk of bone fracture, it is still unclear how these drugs act on bone remodeling, especially in elderly women with severe osteoporosis with disuse syndrome. In the present study, we investigated the effects of a calcium channel blocker (CCB) and an angiotensin II receptor blocker (ARB) on bone metabolism in elderly bedridden women with hypertension and disuse syndrome. Elderly bedridden women (aged >75 years) receiving antihypertensive therapy treated with CCB were recruited in the present study. The participants were divided into two groups--CCB group and ARB group--and followed up to 12 months. Markers of bone resorption were markedly increased, suggesting accelerated bone resorption in the participants of the present study. In the follow-up period, the patients treated with a CCB showed a significant decrease in bone mineral density in a time-dependent manner, accompanied by a significant increase in bone resorption markers, whereas treatment with olmesartan inhibited bone loss, associated with attenuation of increased bone resorption markers. Bone mineral density of femoral neck in the CCB group was significantly lower than that in the ARB group at 6 months. The present study showed inhibitory effects of an ARB on bone resorption in hypertensive patients with accelerated bone resorption, such as elderly bedridden women, and indicated an important role of the renin-angiotensin system in bone metabolism. In elderly hypertensive patients, ARB might be expected to have additional beneficial potential to maintain bone health in bedridden patients. © 2014 Japan Geriatrics Society.

High fat diet promotes achievement of peak bone mass in young rats

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

Malvi, Parmanand; Piprode, Vikrant; Chaube, Balkrishna

Highlights: • High fat diet helps in achieving peak bone mass at younger age. • Shifting from high fat to normal diet normalizes obese parameters. • Bone parameters are sustained even after withdrawal of high fat diet. - Abstract: The relationship between obesity and bone is complex. Epidemiological studies demonstrate positive as well as negative correlation between obesity and bone health. In the present study, we investigated the impact of high fat diet-induced obesity on peak bone mass. After 9 months of feeding young rats with high fat diet, we observed obesity phenotype in rats with increased body weight, fatmore » mass, serum triglycerides and cholesterol. There were significant increases in serum total alkaline phosphatase, bone mineral density and bone mineral content. By micro-computed tomography (μ-CT), we observed a trend of better trabecular bones with respect to their microarchitecture and geometry. This indicated that high fat diet helps in achieving peak bone mass and microstructure at younger age. We subsequently shifted rats from high fat diet to normal diet for 6 months and evaluated bone/obesity parameters. It was observed that after shifting rats from high fat diet to normal diet, fat mass, serum triglycerides and cholesterol were significantly decreased. Interestingly, the gain in bone mineral density, bone mineral content and trabecular bone parameters by HFD was retained even after body weight and obesity were normalized. These results suggest that fat rich diet during growth could accelerate achievement of peak bone mass that is sustainable even after withdrawal of high fat diet.« less

[Role of bones in the physiopathology of idiopathic hypercalciuria: effect of amino-bisphosphonate alendronate].

PubMed

Weisinger, J R; Alonzo, E; Machado, C; Carlini, R; Martinis, R; Paz-Martínez, V; Bellorín-Font, E

1997-01-01

Previous studies from our laboratory demonstrated that bone mineral content is affected in patients with idiopathic hypercalciuria and that there is a correlation between bone mineral loss and in-vitro cytokine production. At the same time we found that short term treatment with alendronate decreased urinary calcium in these subjects. In the present study we have examined the long-term effects of alendronate treatment (10 mg/day for one year) on urinary calcium, urinary hydroxyproline and bone mineral content in 18 idiopathic hypercalciuric and 8 normocalciuric stone formers. Clinical characteristics, as well as gender and age distribution were similar in both groups. Urinary calcium and hydroxyproline, were measured monthly. Calcium excretion decreased significantly at the end of the first month, and remained lower thereafter (277 +/- 28, before vs. 202 +/- 26 mg/g creatinine, after 12 months on alendronate, p < 0.01). Urinary hydroxyproline decreased significantly during the study (125.5 +/- 32.1 vs. 39.66 +/- 17.5 mg/g creatinine, p < 0.05). Serum calcium, glomerular filtration rate, and urinary sodium, did not change during the study. Lumbar spine bone density (trabecular bone) obtained with X ray absorptiometry revealed a significant increase from 1.162 +/- 0.231 to 1.197 +/- 0.248 g/cm2 (p < 0.01). These changes were associated with a significant decrease in IL-1 alpha mRNA transcription by unstimulated and lipopolysaccharide stimulated blood mononuclear cells, as tested by the reverse transcriptase polymerase chain reaction. No changes were observed in bone cortical sites (femoral neck). Normocalciuric subjects showed no significant changes in urinary calcium. In summary, the changes observed in urinary calcium excretion and different bone metabolic parameters, suggest a role of bone in the pathophysiology of idiopathic hypercalciuria.

The biological effects of tocotrienol on bone: a review on evidence from rodent models.

PubMed

Chin, Kok-Yong; Ima-Nirwana, Soelaiman

2015-01-01

Osteoporosis causes significant health care and economic burden to society, leading to a relentless search for effective preventive agents. Tocotrienol, a member of the vitamin E family, has demonstrated promising potential as an osteoporosis-preventing agent. This review summarizes evidence on the effects of tocotrienol on bone in animal models. Techniques used to examine the effects of tocotrienol on bone in animals included bone histomorphometry, X-ray microtomography, dual-energy X-ray absorptiometry, bone turnover markers, bone calcium content, and biomechanical strength. Tocotrienol was shown to improve osteoblast number, bone formation, mineral deposition, and bone microarchitecture in osteopenic rats. It also decreased osteoclast number and bone erosion in the rats. Tocotrienol supplementation resulted in an improvement in bone mineral density, although biomechanical strength was not significantly altered in the rats. The beneficial effects of tocotrienol on bone can be attributed to its role as an antioxidant, anti-inflammatory agent, suppressor of the mevalonate pathway, and modulator of genes favorable to bone formation.

The biological effects of tocotrienol on bone: a review on evidence from rodent models

PubMed Central

Chin, Kok-Yong; Ima-Nirwana, Soelaiman

2015-01-01

Osteoporosis causes significant health care and economic burden to society, leading to a relentless search for effective preventive agents. Tocotrienol, a member of the vitamin E family, has demonstrated promising potential as an osteoporosis-preventing agent. This review summarizes evidence on the effects of tocotrienol on bone in animal models. Techniques used to examine the effects of tocotrienol on bone in animals included bone histomorphometry, X-ray microtomography, dual-energy X-ray absorptiometry, bone turnover markers, bone calcium content, and biomechanical strength. Tocotrienol was shown to improve osteoblast number, bone formation, mineral deposition, and bone microarchitecture in osteopenic rats. It also decreased osteoclast number and bone erosion in the rats. Tocotrienol supplementation resulted in an improvement in bone mineral density, although biomechanical strength was not significantly altered in the rats. The beneficial effects of tocotrienol on bone can be attributed to its role as an antioxidant, anti-inflammatory agent, suppressor of the mevalonate pathway, and modulator of genes favorable to bone formation. PMID:25897211

Cross-sex testosterone therapy in ovariectomized mice: addition of low-dose estrogen preserves bone architecture.

PubMed

Goetz, Laura G; Mamillapalli, Ramanaiah; Devlin, Maureen J; Robbins, Amy E; Majidi-Zolbin, Masoumeh; Taylor, Hugh S

2017-11-01

Cross-sex hormone therapy (XHT) is widely used by transgender people to alter secondary sex characteristics to match their desired gender presentation. Here, we investigate the long-term effects of XHT on bone health using a murine model. Female mice underwent ovariectomy at either 6 or 10 wk and began weekly testosterone or vehicle injections. Dual-energy X-ray absorptiometry (DXA) was performed (20 wk) to measure bone mineral density (BMD), and microcomputed tomography was performed to compare femoral cortical and trabecular bone architecture. The 6-wk testosterone group had comparable BMD with controls by DXA but reduced bone volume fraction, trabecular number, and cortical area fraction and increased trabecular separation by microcomputed tomography. Ten-week ovariectomy/XHT maintained microarchitecture, suggesting that estrogen is critical for bone acquisition during adolescence and that late, but not early, estrogen loss can be sufficiently replaced by testosterone alone. Given these findings, we then compared effects of testosterone with effects of weekly estrogen or combined testosterone/low-dose estrogen treatment after a 6-wk ovariectomy. Estrogen treatment increased spine BMD and microarchitecture, including bone volume fraction, trabecular number, trabecular thickness, and connectivity density, and decreased trabecular separation. Combined testosterone-estrogen therapy caused similar increases in femur and spine BMD and improved architecture (increased bone volume fraction, trabecular number, trabecular thickness, and connectivity density) to estrogen therapy and were superior compared with mice treated with testosterone only. These results demonstrate estradiol is critical for bone acquisition and suggest a new cross-sex hormone therapy adding estrogens to testosterone treatments with potential future clinical implications for treating transgender youth or men with estrogen deficiency. Copyright © 2017 the American Physiological Society.

Effect of Dietary Nutrient Density on Small Intestinal Phosphate Transport and Bone Mineralization of Broilers during the Growing Period.

PubMed

Li, Jianhui; Yuan, Jianmin; Miao, Zhiqiang; Song, Zhigang; Yang, Yu; Tian, Wenxia; Guo, Yuming

2016-01-01

A 2 × 4 factorial experiment was conducted to determine the effects of dietary nutrient density on growth performance, small intestinal epithelial phosphate transporter expression, and bone mineralization of broiler chicks fed with diets with different nutrient densities and nonphytate phosphorus (NPP) levels. The broilers were fed with the same starter diets from 0 to 21 days of age. In the grower phase (day 22 to 42), the broilers were randomly divided into eight groups according to body weight. Relatively high dietary nutrient density (HDND) and low dietary nutrient density (LDND) diets were assigned metabolic energy (ME) values of 3,150 and 2,950 kcal/kg, respectively. Crude protein and essential amino acid levels were maintained in the same proportion as ME to prepare the two diet types. NPP levels were 0.25%, 0.30%, 0.35%, and 0.40% of the diets. Results showed that a HDND diet significantly increased the body weight gain (BWG) of broilers and significantly decreased the feed conversion ratio and NPP consumed per BWG. HDND significantly decreased tibial P content of the broilers. Conversely, mRNA expression of NaPi-IIb and protein expression of calbindin were significantly increased in the intestine of broilers fed a HDND diet. HDND also increased vitamin D receptor (VDR) expression, especially at a relatively low dietary NPP level (0.25%). The mRNA expression of NaPi-IIa in the kidneys was significantly increased at a relatively low dietary NPP level (0.25%) to maintain P balance. Tibial P, calcium, and ash content were significantly decreased, as were calbindin and VDR expression levels in the intestine at a low NPP level. Therefore, HDND improved the growth rate of broilers and increased the expression of phosphate and calcium transporter in the small intestine, but adversely affected bone mineralization.

The inhibition of RANK-ligand in the management of postmenopausal osteoporosis and related fractures: the role of denosumab.

PubMed

Capozzi, Anna; Lello, Stefano; Pontecorvi, Alfredo

2014-06-01

There is great interest in new treatments of osteoporosis owing to general ageing of population and increased risk for fragility fractures in the elderly. Current therapies show a good efficacy in improving bone quality and bone density, but, in spite of a certain reduction in fracture rate, according to each treatment, the problem of osteoporotic fractures is yet far from to be solved. Moreover, some treatments may produce different side effects. Denosumab (Dmab), a receptor activator of nuclear factor kappa-B ligand (RANKL)-inhibitor, is an agent recently introduced in clinical practice for treatment of osteoporosis of postmenopausal women. Dmab has improved bone mineral density and prevented new vertebral and non-vertebral fractures with a similar efficacy in comparison with alendronate. Many clinical studies showed Dmab produces also significant improvement versus placebo in bone quality as indicated by decreasing markers of bone turnover. Patients using Dmab reported less risk of AFF (Atypical Femoral Fractures) and ONJ (Osteonecrosis of the Jaw) with an increased number of cellulitis. Here, we review articles using Dmab for female post-menopausal osteoporosis.

The functional muscle-bone unit in children with cerebral palsy.

PubMed

Duran, I; Schütz, F; Hamacher, S; Semler, O; Stark, C; Schulze, J; Rittweger, J; Schoenau, E

2017-07-01

Our results suggest that the prevalence of bone health deficits in children with CP was overestimated, when using only age- and height-adjusted bone mineral content (BMC) and areal bone mineral density (aBMD). When applying the functional muscle-bone unit diagnostic algorithm (FMBU-A), the prevalence of positive results decreased significantly. We recommend applying the FMBU-A when assessing bone health in children with CP. The prevalence of bone health deficits in children with cerebral palsy (CP) might be overestimated because age- and height-adjusted reference percentiles for bone mineral content (BMC) and areal bone mineral density (aBMD) assessed by dual-energy X-ray absorptiometry (DXA) do not consider reduced muscle activity. The aim of this study was to compare the prevalence of positive DXA-based indicators for bone health deficits in children with CP to the prevalence of positive findings after applying a functional muscle-bone unit diagnostic algorithm (FMBU-A) considering reduced muscle activity. The present study was a monocentric retrospective analysis of 297 whole body DXA scans of children with CP. The prevalence of positive results of age- and height-adjusted BMC and aBMD defined as BMC and aBMD below the P3 percentile and of the FMBU-A was calculated. In children with CP, the prevalence of positive results of age-adjusted BMC were 33.3% and of aBMD 50.8%. Height-adjusted results for BMC and aBMD were positive in 16.8 and 36.0% of cases. The prevalence of positive results applying the FMBU-A regarding BMC and aBMD were significantly (p < 0.001) lower than using age- and height-adjusted BMC and aBMD (8.8 and 14.8%). Our results suggest that the prevalence of bone health deficits in children with CP was overestimated, when using age- and height-adjusted BMC and aBMD. When applying the FMBU-A, the prevalence decreased significantly. We recommend applying the FMBU-A when assessing bone health in children with CP.

Dried plum prevents bone loss in a male osteoporosis model via IGF-I and the RANK pathway.

PubMed

Franklin, M; Bu, S Y; Lerner, M R; Lancaster, E A; Bellmer, D; Marlow, D; Lightfoot, S A; Arjmandi, B H; Brackett, D J; Lucas, E A; Smith, B J

2006-12-01

Previously, dietary supplementation with dried plums, a rich source of polyphenolic compounds with antioxidant and anti-inflammatory properties, has been shown to improve bone density, microstructure and biomechanics in female animal models of osteopenia. We designed this study to determine the extent to which dried plum prevents skeletal deterioration in gonadal hormone deficient male animals and to begin to understand its mechanism of action. Sixty 6-month-old male Sprague-Dawley rats were either sham-operated (Sham = 1 group) or orchidectomized (ORX = 4 groups) and randomly assigned to dietary treatments: standard semi-purified diet (Control) with either LD = 5%, MD = 15%, or HD = 25% (w/w) dried plum for 90 days. At the end of the treatment period, both the MD and HD dried plum completely prevented the ORX-induced decrease in whole body, femur, and lumbar vertebra bone mineral density (BMD). Biomechanical testing indicated that the MD and HD of dried plum prevented the ORX-induced decrease in ultimate load of the cortical bone as well as the compressive force and stiffness of trabecular bone within the vertebrae. Analyses of trabecular microarchitecture of the distal femur metaphysis and vertebral body revealed that HD dried plum protected against the decrease in trabecular bone volume (BV/TV) induced by ORX. In the distal femur, all doses of dried plum improved trabecular number (TbN) and separation (TbSp) compared to the ORX-control group, while MD and HD dried plum prevented the ORX-induced changes in vertebral TbN and TbSp. At the end of the 90-day treatment, no remarkable changes in serum osteocalcin or alkaline phosphatase in any of the treatment groups were observed, while serum insulin-like growth factor (IGF)-I was increased by dried plum. The ORX-induced increase in urinary deoxypyridinoline (DPD) excretion was completely prevented by all doses of dried plum coinciding with down-regulation of gene expression for receptor activator of NFkappa-B ligand (RANKL) and osteoprotegerin (OPG) in the bone. We conclude that dried plum prevents osteopenia in androgen deficient male rats, and these beneficial effects may be attributed in part to a decrease in osteoclastogenesis via down-regulation of RANKL and stimulation of bone formation mediated by IGF-I.

Radiographic absorptiometry method in measurement of localized alveolar bone density changes.

PubMed

Kuhl, E D; Nummikoski, P V

2000-03-01

The objective of this study was to measure the accuracy and precision of a radiographic absorptiometry method by using an occlusal density reference wedge in quantification of localized alveolar bone density changes. Twenty-two volunteer subjects had baseline and follow-up radiographs taken of mandibular premolar-molar regions with an occlusal density reference wedge in both films and added bone chips in the baseline films. The absolute bone equivalent densities were calculated in the areas that contained bone chips from the baseline and follow-up radiographs. The differences in densities described the masses of the added bone chips that were then compared with the true masses by using regression analysis. The correlation between the estimated and true bone-chip masses ranged from R = 0.82 to 0.94, depending on the background bone density. There was an average 22% overestimation of the mass of the bone chips when they were in low-density background, and up to 69% overestimation when in high-density background. The precision error of the method, which was calculated from duplicate bone density measurements of non-changing areas in both films, was 4.5%. The accuracy of the intraoral radiographic absorptiometry method is low when used for absolute quantification of bone density. However, the precision of the method is good and the correlation is linear, indicating that the method can be used for serial assessment of bone density changes at individual sites.

Acute ketamine administration corrects abnormal inflammatory bone markers in major depressive disorder.

PubMed

Kadriu, B; Gold, P W; Luckenbaugh, D A; Lener, M S; Ballard, E D; Niciu, M J; Henter, I D; Park, L T; De Sousa, R T; Yuan, P; Machado-Vieira, R; Zarate, C A

2017-05-30

Patients with major depressive disorder (MDD) have clinically relevant, significant decreases in bone mineral density (BMD). We sought to determine if predictive markers of bone inflammation-the osteoprotegerin (OPG)-RANK-RANKL system or osteopontin (OPN)-play a role in the bone abnormalities associated with MDD and, if so, whether ketamine treatment corrected the abnormalities. The OPG-RANK-RANKL system plays the principal role in determining the balance between bone resorption and bone formation. RANKL is the osteoclast differentiating factor and diminishes BMD. OPG is a decoy receptor for RANKL, thereby increasing BMD. OPN is the bone glue that acts as a scaffold between bone tissues matrix composition to bind them together and is an important component of bone strength and fracture resistance. Twenty-eight medication-free inpatients with treatment-resistant MDD and 16 healthy controls (HCs) participated in the study. Peripheral bone marker levels and their responses to IV ketamine infusion in MDD patients and HCs were measured at four time points: at baseline, and post-infusion at 230 min, Day 1, and Day 3. Patients with MDD had significant decreases in baseline OPG/RANKL ratio and in plasma OPN levels. Ketamine significantly increased both the OPG/RANKL ratio and plasma OPN levels, and significantly decreased RANKL levels. Bone marker levels in HCs remained unaltered. We conclude that the OPG-RANK-RANKL system and the OPN system play important roles in the serious bone abnormalities associated with MDD. These data suggest that, in addition to its antidepressant effects, ketamine also has a salutary effect on a major medical complication of depressive illness.Molecular Psychiatry advance online publication, 30 May 2017; doi:10.1038/mp.2017.109.

Changes of bone mineral density after cementless total hip arthroplasty with two different stems

PubMed Central

Ito, Kouji; Yamamoto, Kengo

2007-01-01

Cementless total hip arthroplasty has achieved reliable long-term results since porous coatings were developed, but postoperative changes around the stem remain poorly documented. In this study, changes of the bone mineral density (BMD) were compared between two types of cementless stem. In group B (28 patients with 31 hips), a straight tapered stem with porous plasma spray coating on the proximal 1/4 was used, while group S (24 patients with 26 hips) was given a fluted, tri-slot stem with porous hydroxyapatite coating on the proximal 1/3. In group B, there was an early decrease of BMD, which recovered after 12 months, indicating that stress shielding was minimal. In group S, however, BMD continued to decrease without recovery. The stem shape and radiological findings suggested that the cause of stress shielding in group S was distal fixation. PMID:17225187

Experiment K305: Quantitative analysis of selected bone parameters. Supplement 3A: Trabecular spacing and orientation in the long bones

NASA Technical Reports Server (NTRS)

Judy, M. M.

1981-01-01

Values of mean trabecular spacing computed from optical diffraction patterns of 1:1 X-ray micrographs of tibial metaphysis and those obtained by standard image digitization techniques show excellent agreement. Upper limits on values of mean trabecular orientation deduced from diffraction patterns and the images are also in excellent agreement. Values of the ratio of mean trabecular spatial density in a region of 300 micrometers distal to the downwardly directed convexity in the cartilage growth plate to the value adjacent to the plate determined for flight animals sacrificed at recovery were significantly smaller than values for vivarium control animals. No significant differences were found in proximal regions. No significant differences in mean trabecular orientation were detected. Decreased values of trabecular spatial density and of both obsteoblastic activity and trabecular cross-sectional area noted in collateral researches suggest decreased modeling activity under weightlessness.

Skeletal unloading and dietary copper depletion are detrimental to bone quality of mature rats

NASA Technical Reports Server (NTRS)

Smith, Brenda J.; King, Jarrod B.; Lucas, Edralin A.; Akhter, Mohammed P.; Arjmandi, Bahram H.; Stoecker, Barbara J.

2002-01-01

This study was designed to examine the skeletal response to copper depletion and mechanical unloading in mature animals. In a 2 x 2 experimental design, 5.5-mo-old male Sprague-Dawley rats (n = 36) consumed either the control (AIN-93M) or Cu-depletion ((-)Cu) diet beginning 21 d before suspension and throughout the remainder of the study. Half of the rats in each dietary treatment group were either tail-suspended (TS) or kept ambulatory (AMB) for 28 d. Lower bone mineral densities (BMD) of 5th lumbar vertebra (L5) (P < 0.05) and femur were observed with (-)Cu and TS, but no differences were noted in the BMD of the humerus. Mechanical strength in the femur and vertebra decreased in response to TS, but were unaffected by copper depletion. Urinary deoxypyridinoline, an index of bone resorption, was significantly greater in TS rats, but unaltered by (-)Cu. No changes in serum or bone alkaline phosphatase activity, an indicator of bone formation, were observed. Our findings suggest that TS and (-)Cu decreased BMD in unloaded femur and vertebra but had no effect on normally loaded humerus. Bone loss with TS appeared to be related to accelerated bone resorption. Alterations in bone metabolism and bone mechanical properties in the mature skeleton resulting from (-)Cu warrant further investigation.

Histomorphometry and cortical robusticity of the adult human femur.

PubMed

Miszkiewicz, Justyna Jolanta; Mahoney, Patrick

2018-01-13

Recent quantitative analyses of human bone microanatomy, as well as theoretical models that propose bone microstructure and gross anatomical associations, have started to reveal insights into biological links that may facilitate remodeling processes. However, relationships between bone size and the underlying cortical bone histology remain largely unexplored. The goal of this study is to determine the extent to which static indicators of bone remodeling and vascularity, measured using histomorphometric techniques, relate to femoral midshaft cortical width and robusticity. Using previously published and new quantitative data from 450 adult human male (n = 233) and female (n = 217) femora, we determine if these aspects of femoral size relate to bone microanatomy. Scaling relationships are explored and interpreted within the context of tissue form and function. Analyses revealed that the area and diameter of Haversian canals and secondary osteons, and densities of secondary osteons and osteocyte lacunae from the sub-periosteal region of the posterior midshaft femur cortex were significantly, but not consistently, associated with femoral size. Cortical width and bone robusticity were correlated with osteocyte lacunae density and scaled with positive allometry. Diameter and area of osteons and Haversian canals decreased as the width of cortex and bone robusticity increased, revealing a negative allometric relationship. These results indicate that microscopic products of cortical bone remodeling and vascularity are linked to femur size. Allometric relationships between more robust human femora with thicker cortical bone and histological products of bone remodeling correspond with principles of bone functional adaptation. Future studies may benefit from exploring scaling relationships between bone histomorphometric data and measurements of bone macrostructure.

Spine Trabecular Bone Score as an Indicator of Bone Microarchitecture at the Peripheral Skeleton in Kidney Transplant Recipients.

PubMed

Luckman, Matthew; Hans, Didier; Cortez, Natalia; Nishiyama, Kyle K; Agarawal, Sanchita; Zhang, Chengchen; Nikkel, Lucas; Iyer, Sapna; Fusaro, Maria; Guo, Edward X; McMahon, Donald J; Shane, Elizabeth; Nickolas, Thomas L

2017-04-03

Studies using high-resolution peripheral quantitative computed tomography showed progressive abnormalities in cortical and trabecular microarchitecture and biomechanical competence over the first year after kidney transplantation. However, high-resolution peripheral computed tomography is a research tool lacking wide availability. In contrast, the trabecular bone score is a novel and widely available tool that uses gray-scale variograms of the spine image from dual-energy x-ray absorptiometry to assess trabecular quality. There are no studies assessing whether trabecular bone score characterizes bone quality in kidney transplant recipients. Between 2009 and 2010, we conducted a study to assess changes in peripheral skeletal microarchitecture, measured by high-resolution peripheral computed tomography, during the first year after transplantation in 47 patients managed with early corticosteroid-withdrawal immunosuppression. All adult first-time transplant candidates were eligible. Patients underwent imaging with high-resolution peripheral computed tomography and dual-energy x-ray absorptiometry pretransplantation and 3, 6, and 12 months post-transplantation. We now test if, during the first year after transplantation, trabecular bone score assesses the evolution of bone microarchitecture and biomechanical competence as determined by high-resolution peripheral computed tomography. At baseline and follow-up, among the 72% and 78%, respectively, of patients having normal bone mineral density by dual-energy x-ray absorptiometry, 53% and 50%, respectively, were classified by trabecular bone score as having high fracture risk. At baseline, trabecular bone score correlated with spine, hip, and ultradistal radius bone mineral density by dual-energy x-ray absorptiometry and cortical area, density, thickness, and porosity; trabecular density, thickness, separation, and heterogeneity; and stiffness and failure load by high-resolution peripheral computed tomography. Longitudinally, each percentage increase in trabecular bone score was associated with increases in trabecular number (0.35%±1.4%); decreases in trabecular thickness (-0.45%±0.15%), separation (-0.40%±0.15%), and network heterogeneity (-0.48%±0.20%); and increases in failure load (0.22%±0.09%) by high-resolution peripheral computed tomography (all P <0.05). Trabecular bone score may be a useful method to assess and monitor bone quality and strength and classify fracture risk in kidney transplant recipients. Copyright © 2017 by the American Society of Nephrology.

Spine Trabecular Bone Score as an Indicator of Bone Microarchitecture at the Peripheral Skeleton in Kidney Transplant Recipients

PubMed Central

Luckman, Matthew; Hans, Didier; Cortez, Natalia; Nishiyama, Kyle K.; Agarawal, Sanchita; Zhang, Chengchen; Nikkel, Lucas; Iyer, Sapna; Fusaro, Maria; Guo, Edward X.; McMahon, Donald J.; Shane, Elizabeth

2017-01-01

Background and objectives Studies using high-resolution peripheral quantitative computed tomography showed progressive abnormalities in cortical and trabecular microarchitecture and biomechanical competence over the first year after kidney transplantation. However, high-resolution peripheral computed tomography is a research tool lacking wide availability. In contrast, the trabecular bone score is a novel and widely available tool that uses gray-scale variograms of the spine image from dual-energy x-ray absorptiometry to assess trabecular quality. There are no studies assessing whether trabecular bone score characterizes bone quality in kidney transplant recipients. Design, settings, participants, & measurements Between 2009 and 2010, we conducted a study to assess changes in peripheral skeletal microarchitecture, measured by high-resolution peripheral computed tomography, during the first year after transplantation in 47 patients managed with early corticosteroid–withdrawal immunosuppression. All adult first-time transplant candidates were eligible. Patients underwent imaging with high-resolution peripheral computed tomography and dual-energy x-ray absorptiometry pretransplantation and 3, 6, and 12 months post-transplantation. We now test if, during the first year after transplantation, trabecular bone score assesses the evolution of bone microarchitecture and biomechanical competence as determined by high-resolution peripheral computed tomography. Results At baseline and follow-up, among the 72% and 78%, respectively, of patients having normal bone mineral density by dual-energy x-ray absorptiometry, 53% and 50%, respectively, were classified by trabecular bone score as having high fracture risk. At baseline, trabecular bone score correlated with spine, hip, and ultradistal radius bone mineral density by dual-energy x-ray absorptiometry and cortical area, density, thickness, and porosity; trabecular density, thickness, separation, and heterogeneity; and stiffness and failure load by high-resolution peripheral computed tomography. Longitudinally, each percentage increase in trabecular bone score was associated with increases in trabecular number (0.35%±1.4%); decreases in trabecular thickness (−0.45%±0.15%), separation (−0.40%±0.15%), and network heterogeneity (−0.48%±0.20%); and increases in failure load (0.22%±0.09%) by high-resolution peripheral computed tomography (all P<0.05). Conclusions Trabecular bone score may be a useful method to assess and monitor bone quality and strength and classify fracture risk in kidney transplant recipients. PMID:28348031

The use of a magnesium-based bone adhesive for flexor tendon-to-bone healing

PubMed Central

Stavros, Thomopoulos; Emmanouil, Zampiakis; Rosalina, Das; Hyun-Min, Kim; J., Silva, Matthew; Necat, Havlioglu; H., Gelberman, Richard

2010-01-01

Purpose Our previous studies in a canine animal model demonstrated that the flexor tendon-to-bone insertion site has a poor capacity to heal. Magnesium based adhesives have the potential to improve tendon-to-bone healing. Therefore, we hypothesized that magnesium based bone adhesive (MBA) will improve the tendon-to-bone biomechanical properties initially and in the early period after repair. Methods Flexor digitorum profundus tendons were injured and repaired into bone tunnels in the distal phalanges of dogs. The bone tunnels were either filled with MBA prior to completing the repair or left empty (CTL). Histologic appearance, tensile properties, range of motion, and bone density were examined at time zero and 21 days after the repair. Results There was no histologic evidence of acute inflammation. There appeared to be more mast cells in the MBA group than in the CTL group. Chronic inflammatory infiltrate and fibrosis was slightly higher in the MBA group compared to the CTL group. Tensile properties at time zero were significantly higher in the MBA group compared to the CTL group. However, tensile properties were significantly lower in the MBA group compared to the CTL group at 21 days. Range of motion and bone density were significantly lower in the MBA and CTL groups compared to normal (i.e., uninjured) at 21 days; no differences were seen when comparing MBA to CTL. Conclusions We found that the initial biomechanical properties of flexor tendon-to-bone repairs can be improved with MBA. However, MBA use in vivo led to a decrease in the biomechanical properties of the repair. There was no effect of MBA on bone density or range of motion in the early period after repair. Our histologic analysis suggests that the poor healing in the MBA group may have been due to an allergic response or to increased chronic inflammation due to the foreign material. PMID:19643291

Effects of Arsenic on Osteoblast Differentiation in Vitro and on Bone Mineral Density and Microstructure in Rats

PubMed Central

Wu, Cheng-Tien; Lu, Tung-Ying; Chan, Ding-Cheng; Tsai, Keh-Sung; Yang, Rong-Sen

2014-01-01

Background: Arsenic is a ubiquitous toxic element and is known to contaminate drinking water in many countries. Several epidemiological studies have shown that arsenic exposure augments the risk of bone disorders. However, the detailed effect and mechanism of inorganic arsenic on osteoblast differentiation of bone marrow stromal cells and bone loss still remain unclear. Objectives: We investigated the effects and mechanism of arsenic on osteoblast differentiation in vitro and evaluated bone mineral density (BMD) and bone microstructure in rats at doses relevant to human exposure from drinking water. Methods: We used a cell model of rat primary bone marrow stromal cells (BMSCs) and a rat model of long-term exposure with arsenic-contaminated drinking water, and determined bone microstructure and BMD in rats by microcomputed tomography (μCT). Results: We observed significant attenuation of osteoblast differentiation after exposure of BMSCs to arsenic trioxide (0.5 or 1 μM). After arsenic treatment during differentiation, expression of runt-related transcription factor-2 (Runx2), bone morphogenetic protein-2 (BMP-2), and osteocalcin in BMSCs was inhibited and phosphorylation of enhanced extracellular signal-regulated kinase (ERK) was increased. These altered differentiation-related molecules could be reversed by the ERK inhibitor PD98059. Exposure of rats to arsenic trioxide (0.05 or 0.5 ppm) in drinking water for 12 weeks altered BMD and microstructure, decreased Runx2 expression, and increased ERK phosphorylation in bones. In BMSCs isolated from arsenic-treated rats, osteoblast differentiation was inhibited. Conclusions: Our results suggest that arsenic is capable of inhibiting osteoblast differentiation of BMSCs via an ERK-dependent signaling pathway and thus increasing bone loss. Citation: Wu CT, Lu TY, Chan DC, Tsai KS, Yang RS, Liu SH. 2014. Effects of arsenic on osteoblast differentiation in vitro and on bone mineral density and microstructure in rats. Environ Health Perspect 122:559–565; http://dx.doi.org/10.1289/ehp.1307832 PMID:24531206

ZIP4 silencing improves bone loss in pancreatic cancer

PubMed Central

Yang, Jingxuan; Ding, Hao; LeBrun, Drake; Ding, Kai; Houchen, Courtney W.; Postier, Russell G.; Ambrose, Catherine G.; Li, Zhaoshen; Bi, Xiaohong; Li, Min

2015-01-01

Metabolic bone disorders are associated with several types of human cancers. Pancreatic cancer patients usually suffer from severe nutrition deficiency, muscle wasting, and loss of bone mass. We have previously found that silencing of a zinc transporter ZIP4 prolongs the survival and reduces the severity of the cachexia in vivo. However, the role of ZIP4 in the pancreatic cancer related bone loss remains unknown. In this study we investigated the effect of ZIP4 knockdown on the bone structure, composition and mechanical properties of femurs in an orthotopic xenograft mouse model. Our data showed that silencing of ZIP4 resulted in increased bone tissue mineral density, decreased bone crystallinity and restoration of bone strength through the RANK/RANKL pathway. The results further support the impact of ZIP4 on the progression of pancreatic cancer, and suggest its potential significance as a therapeutic target for treating patients with such devastating disease and cancer related disorders. PMID:26305676

Microstructures and properties of cancellous bone of avascular necrosis of femoral heads

NASA Astrophysics Data System (ADS)

Yao, Xuefeng; Wang, Peng; Dai, Ruchun; Yeh, Hsien Yang

2010-03-01

The aim of this study is to investigate microscopic structure and characterize cancellous bone of avascular necrosis of the femoral head (ANFH). The rabbit model of the ANFH is established. The histopathologic features are studied successfully. The differences between the steroid-injection group (S.G.) and the controlled group (C.G.) are examined, including the weight of rabbits, the hematological examination and the three-dimensional structures. It is found that the plasma levels of cholesterol (CHO), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) in S.G. are lower than those in C.G. when the triglyceride (TG) increased in the S.G.; but the bone mineral content (BMC) and the structural model index (SMI) of the organ and tissue decreased significantly in S.G. Three-dimensional structures of the femoral head are obtained using micro-computed tomography (CT) scanning and the mechanical model is established to analyze the influences of these structural changes on the mechanical properties of the cancellous bone.

Microcomputed tomographic and histomorphometric analyses of novel titanium mesh membranes for guided bone regeneration: a study in rat calvarial defects.

PubMed

Rakhmatia, Yunia Dwi; Ayukawa, Yasunori; Furuhashi, Akihiro; Koyano, Kiyoshi

2014-01-01

The objective of this study was to evaluate the optimal thickness and porosity of novel titanium mesh membranes to enhance bone augmentation, prevent soft tissue ingrowth, and prevent membrane exposure. Six types of novel titanium meshes with different thicknesses and pore sizes, along with three commercially available membranes, were used to cover surgically created calvarial defects in 6-week-old Sprague-Dawley rats. The animals were killed after 4 or 8 weeks. Microcomputed tomographic analyses were performed to analyze the three-dimensional bone volume and bone mineral density. Soft tissue ingrowth was also evaluated histologically and histomorphometrically. The novel titanium membranes used in this study were as effective at augmenting bone in the rat calvarial defect model as the commercially available membranes. The greatest bone volume was observed on 100-μm-thick membranes with larger pores, although these membranes promoted growth of bone with lower mineral density. Soft tissue ingrowth when 100-μm membranes were used was increased at 4 weeks but decreased again by 8 weeks to a level not statistically significantly different from other membranes. Membrane thickness affects the total amount of new bone formation, and membrane porosity is an essential factor for guided bone regeneration, especially during the initial healing period, although the final bone volume obtained is essentially the same. Newly developed titanium mesh membranes of 100 μm in thickness and with large pores appear to be optimal for guided bone regeneration.

Relationship of American Indian blood quantum with osteoporosis risk: a cross-sectional study of American Indian women in Oklahoma.

PubMed

Smith, B J; Leyva, M J; Stephens, L D; Aston, C E; Hermann, J; Payton, M; Baker, M Z

2018-06-25

Information regarding the prevalence and risk of osteoporosis among American Indian (AI) women is limited. This study showed that with increasing AI blood quantum, the prevalence of osteoporosis at the hip based on BMD T-scores decreased and this appeared to be independent of other risk factors. This study was designed to investigate the effects of AI blood quantum (BQ) on osteoporosis prevalence and risk in a cohort of AI women in Oklahoma. Women (n = 301), aged 50 years and older, were recruited to participate in the Oklahoma American Indian Women's Osteoporosis Study. Baseline bone density, fracture history, bone biochemical markers, and potential risk factors were assessed. Participants were stratified by AI BQ into BQ1 ≤ 25%, BQ2 = 25-49%, BQ3 = 50-74%, and BQ4 = 75-100%. The effects of BQ on the prevalence and risk of osteoporosis were evaluated. Based on T-scores, one in approximately eight women in the study was osteoporotic at one or more sites. The prevalence of osteoporosis decreased (p < 0.05) with increasing BQ, especially at the hip, trochanteric, and intertrochanter regions. No differences in bone-specific alkaline phosphatase and C-telopeptide were observed across BQ that could account for the differences in bone density. 25-OH vitamin D decreased with increasing BQ, but mean for each BQ1-4 was > 40 ng/mL. Fracture history did not differ across BQ, and though 52% of the population consumed less than the RDA for calcium, no effect of BQ was observed. In this cohort of women who identified as AI, greater Indian BQ was associated with a decrease in the prevalence of osteoporosis.

The Skeletal Biology of Hibernating Woodchucks (Marmota monax)

NASA Astrophysics Data System (ADS)

Doherty, Alison H.

Long periods of inactivity in most mammals lead to significant bone loss that may not be completely recovered during an individual's lifetime regardless of future activity. Extended bouts of inactivity are the norm for hibernating mammals. It remains largely unknown, however, how these animals avoid adversely affecting bone, their quality, and ultimately survival given the challenges posed to their skeletons by inactivity and nutritional deprivation during hibernation. The primary goal of this project was to identify the physiological mechanisms regulating bone density, area and strength during extended periods of annual inactivity in hibernating woodchucks (Marmota monax). The overall hypothesis that bone integrity is unaffected by several months of inactivity during hibernation in woodchucks was tested across multiple levels of biological function. To gain a holistic assessment of seasonal bone integrity, the locomotor behavior and estimated stresses acting on woodchuck bones were investigated in conjunction with computed tomography scans and three-point bending tests to determine bone density, geometry, and mechanical properties of the long bones throughout the year. In addition, serum protein expression was examined to ascertain bone resorption and formation processes indicative of overall annual skeletal health. It was determined that woodchucks avoid significant changes in gait preference, but experience a decrease in bending stresses acting on distal limb bones following hibernation. Computed tomography scans indicated that bone mass, distribution, and trabecular structure are maintained in these animals throughout the year. Surprisingly, cortical density increased significantly posthibernation. Furthermore, three-point bending tests revealed that although less stiff, woodchuck femora were just as tough during the hibernation season, unlike brittle bones associated with osteoporosis. Finally, bone serum markers suggested a net maintenance of bone resorption and formation processes throughout the year. Taken together, these findings strongly suggest that woodchucks do not lose bone to the extent that would be expected from a non-hibernating animal during four months of inactivity. It is concluded that bone integrity is not adversely affected by hibernation in woodchucks. The results of this work have several broader implications toward skeletal biology research, the evolution of skeletal plasticity, and biomedical applications to osteoporosis prevention and treatment.

The Effect of Naturally Occurring Chronic Kidney Disease on the Micro-Structural and Mechanical Properties of Bone

PubMed Central

Meltzer, Hagar; Milrad, Moran; Brenner, Ori; Atkins, Ayelet; Shahar, Ron

2014-01-01

Chronic kidney disease (CKD) is a growing public health concern worldwide, and is associated with marked increase of bone fragility. Previous studies assessing the effect of CKD on bone quality were based on biopsies from human patients or on laboratory animal models. Such studies provide information of limited relevance due to the small size of the samples (biopsies) or the non-physiologic CKD syndrome studied (rodent models with artificially induced CKD). Furthermore, the type, architecture, structure and biology of the bone of rodents are remarkably different from human bones; therefore similar clinicopathologic circumstances may affect their bones differently. We describe the effects of naturally occurring CKD with features resembling human CKD on the skeleton of cats, whose bone biology, structure and composition are remarkably similar to those of humans. We show that CKD causes significant increase of resorption cavity density compared with healthy controls, as well as significantly lower cortical mineral density, cortical cross-sectional area and cortical cross-sectional thickness. Young's modulus, yield stress, and ultimate stress of the cortical bone material were all significantly decreased in the skeleton of CKD cats. Cancellous bone was also affected, having significantly lower trabecular thickness and bone volume over total volume in CKD cats compared with controls. This study shows that naturally occurring CKD has deleterious effects on bone quality and strength. Since many similarities exist between human and feline CKD patients, including the clinicopathologic features of the syndrome and bone microarchitecture and biology, these results contribute to better understanding of bone abnormalities associated with CKD. PMID:25333360

Lycopene intake facilitates the increase of bone mineral density in growing female rats.

PubMed

Iimura, Yuki; Agata, Umon; Takeda, Satoko; Kobayashi, Yuki; Yoshida, Shigeki; Ezawa, Ikuko; Omi, Naomi

2014-01-01

Intake of the antioxidant lycopene has been reported to decrease oxidative stress and have beneficial effects on bone health. However, few in vivo studies have addressed these beneficial effects in growing female rodents or young women. The aim of this study was to investigate the effect of lycopene intake on bone metabolism through circulating oxidative stress in growing female rats. Six-week-old Sprague-Dawley female rats were randomly divided into 3 groups according to the lycopene content in their diet: 0, 50, and 100 ppm. The bone mineral density (BMD) of the lumbar spine and the tibial proximal metaphysis increased with lycopene content in a dose-dependent manner; the BMD in 100 ppm group was significantly higher than in the 0 ppm group. The urine deoxypyridinoline concentrations were significantly lower in the 50 and 100 ppm groups than in the 0 ppm group, and the serum bone-type alkaline phosphatase activity was significantly higher in 100 ppm group than in the 0 ppm group. No difference in systemic oxidative stress level was observed; however, the oxidative stress level inversely correlated with the tibial BMD. Our findings suggested that lycopene intake facilitates bone formation and inhibits bone resorption, leading to an increase of BMD in growing female rats.

Computerized tomography of the otic capsule and otoliths in the oyster toadfish, Opsanus tau.

PubMed

Edds-Walton, Peggy L; Arruda, Julie; Fay, Richard R; Ketten, Darlene R

2015-02-01

The neurocranium of the toadfish (Opsanus tau) exhibits a distinct translucent region in the otic capsule (OC) that may have functional significance for the auditory pathway. This study used ultrahigh resolution computerized tomography (100 µm voxels) to compare the relative density of three sites along the OC (dorsolateral, midlateral, and ventromedial) and two reference sites (dorsal: supraoccipital crest; ventral: parasphenoid bone) in the neurocranium. Higher attenuation occurs where structural density is greater; thus, we compared the X-ray attenuations measured, which provided a measure of relative density. The maximum attenuation value was recorded for each of the five sites (x and y) on consecutive sections throughout the OC and for each of the three calcareous otoliths associated with the sensory maculae (lagena, saccule, and utricle) in the OC. All three otoliths had higher attenuations than any sites in the neurocranium. Both dorsal and ventral reference sites (supraoccipital crest and parasphenoid bone, respectively) had attenuation levels consistent with calcified bone and had relatively small, irregular variations along the length of the OC in all individuals. The lowest relative attenuations (lowest densities) occurred consistently at the three sites along the OC. In addition, the lowest attenuations measured along the OC occurred at the ventromedial site around the saccular otolith for all seven fish. The decrease in bone density along the OC is consistent with the hypothesis that there is a low-density channel in the skull to facilitate transmission of acoustic stimuli to the auditory endorgans of the ear. © 2014 Wiley Periodicals, Inc.

Effect of two forms of alendronate administration upon bone mass after two years of treatment.

PubMed

Sosa, M; Hernández, D; Segarra, M C; Gómez, A; de la Peña, E; Betancor, P

2002-01-01

The efficacy of alendronate in slowing the loss of bone mass, or even in increasing it, in osteoporotic patients and thus reducing the risk of new fractures has been described. Nevertheless, the way of taking this drug, together with its side effects, sometimes produces withdrawals. In this study, we analyzed if an alternative way of taking the alendronate improves the follow-up of the treatment and if it had the same effect on bone mineral metabolism than the traditional way of prescription. An open, intention-to-treat study, with follow-up of 2 yr was conducted. Eighty women suffering from postmenopausal osteoporosis were included in the study. They were classified in a random manner into two groups, each one of them received 10 mg/d alendronate, together with 1.2 g of calcium and 800 IU of Vitamin D3. Group I received the drug fasting, before breakfast, as usually prescribed and group II received the alendronate fasting, at noon, before lunch. Biochemical markers of bone remodeling were determined. Total alkaline phosphatase, osteocalcin, tartrate-resistant acid phosphatase, urine calcium/creatinine ratio, crosslinked N-telopeptides of type I collagen/creatinine ratio, serum calcium, and parathyroid hormone were also determined, and a lateral dorsolumbar radiography of the spine was performed. Bone mineral density was determined in the lumbar spine by dual-energy X-ray absorptiometry and quantitative computed tomography and by dual-energy X-ray absorptiometry in the proximal femur. Both groups showed an increase in bone mineral density in the lumbar spine and in the proximal femur, which was statistically significant after 1 yr of treatment in the range between 1.5% and 4.3%, depending on the anatomical localization where bone mineral density was measured. There was also an important decrease in the biochemical markers of bone remodeling, between 5.6% and 42.5%, depending on the biochemical marker; the decrease of amino-terminal telopetide during the first year was more important. The group that received alendronate in the morning reported a significantly higher number of withdrawals than the group that received the drug at noon. The alternative administration of 10 mg alendronate at noon had the same effect on bone mineral metabolism than its traditional administration in the morning, but the rate of withdrawals was significantly lower.

Chronic administration of anticonvulsants but not antidepressants impairs bone strength: clinical implications

PubMed Central

Gold, P W; Pavlatou, M G; Michelson, D; Mouro, C M; Kling, M A; Wong, M-L; Licinio, J; Goldstein, S A

2015-01-01

Major depression and bipolar disorder are associated with decreased bone mineral density (BMD). Antidepressants such as imipramine (IMIP) and specific serotonin reuptake inhibitors (SSRIs) have been implicated in reduced BMD and/or fracture in older depressed patients. Moreover, anticonvulsants such as valproate (VAL) and carbamazepine (CBZ) are also known to increase fracture rates. Although BMD is a predictor of susceptibility to fracture, bone strength is a more sensitive predictor. We measured mechanical and geometrical properties of bone in 68 male Sprague Dawley rats on IMIP, fluoxetine (FLX), VAL, CBZ, CBZ vehicle and saline (SAL), given intraperitoneally daily for 8 weeks. Distinct regions were tested to failure by four-point bending, whereas load displacement was used to determine stiffness. The left femurs were scanned in a MicroCT system to calculate mid-diaphyseal moments of inertia. None of these parameters were affected by antidepressants. However, VAL resulted in a significant decrease in stiffness and a reduction in yield, and CBZ induced a decrease in stiffness. Only CBZ induced alterations in mechanical properties that were accompanied by significant geometrical changes. These data reveal that chronic antidepressant treatment does not reduce bone strength, in contrast to chronic anticonvulsant treatment. Thus, decreased BMD and increased fracture rates in older patients on antidepressants are more likely to represent factors intrinsic to depression that weaken bone rather than antidepressants per se. Patients with affective illness on anticonvulsants may be at particularly high risk for fracture, especially as they grow older, as bone strength falls progressively with age. PMID:26035060

Protective Effects of Vildagliptin against Pioglitazone-Induced Bone Loss in Type 2 Diabetic Rats

PubMed Central

Kwak, Kyung Min; Kim, Ju-Young; Yu, Seung Hee; Lee, Sihoon; Kim, Yeun Sun; Park, Ie Byung; Kim, Kwang-Won; Lee, Kiyoung

2016-01-01

Long-term use of thiazolidinediones (TZDs) is associated with bone loss and an increased risk of fracture in patients with type 2 diabetes (T2DM). Incretin-based drugs (glucagon-like peptide-1 (GLP-1) agonists and dipeptidylpeptidase-4 (DPP-4) inhibitors) have several benefits in many systems in addition to glycemic control. In a previous study, we reported that exendin-4 might increase bone mineral density (BMD) by decreasing the expression of SOST/sclerostin in osteocytes in a T2DM animal model. In this study, we investigated the effects of a DPP-4 inhibitor on TZD-induced bone loss in a T2DM animal model. We randomly divided 12-week-old male Zucker Diabetic Fatty (ZDF) rats into four groups; control, vildagliptin, pioglitazone, and vildagliptin and pioglitazone combination. Animals in each group received the respective treatments for 5 weeks. We performed an intraperitoneal glucose tolerance test (IPGTT) before and after treatment. BMD and the trabecular micro-architecture were measured by DEXA and micro CT, respectively, at the end of the treatment. The circulating levels of active GLP-1, bone turnover markers, and sclerostin were assayed. Vildagliptin treatment significantly increased BMD and trabecular bone volume. The combination therapy restored BMD, trabecular bone volume, and trabecular bone thickness that were decreased by pioglitazone. The levels of the bone formation marker, osteocalcin, decreased and that of the bone resorption marker, tartrate-resistant acid phosphatase (TRAP) 5b increased in the pioglitazone group. These biomarkers were ameliorated and the pioglitazone-induced increase in sclerostin level was lowered to control values by the addition of vildagliptin. In conclusion, our results indicate that orally administered vildagliptin demonstrated a protective effect on pioglitazone-induced bone loss in a type 2 diabetic rat model. PMID:27997588

Protective Effects of Vildagliptin against Pioglitazone-Induced Bone Loss in Type 2 Diabetic Rats.

PubMed

Eom, Young Sil; Gwon, A-Ryeong; Kwak, Kyung Min; Kim, Ju-Young; Yu, Seung Hee; Lee, Sihoon; Kim, Yeun Sun; Park, Ie Byung; Kim, Kwang-Won; Lee, Kiyoung; Kim, Byung-Joon

2016-01-01

Long-term use of thiazolidinediones (TZDs) is associated with bone loss and an increased risk of fracture in patients with type 2 diabetes (T2DM). Incretin-based drugs (glucagon-like peptide-1 (GLP-1) agonists and dipeptidylpeptidase-4 (DPP-4) inhibitors) have several benefits in many systems in addition to glycemic control. In a previous study, we reported that exendin-4 might increase bone mineral density (BMD) by decreasing the expression of SOST/sclerostin in osteocytes in a T2DM animal model. In this study, we investigated the effects of a DPP-4 inhibitor on TZD-induced bone loss in a T2DM animal model. We randomly divided 12-week-old male Zucker Diabetic Fatty (ZDF) rats into four groups; control, vildagliptin, pioglitazone, and vildagliptin and pioglitazone combination. Animals in each group received the respective treatments for 5 weeks. We performed an intraperitoneal glucose tolerance test (IPGTT) before and after treatment. BMD and the trabecular micro-architecture were measured by DEXA and micro CT, respectively, at the end of the treatment. The circulating levels of active GLP-1, bone turnover markers, and sclerostin were assayed. Vildagliptin treatment significantly increased BMD and trabecular bone volume. The combination therapy restored BMD, trabecular bone volume, and trabecular bone thickness that were decreased by pioglitazone. The levels of the bone formation marker, osteocalcin, decreased and that of the bone resorption marker, tartrate-resistant acid phosphatase (TRAP) 5b increased in the pioglitazone group. These biomarkers were ameliorated and the pioglitazone-induced increase in sclerostin level was lowered to control values by the addition of vildagliptin. In conclusion, our results indicate that orally administered vildagliptin demonstrated a protective effect on pioglitazone-induced bone loss in a type 2 diabetic rat model.

Bone metabolism in galactosemia.

PubMed

Panis, B; Forget, P Ph; van Kroonenburgh, M J P G; Vermeer, C; Menheere, P P; Nieman, F H; Rubio-Gozalbo, M E

2004-10-01

Classical galactosemia is an autosomal recessively inherited disorder of galactose metabolism. Treatment consists of life-long dietary restriction of galactose. Despite treatment, long-term complications occur such as a decreased bone mineral density (BMD). A decreased BMD might be the result of either dietary deficiencies secondary to the galactose-restricted diet or unknown intrinsic factors. In this study, 40 children with classical galactosemia (13 males and 27 females, aged 3-17 years) on dietary treatment were included to gain insight in the bone metabolism of galactosemics. We found weight and height Z scores significantly decreased in galactosemics. Mean areal BMD Z scores of lumbar spine and of femoral neck as measured by Dual energy X-ray Absorptiometry (DXA) were -0.6 (P < 0.001) and -0.3 (P = 0.066), respectively. Mean volumetric BMD of the femoral neck was significant lower in galactosemics (P < 0.001). The recommended dietary allowances (RDA) for calcium, magnesium, zinc, vitamin D, and protein were met in all patients. Mean serum levels of calcium, phosphate, magnesium, zinc, 1,25-dihydroxy vitamin D (1,25OHD), parathormone (PTH), 17-beta estradiol, bone alkaline phosphatase (BAP), and under-carboxylated osteocalcin (ucOC) were normal. Serum levels of IGF-1 Z score, carboxylated osteocalcin (cOC), N-terminal telopeptide (NTX), and C-terminal telopeptide (CTX) were significantly lower in galactosemics than in control subjects. The different bone markers were strongly correlated. The low levels of IGF-1 Z score, formation marker cOC, and resorption markers NTX and CTX suggest a decreased bone metabolism in galactosemics.

Protective effect of amlodipine on rat bone tissue after orchidectomy.

PubMed

Gradosova, Iveta; Zivna, Helena; Palicka, Vladimir; Hubena, Sona; Svejkovska, Klara; Zivny, Pavel

2012-01-01

Our study aimed to investigate the effect of amlodipine on bone metabolism in orchidectomized rats. Eight-week-old rats were divided into three groups. The sham-operated control group (SHAM) and the control group after orchidectomy (ORX) received the standard laboratory diet (SLD). The experimental group after orchidectomy (ORX+AML) received SLD enriched with amlodipine for 12 weeks. Bone marker concentrations in serum of PINP, OPG and IGF-1, and the levels of CTX-I, BAP and BMP-2 in a bone homogenate were measured using enzyme-linked immunosorbent assay. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry. The femurs were used for biomechanical testing. Bone markers (CTX-I, BAP, BMP-2) in ORX were higher versus SHAM. In ORX+AML there was a decrease in PINP, CTX-I, BAP, BMP-2 and OPG versus ORX. IGF-1 was decreased in ORX versus SHAM. In ORX+AML it was increased versus ORX. In ORX, a decrease was demonstrated versus SHAM in BMD of the whole body, in the lumbar vertebrae and in both femurs. In ORX+AML there was an increase in BMD of the whole body versus ORX. Three-point bending test revealed a decrease in maximal load values in ORX versus SHAM. After amlodipine administration there was an increase in the left femur versus ORX. Amlodipine is capable of mitigating the negative effects of orchidectomy and could be a good prevention of osteoporosis. Copyright © 2012 S. Karger AG, Basel.

[Is there a relation between weight in rats, bone density, ash weight and histomorphometric indicators of trabecular volume and thickness in the bones of extremities?].

PubMed

Zák, J; Kapitola, J; Povýsil, C

2003-01-01

Authors deal with question, if there is possibility to infer bone histological structure (described by histomorphometric parameters of trabecular bone volume and trabecular thickness) from bone density, ash weight or even from weight of animal (rat). Both tibias of each of 30 intact male rats, 90 days old, were processed. Left tibia was utilized to the determination of histomorphometric parameters of undecalcified bone tissue patterns by automatic image analysis. Right tibia was used to the determination of values of bone density, using Archimedes' principle. Values of bone density, ash weight, ash weight related to bone volume and animal weight were correlated with histomorphometric parameters (trabecular bone volume, trabecular thickness) by Pearson's correlation test. One could presume the existence of relation between data, describing bone mass at the histological level (trabecular bone of tibia) and other data, describing mass of whole bone or even animal mass (weight). But no statistically significant correlation was found. The reason of the present results could be in the deviations of trabecular density in marrow of tibia. Because of higher trabecular bone density in metaphyseal and epiphyseal regions, the histomorphometric analysis of trabecular bone is preferentially done in these areas. It is possible, that this irregularity of trabecular tibial density could be the source of the deviations, which could influence the results of correlations determined. The values of bone density, ash weight and animal weight do not influence trabecular bone volume and vice versa: static histomorphometric parameters of trabecular bone do not reflect bone density, ash weight and weight of animal.

Effects of whole-body vibration exercise on bone mineral content and density in thermally injured children.

PubMed

Edionwe, Joel; Hess, Cameron; Fernandez-Rio, Javier; Herndon, David N; Andersen, Clark R; Klein, Gordon L; Suman, Oscar E; Amonette, William E

2016-05-01

Loss of bone mass, muscle mass, and strength leads to significant disability in severely burned children. We assessed the effects of exercise combined with whole-body vibration (WBV) on bone mass, lean mass (LM), and muscle strength in children recovering from burns. Nineteen burned children (≥30% total body surface area [TBSA] burns) were randomly assigned to a 6-week exercise regimen either alone (EX; n=10) or in combination with a 6-week WBV training regimen (EX+WBV; n=9). WBV was performed concurrent to the exercise regimen for 5days/week on a vibrating platform. Dual-energy X-ray absorptiometry quantified bone mineral content (BMC), bone mineral density (BMD), and LM; knee extension strength was assessed using isokinetic dynamometry before and after training. Alpha was set at p<0.05. Both groups were similar in age, height, weight, TBSA burned, and length of hospitalization. Whole-body LM increased in the EX group (p=0.041) and trended toward an increase in the EX+WBV group (p=0.055). On the other hand, there were decreases in leg BMC for both groups (EX, p=0.011; EX+WBV, p=0.047), and in leg BMD for only the EX group (EX, p<0.001; EX+WBV, p=0.26). Truncal BMC decreased in only the EX group (EX, p=0.009; EX+WBV, p=0.61), while BMD decreased in both groups (EX, p<0.001; EX+WBV group, p<0.001). Leg strength increased over time in the EX group (p<0.001) and the EX+WBV group (p<0.001; between-group p=0.31). Exercise in combination with WBV may help attenuate regional bone loss in children recovering from burns. Studies are needed to determine the optimal magnitude, frequency, and duration of the vibration protocol, with attention to minimizing any potential interference with wound healing and graft closure. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.

Factors affecting the pullout strength of cancellous bone screws.

PubMed

Chapman, J R; Harrington, R M; Lee, K M; Anderson, P A; Tencer, A F; Kowalski, D

1996-08-01

Screws placed into cancellous bone in orthopedic surgical applications, such as fixation of fractures of the femoral neck or the lumbar spine, can be subjected to high loads. Screw pullout is a possibility, especially if low density osteoporotic bone is encountered. The overall goal of this study was to determine how screw thread geometry, tapping, and cannulation affect the holding power of screws in cancellous bone and determine whether current designs achieve maximum purchase strength. Twelve types of commercially available cannulated and noncannulated cancellous bone screws were tested for pullout strength in rigid unicellular polyurethane foams of apparent densities and shear strengths within the range reported for human cancellous bone. The experimentally derived pullout strength was compared to a predicted shear failure force of the internal threads formed in the polyurethane foam. Screws embedded in porous materials pullout by shearing the internal threads in the porous material. Experimental pullout force was highly correlated to the predicted shear failure force (slope = 1.05, R2 = 0.947) demonstrating that it is controlled by the major diameter of the screw, the length of engagement of the thread, the shear strength of the material into which the screw is embedded, and a thread shape factor (TSF) which accounts for screw thread depth and pitch. The average TSF for cannulated screws was 17 percent lower than that of noncannulated cancellous screws, and the pullout force was correspondingly less. Increasing the TSF, a result of decreasing thread pitch or increasing thread depth, increases screw purchase strength in porous materials. Tapping was found to reduce pullout force by an average of 8 percent compared with nontapped holes (p = 0.0001). Tapping in porous materials decreases screw pullout strength because the removal of material by the tap enlarges hole volume by an average of 27 percent, in effect decreasing the depth and shear area of the internal threads in the porous material.

Effects of Whole-Body Vibration Exercise on Bone Mineral Content and Density in Thermally Injured Children

PubMed Central

Edionwe, Joel; Hess, Cameron; Fernandez-Rio, Javier; Herndon, David N.; Andersen, Clark R.; Klein, Gordon L.; Suman, Oscar E.; Amonette, William E.

2015-01-01

Background Loss of bone mass, muscle mass, and strength leads to significant disability in severely burned children. We assessed the effects of exercise combined with whole-body vibration (WBV) on bone mass, lean mass (LM), and muscle strength in children recovering from burns. Methods Nineteen burned children (≥30% total body surface area [TBSA] burns) were randomly assigned to a 6-week exercise regimen either alone (EX; n = 10) or in combination with a 6-week WBV training regimen (EX+WBV; n = 9). WBV was performed concurrent to the exercise regimen for 5 days/week on a vibrating platform. Dual-energy X-ray absorptiometry quantified bone mineral content (BMC), bone mineral density (BMD) and LM; knee extension strength was assessed using isokinetic dynamometry before and after training. Alpha was set at p < 0.05. Results Both groups were similar in age, height, weight, TBSA burned, and length of hospitalization. Whole-body LM increased in the EX group (p = 0.041) and trended toward an increase in the EX+WBV group (p = 0.055). On the other hand, there were decreases in leg BMC for both groups (EX, p = 0.011; EX+WBV, p = 0.047), and in leg BMD for only the EX group (EX, p < 0.001; EX+WBV, p = 0.26). Truncal BMC decreased in only the EX group (EX, p = 0.009; EX+WBV, p = 0.61), while BMD decreased in both groups (EX, p < 0.001; EX+WBV group, p < 0.001). Leg strength increased over time in the EX group (p < 0.001) and the EX+WBV group (p < 0.001; between-group P = 0.31). Conclusions Exercise in combination with WBV may help attenuate regional bone loss in children recovering from burns. Studies are needed to determine the optimal magnitude, frequency, and duration of the vibration protocol, with attention to minimizing any potential interference with wound healing and graft closure. PMID:26796240

Development of new experimental platform 'MARS'-Multiple Artificial-gravity Research System-to elucidate the impacts of micro/partial gravity on mice.

PubMed

Shiba, Dai; Mizuno, Hiroyasu; Yumoto, Akane; Shimomura, Michihiko; Kobayashi, Hiroe; Morita, Hironobu; Shimbo, Miki; Hamada, Michito; Kudo, Takashi; Shinohara, Masahiro; Asahara, Hiroshi; Shirakawa, Masaki; Takahashi, Satoru

2017-09-07

This Japan Aerospace Exploration Agency project focused on elucidating the impacts of partial gravity (partial g) and microgravity (μg) on mice using newly developed mouse habitat cage units (HCU) that can be installed in the Centrifuge-equipped Biological Experiment Facility in the International Space Station. In the first mission, 12 C57BL/6 J male mice were housed under μg or artificial earth-gravity (1 g). Mouse activity was monitored daily via downlinked videos; μg mice floated inside the HCU, whereas artificial 1 g mice were on their feet on the floor. After 35 days of habitation, all mice were returned to the Earth and processed. Significant decreases were evident in femur bone density and the soleus/gastrocnemius muscle weights of μg mice, whereas artificial 1 g mice maintained the same bone density and muscle weight as mice in the ground control experiment, in which housing conditions in the flight experiment were replicated. These data indicate that these changes were particularly because of gravity. They also present the first evidence that the addition of gravity can prevent decreases in bone density and muscle mass, and that the new platform 'MARS' may provide novel insights on the molecular-mechanisms regulating biological processes controlled by partial g/μg.

Bone mineral density at distal forearm in men over 40 years of age in Mae Chaem district, Chiang Mai Province, Thailand: a pilot study.

PubMed

Tungjai, Montree; Kaewjaeng, Siriprapa; Jumpee, Chayanit; Sriburee, Sompong; Hongsriti, Pongsiri; Tapanya, Monruedee; Maghanemi, Utumma; Ratanasthien, Kwanchai; Kothan, Suchart

2017-09-01

To study the prevalence of bone mineral density (BMD) and osteoporosis in the distal forearm among Thai men over 40 years of age in Mae Chaem District, Chiang Mai Province, Thailand. The subjects in this study were 194 Thai men, aged between 40 and 87 years who resided in Mae Chaem District, Chiang Mai Province, Thailand. Self-administered questionnaires were used for receiving the demographic characteristics information. BMD was measured by peripheral dual energy X-ray absorptiometry at the nondominant distal forearm in all men. The BMD was highest in the age-group 40-49 years and lowest in the age-group 70-87 years. The average T-score at the distal forearm was also highest in the age-group 40-49 years and lowest in the age-group 70-87 years. The BMD decreased as a function of age-group (p < .05). In contrast, the BMD increased as a function of weight (p < .05). Height had weak impact on the BMD in the distal forearm (p > .05). The percentage of osteopenia and osteoporosis are increased as a function of age-group in, while decreased in that of normal bone density. We found the prevalence of osteoporosis in men who resided in Mae Chaem District, Chiang Mai Province, Thailand.

Hypercortisolemia is associated with severity of bone loss and depression in hypothalamic amenorrhea and anorexia nervosa.

PubMed

Lawson, Elizabeth A; Donoho, Daniel; Miller, Karen K; Misra, Madhusmita; Meenaghan, Erinne; Lydecker, Janet; Wexler, Tamara; Herzog, David B; Klibanski, Anne

2009-12-01

Anorexia nervosa (AN) and functional hypothalamic amenorrhea (HA) are associated with low bone density, anxiety, and depression. Women with AN and HA have elevated cortisol levels. Significant hypercortisolemia, as in Cushing's disease, causes bone loss. It is unknown whether anxiety and depression and/or cortisol dysregulation contribute to low bone density in AN or HA. Our objective was to investigate whether hypercortisolemia is associated with bone loss and mood disturbance in women with HA and AN. We conducted a cross-sectional study in a clinical research center. We studied 52 women [21 healthy controls (HC), 13 normal-weight women with functional HA, and 18 amenorrheic women with AN]. Serum samples were measured every 20 min for 12 h overnight and pooled for average cortisol levels. Bone mineral density (BMD) was assessed by dual-energy x-ray absorptiometry (DXA) at anteroposterior and lateral spine and hip. Hamilton Rating Scales for Anxiety (HAM-A) and Depression (HAM-D) were administered. BMD was lower in AN and HA than HC at all sites and lower in AN than HA at the spine. On the HAM-D and HAM-A, AN scored higher than HA, and HA scored higher than HC. Cortisol levels were highest in AN, intermediate in HA, and lowest in HC. HAM-A and HAM-D scores were associated with decreased BMD. Cortisol levels were positively associated with HAM-A and HAM-D scores and negatively associated with BMD. Hypercortisolemia is a potential mediator of bone loss and mood disturbance in these disorders.

The effect of varying implant position in immediately loaded implant-supported mandibular overdentures.

PubMed

Shaarawy, Mohammed A; Aboelross, Ehab M

2013-06-01

This study was carried out to evaluate the effect of varying implant position in immediately loaded implant-supported mandibular overdentures on peri-implant bone density, muscle activity, and patient satisfaction. Fourteen completely edentulous patients were selected for the study. After complete denture construction, patients were divided into 2 equal groups. Four dental implants were installed bilaterally in the interforaminal region in the first group, while in the second group, 4 dental implants were inserted bilaterally: 2 in the interforaminal region and 2 in the first molar area. Immediately after suturing, telescopic abutments were screwed to the implants, and the retaining caps were picked up into the fitting surface of the lower denture, which was delivered to the patient. Patients were recalled for radiographic bone density evaluation just after denture delivery and then at 3, 6, and 12 months thereafter. Muscle activities of masseter and temporalis muscles as well as patient satisfaction were also evaluated. The results of the study showed a high success rate approximating 98.2% of the immediately loaded implants. The electromyographic (EMG) records of both muscles in group 1 were significantly higher during chewing hard food after 3 months compared with group 2 (P < .05). Bone density changes were comparable in the 2 groups except at the end of the follow-up period, when group 2 showed a significant increase in peri-implant bone density values of the posteriorly placed implants compared with group 1 (P < .05). From the results of this study, it may be concluded that wide distribution of immediately loaded implants used for supporting mandibular overdentures through posterior placement beyond the interforaminal area results in a favorable response in terms of increased peri-implant bone density as well as decreased EMG activity of masseter and temporalis muscles.

Myostatin--the holy grail for muscle, bone, and fat?

PubMed

Buehring, B; Binkley, N

2013-12-01

Myostatin, a member of the transforming growth factor beta (TGF-β) superfamily, was first described in 1997. Since then, myostatin has gained growing attention because of the discovery that myostatin inhibition leads to muscle mass accrual. Myostatin not only plays a key role in muscle homeostasis, but also affects fat and bone. This review will focus on the impact of myostatin and its inhibition on muscle mass/function, adipose tissue and bone density/geometry in humans. Although existing data are sparse, myostatin inhibition leads to increased lean mass and 1 study found a decrease in fat mass and increase in bone formation. In addition, myostatin levels are increased in sarcopenia, cachexia and bed rest whereas they are increased after resistance training, suggesting physiological regulatory of myostatin. Increased myostatin levels have also been found in obesity and levels decrease after weight loss from caloric restriction. Knowledge on the relationship of myostatin with bone is largely based on animal data where elevated myostatin levels lead to decreased BMD and myostatin inhibition improved BMD. In summary, myostatin appears to be a key factor in the integrated physiology of muscle, fat, and bone. It is unclear whether myostatin directly affects fat and bone, or indirectly via muscle. Whether via direct or indirect effects, myostatin inhibition appears to increase muscle and bone mass and decrease fat tissue-a combination that truly appears to be a holy grail. However, at this time, human data for both efficacy and safety are extremely limited. Moreover, whether increased muscle mass also leads to improved function remains to be determined. Ultimately potential beneficial effects of myostatin inhibition will need to be determined based on hard outcomes such as falls and fractures.

Bone loss from the hand in women following distal forearm fracture.

PubMed

Ingle, B M; Eastell, R

2001-01-01

Bone loss occurs after distal forearm fracture, but it is unclear if this bone loss is fully recovered. We designed a cross-sectional study to evaluate the time course of the bone loss from the hand after distal forearm fracture. We identified 40 women who had a fracture of the distal forearm within the previous 4.5 years. Their ages ranged from 42 to 81 (mean 64 years) and time since fracture 6 to 54 (mean 28 months). These were compared with 95 women (mean age 67, range 57 to 80 years) from a population-based cohort. Lumbar spine (LS) and hand bone mineral density (BMD) were measured in all subjects using a Hologic QDR 1000/W densitometer. Ultrasound of the fingers of both hands was measured in the forearm fracture group using a DBM Sonic 1200 R model. Compared to controls, LS BMD was decreased by 6.4% (p<0.001), non-fractured hand by 3.2% (p<0.001) and the fractured hand by 6.1% (p<0.001) in the forearm fracture group. The mean difference in bone density between the fractured and non-fractured hand was 0.0207 g/cm2, the average value for the non-fractured hand being 0.304 g/cm2. The decement in hand BMD was equivalent to 6.2% (p<0.0001). The difference in hand BMD between the fractured and non-fractured side was greatest when the time since fracture was short; there was no further difference in hand BMD after 2 years. Ultrasound showed a mean difference of 18.7 m/s in amplitude-dependent speed of sound (AD-SoS) with the average value being 1893 m/s. A 1.0% decrease was observed in the fractured hand AD-SoS (p<0.05). A strong relationship was observed between AD-SoS and BMD in both hands (r = 0.70, p<0.001). We conclude that distal forearm fracture results in a significant decrease in hand BMD that is partially reversible. The decrease in hand BMD is reflected in the ultrasound properties of the finger phalanx.

[Osteoporosis treatment in patients with hyperthyroidism].

PubMed

Saito, Jun; Nishikawa, Tetsuo

2009-05-01

Childhood thyroid hormone (T3) is essential for the normal development of endochondral and intramembranous bone and plays an important role in the linear growth and maintenance of bone mass. In adult, T3 stimulates osteoclastic bone resorption mediated primarily by TR alpha and local conversion by deiodinase D2 may play a role in local activation. TSH seems to be an inhibitor of bone resorption and formation. In thyrotoxicosis patients with Graves' disease, there is increased bone remodelling, characterized by an imbalance between bone resorption and formation, which results in a decrease of bone mineral density (BMD) and an increased risk for osteoporotic fracture. Antithyroid treatment is able to reduce dramatically the bone resorption and to normalize BMD reduction. But previous hyperthyroidism is independently associated with an increased risk for fracture. Although further studies relating to the mechanism for possible impaired bone strength in these patients will be needed, bisphosphonates may be beneficial treatment for prevention of bone fractures in patients with severe risk for fractures, such as post-menopausal women.

Low bone mineral mass is associated with decreased bone formation and diet in girls with Rett syndrome.

PubMed

Motil, Kathleen J; Barrish, Judy O; Neul, Jeffrey L; Glaze, Daniel G

2014-09-01

The aim of the present study was to characterize biomarkers of bone turnover and their relation with bone mineral mass in a cross-sectional cohort of girls with Rett syndrome (RTT) and to examine the role of dietary, biochemical, hormonal, and inflammatory factors on bone mineral mass and bone biomarkers in this disorder. Total body bone mineral content (BMC) and bone mineral density (BMD) were determined by dual-energy x-ray absorptiometry. Dietary nutrient intakes were determined from 3-day food records. Biomarkers of bone turnover, bone metabolites, vitamin D metabolites, hormones, and inflammatory markers were measured by standard clinical laboratory methods. Serum osteocalcin, bone alkaline phosphatase, and C-telopeptide showed significant inverse relations with age in the RTT cohort. Mean osteocalcin concentrations were significantly lower and mean bone alkaline phosphatase concentrations were significantly higher for individual age groups in the RTT cohort than mean values for their respective age ranges in the reference population. Significant inverse associations were identified between urinary calcium losses, expressed as calcium:creatinine ratios, and total body BMC and BMD z scores. Dietary protein, calcium, and phosphorus intakes, expressed as a proportion of Dietary Reference Intakes for age and sex, showed significant positive associations with total body BMD z scores. The present study suggests decreased bone formation instead of increased bone resorption may explain in part the deficits in bone mineral mass in RTT and that attention to the adequacy of dietary protein, calcium, and phosphorus intakes may offer an opportunity to improve bone health in RTT.

Clinical application of quantitative computed tomography in osteogenesis imperfecta-suspected cat.

PubMed

Won, Sungjun; Chung, Woo-Jo; Yoon, Junghee

2017-09-30

One-year-old male Persian cat presented with multiple fractures and no known traumatic history. Marked decrease of bone radiopacity and thin cortices of all long bones were identified on radiography. Tentative diagnosis was osteogenesis imperfecta, a congenital disorder characterized by fragile bone. To determine bone mineral density (BMD), quantitative computed tomography (QCT) was performed. The QCT results revealed a mean trabecular BMD of vertebral bodies of 149.9 ± 86.5 mg/cm 3 . After bisphosphonate therapy, BMD of the same site increased significantly (218.5 ± 117.1 mg/cm 3 , p ＜ 0.05). QCT was a useful diagnostic tool to diagnose osteopenia and quantify response to medical treatment.

Bone Density and High Salt Diets in a Space Flight Model

NASA Technical Reports Server (NTRS)

Arnaud, S. B.; Navidi, M.; Liang, M. T. C.; Wolinsky, I.

1999-01-01

High salt diets accelerate bone loss with aging in patients with postmenopausal osteoporosis except when calcium supplementation is provided. We have observed that the decrease in mineral content of growing femurs in juvenile rats, exposed to a space flight model which unloads the hind limbs , is substantially less in animals fed excess salt. To determine whether excess dietary salt has the same effect on the skeleton of the mature animal whose response to unloading is increased resorption and bone loss rather than impaired growth, we carried out a metabolic study in mature rats with hindlimbs unloaded by tailsuspension.

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

Depression, antidepressants, and bone mineral density in a population-based cohort.

PubMed

Mezuk, Briana; Eaton, William W; Golden, Sherita Hill; Wand, Gary; Lee, Hochang Benjamin

2008-12-01

It is uncertain whether depression and antidepressant use are associated with decreased bone mineral density (BMD) and whether these relationships differ for men and women. The study used a case-cohort design within the Baltimore Epidemiologic Catchment Area Study, a population-based sample of adults that recently completed its 23-year follow-up. Depression was measured at four time points during the follow-up period by the Diagnostic Interview Schedule. Lower spine BMD was measured at the fourth wave by dual-energy x-ray absorptiometry. The association of BMD with lifetime history of depression and antidepressant medication use was studied using linear regression with bootstrap standard errors. A history of depression was associated with lower spine BMD after controlling for age, sex, race, calcium intake, alcohol use, smoking status, level of physical activity, percent body fat, and antidepressant medication use (-0.140 g/cm(2); p <.002). After controlling for depression, antidepressant medication use was associated with decreased BMD in women but not in men (-0.218 g/cm(2); p <.016). A history of depression predicted decreased lumbar spine BMD in men and women, and antidepressant use predicted decreased BMD in women even after controlling for depression. The magnitude of the effect of depression on BMD was approximately equivalent to 1 standard deviation in BMD and was therefore clinically significant. Providers should be aware of the physiologic consequences of depression as well as the possible risks to bone strength associated with antidepressant use in older patients.

Comparison of collagen matrix treatment impregnated with platelet rich plasma vs bone marrow.

PubMed

Minamimura, Ai; Ichioka, Shigeru; Sano, Hitomi; Sekiya, Naomi

2014-02-01

This study has reported the efficacy of an autologous bone marrow-impregnated collagen matrix experimentally and clinically. Then, it reflected that platelet rich plasma (PRP) was as good a source of growth factors as bone marrow and available in a less invasive procedure. This study aimed to compare the efficacy of a PRP-impregnated collagen matrix with that of a bone marrow-impregnated collagen matrix by quantifying wound size and capillary density using genetically diabetic db/db mice. Bone marrow cells were obtained from femurs of ddy mice. Then, a small amount of collagen matrix was immersed in bone marrow suspension. This is called a bone marrow-impregnated collagen matrix. PRP was obtained from healthy human blood and a small amount of collagen matrix was immersed in PRP. This is called a PRP-impregnated collagen matrix. A bone marrow-impregnated collagen matrix and PRP-impregnated collagen matrix were applied to excisional skin wounds on a genetically healing-impaired mouse (n = 6) and wounds were evaluated 6 days after the procedure. Wounds were divided into two groups: PRP (n = 6), in which a PRP-impregnated collagen matrix was applied; and bone marrow (n = 6), in which collagen immersed in a bone marrow suspension was applied. There was no significant difference between the PRP and bone-marrow groups in the rate of vascular density increase or wound size decrease. The present study suggested that the PRP-impregnated collagen matrix promotes repair processes at least as strongly as the bone marrow-impregnated collagen matrix. Given lower invasiveness, the PRP-impregnated collagen matrix would have advantages in clinical use.

MECHANISMS IN ENDOCRINOLOGY: Mechanisms and evaluation of bone fragility in type 1 diabetes mellitus.

PubMed

Hough, F S; Pierroz, D D; Cooper, C; Ferrari, S L

2016-04-01

Subjects with type 1 diabetes mellitus (T1DM) have decreased bone mineral density and an up to sixfold increase in fracture risk. Yet bone fragility is not commonly regarded as another unique complication of diabetes. Both animals with experimentally induced insulin deficiency syndromes and patients with T1DM have impaired osteoblastic bone formation, with or without increased bone resorption. Insulin/IGF1 deficiency appears to be a major pathogenetic mechanism involved, along with glucose toxicity, marrow adiposity, inflammation, adipokine and other metabolic alterations that may all play a role on altering bone turnover. In turn, increasing physical activity in children with diabetes as well as good glycaemic control appears to provide some improvement of bone parameters, although robust clinical studies are still lacking. In this context, the role of osteoporosis drugs remains unknown. © 2016 European Society of Endocrinology.

Measurement of radial bone mineral density in patients after heart transplantation.

PubMed

Garlicki, A M; Orchowski, F; Myrdko, T; Wójcik, S; Czerwiński, E; Kukiełka, R; Kapelak, B; Dziatkowiak, A

1996-01-01

Limited physical activity, steroidotherapy and immunosuppression are known risk factors for the development of osteoporosis. The purpose of our current work was to investigate whether patients after heart transplantation (Htx) have an increased incidence of osteoporosis. We compared bone mineral density (BMD) in 32 post-transplant patients with a reference group of 1548 healthy age-matched males. Measurement of BMD was carried out with a Dtx 100 Osteometer on the distal and ultradistal segment of the non-dominant radius. Our results revealed a decreased BMD in HTx patients ranging from 6.9 to 10% in the ultradistal (p = 0.0446) and from 0.4 to 3.5% in the distal segment (p = 0.0593).

Low Bone Mineral Mass Is Associated with Decreased Bone Formation and Diet in Females with Rett Syndrome

PubMed Central

Motil, Kathleen J.; Barrish, Judy O.; Neul, Jeffrey L.; Glaze, Daniel G.

2014-01-01

Objective To characterize biomarkers of bone turnover and their relation with bone mineral mass in a cross-sectional cohort of females with Rett syndrome (RTT) and to examine the role of dietary, biochemical, hormonal, and inflammatory factors on bone mineral mass and bone biomarkers in this disorder. Methods Total body bone mineral content (BMC) and density (BMD) were determined by dual-energy x-ray absorptiometry. Dietary nutrient intakes were determined from 3-day food records. Biomarkers of bone turnover, bone metabolites, vitamin D metabolites, hormones, and inflammatory markers were measured by standard clinical laboratory methods. Results Serum osteocalcin, bone alkaline phosphatase, and C-telopeptide showed significant inverse relations with age in the RTT cohort. Mean osteocalcin concentrations were significantly lower and mean bone alkaline phosphatase concentrations were significantly higher for individual age groups in the RTT cohort than mean values for their respective age ranges in the reference population. Significant inverse associations were identified between urinary calcium losses, expressed as calcium:creatinine ratios, and total body BMC and BMD z-scores. Dietary protein, calcium, and phosphorus intakes, expressed as a proportion of Dietary Reference Intakes for age and gender, showed significant positive associations with total body BMD z-scores. Conclusion This study suggests decreased bone formation rather than increased bone resorption may explain in part the deficits in bone mineral mass in RTT and that attention to the adequacy of dietary protein, calcium and phosphorus intakes may offer an opportunity to improve bone health in RTT. PMID:25144778

The peak bone mass concept: is it still relevant?

PubMed

Schönau, Eckhard

2004-08-01

The peak bone mass concept implies that optimal skeletal development during childhood and adolescence will prevent fractures in late adulthood. This concept is based on the observation that areal bone density increases with growth during childhood, is highest around 20 years of age and declines thereafter. However, it is now clear that strong bones in the youngster do not necessarily lead to a fracture-free old age. In the recent bone densitometric literature, the terms bone mass and bone density are typically used synonymously. In physics, density has been defined as the mass of a body divided by its volume. In clinical practice and science, "bone density" usually has a different meaning-the degree to which a radiation beam is attenuated by a bone, as judged from a two-dimensional projection image (areal bone density). The attenuation of a radiation beam does not only depend on physical density, but also on bone size. A small bone therefore has a lower areal bone density than a larger bone, even if the physical density is the same. Consequently, a low areal bone density value can simply reflect the small size of an otherwise normal bone. At present, bone mass analysis is very useful for epidemiological studies on factors that may have an impact on bone development. There is an ongoing discussion about whether the World Health Organization (WHO) definition of osteoporosis is over-simplistic and requires upgrading to include indices representing the distribution of bone and mineral (bone strength indices). The following suggestions and recommendations outline a new concept: bone mass should not be related to age. There is now more and more evidence that bone mass should be related to bone size or muscle function. Thus analyzed, there is no such entity as a "peak bone mass". Many studies are currently under way to evaluate whether these novel approaches increase sensitivity and specificity of fracture prediction in an individual. Furthermore, the focus of many bone researchers is shifting away from bone mass to bone geometry or bone strength. Bone mass is one surrogate marker of bone strength. Widely available techniques for measurement of bone mass, such as dual-energy X-ray absorptiometry, radiogrammetry, and computed tomography, can also be used to measure variables of bone geometry such as cortical thickness, cortical area, and moment of inertia.

Individual Trabecula Segmentation (ITS)-Based Morphological Analyses and Micro Finite Element Analysis of HR-pQCT Images Discriminate Postmenopausal Fragility Fractures Independent of DXA Measurements

PubMed Central

Liu, X. Sherry; Stein, Emily M.; Zhou, Bin; Zhang, Chiyuan A.; Nickolas, Thomas L.; Cohen, Adi; Thomas, Valerie; McMahon, Donald J.; Cosman, Felicia; Nieves, Jeri; Shane, Elizabeth; Guo, X. Edward

2011-01-01

Osteoporosis is typically diagnosed by dual energy x-ray absorptiometry (DXA) measurements of areal bone mineral density (aBMD). Emerging technologies, such as high-resolution peripheral quantitative computed tomography (HR-pQCT), may increase the diagnostic accuracy of DXA and enhance our mechanistic understanding of decreased bone strength in osteoporosis. Women with (n=68) and without (n=101) a history of postmenopausal fragility fracture had aBMD measured by DXA, trabecular plate and rod microarchitecture measured by HR-pQCT image-based individual trabeculae segmentation (ITS) analysis, and whole bone and trabecular bone stiffness by micro finite element analysis (μFEA) of HR-pQCT images at the radius and tibia. DXA T-scores were similar in women with and without fractures at the spine, hip and 1/3 radius, but lower in fracture subjects at the ultradistal radius. Trabecular microarchitecture of fracture subjects was characterized by preferential reductions in trabecular plate bone volume, number, and connectivity over rod trabecular parameters, loss of axially aligned trabeculae, and a more rod-like trabecular network. In addition, decreased thickness and size of trabecular plates were observed at the tibia. The differences between groups were greater at the radius than the tibia for plate number, rod bone volume fraction and number and plate-rod and rod-rod junction densities. Most differences between groups remained after adjustment for T-score by DXA. At a fixed bone volume fraction, trabecular plate volume, number and connectivity were directly associated with bone stiffness. In contrast, rod volume, number and connectivity were inversely associated with bone stiffness. In summary, HR-pQCT-based ITS and μFEA measurements discriminate fracture status in postmenopausal women independent of DXA measurements. Moreover, these results suggest that preferential loss of plate-like trabeculae contribute to lower trabecular bone and whole bone stiffness in women with fractures. We conclude that HR-pQCT-based ITS and μFEA measurements increase our understanding of the microstructural pathogenesis of fragility fracture in postmenopausal women. PMID:22072446

Hydroxychloroquine affects bone resorption both in vitro and in vivo.

PubMed

Both, Tim; Zillikens, M Carola; Schreuders-Koedam, Marijke; Vis, Marijn; Lam, Wai-Kwan; Weel, Angelique E A M; van Leeuwen, Johannes P T M; van Hagen, P Martin; van der Eerden, Bram C J; van Daele, Paul L A

2018-02-01

We recently showed that patients with primary Sjögren syndrome (pSS) have significantly higher bone mineral density (BMD) compared to healthy controls. The majority of those patients (69%) was using hydroxychloroquine (HCQ), which may have favorable effects on BMD. The aim of the study was to evaluate whether HCQ modulates osteoclast function. Osteoclasts were cultured from PBMC-sorted monocytes for 14 days and treated with different HCQ doses (controls 1 and 5 μg/ml). TRAP staining and resorption assays were performed to evaluate osteoclast differentiation and activity, respectively. Staining with an acidification marker (acridine orange) was performed to evaluate intracellular pH at multiple timepoints. Additionally, a fluorescent cholesterol uptake assay was performed to evaluate cholesterol trafficking. Serum bone resorption marker β-CTx was evaluated in rheumatoid arthritis patients. HCQ inhibits the formation of multinuclear osteoclasts and leads to decreased bone resorption. Continuous HCQ treatment significantly decreases intracellular pH and significantly enhanced cholesterol uptake in mature osteoclasts along with increased expression of the lowdensity lipoprotein receptor. Serum β-CTx was significantly decreased after 6 months of HCQ treatment. In agreement with our clinical data, we demonstrate that HCQ suppresses bone resorption in vitro and decreases the resorption marker β-CTx in vivo. We also showed that HCQ decreases the intracellular pH in mature osteoclasts and stimulates cholesterol uptake, suggesting that HCQ induces osteoclastic lysosomal membrane permeabilization (LMP) leading to decreased resorption without changes in apoptosis. We hypothesize that skeletal health of patients with increased risk of osteoporosis and fractures may benefit from HCQ by preventing BMD loss. © 2017 Wiley Periodicals, Inc.

Anorexia Nervosa: Analysis of Trabecular Texture with CT

PubMed Central

Tabari, Azadeh; Torriani, Martin; Miller, Karen K.; Klibanski, Anne; Kalra, Mannudeep K.

2017-01-01

Purpose To determine indexes of skeletal integrity by using computed tomographic (CT) trabecular texture analysis of the lumbar spine in patients with anorexia nervosa and normal-weight control subjects and to determine body composition predictors of trabecular texture. Materials and Methods This cross-sectional study was approved by the institutional review board and compliant with HIPAA. Written informed consent was obtained. The study included 30 women with anorexia nervosa (mean age ± standard deviation, 26 years ± 6) and 30 normal-weight age-matched women (control group). All participants underwent low-dose single-section quantitative CT of the L4 vertebral body with use of a calibration phantom. Trabecular texture analysis was performed by using software. Skewness (asymmetry of gray-level pixel distribution), kurtosis (pointiness of pixel distribution), entropy (inhomogeneity of pixel distribution), and mean value of positive pixels (MPP) were assessed. Bone mineral density and abdominal fat and paraspinal muscle areas were quantified with quantitative CT. Women with anorexia nervosa and normal-weight control subjects were compared by using the Student t test. Linear regression analyses were performed to determine associations between trabecular texture and body composition. Results Women with anorexia nervosa had higher skewness and kurtosis, lower MPP (P < .001), and a trend toward lower entropy (P = .07) compared with control subjects. Bone mineral density, abdominal fat area, and paraspinal muscle area were inversely associated with skewness and kurtosis and positively associated with MPP and entropy. Texture parameters, but not bone mineral density, were associated with lowest lifetime weight and duration of amenorrhea in anorexia nervosa. Conclusion Patients with anorexia nervosa had increased skewness and kurtosis and decreased entropy and MPP compared with normal-weight control subjects. These parameters were associated with lowest lifetime weight and duration of amenorrhea, but there were no such associations with bone mineral density. These findings suggest that trabecular texture analysis might contribute information about bone health in anorexia nervosa that is independent of that provided with bone mineral density. © RSNA, 2016 PMID:27797678

Anorexia Nervosa: Analysis of Trabecular Texture with CT.

PubMed

Tabari, Azadeh; Torriani, Martin; Miller, Karen K; Klibanski, Anne; Kalra, Mannudeep K; Bredella, Miriam A

2017-04-01

Purpose To determine indexes of skeletal integrity by using computed tomographic (CT) trabecular texture analysis of the lumbar spine in patients with anorexia nervosa and normal-weight control subjects and to determine body composition predictors of trabecular texture. Materials and Methods This cross-sectional study was approved by the institutional review board and compliant with HIPAA. Written informed consent was obtained. The study included 30 women with anorexia nervosa (mean age ± standard deviation, 26 years ± 6) and 30 normal-weight age-matched women (control group). All participants underwent low-dose single-section quantitative CT of the L4 vertebral body with use of a calibration phantom. Trabecular texture analysis was performed by using software. Skewness (asymmetry of gray-level pixel distribution), kurtosis (pointiness of pixel distribution), entropy (inhomogeneity of pixel distribution), and mean value of positive pixels (MPP) were assessed. Bone mineral density and abdominal fat and paraspinal muscle areas were quantified with quantitative CT. Women with anorexia nervosa and normal-weight control subjects were compared by using the Student t test. Linear regression analyses were performed to determine associations between trabecular texture and body composition. Results Women with anorexia nervosa had higher skewness and kurtosis, lower MPP (P < .001), and a trend toward lower entropy (P = .07) compared with control subjects. Bone mineral density, abdominal fat area, and paraspinal muscle area were inversely associated with skewness and kurtosis and positively associated with MPP and entropy. Texture parameters, but not bone mineral density, were associated with lowest lifetime weight and duration of amenorrhea in anorexia nervosa. Conclusion Patients with anorexia nervosa had increased skewness and kurtosis and decreased entropy and MPP compared with normal-weight control subjects. These parameters were associated with lowest lifetime weight and duration of amenorrhea, but there were no such associations with bone mineral density. These findings suggest that trabecular texture analysis might contribute information about bone health in anorexia nervosa that is independent of that provided with bone mineral density. © RSNA, 2016.

Bone mineral density of vegetarian and non-vegetarian adults in Taiwan.

PubMed

Wang, Yuh-Feng; Chiu, Jainn-Shiun; Chuang, Mei-Hua; Chiu, Jing-Er; Lin, Chin-Lon

2008-01-01

Diet is thought to be one of the leading causes of bone mineral loss in aging people. In this study, we explored the potential impact of a vegetarian diet on bone mineral density (BMD) in adult Taiwanese men and women. This was a cross-sectional study of the relationship between diet (vegetarian versus non-vegetarian) and BMD and the incidence of osteoporosis. Bone mineral density was determined in a cohort of 1865 adult male and female patients who underwent routine examination in a regional teaching hospital in Taiwan between February 2003 and February 2004. Subjects with definite vertebral problems, known osteopathy, or poor posture were excluded. Dual-energy X-ray absorptiometry (DEXA) was used to determine BMD, on the right hip in men and on lumbar vertebrae L2 to L4 in women. The subjects were grouped according to sex and diet, and were then stratified by age within each of the four groups. The outcome measures were the BMD value and the incidence of osteopenia or osteoporosis according to defined criteria. Bone mineral density gradually declined with increasing age in Taiwanese men, while Taiwanese women showed a precipitous decrease in BMD after the 5th decade. However, no statistical differences in BMD were observed between vegetarians and non-vegetarians of either sex. The proportion of subjects with osteopenia or osteoporosis also appeared comparable between vegetarians and non-vegetarians of either sex. BMD shows an age-related decline in Taiwanese men and women, and eating a vegetarian diet does not appear to affect this decline.

Increased Intake of Selected Vegetables, Herbs and Fruit may Reduce Bone Turnover in Post-Menopausal Women

PubMed Central

Gunn, Caroline Ann; Weber, Janet Louise; McGill, Anne-Thea; Kruger, Marlena Cathorina

2015-01-01

Increased consumption of vegetables/herbs/fruit may reduce bone turnover and urinary calcium loss in post-menopausal women because of increased intake of polyphenols and potassium, but comparative human studies are lacking. The main aim was to compare bone turnover markers and urinary calcium excretion in two randomised groups (n = 50) of healthy post-menopausal women consuming ≥9 servings of different vegetables/herbs/fruit combinations (three months). Group A emphasised a generic range of vegetables/herbs/fruit, whereas Group B emphasised specific vegetables/herbs/fruit with bone resorption-inhibiting properties (Scarborough Fair Diet), with both diets controlled for potential renal acid load (PRAL). Group C consumed their usual diet. Plasma bone markers, urinary electrolytes (24 h) and estimated dietary PRAL were assessed at baseline and 12 weeks. Procollagen type I N propeptide (PINP) decreased (−3.2 μg/L, p < 0.01) in the B group only, as did C-terminal telopeptide of type I collagen (CTX) (−0.065 μg/L, p < 0.01) in women with osteopenia compared to those with normal bone mineral density (BMD) within this group. Intervention Groups A and B had decreased PRAL, increased urine pH and significantly decreased urinary calcium loss. Urinary potassium increased in all groups, reflecting a dietary change. In conclusion, Group B demonstrated positive changes in both turnover markers and calcium conservation. PMID:25856221

Pueraria mirifica alleviates cortical bone loss in naturally menopausal monkeys.

PubMed

Kittivanichkul, Donlaporn; Charoenphandhu, Narattaphol; Khemawoot, Phisit; Malaivijitnond, Suchinda

2016-11-01

Since the in vitro and in vivo anti-osteoporotic effects of Pueraria mirifica (PM) in rodents have been verified, its activity in menopausal monkeys was evaluated as required before it can be applicable for human use. In this study, postmenopausal osteoporotic monkeys were divided into two groups (five per group), and fed daily with standard diet alone (PMP0 group) or diet mixed with 1000 mg/kg body weight (BW) of PM powder (PMP1000 group) for 16 months. Every 2 months, the bone mineral density (BMD), bone mineral content (BMC) and bone geometry parameters (cortical area and thickness and periosteal and endosteal circumference) at the distal radius and proximal tibia were determined using peripheral quantitative computed tomography together with plasma and urinary bone markers. Compared with the baseline (month 0) values, the cortical, but not trabecular, BMDs and BMCs and the cortical area and thickness at the metaphysis and diaphysis of the radius and tibia of the PMP0 group continuously decreased during the 16-month study period. In contrast, PMP1000 treatment ameliorated the bone loss mainly at the cortical diaphysis by decreasing bone turnover, as indicated by the lowered plasma bone-specific alkaline phosphatase and osteocalcin levels. Generally, changes in the cortical bone geometry were in the opposite direction to the cortical bone mass after PMP1000 treatment. This study indicated that postmenopausal monkeys continuously lose their cortical bone compartment, and they have a higher possibility for long bone fractures. Oral PMP treatment could improve both the bone quantity (BMC and BMD) and quality (bone geometry). © 2016 Society for Endocrinology.

Phenotypic research on senile osteoporosis caused by SIRT6 deficiency

PubMed Central

Zhang, De-Mao; Cui, Di-Xin; Xu, Ruo-Shi; Zhou, Ya-Chuan; Zheng, Li-Wei; Liu, Peng; Zhou, Xue-Dong

2016-01-01

Osteoporosis is a serious public bone metabolic disease. However, the mechanisms underlying bone loss combined with ageing, which is known as senile osteoporosis, remains unknown. Here we show the detailed phenotype of this disease caused by SIRT6 knock out (KO) in mice. To the best of our knowledge, this is the first study to reveal that SIRT6 is expressed in both bone marrow stroma cells and bone-related cells in both mouse and human models, which suggests that SIRT6 is an important regulator in bone metabolism. SIRT6-KO mice exhibit a significant decrease in body weight and remarkable dwarfism. The skeleton of the SIRT6-KO mouse is deficient in cartilage and mineralized bone tissue. Moreover, the osteocalcin concentration in blood is lower, which suggests that bone mass is markedly lost. Besides, the tartrate-resistant acid phosphatase 5b (TRAP5b) concentration is much higher, which suggests that bone resorption is overactive. Both trabecular and cortical bones exhibit severe osteopenia, and the bone mineral density is decreased. Moreover, double-labelling analysis shows that bone formation is much slower. To determine whether SIRT6 directly regulates bone metabolism, we cultured primary bone marrow stromal cells for osteogenesis and osteoclastogenesis separately to avoid indirect interference in vivo responses such as inflammation. Taken together, these results show that SIRT6 can directly regulate osteoblast proliferation and differentiation, resulting in attenuation in mineralization. Furthermore, SIRT6 can directly regulate osteoclast differentiation and results in a higher number of small osteoclasts, which may be related to overactive bone resorption. PMID:27357320

Characteristics of bone turnover in the long bone metaphysis fractured patients with normal or low Bone Mineral Density (BMD).

PubMed

Wölfl, Christoph; Schweppenhäuser, Daniela; Gühring, Thorsten; Takur, Caner; Höner, Bernd; Kneser, Ulrich; Grützner, Paul Alfred; Kolios, Leila

2014-01-01

The incidence of osteoporotic fractures increases as our population ages. Until now, the exact biochemical processes that occur during the healing of metaphyseal fractures remain unclear. Diagnostic instruments that allow a dynamic insight into the fracture healing process are as yet unavailable. In the present matched pair analysis, we study the time course of the osteoanabolic markers bone specific alkaline phosphatase (BAP) and transforming growth factor β1 (TGFβ1), as well as the osteocatabolic markers crosslinked C-telopeptide of type-I-collagen (β-CTX) and serum band 5 tartrate-resistant acid phosphatase (TRAP5b), during the healing of fractures that have a low level of bone mineral density (BMD) compared with fractures that have a normal BMD. Between March 2007 and February 2009, 30 patients aged older than 50 years who suffered a metaphyseal fracture were included in our study. BMDs were verified by dual energy Xray absorptiometry (DXEA) scans. The levels of BTMs were examined over an 8-week period. Osteoanabolic BAP levels in those with low levels of BMD were significantly different from the BAP levels in those with normal BMD. BAP levels in the former group increased constantly, whereas the latter group showed an initial strong decrease in BAP followed by slowly rising values. Osteocatabolic β-CTX increased in the bone of the normal BMD group constantly, whereas these levels decreased significantly in the bone of the group with low BMD from the first week. TRAP5b was significantly reduced in the low level BMD group. With this work, we conduct first insights into the molecular biology of the fracture healing process in patients with low levels of BMD that explains the mechanism of its fracture healing. The results may be one reason for the reduced healing qualities in bones with low BMD.

Anorexia Nervosa and its Associated Endocrinopathy in Young People

PubMed Central

Misra, Madhusmita; Klibanski, Anne

2016-01-01

Anorexia nervosa (AN) is a condition of severe undernutrition associated with adaptive changes in many endocrine axes. These changes include hypogonadotropic hypogonadism, acquired growth hormone resistance with low insulin like growth factor-1 (IGF-1) levels, hypercortisolemia, altered secretion of adipokines and appetite regulating hormones, and low bone mineral density (BMD). Bone health is impaired subsequent to low BMI, decreased lean mass, and the endocrine changes described above. In addition to low areal BMD, AN is characterized by a decrease in volumetric BMD, changes in bone geometry, and reductions in strength estimates, leading to an increased risk for fracture. Weight restoration is essential for restoration of normal endocrine function; however, hypercortisolemia, high PYY levels, and ghrelin dynamics may not completely normalize. In some patients, hypogonadotropic hypogonadism persists despite weight restoration. Weight gain and menstrual recovery are critical for improving bone health in AN, however, residual deficits may persist. Physiologic estrogen replacement using transdermal, but not oral, estrogen increases bone accrual in adolescents with AN, while bisphosphonates improve BMD in adults. Recombinant human IGF-1 and teriparatide have been used in a few studies as bone anabolic therapies. More data are necessary to determine the optimal therapeutic strategies for low BMD in AN. PMID:26863308

Composition and functionality of bone affected by dietary glycated compounds.

PubMed

Delgado-Andrade, Cristina; Roncero-Ramos, Irene; Carballo, José; Rufián-Henares, Joséángel; Seiquer, Isabel; Navarro, María Pilar

2013-04-25

Our aim was to investigate the effects of Maillard reaction products (MRPs) from bread crust (BC) on bone composition and its mechanical properties, determining whether any such effects are related to the molecular weight of different MRPs. For 88 days after weaning rats were fed a control diet or diets containing BC, or its soluble low molecular weight (LMW), soluble high molecular weight (HMW) or insoluble fractions. Animals' food consumption and body weights were monitored. After sacrifice, the femur, pelvic bone and tibia were removed for composition, physical and biomechanical properties analysis. It was found that body and femur weights, density, volume and organic matrix decreased, whereas pentosidine increased after consumption of experimental diets, especially in the HMW and insoluble groups (104.7 and 102.9 mmol mol(-1) collagen) vs. the control group (41.7 mmol mol(-1) collagen). Bone stiffness fell by 50% in the LMW, HMW and insoluble groups and failure load and energy to failure tended to decrease in the same animals after MRPs intake. Consumption of diets containing assayed MRPs during growth leads to lower bone size and introduces some changes in its mechanical behavior which appear to be related to an increase in the pentosidine level of bone.

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.

Strategies for skeletal health in the elderly.

PubMed

Eastell, Richard; Lambert, Helen

2002-05-01

Osteoporosis is a common disease in the elderly, and the fractures that result from this disorder affect 40 % of women and 14 % of men over the age of 50 years. The risk of fracture relates to bone mineral density and the risk of falling, among other factors. Low bone mineral density in the elderly can result from either low peak bone mass or accelerated bone loss, or a combination of the two. Nutritional factors play a role in both the attainment of peak bone mass and in the rate of age-related bone loss. The main determinants of peak bone mass are genetic factors, early-life nutrition, diet and exercise. Of the nutritional factors Ca, and particularly milk, are the most important contributors to peak bone mass. Some of these factors may interact; for example, a low dietary Ca in addition to an unfavourable vitamin D receptor gene polymorphism may result in low peak bone mass. The age-related changes in bone mass may also have a genetic basis, but deficiency of oestrogen is a major contributor. In addition, undernutrition is common in the elderly, and lack of dietary protein contributes both to impaired bone mineral conservation and increased propensity to fall. There is a decreased ability of the intestine to adapt to a low-Ca diet with increasing age. Other dietary factors include vitamin K, Zn and fruit and vegetables. Adequate nutritional status, particularly of Ca and vitamin D, is essential for the successful pharmaceutical treatment of osteoporosis. Thus, strategies for enhancing skeletal health in the elderly must begin in early childhood, and continue throughout life.

p38α MAPK regulates proliferation and differentiation of osteoclast progenitors and bone remodeling in an aging-dependent manner

PubMed Central

Cong, Qian; Jia, Hao; Li, Ping; Qiu, Shoutao; Yeh, James; Wang, Yibin; Zhang, Zhen-Lin; Ao, Junping; Li, Baojie; Liu, Huijuan

2017-01-01

Bone mass is determined by the balance between bone formation, carried out by mesenchymal stem cell-derived osteoblasts, and bone resorption, carried out by monocyte-derived osteoclasts. Here we investigated the potential roles of p38 MAPKs, which are activated by growth factors and cytokines including RANKL and BMPs, in osteoclastogenesis and bone resorption by ablating p38α MAPK in LysM+monocytes. p38α deficiency promoted monocyte proliferation but regulated monocyte osteoclastic differentiation in a cell-density dependent manner, with proliferating p38α−/− cultures showing increased differentiation. While young mutant mice showed minor increase in bone mass, 6-month-old mutant mice developed osteoporosis, associated with an increase in osteoclastogenesis and bone resorption and an increase in the pool of monocytes. Moreover, monocyte-specific p38α ablation resulted in a decrease in bone formation and the number of bone marrow mesenchymal stem/stromal cells, likely due to decreased expression of PDGF-AA and BMP2. The expression of PDGF-AA and BMP2 was positively regulated by the p38 MAPK-Creb axis in osteoclasts, with the promoters of PDGF-AA and BMP2 having Creb binding sites. These findings uncovered the molecular mechanisms by which p38α MAPK regulates osteoclastogenesis and coordinates osteoclastogenesis and osteoblastogenesis. PMID:28382965

Bone mineral content in the senescent rat femur: an assessment using single photon absorptiometry

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

Kiebzak, G.M.; Smith, R.; Howe, J.C.

1988-06-01

The single photon absorptiometry technique was evaluated for measuring bone mineral content (BMC) of the excised femurs of the rat, and the system was used to examine the changes in cortical and trabecular bone from young adult (6 mo), mature adult (12 mo), and senescent (24 mo) male and female animals. BMC of the femur midshaft, representing cortical bone, apparently increased progressively with advancing age. The width of the femur at the scan site also increased with age. Normalizing the midshaft BMC by width partially compensated for the age-associated increase. However, when bone mineral values were normalized by the corticalmore » area at the scan site, to take into account the geometric differences in the femurs of different aged animals, maximum bone densities were found in the mature adult and these values decreased slightly in the femurs from senescent rats. In contrast, the BMC of the femur distal metaphysis, representing trabecular bone, decreased markedly in the aged rat. The loss of trabecular bone was also evident from morphological examination of the distal metaphysis. These findings indicated that bone mineral loss with age was site specific in the rat femur. These studies provided additional evidence that the rat might serve as a useful animal model for specific experiments related to the pathogenesis of age-associated osteopenia.« less

Impacts of the N-terminal fragment analog of human parathyroid hormone on structure, composition and biomechanics of bone.

PubMed

Chunxiao, Wang; Yu, Zhang; Wentao, Liu; Jingjing, Liu; Jiahui, Ye; Qingmei, Chen

2012-12-18

Osteoporosis is a skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, and it is a serious threat to human lives. We previously showed that the N-terminal peptide analog of human parathyroid hormone (Pro-Pro-PTH(1-34)) enhanced plasma calcium concentration. In this paper, we study the impact of PTH N-terminal fragment analog on the structure, component, and mechanical properties of the rat bones. Daily subcutaneous injections of Pro-Pro-hPTH (1-34) induces 26.5-32.8% increase in femur bone mineral density (BMD), 23.0-34.2% decrease the marrow cavity or increase in trabecular bone area. The peptide also increases 16.0-59.5%, 28.8-48.2% and 14.0-17.8% of bone components of calcium, phosphorus and collagen, respectively. In terms of mechanic properties, administration of the peptide elevates the bone rigidity by 45.4-76.6%, decreases the flexibility by 23.0-31.6%, and improves modulus of elasticity by 32.8-63.4%. The results suggest that Pro-Pro-hPTH (1-34) has a positive effect on bone growth and strength, and possesses anti-fracture capability, thus a potential candidate for the application for the treatment of osteoporosis. Copyright © 2012 Elsevier B.V. All rights reserved.

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.

Bone Density and Dental External Apical Root Resorption

PubMed Central

Iglesias-Linares, Alejandro; Morford, Lorri Ann

2016-01-01

When orthodontic patients desire shorter treatment times with aesthetic results and long-term stability, it is important for the orthodontist to understand the potential limitations and problems that may arise during standard and/or technology-assisted accelerated treatment. Bone density plays an important role in facilitating orthodontic tooth movement (OTM), such that reductions in bone density can significantly increase movement velocity. Lifestyle, genetic background, environmental factors and disease status all can influence a patients’ overall health and bone density. In some individuals, these factors may create specific conditions that influence systemic-wide bone metabolism. Both genetic variation and the onset of a bone-related disease can influence systemic bone density and local bone density, such as is observed in the mandible and maxilla. These types of localized density changes can affect the rate of OTM and may also influence the risk of unwanted outcomes, i.e., the occurrence of dental external apical root resorption (EARR). PMID:27766484

Numeric simulation of bone remodelling patterns after implantation of a cementless straight stem.

PubMed

Lerch, Matthias; Windhagen, Henning; Stukenborg-Colsman, Christina M; Kurtz, Agnes; Behrens, Bernd A; Almohallami, Amer; Bouguecha, Anas

2013-12-01

For further development of better bone-preserving implants in total hip arthroplasty (THA), we need to look back and analyse established and clinically approved implants to find out what made them successful. Finite element analysis can help do this by simulating periprosthetic bone remodelling under different conditions. Our aim was thus to establish a numerical model of the cementless straight stem for which good long-term results have been obtained. We performed a numeric simulation of a cementless straight stem, which has been successfully used in its unaltered form since 1986/1987. We have 20 years of experience with this THA system and implanted it 555 times in 2012. We performed qualitative and quantitative validation using bone density data derived from a prospective dual-energy X-ray absorptiometry (DEXA) investigation. Bone mass loss converged to 9.25% for the entire femur. No change in bone density was calculated distal to the tip of the prosthesis. Bone mass decreased by 46.2% around the proximal half of the implant and by 7.6% in the diaphysis. The numeric model was in excellent agreement with DEXA data except for the calcar region, where deviation was 67.7%. The higher deviation in the calcar region is possibly a sign of the complex interactions between the titanium coating on the stem and the surrounding bone. We developed a validated numeric model to simulate bone remodelling for different stem-design modifications. We recommend that new THA implants undergo critical numeric simulation before clinical application.

Nanoparticles of cobalt-substituted hydroxyapatite in regeneration of mandibular osteoporotic bones.

PubMed

Ignjatović, Nenad; Ajduković, Zorica; Savić, Vojin; Najman, Stevo; Mihailović, Dragan; Vasiljević, Perica; Stojanović, Zoran; Uskoković, Vuk; Uskoković, Dragan

2013-02-01

Indications exist that paramagnetic calcium phosphates may be able to promote regeneration of bone faster than their regular, diamagnetic counterparts. In this study, analyzed was the influence of paramagnetic cobalt-substituted hydroxyapatite nanoparticles on osteoporotic alveolar bone regeneration in rats. Simultaneously, biocompatibility of the material was tested in vitro, on osteoblastic MC3T3-E1 and epithelial Caco-2 cells in culture. The material was shown to be biocompatible and nontoxic when added to epithelial monolayers in vitro, while it caused a substantial decrease in the cell viability as well as deformation of the cytoskeleton and cell morphology when incubated with the osteoblastic cells. In the course of 6 months after the implantation of the material containing different amounts of cobalt, ranging from 5 to 12 wt%, in the osteoporotic alveolar bone of the lower jaw, the following parameters were investigated: histopathological parameters, alkaline phosphatase and alveolar bone density. The best result in terms of osteoporotic bone tissue regeneration was observed for hydroxyapatite nanoparticles with the largest content of cobalt ions. The histological analysis showed a high level of reparatory ability of the nanoparticulate material implanted in the bone defect, paralleled by a corresponding increase in the alveolar bone density. The combined effect of growth factors from autologous plasma admixed to cobalt-substituted hydroxyapatite was furthermore shown to have a crucial effect on the augmented osteoporotic bone regeneration upon the implantation of the biomaterial investigated in this study.

Setup of a bone aging experimental model in the rabbit comparing changes in cortical and trabecular bone: Morphological and morphometric study in the femur.

PubMed

Pazzaglia, Ugo E; Sibilia, Valeria; Congiu, Terenzio; Pagani, Francesca; Ravanelli, Marco; Zarattini, Guido

2015-07-01

Bone aging was studied in an experimental model (rabbit femur) in three populations aged 0.5, 1.5, and 7.5 years. Cortical bone histology was compared with a data set from a 1.5-month-old population of an earlier published paper. From 0.5-year-old onward, the mean femur length did not increase further. Thereafter, the mean marrow area increased and the cortical area decreased significantly with aging. This was associated with a structural pattern transformation from plexiform to laminar and then Haversian-like type. The distal meta-epiphysis bone trabecular density of the oldest populations also was significantly lower in specific regions of interest (ROI). Percentage sealed primary vascular canals in laminar bone significantly increased with aging without variation of percentage sealed secondary osteons. Remodeling rate reflected by the density of cutting cones did not significantly change among the age populations. These data suggest that laminar bone vascular pattern is more functional in the fast diaphyseal expansion but not much streamlined with the renewal of blood flow during secondary remodeling. Bone aging was characterized by: 1) secondary remodeling subendosteally; 2) increment of sealed primary vascular canals number; 3) increased calcium content of the cortex; 4) cortical and trabecular bone mass loss in specific ROIs. Taken together, the present data may give a morphological and morphometric basis to perform comparative studies on experimental models of osteoporosis in the rabbit. © 2015 Wiley Periodicals, Inc.

Nanoparticles of cobalt-substituted hydroxyapatite in regeneration of mandibular osteoporotic bones

PubMed Central

Ignjatović, Nenad; Ajduković, Zorica; Savić, Vojin; Najman, Stevo; Mihailović, Dragan; Vasiljević, Perica; Stojanović, Zoran; Uskoković, Vuk; Uskoković, Dragan

2012-01-01

Indications exist that paramagnetic calcium phosphates may be able to promote regeneration of bone faster than their regular, diamagnetic counterparts. In this study, analyzed was the influence of paramagnetic cobalt-substituted hydroxyapatite nanoparticles on osteoporotic alveolar bone regeneration in rats. Simultaneously, biocompatibility of the material was tested in vitro, on osteoblastic MC3T3-E1 and epithelial Caco-2 cells in culture. The material was shown to be biocompatible and nontoxic when added to epithelial monolayers in vitro, while it caused a substantial decrease in the cell viability as well as deformation of the cytoskeleton and cell morphology when incubated with the osteoblastic cells. In the course of six months after the implantation of the material containing different amounts of cobalt, ranging from 5 – 12 wt%, in the osteoporotic alveolar bone of the lower jaw, the following parameters were investigated: histopathological parameters, alkaline phosphatase and alveolar bone density. The best result in terms of osteoporotic bone tissue regeneration was observed for hydroxyapatite nanoparticles with the largest content of cobalt ions. The histological analysis showed a high level of reparatory ability of the nanoparticulate material implanted in the bone defect, paralleled by a corresponding increase in the alveolar bone density. The combined effect of growth factors from autologous plasma admixed to cobalt-substituted hydroxyapatite was furthermore shown to have a crucial effect on the augmented osteoporotic bone regeneration upon the implantation of the biomaterial investigated in this study. PMID:23090835

High-Dietary Alpha-Tocopherol or Mixed Tocotrienols Have No Effect on Bone Mass, Density, or Turnover in Male Rats During Skeletal Maturation.

PubMed

Tennant, Katherine G; Leonard, Scott W; Wong, Carmen P; Iwaniec, Urszula T; Turner, Russell T; Traber, Maret G

2017-07-01

High levels of alpha-tocopherol, the usual vitamin E supplement, are reported to decrease bone mass in rodents; however, the effects of other vitamin E forms on the skeleton are unknown. To test the hypothesis that high intakes of various vitamin E forms or the vitamin E metabolite, carboxyethyl hydroxy chromanol, were detrimental to bone status, Sprague-Dawley rats (n = 6 per group, 11-week males) for 18 weeks consumed semipurified diets that contained adequate alpha-tocopherol, high alpha-tocopherol (500 mg/kg diet), or 50% Tocomin (250 mg mixed tocopherols and tocotrienols/kg diet). Vitamin E status was evaluated by measuring plasma, liver, and bone marrow vitamin E concentrations. Bone density, microarchitecture (cross-sectional volume, cortical volume, marrow volume, cortical thickness, and cancellous bone volume fraction, trabecular number, thickness, and spacing), and cancellous bone formation were assessed in the tibia using dual-energy X-ray absorptiometry, microcomputed tomography, and histomorphometry, respectively. In addition, serum osteocalcin was assessed as a global marker of bone turnover; gene expression in response to treatment was evaluated in the femur using targeted (osteogenesis related) gene profiling. No significant differences were detected between treatment groups for any of the bone endpoints measured. Vitamin E supplementation, either as alpha-tocopherol or mixed tocotrienols, while increasing vitamin E concentrations both in plasma and tissues, had no effect on the skeleton in rats.

Genetic predisposition for adult lactose intolerance and relation to diet, bone density, and bone fractures.

PubMed

Obermayer-Pietsch, Barbara M; Bonelli, Christine M; Walter, Daniela E; Kuhn, Regina J; Fahrleitner-Pammer, Astrid; Berghold, Andrea; Goessler, Walter; Stepan, Vinzenz; Dobnig, Harald; Leb, Georg; Renner, Wilfried

2004-01-01

Evidence that genetic disposition for adult lactose intolerance significantly affects calcium intake, bone density, and fractures in postmenopausal women is presented. PCR-based genotyping of lactase gene polymorphisms may complement diagnostic procedures to identify persons at risk for both lactose malabsorption and osteoporosis. Lactase deficiency is a common autosomal recessive condition resulting in decreased intestinal lactose degradation. A -13910 T/C dimorphism (LCT) near the lactase phlorizin hydrolase gene, reported to be strongly associated with adult lactase nonpersistence, may have an impact on calcium supply, bone density, and osteoporotic fractures in the elderly. We determined LCT genotypes TT, TC, and CC in 258 postmenopausal women using a polymerase chain reaction-based assay. Genotypes were related to milk intolerance, nutritional calcium intake, intestinal calcium absorption, bone mineral density (BMD), and nonvertebral fractures. Twenty-four percent of all women were found to have CC genotypes and genetic lactase deficiency. Age-adjusted BMD at the hip in CC genotypes and at the spine in CC and TC genotypes was reduced by -7% to -11% depending on the site measured (p = 0.04). LCT(T/C-13910) polymorphisms alone accounted for 2-4% of BMD in a multiple regression model. Bone fracture incidence was significantly associated with CC genotypes (p = 0.001). Milk calcium intake was significantly lower (-55%, p = 0.004) and aversion to milk consumption was significantly higher (+166%, p = 0.01) in women with the CC genotype, but there were no differences in overall dietary calcium intake or in intestinal calcium absorption test values. The LCT(T/C-13910) polymorphism is associated with subjective milk intolerance, reduced milk calcium intake, and reduced BMD at the hip and the lumbar spine and may predispose to bone fractures. Genetic testing for lactase deficiency may complement indirect methods in the detection of individuals at risk for both lactose malabsorption and osteoporosis.

Exogenous PTHrP Repairs the Damaged Fracture Healing of PTHrP+/− Mice and Accelerates Fracture Healing of Wild Mice

PubMed Central

Wang, Yinhe; Fang, Xin; Wang, Chun; Ding, Congzhu; Lin, Hua; Liu, Anlong; Wang, Lei; Cao, Yang

2017-01-01

Bone fracture healing is a complicated physiological regenerative process initiated in response to injury and is similar to bone development. To demonstrate whether an exogenous supply of parathyroid hormone–related protein (PTHrP) helps in bone fracture healing, closed mid-diaphyseal femur fractures were created and stabilized with intramedullary pins in eight-week-old wild-type (WT) PTHrP+/+ and PTHrP+/− mice. After administering PTHrP for two weeks, callus tissue properties were analyzed at one, two, and four weeks post-fracture (PF) by various methods. Bone formation–related genes and protein expression levels were evaluated by real-time reverse transcriptase–polymerase chain reaction and Western blots. At two weeks PF, mineral density of callus, bony callus areas, mRNA levels of alkaline phosphatase (ALP), type I collagen, Runt-related transcription factor 2 (Runx-2), and protein levels of Runx-2 and insulin-like growth factor-1 decreased in PTHrP+/− mice compared with WT mice. At four weeks PF, total collagen-positive bony callus areas, osteoblast number, ALP-positive areas, and type I collagen-positive areas all decreased in PTHrP+/− mice. At both two and four weeks PF, tartrate-resistant acid phosphatase–positive osteoclast number and surface decreased a little in PTHrP+/− mice. The study indicates that exogenous PTHrP provided by subcutaneous injection could redress impaired bone fracture healing, leading to mutation of activated PTHrP by influencing callus areas, endochondral bone formation, osteoblastic bone formation, and bone turnover. PMID:28178186

High vitamin D3 diet administered during active colitis negatively affects bone metabolism in an adoptive T cell transfer model

PubMed Central

Larmonier, C. B.; McFadden, R.-M. T.; Hill, F. M.; Schreiner, R.; Ramalingam, R.; Besselsen, D. G.; Ghishan, F. K.

2013-01-01

Decreased bone mineral density (BMD) represents an extraintestinal complication of inflammatory bowel disease (IBD). Vitamin D3 has been considered a viable adjunctive therapy in IBD. However, vitamin D3 plays a pleiotropic role in bone modeling and regulates the bone formation-resorption balance, depending on the physiological environment, and supplementation during active IBD may have unintended consequences. We evaluated the effects of vitamin D3 supplementation during the active phase of disease on colonic inflammation, BMD, and bone metabolism in an adoptive IL-10−/− CD4+ T cell transfer model of chronic colitis. High-dose vitamin D3 supplementation for 12 days during established disease had negligible effects on mucosal inflammation. Plasma vitamin D3 metabolites correlated with diet, but not disease, status. Colitis significantly reduced BMD. High-dose vitamin D3 supplementation did not affect cortical bone but led to a further deterioration of trabecular bone morphology. In mice fed a high vitamin D3 diet, colitis more severely impacted bone formation markers (osteocalcin and bone alkaline phosphatase) and increased bone resorption markers, ratio of receptor activator of NF-κB ligand to osteoprotegrin transcript, plasma osteoprotegrin level, and the osteoclast activation marker tartrate-resistant acid phosphatase (ACp5). Bone vitamin D receptor expression was increased in mice with chronic colitis, especially in the high vitamin D3 group. Our data suggest that vitamin D3, at a dose that does not improve inflammation, has no beneficial effects on bone metabolism and density during active colitis or may adversely affect BMD and bone turnover. These observations should be taken into consideration in the planning of further clinical studies with high-dose vitamin D3 supplementation in patients with active IBD. PMID:23639807

High vitamin D3 diet administered during active colitis negatively affects bone metabolism in an adoptive T cell transfer model.

PubMed

Larmonier, C B; McFadden, R-M T; Hill, F M; Schreiner, R; Ramalingam, R; Besselsen, D G; Ghishan, F K; Kiela, P R

2013-07-01

Decreased bone mineral density (BMD) represents an extraintestinal complication of inflammatory bowel disease (IBD). Vitamin D₃ has been considered a viable adjunctive therapy in IBD. However, vitamin D₃ plays a pleiotropic role in bone modeling and regulates the bone formation-resorption balance, depending on the physiological environment, and supplementation during active IBD may have unintended consequences. We evaluated the effects of vitamin D₃ supplementation during the active phase of disease on colonic inflammation, BMD, and bone metabolism in an adoptive IL-10-/- CD4⁺ T cell transfer model of chronic colitis. High-dose vitamin D₃ supplementation for 12 days during established disease had negligible effects on mucosal inflammation. Plasma vitamin D₃ metabolites correlated with diet, but not disease, status. Colitis significantly reduced BMD. High-dose vitamin D₃ supplementation did not affect cortical bone but led to a further deterioration of trabecular bone morphology. In mice fed a high vitamin D₃ diet, colitis more severely impacted bone formation markers (osteocalcin and bone alkaline phosphatase) and increased bone resorption markers, ratio of receptor activator of NF-κB ligand to osteoprotegrin transcript, plasma osteoprotegrin level, and the osteoclast activation marker tartrate-resistant acid phosphatase (ACp5). Bone vitamin D receptor expression was increased in mice with chronic colitis, especially in the high vitamin D₃ group. Our data suggest that vitamin D₃, at a dose that does not improve inflammation, has no beneficial effects on bone metabolism and density during active colitis or may adversely affect BMD and bone turnover. These observations should be taken into consideration in the planning of further clinical studies with high-dose vitamin D₃ supplementation in patients with active IBD.

Relation between body composition and bone mineral density in young undregraduate students with different nutritional status

PubMed Central

Rodrigues, Edil de Albuquerque; dos Santos, Marcos André Moura; da Silva, Amanda Tabosa Pereira; Farah, Breno Quintella; Costa, Manoel da Cunha; Campos, Florisbela de Arruda Camara e Siqueira; Falcão, Ana Patrícia Siqueira Tavares

2016-01-01

ABSTRACT Objective To investigate the relationship between total and segmental body fat, bone mineral density and bone mineral content in undergraduate students stratified according to nutritional status. Methods The study included 45 male undergraduate students aged between 20 and 30 years. Total and segmental body composition, bone mineral density and bone mineral content assessments were performed using dual energy X-ray absorptiometry. Subjects were allocated into three groups (eutrophic, overweight and obese). Results With the exception of upper limb bone mineral content, significantly higher (p<0.05) mean bone mineral density, bone mineral content, and relative body fat values were documented in the obese group. Total body and segmental relative body fat (lower limbs and trunk) were positively correlated (p<0.05) with bone mineral density in the overweight group. Upper limb fat was negatively correlated (p<0.05) with bone mineral content in the normal and eutrophic groups. Conclusion Total body and segmental body fat were correlated with bone mineral density and bone mineral content in male undergraduate students, particularly in overweight individuals. PMID:27074228

Sublingual testosterone replacement improves muscle mass and strength, decreases bone resorption, and increases bone formation markers in hypogonadal men--a clinical research center study.

PubMed

Wang, C; Eyre, D R; Clark, R; Kleinberg, D; Newman, C; Iranmanesh, A; Veldhuis, J; Dudley, R E; Berman, N; Davidson, T; Barstow, T J; Sinow, R; Alexander, G; Swerdloff, R S

1996-10-01

To study the effects of androgen replacement therapy on muscle mass and strength and bone turnover markers in hypogonadal men, we administered sublingual testosterone (T) cyclodextrin (SLT; 5 mg, three times daily) to 67 hypogonadal men (baseline serum T, < 8.4 nmol/L) recruited from 4 centers in the U.S.: Torrance (n = 34), Durham (n = 12), New York (n = 9), and Salem (n = 12). Subjects who had received prior T therapy were withdrawn from injections for at least 6 weeks and from oral therapy for 4 weeks. Body composition, muscle strength, and serum and urinary bone turnover markers were measured before and after 6 months of SLT. We have shown previously that this regimen for 60 days will maintain adequate serum T levels and restore sexual function. Total body (P = 0.0104) and lean body mass (P = 0.007) increased with SLT treatment in the 34 subjects in whom body composition was assessed. There was no significant change in total body fat or percent fat. The increase in lean body mass was mainly in the legs; the right leg lean mass increased from 8.9 +/- 0.3 kg at 0 months to 9.2 +/- 0.3 kg at 6 months (P = 0.0008). This increase in leg lean mass was associated with increased leg muscle strength, assessed by leg press (0 months, 139.0 +/- 4.0 kg; 6 months, 147.7 +/- 4.2 kg; P = 0.0038). SLT replacement in hypogonadal men led to small, but significant, decreases in serum Ca (P = 0.0029) and the urinary calcium/creatinine ratio (P = 0.0066), which were associated with increases in serum PTH (P = 0.0001). At baseline, the urinary type I collagen-cross linked N-telopeptides/creatinine ratio [75.6 +/- 7.9 nmol bone collagen equivalents (BCE/mmol] was twice the normal adult male mean (41.0 +/- 3.6 nmol BCE/mmol) and was significantly decreased in response to SLT treatment at 6 months (68.2 +/- 7.7 nmol BCE/mmol; P = 0.0304) without significant changes in urinary creatinine. Serum skeletal alkaline phosphatase did not change. In addition, SLT replacement caused significant increases in serum osteocalcin (P = 0.0001) and type I procollagen (P = 0.0012). Bone mineral density did not change during the 6 months of SLT treatment. We conclude that SLT replacement therapy resulted in increases in lean muscle mass and muscle strength. Like estrogen replacement in hypogonadal postmenopausal females, androgen replacement therapy led to decreased bone resorption and urinary calcium excretion. Moreover, androgen replacement therapy may have the additional benefit of increasing bone formation. A longer term study for several years duration would be necessary to demonstrate whether these changes in bone turnover marker levels will result in increased bone mineral density decreased fracture risks, and reduced frailty in hypogonadal men.

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

Intermittent fasting protects against the deterioration of cognitive function, energy metabolism and dyslipidemia in Alzheimer's disease-induced estrogen deficient rats.

PubMed

Shin, Bae Kun; Kang, Suna; Kim, Da Sol; Park, Sunmin

2018-02-01

Intermittent fasting may be an effective intervention to protect against age-related metabolic disturbances, although it is still controversial. Here, we investigated the effect of intermittent fasting on the deterioration of the metabolism and cognitive functions in rats with estrogen deficiency and its mechanism was also explored. Ovariectomized rats were infused with β-amyloid (25-35; Alzheimer's disease) or β-amyloid (35-25, Non-Alzheimer's disease; normal cognitive function) into the hippocampus. Each group was randomly divided into two sub-groups: one with intermittent fasting and the other fed ad libitum: Alzheimer's disease-ad libitum, Alzheimer's disease-intermittent fasting, Non-Alzheimer's disease-ad libitum, and Non-Alzheimer's disease-intermittent fasting. Rats in the intermittent fasting groups had a restriction of food consumption to a 3-h period every day. Each group included 10 rats and all rats fed a high-fat diet for four weeks. Interestingly, Alzheimer's disease increased tail skin temperature more than Non-Alzheimer's disease and intermittent fasting prevented the increase. Alzheimer's disease reduced bone mineral density in the spine and femur compared to the Non-Alzheimer's disease, whereas bone mineral density in the hip and leg was reduced by intermittent fasting. Fat mass only in the abdomen was decreased by intermittent fasting. Intermittent fasting decreased food intake without changing energy expenditure. Alzheimer's disease increased glucose oxidation, whereas intermittent fasting elevated fat oxidation as a fuel source. Alzheimer's disease and intermittent fasting deteriorated insulin resistance in the fasting state but intermittent fasting decreased serum glucose levels after oral glucose challenge by increasing insulin secretion. Alzheimer's disease deteriorated short and spatial memory function compared to the Non-Alzheimer's disease, whereas intermittent fasting prevented memory loss in comparison to ad libitum. Unexpectedly, cortisol levels were increased by Alzheimer's disease but decreased by intermittent fasting. Intermittent fasting improved dyslipidemia and liver damage index compared to ad libitum. Alzheimer's disease lowered low-density lipoprotein cholesterol and serum triglyceride levels compared to Non-Alzheimer's disease. In conclusion, Alzheimer's disease impaired not only cognitive function but also disturbed energy, glucose, lipid, and bone metabolism in ovariectomized rats. Intermittent fasting protected against the deterioration of these metabolic parameters, but it exacerbated bone mineral density loss and insulin resistance at fasting in Alzheimer's disease-induced estrogen-deficient rats. Impact statement Intermittent fasting was evaluated for its effects on cognitive function and metabolic disturbances in a rat model of menopause and Alzheimer's disease. Intermittent fasting decreased skin temperature and fat mass, and improved glucose tolerance with decreasing food intake. Intermittent fasting also prevented memory loss: short-term and special memory loss. Therefore, intermittent fasting may prevent some of the metabolic pathologies associated with menopause and protect against age-related memory decline.

Raman spectroscopy of murine bone in response to simulated spaceflight conditions

NASA Astrophysics Data System (ADS)

Mandair, Gurjit S.; Bateman, Ted A.; Morris, Michael D.

2009-02-01

Astronauts exposed to spaceflight conditions can lose 1-2% of their bone mineral density per month from the weight-bearing portions of the skeletal system. Low bone mineral density, termed osteopenia, is the result of decreased bone formation and/or increased bone resorption. In this study, Raman spectroscopy is used to examine if the physicochemical composition of murine femurs is altered in response to simulated spaceflight conditions (hindlimb suspension). Female C57BL/6J mice, aged 53 days, were divided into ground control and simulated spaceflight groups for a period of 12 days, modeling the experiment profile of mice flown on Space Shuttle flight STS-108. After the study, the mice were sacrificed and femur specimens harvested. Mid-diaphysis sections were probed using near-infrared Raman microscopy. Spectra were collected at various anatomical sites (anterior, lateral, medial, and posterior quadrants) and/or cortical locations (periosteal, midosteal, and endosteal). Chemometric recovery of spectra was employed to reduce signal contributions from the epoxy embedding agent. Mean values for mineralization, carbonation, crystallinity, and other parameters associated with the matrix were estimated. Correlations between mineralization and carbonation were observed, despite the small absolute changes between the two groups. We present more detailed analysis of this data and comment on the prospects for Raman spectroscopic evaluation of bone quality in hindlimb suspended (HLS) specimens.

Skeletal Maturation and Mineralisation of Children with Moderate to Severe Spastic Quadriplegia.

PubMed

Sharawat, Indar Kumar; Sitaraman, Sadasivan

2016-06-01

Diminished bone mineral density and delayed skeletal maturation are common in children with spastic quadriplegia. The purpose of our study was to evaluate the Bone Mineral Density (BMD) of children with moderate to severe spastic quadriplegia and its relationship with other variables like nutrition and growth. This was a hospital based, cross- sectional, case-control study. Forty-two (28 males, 14 females) children with spastic quadriplegia and 42 (24 males, 18 females) healthy children were included in the study. BMD of cases and control were measured by Dual Energy X-ray Absorptiometry (DEXA). Radiographs of left hand and wrist of cases and controls were taken and bone age was determined. BMD values of upper extremity, lower extremity, thoraco-lumbar spine and pelvis in cases were lower than those of controls (p <0.0001). In children with non severe malnutrition, 75% of the cases had lower bone age than chronological age, whereas all cases with severe malnutrition had lower bone age than chronological age. Step wise regression analysis showed that nutritional status independently contributed to lower BMD values but the BMD values did not correlate significantly with the use of anticonvulsant drugs and presence of physical therapy. Decreased BMD and delayed bone age is prevalent in children with spastic quadriplegia and nutritional status is an important contributing factor.

Reduced vertebral bone density in hypercalciuric nephrolithiasis

NASA Technical Reports Server (NTRS)

Pietschmann, F.; Breslau, N. A.; Pak, C. Y.

1992-01-01

Dual-energy x-ray absorptiometry and single-photon absorptiometry were used to determine bone density at the lumbar spine and radial shaft in 62 patients with absorptive hypercalciuria, 27 patients with fasting hypercalciuria, and 31 nonhypercalciuric stone formers. Lumbar bone density was significantly lower in patients with absorptive (-10%) as well as in those with fasting hypercalciuria (-12%), with 74 and 92% of patients displaying values below the normal mean, whereas only 48% of the nonhypercalciuric stone formers had bone density values below the normal mean. In contrast, radial bone density was similar in all three groups of renal stone formers investigated. The comparison of urinary chemistry in patients with absorptive hypercalciuria and low normal bone density compared to those with high normal bone density showed a significantly increased 24 h urinary calcium excretion on random diet and a trend toward a higher 24 h urinary uric acid excretion and a higher body mass index in patients with low normal bone density. Moreover, among the patients with absorptive hypercalciuria we found a statistically significant correlation between the spinal bone density and the 24 h sodium and sulfate excretion and the urinary pH. These results gave evidence for an additional role of environmental factors (sodium and animal proteins) in the pathogenesis of bone loss in absorptive hypercalciuria. In conclusion, our data suggest an osteopenia of trabecular-rich bone tissues in patients with fasting and absorptive hypercalciurias.

Oxygen mapping: Probing a novel seeding strategy for bone tissue engineering.

PubMed

Westphal, Ines; Jedelhauser, Claudia; Liebsch, Gregor; Wilhelmi, Arnd; Aszodi, Attila; Schieker, Matthias

2017-04-01

Bone tissue engineering (BTE) utilizing biomaterial scaffolds and human mesenchymal stem cells (hMSCs) is a promising approach for the treatment of bone defects. The quality of engineered tissue is crucially affected by numerous parameters including cell density and the oxygen supply. In this study, a novel oxygen-imaging sensor was introduced to monitor the oxygen distribution in three dimensional (3D) scaffolds in order to analyze a new cell-seeding strategy. Immortalized hMSCs, pre-cultured in a monolayer for 30-40% or 70-80% confluence, were used to seed demineralized bone matrix (DBM) scaffolds. Real-time measurements of oxygen consumption in vitro were simultaneously performed by the novel planar sensor and a conventional needle-type sensor over 24 h. Recorded oxygen maps of the novel planar sensor revealed that scaffolds, seeded with hMSCs harvested at lower densities (30-40% confluence), exhibited rapid exponential oxygen consumption profile. In contrast, harvesting cells at higher densities (70-80% confluence) resulted in a very slow, almost linear, oxygen decrease due to gradual achieving the stationary growth phase. In conclusion, it could be shown that not only the seeding density on a scaffold, but also the cell density at the time point of harvest is of major importance for BTE. The new cell seeding strategy of harvested MSCs at low density during its log phase could be a useful strategy for an early in vivo implantation of cell-seeded scaffolds after a shorter in vitro culture period. Furthermore, the novel oxygen imaging sensor enables a continuous, two-dimensional, quick and convenient to handle oxygen mapping for the development and optimization of tissue engineered scaffolds. Biotechnol. Bioeng. 2017;114: 894-902. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

INVESTIGATION OF BONE MINERALIZATION IN PATIENTS WITH CORONARY HEART DISEASE COMPLICATED BY CHRONIC HEART FAILURE, STAGE II-A.

PubMed

Krynytska, I; Marushchak, M; Zaets, T; Savchenko, I; Habor, H

2017-06-01

The majority of the studies have shown that individuals with cardiovascular diseases have a higher risk of experiencing bone loss and thus greater predisposition to risk of fracture. On the other hand there is growing evidence that individuals with low bone mass have higher mortality for cardiovascular events compared to patients with cardiovascular disease with normal bone mass. This research aims to investigate bone mineralization in patients with coronary heart disease complicated by stage II-A chronic heart failure. The study involved 33 men with coronary heart disease complicated by Stage II-A chronic heart failure. Bone mineral density was measured using dual energy x-ray densitometry of lumbar region of spine. Structural and functional changes of bone tissue of the lumbar spine have been found in 49,2% patients with coronary heart disease complicated by Stage II-A chronic heart failure, in particular, I stage of osteopenia - in 44,6%, II stage of osteopenia - in 27,7%, III stage of osteopenia - in 10,8% and osteoporosis - in 16,9%. It was established the same type of downward trend for BMD decreasing in L1 of patients with different stages of osteopenia, but in case of osteoporosis mineralization decreased equally in all vertebrae.

Bioimpedance analysis vs. DEXA as a screening tool for osteosarcopenia in lean, overweight and obese Caucasian postmenopausal females.

PubMed

Peppa, Melpomeni; Stefanaki, Charikleia; Papaefstathiou, Athanasios; Boschiero, Dario; Dimitriadis, George; Chrousos, George P

2017-04-01

We aimed at evaluating the efficiency of a newly developed, advanced Bioimpedance Analysis (BIA-ACC®) device as a screening tool for determining the degree of obesity and osteosarcopenia in postmenopausal women with normal or decreased bone density determined by Dual-Energy X-Ray absorptiometry (DEXA) in a representative sample of Greek postmenopausal women. This is a single-gate cross-sectional study of body composition measured by BIA-ACC® and DEXA. Postmenopausal females with BMI ranging from 18.5 to 40 kg/m2 were subjected to two consecutive measurements of DEXA and BIA-ACC® within 5-10 minutes of each other. We used Pearson's co-efficient to examine linear correlations, the intraclass correlation co-efficient (ICC) to test reliability, Bland-Atman plots to assess bias and Deming regressions to establish the agreement in parameters measured by BIA-ACC® and DEXA. Last, we used ANOVA, with Bonferroni correction and Dunnett T3 post hoc tests, for assessing the differences between quantitative and Pearson's x2 between qualitative variables. Our sample consisted of 84 overweight/obese postmenopausal women, aged 39-83 years, of whom 22 had normal bone density, 38 had osteopenia and 24 had osteoporosis based on DEXA measurements, using quota sampling. ICCs and Deming regressions showed strong agreement between BIA-ACC® and DEXA and demonstrated minimal proportional differences of no apparent clinical significance. Bland-Altman plots indicated minimal biases. Fat, skeletal and bone mass measured by BIA-ACC® and DEXA were increased in the non-osteopenic/non-osteoporotic women compared with those of the osteopenic and osteoporotic groups. BIA-ACC® is a rapid, bloodless and useful screening tool for determining body composition adiposity and presence of osteo-sarcopenic features in postmenopausal women. Women with osteopenia and osteoporosis evaluated by DEXA had decreased fat, skeletal and bone mass compared with normal bone density women, suggesting concordance in the change of these three organ masses in postmenopausal women.

Sclerostin antibody and interval treadmill training effects in a rodent model of glucocorticoid-induced osteopenia.

PubMed

Achiou, Zahra; Toumi, Hechmi; Touvier, Jérome; Boudenot, Arnaud; Uzbekov, Rustem; Ominsky, Michael S; Pallu, Stéphane; Lespessailles, Eric

2015-12-01

Glucocorticoids have a beneficial anti-inflammatory and immunosuppressive effect, but their use is associated with decreased bone formation, bone mass and bone quality, resulting in an elevated fracture risk. Exercise and sclerostin antibody (Scl-Ab) administration have both been shown to increase bone formation and bone mass, therefore the ability of these treatments to inhibit glucocorticoid-induced osteopenia alone or in combination were assessed in a rodent model. Adult (4 months-old) male Wistar rats were allocated to a control group (C) or one of 4 groups injected subcutaneously with methylprednisolone (5mg/kg/day, 5 days/week). Methylprednisolone treated rats were injected subcutaneously 2 days/week with vehicle (M) or Scl-Ab-VI (M+S: 25mg/kg/day) and were submitted or not to treadmill interval training exercise (1h/day, 5 days/week) for 9 weeks (M+E, M+E+S). Methylprednisolone treatment increased % fat mass and % apoptotic osteocytes, reduced whole body and femoral bone mineral content (BMC), reduced femoral bone mineral density (BMD) and osteocyte lacunae occupancy. This effect was associated with lower trabecular bone volume (BV/TV) at the distal femur. Exercise increased BV/TV, osteocyte lacunae occupancy, while reducing fat mass, the bone resorption marker NTx, and osteocyte apoptosis. Exercise did not affect BMC or cortical microarchitectural parameters. Scl-Ab increased the bone formation marker osteocalcin and prevented the deleterious effects of M on bone mass, further increasing BMC, BMD and BV/TV to levels above the C group. Scl-Ab increased femoral cortical bone parameters at distal part and midshaft. Scl-Ab prevented the decrease in osteocyte lacunae occupancy and the increase in osteocyte apoptosis induced by M. The addition of exercise to Scl-Ab treatment did not result in additional improvements in bone mass or bone strength parameters. These data suggest that although our exercise regimen did prevent some of the bone deleterious effects of glucocorticoid treatment, particularly in trabecular bone volume and osteocyte apoptosis, Scl-Ab treatment resulted in marked improvements in bone mass across the skeleton and in osteocyte viability, resulting in decreased bone fragility. Copyright © 2015 Elsevier Inc. All rights reserved.

An Intraoperative Site-specific Bone Density Device: A Pilot Test Case.

PubMed

Arosio, Paolo; Moschioni, Monica; Banfi, Luca Maria; Di Stefano, Anilo Alessio

2015-08-01

This paper reports a case of all-on-four rehabilitation where bone density at implant sites was assessed both through preoperative computed tomographic (CT) scans and using a micromotor working as an intraoperative bone density measurement device. Implant-supported rehabilitation is a predictable treatment option for tooth replacement whose success depends on the clinician's experience, the implant characteristics and location and patient-related factors. Among the latter, bone density is a determinant for the achievement of primary implant stability and, eventually, for implant success. The ability to measure bone density at the placement site before implant insertion could be important in the clinical setting. A patient complaining of masticatory impairment was presented with a plan calling for extraction of all her compromised teeth, followed by implant rehabilitation. A week before surgery, she underwent CT examination, and the bone density on the CT scans was measured. When the implant osteotomies were created, the bone density was again measured with a micromotor endowed with an instantaneous torque-measuring system. The implant placement protocols were adapted for each implant, according to the intraoperative measurements, and the patient was rehabilitated following an all-on-four immediate loading protocol. The bone density device provided valuable information beyond that obtained from CT scans, allowing for site-specific, intraoperative assessment of bone density immediately before implant placement and an estimation of primary stability just after implant insertion. Measuring jaw-bone density could help clinicians to select implant-placement protocols and loading strategies based on site-specific bone features.

Individualized Fracture Risk Feedback and Long-term Benefits After 10 Years.

PubMed

Wu, Feitong; Wills, Karen; Laslett, Laura L; Riley, Malcolm D; Oldenburg, Brian; Jones, Graeme; Winzenberg, Tania

2018-02-01

This study aimed to determine if beneficial effects of individualized feedback of fracture risk on osteoporosis preventive behaviors and bone mineral density observed in a 2-year trial were sustained long-term. This was a 10-year follow-up of a 2-year RCT in 470 premenopausal women aged 25-44 years, who were randomized to one of two educational interventions (the Osteoporosis Prevention and Self-Management Course [OPSMC] or an osteoporosis information leaflet) and received tailored feedback of their relative risk of fracture in later life (high versus normal risk groups). Bone mineral density of lumbar spine and femoral neck were measured by dual-energy X-ray absorptiometry. Physical activity, dietary calcium intake, calcium and vitamin D supplements, and smoking status were measured by questionnaires. From 2 to 12 years, the high-risk group had a smaller decrease in femoral neck bone mineral density (β=0.023, 95% CI=0.005, 0.041 g/cm 2 ) but similar lumbar spine bone mineral density change as the normal-risk group. They were more likely to use calcium (relative risk=1.66, 95% CI=1.22, 2.24) and vitamin D supplements (1.99, 95% CI=1.27, 3.11). The OPSMC had no effects on bone mineral density change. Both high-risk (versus normal-risk) and the OPSMC groups (versus leaflet) had a more favorable pattern of smoking behavior change (relative risk=1.85, 95% CI=0.70, 4.89 and relative risk=2.27, 95% CI=0.86, 6.01 for smoking cessation; relative risk=0.33, 95% CI=0.13, 0.80 and relative risk=0.28, 95% CI=0.10, 0.79 for commenced or persistent smoking). Feedback of high fracture risk to younger women was associated with long-term improvements in osteoporosis preventive behaviors and attenuated femoral neck bone mineral density loss. Therefore, this could be considered as a strategy to prevent osteoporosis. Australian New Zealand Clinical Trials Registry (ANZCTR) NCT00273260. Copyright © 2018 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Disordered eating, menstrual disturbances, and low bone mineral density in dancers: a systematic review.

PubMed

Hincapié, Cesar A; Cassidy, J David

2010-11-01

To assemble and synthesize the best evidence on the epidemiology, diagnosis, prognosis, treatment, and prevention of disordered eating, menstrual disturbances, and low bone mineral density in dancers. Medline, CINAHL, PsycINFO, Embase, and other electronic databases were searched from 1966 to 2010 using key words such as "dance," "dancer," "dancing," "eating disorders," "menstruation disturbances," and "bone density." In addition, the reference lists of relevant studies were examined, specialized journals were hand-searched, and the websites of major dance associations were scanned for relevant information. Citations were screened for relevance using a priori criteria, and relevant studies were critically reviewed for scientific merit by the best evidence synthesis method. After 2748 abstracts were screened, 124 articles were reviewed, and 23 (18.5%) of these were accepted as scientifically admissible (representing 19 unique studies). Data from accepted studies were abstracted into evidence tables relating to prevalence and associated factors; incidence and risk factors; diagnosis; and prevention of disordered eating, menstrual disturbances, and/or low bone mineral density in dancers. The scientifically admissible studies consisted of 13 (68%) cross-sectional studies and 6 (32%) cohort studies. Disordered eating and menstrual disturbances are common in dancers. The lifetime prevalence of any eating disorder was 50% in professional dancers, while the point prevalence ranged between 13.6% and 26.5% in young student dancers. In their first year of intensive dance training, 32% of university-level dancers developed a menstrual disturbance. The incidence of disordered eating and low bone mineral density in dancers is unknown. Several potential risk factors are suggested by the literature, but there is little compelling evidence for any of these. There is preliminary evidence that multifaceted sociocultural prevention strategies may help decrease the incidence of disordered eating. The dance medicine literature is heterogeneous. The best available evidence suggests that disordered eating, menstrual disturbances, and low bone mineral density are important health issues for dancers at all skill levels. Future research would benefit from clear and relevant research questions being addressed with appropriate study designs and better reporting of studies in line with current scientific standards. Copyright © 2010 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Switching from tenofovir to abacavir in HIV-1-infected patients with low bone mineral density: changes in bone turnover markers and circulating sclerostin levels.

PubMed

Negredo, Eugènia; Diez-Pérez, Adolfo; Bonjoch, Anna; Domingo, Pere; Pérez-Álvarez, Núria; Gutierrez, Mar; Mateo, Gracia; Puig, Jordi; Echeverría, Patricia; Escrig, Roser; Clotet, Bonaventura

2015-07-01

Tenofovir is involved in accelerated bone mineral density (BMD) loss. We recently published a hip BMD improvement at week 48 [+2.1% (95% CI: -0.6, 4.7) (P = 0.043)] in HIV-infected patients with osteopenia/osteoporosis randomized to switch from tenofovir to abacavir (n = 26), although without reaching statistical significance compared with those who maintained tenofovir (n = 28). Here, we present changes at week 48 in bone markers [C-terminal telopeptide of collagen type 1 (CTX), osteocalcin and procollagen type 1 N propeptide (P1NP)] as well as in circulating levels of three proteins involved in bone regulation [osteoprotegerin, receptor activator for NF-κB ligand (RANKL) and sclerostin, a selective regulator of bone formation through the Wnt pathway] in 44 of these patients. χ(2) or Fisher and Student t-tests were performed according to the distribution of the variables. Bone markers decreased only in the abacavir group [mean (SD) CTX changed from 0.543 (0.495) to 0.301 (0.306) ng/mL; mean (SD) osteocalcin changed from 23.72 (22.20) to 13.95 (12.40) ng/mL; and mean (SD) P1NP changed from 54.68 (54.52) to 28.65 (27.48) ng/mL (P < 0.001 in all cases)], reaching statistical significance between the groups at week 48. Osteoprotegerin did not vary, but sclerostin significantly increased in the abacavir group [from 29.53 (27.91) to 35.56 (34.59) pmol/L, P = 0.002]. No significant differences in osteoprotegerin and sclerostin were detected between the groups at week 48. RANKL values were below the limit of detection in all samples. The switch from tenofovir to abacavir seems to induce a positive effect on bone tissue, since bone turnover markers decreased. In addition, circulating sclerostin levels increased, a change associated with improved bone properties. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Conditional disruption of the prolyl hydroxylase domain-containing protein 2 (Phd2) gene defines its key role in skeletal development.

PubMed

Cheng, Shaohong; Xing, Weirong; Pourteymoor, Sheila; Mohan, Subburaman

2014-10-01

We have previously shown that the increase in osterix (Osx) expression during osteoblast maturation is dependent on the activity of the prolyl hydroxylase domain-containing protein 2 (Phd2), a key regulator of protein levels of the hypoxia-inducible factor family proteins in many tissues. In this study, we generated conditional Phd2 knockout mice (cKO) in osteoblast lineage cells by crossing floxed Phd2 mice with a Col1α2-iCre line to investigate the function of Phd2 in vivo. The cKO mice developed short stature and premature death at 12 to 14 weeks of age. Bone mineral content, bone area, and bone mineral density were decreased in femurs and tibias, but not vertebrae of the cKO mice compared to WT mice. The total volume (TV), bone volume (BV), and bone volume fraction (BV/TV) in the femoral trabecular bones of cKO mice were significantly decreased. Cross-sectional area of the femoral mid-diaphysis was also reduced in the cKO mice. The reduced bone size and trabecular bone volume in the cKO mice were a result of impaired bone formation but not bone resorption as revealed by dynamic histomorphometric analyses. Bone marrow stromal cells derived from cKO mice formed fewer and smaller nodules when cultured with mineralization medium. Quantitative RT-PCR and immunohistochemistry detected reduced expression of Osx, osteocalcin, and bone sialoprotein in cKO bone cells. These data indicate that Phd2 plays an important role in regulating bone formation in part by modulating expression of Osx and bone formation marker genes. © 2014 American Society for Bone and Mineral Research.

Bone mineral density and effects of growth hormone treatment in prepubertal children with Prader-Willi syndrome: a randomized controlled trial.

PubMed

de Lind van Wijngaarden, Roderick F A; Festen, Dederieke A M; Otten, Barto J; van Mil, Edgar G A H; Rotteveel, Joost; Odink, Roelof J; van Leeuwen, Mariëtte; Haring, Danny A J P; Bocca, Gianni; Mieke Houdijk, E C A; Hokken-Koelega, Anita C S

2009-10-01

Bone mineral density (BMD) is unknown in children with Prader-Willi syndrome (PWS), but is decreased in adults with PWS. In patients with GH deficiency, BMD increases during GH treatment. The aim of the study was to evaluate BMD in children with PWS and to study the effects of GH treatment. We conducted a randomized controlled GH trial. Forty-six prepubertal children were randomized into either a GH-treated group (1.0 mg/m(2) . d) or a control group for 2 yr. At start, 6, 12, and 24 months of study, total body and lumbar spine BMD were measured by dual-energy x-ray absorptiometry, and lumbar spine bone mineral apparent density (BMAD) was calculated. Baseline total body and lumbar spine BMD sd score (SDS) were normal [mean (sd), -0.2 SDS (1.1) and -0.4 SDS (1.2), respectively]. BMADSDS, which corrects for short stature, was also normal [mean (sd), 0.40 SDS (1.1)]. Total body BMDSDS decreased during the first 6 months of GH (P < 0.0001), but increased during the second year of treatment. After 24 months of study, total body and lumbar spine BMDSDS, and the BMADSDS did not significantly differ between GH-treated children and randomized controls (P = 0.30, P = 0.44, and P = 0.47, respectively). Results were similar when corrected for body mass index SDS. Repeated measurements analysis showed a significant positive association between IGF-I SDS and total body and lumbar spine BMDSDS, but not with BMADSDS. Our results show that prepubertal children with PWS have a normal BMD. GH treatment had no effect on BMD, except for a temporary decrease of total body BMDSDS in the first 6 months.

Incorporation of Scribes Into the Inflammatory Bowel Disease Clinic Improves Quality of Care and Physician Productivity.

PubMed

Ewelukwa, Ofor; Perez, Roque; Carter, Lee Ellen; Fernandez, Alyka; Glover, Sarah

2018-02-15

Electronic health records (EHRs), despite their positive attributes, increase physician workload and decrease efficiency. The aim of this study was to evaluate the impact of scribes in the Inflammatory Bowel Disease Clinic on improvement of the physician-patient relationship, physician productivity, clinical efficiency, and achievement of some Physician Quality Reporting System (PQRS) metrics. We analyzed of pre- and postscribe data between fiscal years 2015 (FY15) and 2016 (FY16) using data from patients at the Inflammatory Bowel Clinic at the University of Florida. The main outcomes were patient satisfaction scores (PSS), qualitative physician interview, clinic appointment lengths, work relative value units (wRVUs), level of coding, revenue, and PQRS data on bone density screening and vaccination. PSS increased from 6.8/10 to 9.2/10 (P < 0.01), clinic appointment length decreased by 13.5 minutes (P < 0.05), and documentation stress decreased. Clinic visits increased by 76, leading to an increase in work RVUs by 332.55, total charges billed by $71,439, and total charges collected by $27,387 between the first quarters of FY15 and FY16. The extra revenue for the first quarter was 536% higher than the salary of the scribe for the same period ($4302.84). There was a 1.8-fold increase in referrals for bone density scans and 2.9-fold and 4.8-fold increases in vaccination rates for influenza and pneumonia, respectively. The use of scribes improved the physician-patient relationship, clinical efficiency, physician productivity, bone density screening, and vaccinations for flu and pneumonia. If adopted by health systems, it may lead to significant cost savings and improved clinical outcomes.

Hypergravity suppresses bone resorption in ovariectomized rats

NASA Astrophysics Data System (ADS)

Ikawa, Tesshu; Kawaguchi, Amu; Okabe, Takahiro; Ninomiya, Tadashi; Nakamichi, Yuko; Nakamura, Midori; Uehara, Shunsuke; Nakamura, Hiroaki; Udagawa, Nobuyuki; Takahashi, Naoyuki; Nakamura, Hiroaki; Wakitani, Shigeyuki

2011-04-01

The effects of gravity on bone metabolism are unclear, and little has been reported about the effects of hypergravity on the mature skeleton. Since low gravity has been shown to decrease bone volume, we hypothesized that hypergravity increases bone volume. To clarify this hypothesis, adult female rats were ovariectomized and exposed to hypergravity (2.9G) using a centrifugation system. The rats were killed 28 days after the start of loading, and the distal femoral metaphysis of the rats was studied. Bone architecture was assessed by micro-computed tomography (micro-CT) and bone mineral density was measured using peripheral quantitative CT (pQCT). Hypergravity increased the trabecular bone volume of ovariectomized rats. Histomorphometric analyses revealed that hypergravity suppressed both bone formation and resorption and increased bone volume in ovariectomized rats. Further, the cell morphology, activity, proliferation, and differentiation of osteoclasts and osteoblasts exposed to hypergravity were evaluated in vitro. Hypergravity inhibited actin ring formation in mature osteoclasts, which suggested that the osteoclast activity was suppressed. However, hypergravity had no effect on osteoblasts. These results suggest that hypergravity can stimulate an increase in bone volume by suppressing bone resorption in ovariectomized rats.

Is there a relation between local bone quality as assessed on panoramic radiographs and alveolar bone level?

PubMed

Nackaerts, Olivia; Gijbels, Frieda; Sanna, Anna-Maria; Jacobs, Reinhilde

2008-03-01

The aim was to explore the relation between radiographic bone quality on panoramic radiographs and relative alveolar bone level. Digital panoramic radiographs of 94 female patients were analysed (mean age, 44.5; range, 35-74). Radiographic density of the alveolar bone in the premolar region was determined using Agfa Musica software. Alveolar bone level and bone quality index (BQI) were also assessed. Relationships between bone density and BQI on one hand and the relative loss of alveolar bone level on the other were assessed. Mandibular bone density and loss of alveolar bone level were weakly but significantly negatively correlated for the lower premolar area (r = -.27). The BQI did not show a statistically significant relation to alveolar bone level. Radiographic mandibular bone density on panoramic radiographs shows a weak but significant relation to alveolar bone level, with more periodontal breakdown for less dense alveolar bone.

Increases in bone density during treatment of men with idiopathic hypogonadotropic hypogonadism

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

Finkelstein, J.S.; Klibanski, A.; Neer, R.M.

To assess the effects of gonadal steroid replacement on bone density in men with osteoporosis due to severe hypogonadism, we measured cortical bone density in the distal radius by 125I photon absorptiometry and trabecular bone density in the lumbar spine by quantitative computed tomography in 21 men with isolated GnRH deficiency while serum testosterone levels were maintained in the normal adult male range for 12-31 months (mean +/- SE, 23.7 +/- 1.1). In men who initially had fused epiphyses (n = 15), cortical bone density increased from 0.71 +/- 0.02 to 0.74 +/- 0.01 g/cm2 (P less than 0.01), whilemore » trabecular bone density did not change (116 +/- 9 compared with 119 +/- 7 mg/cm3). In men who initially had open epiphyses (n = 6), cortical bone density increased from 0.62 +/- 0.01 to 0.70 +/- 0.03 g/cm2 (P less than 0.01), while trabecular bone density increased from 96 +/- 13 to 109 +/- 12 mg/cm3 (P less than 0.01). Cortical bone density increased 0.03 +/- 0.01 g/cm2 in men with fused epiphyses and 0.08 +/- 0.02 g/cm2 in men with open epiphyses (P less than 0.05). Despite these increases, neither cortical nor trabecular bone density returned to normal levels. Histomorphometric analyses of iliac crest bone biopsies demonstrated that most of the men had low turnover osteoporosis, although some men had normal to high turnover osteoporosis. We conclude that bone density increases during gonadal steroid replacement of GnRH-deficient men, particularly in men who are skeletally immature.« less

Hypercortisolemia Is Associated with Severity of Bone Loss and Depression in Hypothalamic Amenorrhea and Anorexia Nervosa

PubMed Central

Lawson, Elizabeth A.; Donoho, Daniel; Miller, Karen K.; Misra, Madhusmita; Meenaghan, Erinne; Lydecker, Janet; Wexler, Tamara; Herzog, David B.; Klibanski, Anne

2009-01-01

Context: Anorexia nervosa (AN) and functional hypothalamic amenorrhea (HA) are associated with low bone density, anxiety, and depression. Women with AN and HA have elevated cortisol levels. Significant hypercortisolemia, as in Cushing’s disease, causes bone loss. It is unknown whether anxiety and depression and/or cortisol dysregulation contribute to low bone density in AN or HA. Objective: Our objective was to investigate whether hypercortisolemia is associated with bone loss and mood disturbance in women with HA and AN. Design and Setting: We conducted a cross-sectional study in a clinical research center. Participants: We studied 52 women [21 healthy controls (HC), 13 normal-weight women with functional HA, and 18 amenorrheic women with AN]. Outcome Measures: Serum samples were measured every 20 min for 12 h overnight and pooled for average cortisol levels. Bone mineral density (BMD) was assessed by dual-energy x-ray absorptiometry (DXA) at anteroposterior and lateral spine and hip. Hamilton Rating Scales for Anxiety (HAM-A) and Depression (HAM-D) were administered. Results: BMD was lower in AN and HA than HC at all sites and lower in AN than HA at the spine. On the HAM-D and HAM-A, AN scored higher than HA, and HA scored higher than HC. Cortisol levels were highest in AN, intermediate in HA, and lowest in HC. HAM-A and HAM-D scores were associated with decreased BMD. Cortisol levels were positively associated with HAM-A and HAM-D scores and negatively associated with BMD. Conclusions: Hypercortisolemia is a potential mediator of bone loss and mood disturbance in these disorders. PMID:19837921

Distal radius geometry and skeletal strength indices after peripubertal artistic gymnastics.

PubMed

Dowthwaite, J N; Scerpella, T A

2011-01-01

Development of optimal skeletal strength should decrease adult bone fragility. Nongymnasts (NON): were compared with girls exposed to gymnastics during growth (EX/GYM: ), using peripheral quantitative computed tomography (pQCT) to evaluate postmenarcheal bone geometry, density, and strength. Pre- and perimenarcheal gymnastic loading yields advantages in indices of postmenarcheal bone geometry and skeletal strength. Two prior studies using pQCT have reported bone density and size advantages in Tanner I/II gymnasts, but none describe gymnasts' bone properties later in adolescence. The current study used pQCT to evaluate whether girls exposed to gymnastics during late childhood growth and perimenarcheal growth exhibited greater indices of distal radius geometry, density, and skeletal strength. Postmenarcheal subjects underwent 4% and 33% distal radius pQCT scans, yielding: 1) vBMD and cross-sectional areas (CSA) (total bone, compartments); 2) polar strength-strain index; 3) index of structural strength in axial compression. Output was compared for EX/GYM: vs. NON: , adjusting for gynecological age and stature (maturity and body size), reporting means, standard errors, and significance. Sixteen postmenarcheal EX/GYM: (age 16.7 years; gynecological age 3.4 years) and 13 NON: (age 16.2 years; gynecological age 3.6 years) were evaluated. At both diaphysis and metaphysis, EX/GYM: exhibited greater CSA and bone strength indices than NON; EX/GYM: exhibited 79% larger intramedullary CSA than NON: (p < 0.05). EX/GYM: had significantly higher 4% trabecular vBMD; differences were not detected for 4% total vBMD and 33% cortical vBMD. Following pre-/perimenarcheal gymnastic exposure, relative to nongymnasts, postmenarcheal EX/GYM: demonstrated greater indices of distal radius geometry and skeletal strength (metaphysis and diaphysis) with greater metaphyseal trabecular vBMD; larger intramedullary cavity size was particularly striking.

Distal radius geometry and skeletal strength indices after peripubertal artistic gymnastics

PubMed Central

Scerpella, T. A.

2011-01-01

Summary Development of optimal skeletal strength should decrease adult bone fragility. Nongymnasts (NON) were compared with girls exposed to gymnastics during growth (EX/GYM), using peripheral quantitative computed tomography (pQCT) to evaluate postmenarcheal bone geometry, density, and strength. Pre- and perimenarcheal gymnastic loading yields advantages in indices of postmenarcheal bone geometry and skeletal strength. Introduction Two prior studies using pQCT have reported bone density and size advantages in Tanner I/II gymnasts, but none describe gymnasts’ bone properties later in adolescence. The current study used pQCT to evaluate whether girls exposed to gymnastics during late childhood growth and perimenarcheal growth exhibited greater indices of distal radius geometry, density, and skeletal strength. Methods Postmenarcheal subjects underwent 4% and 33% distal radius pQCT scans, yielding: 1) vBMD and cross-sectional areas (CSA) (total bone, compartments); 2) polar strength-strain index; 3) index of structural strength in axial compression. Output was compared for EX/GYM vs. NON, adjusting for gynecological age and stature (maturity and body size), reporting means, standard errors, and significance. Results Sixteen postmenarcheal EX/GYM (age 16.7 years; gynecological age 3.4 years) and 13 NON (age 16.2 years; gynecological age 3.6 years) were evaluated. At both diaphysis and metaphysis, EX/GYM exhibited greater CSA and bone strength indices than NON; EX/GYM exhibited 79% larger intramedullary CSA than NON (p<0.05). EX/GYM had significantly higher 4% trabecular vBMD; differences were not detected for 4% total vBMD and 33% cortical vBMD. Conclusions Following pre-/perimenarcheal gymnastic exposure, relative to nongymnasts, postmenarcheal EX/GYM demonstrated greater indices of distal radius geometry and skeletal strength (metaphysis and diaphysis) with greater metaphyseal trabecular vBMD; larger intramedullary cavity size was particularly striking. PMID:20419293

Estrogens and women's health: interrelation of coronary heart disease, breast cancer and osteoporosis.

PubMed

Kuller, L H; Matthews, K A; Meilahn, E N

2000-11-30

The determinants of blood levels of estrogen, estrogen metabolites, and relation to receptors and post-transitional effects are the likely primary cause of breast cancer. Very high risk women for breast cancer can now be identified by measuring bone mineral density and hormone levels. These high risk women have rates of breast cancer similar to risk of myocardial infarction. They are candidates for SERM therapies to reduce risk of breast cancer. The completion of the Women's Health Initiative and other such trials will likely provide a definite association of risk and benefit of both estrogen alone and estrogen-progesterone therapy, coronary heart disease, osteoporotic fracture, and breast cancer. The potential intervention of hormone replacement therapy, obesity, or weight gain and increased atherogenic lipoproteinemia may be of concern and confound the results of clinical trials. Estrogens, clearly, are important in the risk of bone loss and osteoporotic fracture. Obesity is the primary determinant of postmenopausal estrogen levels and reduced risk of fracture. Weight reduction may increase rates of bone loss and fracture. Clinical trials that evaluate weight loss should monitor effects on bone. The beneficial addition of increased physical activity, higher dose of calcium or vitamin D, or use of bone reabsorption drugs in coordination with weight loss should be evaluated. Any therapy that raises blood estrogen or metabolite activity and decreases bone loss may increase risk of breast cancer. Future clinical trials must evaluate multiple endpoints such as CHD, osteoporosis, and breast cancer within the study. The use of surrogate markers such as bone mineral density, coronary calcium, carotid intimal medial thickness and plaque, endothelial function, breast density, hormone levels and metabolites could enhance the evaluation of risk factors, genetic-environmental intervention, and new therapies.

Increased Leg Bone Mineral Density and Content During the Initial Years of College Sport.

PubMed

Scerpella, John J; Buehring, Bjoern; Hetzel, Scott J; Heiderscheit, Bryan C

2018-04-01

Scerpella, JJ, Buehring, B, Hetzel, SJ, and Heiderscheit, BC. Increased leg bone mineral density and content during the initial years of college sport. J Strength Cond Res 32(4): 1123-1130, 2018-Bone mineral density (BMD) and bone mineral content (BMC) data are useful parameters for evaluating how training practices promote bone health. We used dual-energy X-ray absorptiometry (DXA) to longitudinally assess sport-specific growth in leg and total body BMD/BMC over the initial 2 years of collegiate training. Eighty-five Division 1 collegiate basketball, hockey, and soccer athletes (50 males and 35 females; age 19.0 [0.8] years) underwent annual DXA scans. Leg and total body BMD/BMC were compared within and across two 1-year intervals (periods 1 and 2) using repeated-measures analysis of variance, adjusting for age, sex, race, and sport. Leg BMD, leg BMC, and total body BMC all increased over period 1 (0.05 g·cm [p = 0.001], 0.07 kg [p = 0.002], and 0.19 kg [p < 0.001] respectively). Changes in period 2 compared with period 1 were smaller for leg BMD (p = 0.001), leg BMC (p < 0.001), leg fat mass (p = 0.028), and total BMC (p = 0.005). Leg lean mass increased more during period 2 than period 1 (p = 0.018). Sports participation was the only significant predictor of change in leg BMD. Significant increases in both leg BMD and BMC were demonstrated over both 2-year periods, with greater gains during period 1. These gains highlight the importance of attentive training procedures, capitalizing on attendant physical benefits of increased BMD/BMC. Additional research in young adults, evaluating bone mass acquisition, will optimize performance and decrease risk of bone stress injury among collegiate athletes.

Attenuating trabecular morphology associated with low magnesium diet evaluated using micro computed tomography.

PubMed

Tu, Shu-Ju; Wang, Shun-Ping; Cheng, Fu-Chou; Weng, Chia-En; Huang, Wei-Tzu; Chang, Wei-Jeng; Chen, Ying-Ju

2017-01-01

The literature shows that bone mineral density (BMD) and the geometric architecture of trabecular bone in the femur may be affected by inadequate dietary intake of Mg. In this study, we used microcomputed tomography (micro-CT) to characterize and quantify the impact of a low-Mg diet on femoral trabecular bones in mice. Four-week-old C57BL/6J male mice were randomly assigned to 2 groups and supplied either a normal or low-Mg diet for 8weeks. Samples of plasma and urine were collected for biochemical analysis, and femur tissues were removed for micro-CT imaging. In addition to considering standard parameters, we regarded trabecular bone as a cylindrical rod and used computational algorithms for a technical assessment of the morphological characteristics of the bones. BMD (mg-HA/cm3) was obtained using a standard phantom. We observed a decline in the total tissue volume, bone volume, percent bone volume, fractal dimension, number of trabecular segments, number of connecting nodes, bone mineral content (mg-HA), and BMD, as well as an increase in the structural model index and surface-area-to-volume ratio in low-Mg mice. Subsequently, we examined the distributions of the trabecular segment length and radius, and a series of specific local maximums were identified. The biochemical analysis revealed a 43% (96%) decrease in Mg and a 40% (71%) decrease in Ca in plasma (urine excretion). This technical assessment performed using micro-CT revealed a lower population of femoral trabecular bones and a decrease in BMD at the distal metaphysis in the low-Mg mice. Examining the distributions of the length and radius of trabecular segments showed that the average length and radius of the trabecular segments in low-Mg mice are similar to those in normal mice.

Combined effects of soy isoflavone and fish oil on ovariectomy-induced bone loss in mice.

PubMed

Uchida, Raina; Chiba, Hiroshige; Ishimi, Yoshiko; Uehara, Mariko; Suzuki, Kazuharu; Kim, Hyounju; Matsumoto, Akiyo

2011-07-01

Both soy isoflavone and n-3 polyunsaturated fatty acids are known to reduce the levels of bone-resorbing cytokines; however, the synergistic effects of these food ingredients have not been examined yet. This study was performed to elucidate the effect of concomitant intake of soy isoflavone and fish oil on bone mass in ovariectomized mice. Eight-week-old ddY female mice were subjected to ovariectomy (OVX) or sham surgery, and then fed an AIN-93G with safflower oil (So) as a control lipid source, isoflavone-supplemented safflower oil (So + I), fish oil instead of safflower oil (Fo) or isoflavone-supplemented fish oil (Fo + I) for 4 weeks. Femoral bone mineral density was significantly decreased by OVX; however, this decrease was inhibited by the intake of isoflavone and/or fish oil. Histomorphometric analyses showed that bone volume and trabecular thickness in the distal femoral trabecular bone were significantly lower in the So group than in the sham group, but those were restored in the Fo + I groups. The number of osteoclasts was significantly decreased by isoflavone intake. The increased rate of bone resorption after OVX was inhibited by isoflavone and/or fish oil. The serum concentration of tumor necrosis factor alpha was increased after OVX, but was significantly lower with the combination of isoflavone with fish oil than isoflavone or fish oil alone. The results of this study indicated that the intakes of soy isoflavone and/or fish oil might have ameliorating effects on bone loss due to OVX. Further, the concomitant intake of soy isoflavone and fish oil at a low dose showed better effects on cytokines related with bone resorption.

A high-fat diet increases body weight and circulating estradiol concentrations but does not improve bone structural properties in ovariectomized mice.

PubMed

Cao, Jay J; Gregoire, Brian R

2016-04-01

Bone health is influenced by body mass and estrogen. The objective of the study was to determine whether high-fat diet-induced obesity affects bone structure and alters markers of bone turnover in ovariectomized (OVX) mice. We hypothesized that a high-fat diet would increase body weight gain and serum estradiol levels in OVX mice but would not improve bone structural parameter in OVX mice. Thirty-five C57BL/6 mice were either sham operated or OVX at the age of 4 months and then fed either a normal-fat diet (10% energy as fat) or a high-fat diet (45% energy as fat with extra fat from lard) ad libitum for 11 weeks. Ovariectomy increased body weight, serum tartrate-resistant acid phosphatase concentration, and expression of cathepsin K in bone; decreased serum estradiol concentration; and induced significant bone loss manifested by decreased bone volume/total volume (BV/TV), connectivity density (Conn.D), trabecular number, and trabecular thickness with increased trabecular separation and structural model index (P < .01). The high-fat diet increased body weight (P < .01) in OVX mice and nonsignificantly decreased BV/TV (P = .08) and Conn.D (P = .10). Despite having similar serum estradiol concentrations and higher body weight, OVX mice consuming the high-fat diet had lower BV/TV, Conn.D, trabecular number, trabecular thickness, and higher structural model index and trabecular separation than did sham mice fed the normal-fat diet. These findings indicate that increased body weight and elevated serum estradiol concentration induced by a high-fat diet do not mitigate ovariectomy-induced bone loss in mice. Published by Elsevier Inc.

Would Interstitial Fluid Flow be Responsible for Skeletal Maintenance in Tail-Suspended Rats?

NASA Astrophysics Data System (ADS)

Li, Wen-Ting; Huang, Yun-Fei; Sun, Lian-Wen; Luan, Hui-Qin; Zhu, Bao-Zhang; Fan, Yu-Bo

2017-02-01

Despite the fast development of manned space flight, the mechanism and countermeasures of weightlessness osteoporosis in astronauts are still within research. It is accepted that unloading has been considered as primary factor, but the precise mechanism is still unclear. Since bone's interstitial fluid flow (IFF) is believed to be significant to nutrient supply and waste metabolism of bone tissue, it may influence bone quality as well. We investigated IFF's variation in different parts of body (included parietal bone, ulna, lumbar, tibia and tailbone) of rats using a tail-suspended (TS) system. Ten female Sprague-Dawley (SD) rats were divided into two groups: control (CON) and tail-suspension (TS) group. And after 21 days' experiment, the rats were injected reactive red to observe lacuna's condition under a confocal laser scanning microscope. The variations of IFF were analyzed by the number and area of lacuna. Volumetric bone mineral density (vBMD) and microarchitecture of bones were evaluated by micro-CT. The correlation coefficients between lacuna's number/area and vBMD were also analyzed. According to our experimental results, a 21 days' tail-suspension could cause a decrease of IFF in lumbar, tibia and tailbone and an increase of IFF in ulna. But in parietal bone, it showed no significant change. The vBMD and microarchitecture parameters also decreased in lumbar and tibia and increased in ulna. But in parietal bone and tailbone, it showed no significant change. And correlation analysis showed significant correlation between vBMD and lacuna's number in lumbar, tibia and ulna. Therefore, IFF decrease may be partly contribute to bone loss in tail-suspended rats, and it should be further investigated.

Qualitative assessment of bone density at the distal articulating surface of the third metacarpal in Thoroughbred racehorses with and without condylar fracture.

PubMed

Loughridge, A B; Hess, A M; Parkin, T D; Kawcak, C E

2017-03-01

Changes in subchondral bone density, induced by the repetitive cyclical loading of exercise, may potentiate fatigue damage and the risk of fracture. To use computed tomography (CT) to characterise bone density patterns at the articular surface of the third metacarpal bone in racehorses with and without lateral condylar fractures. Case control METHODS: Computed tomographic images of the distal articulating surface of the third metacarpal bone were obtained from Thoroughbred racehorses subjected to euthanasia in the UK. Third metacarpal bones were divided into 3 groups based on lateral condyle status; fractured (FX, n = 42), nonfractured contralateral condyle (NFX, n = 42) and control condyles from horses subjected to euthanasia for reasons unrelated to the third metacarpal bone (control, n = 94). Colour CT images were generated whereby each colour represented a range of pixel values and thus a relative range of bone density. A density value was calculated qualitatively by estimating the percentage of each colour within a specific region. Subchondral bone density was assessed in 6 regions from dorsal to palmar and 1 mm medial and lateral to the centre of the lateral parasagittal groove in NFX and control condyles and 1 mm medial and lateral to the fracture in FX condyles. Bone density was significantly higher in the FX and NFX condyles compared with control condyles for all 6 regions. A significantly higher bone density was observed in FX condyles relative to NFX condyles in the lateral middle and lateral palmar regions. Fractured condyles had increased heterogeneity in density among the 6 regions of interest compared with control and NFX condyles. Adjacent to the fracture, a focal increase in bone density and increased heterogeneity of density were characteristic of limbs with lateral condylar fractures compared with control and NFX condyles. These differences may represent pathological changes in bone density that increase the risk for lateral condylar fractures in racehorses. © 2015 EVJ Ltd.

Altered ovarian function affects skeletal homeostasis independent of the action of follicle-stimulating hormone.

PubMed

Gao, Jianjun; Tiwari-Pandey, Rashmi; Samadfam, Rana; Yang, Yinzhi; Miao, Dengshun; Karaplis, Andrew C; Sairam, M Ram; Goltzman, David

2007-06-01

Osteoporosis is a leading public health problem. Although a major cause in women is thought to be a decline in estrogen, it has recently been proposed that FSH or follitropin is required for osteoporotic bone loss. We examined the FSH receptor null mouse (FORKO mouse) to determine whether altered ovarian function could induce bone loss independent of FSH action. By 3 months of age, FORKO mice developed age-dependent declines in bone mineral density and trabecular bone volume of the lumbar spine and femur, which could be partly reversed by ovarian transplantation. Bilateral ovariectomy reduced elevated circulating testosterone levels in FORKO mice and decreased bone mass to levels indistinguishable from those in ovariectomized wild-type controls. Androgen receptor blockade and especially aromatase inhibition each produced bone volume reductions in the FORKO mouse. The results indicate that ovarian secretory products, notably estrogen, and peripheral conversion of ovarian androgen to estrogen can alter bone homeostasis independent of any bone resorptive action of FSH.

Bone metabolism in oxalosis: a single-center study using new imaging techniques and biomarkers.

PubMed

Bacchetta, Justine; Fargue, Sonia; Boutroy, Stéphanie; Basmaison, Odile; Vilayphiou, Nicolas; Plotton, Ingrid; Guebre-Egziabher, Fitsum; Dohin, Bruno; Kohler, Rémi; Cochat, Pierre

2010-06-01

The deposition of calcium oxalate crystals in the kidney and bone is a hallmark of primary hyperoxaluria type 1 (PH1). We report here an evaluation of the bone status of 12 PH1 children based on bone biomarkers [parathyroid hormone, vitamin D, fibroblast growth factor 23 (FGF23)] and radiological assessments (skeletal age, three-dimensional high-resolution peripheral quantitative computed tomography, HR-pQCT) carried out within the framework of a cross-sectional single-center study. The controls consisted of healthy and children with chronic kidney disease already enrolled in local bone and mineral metabolism studies. The mean age (+ or - standard deviation) age of the patients was 99 (+ or - 63) months. Six children suffered from fracture. Bone maturation was accelerated in five patients, four of whom were <5 years. The combination of new imaging techniques and biomarkers highlighted new and unexplained features of PH1: advanced skeletal age in young PH1 patients, increased FGF23 levels and decreased total volumetric bone mineral density with bone microarchitecture alteration.

Evidence for the adverse effect of starvation on bone quality: a review of the literature.

PubMed

Kueper, Janina; Beyth, Shaul; Liebergall, Meir; Kaplan, Leon; Schroeder, Josh E

2015-01-01

Malnutrition and starvation's possible adverse impacts on bone health and bone quality first came into the spotlight after the horrors of the Holocaust and the ghettos of World War II. Famine and food restrictions led to a mean caloric intake of 200-800 calories a day in the ghettos and concentration camps, resulting in catabolysis and starvation of the inhabitants and prisoners. Severely increased risks of fracture, poor bone mineral density, and decreased cortical strength were noted in several case series and descriptive reports addressing the medical issues of these individuals. A severe effect of severely diminished food intake and frequently concomitant calcium- and Vitamin D deficiencies was subsequently proven in both animal models and the most common cause of starvation in developed countries is anorexia nervosa. This review attempts to summarize the literature available on the impact of the metabolic response to Starvation on overall bone health and bone quality.

Musculoskeletal Complications and Bone Metastases in Breast Cancer Patients Undergoing Estrogen Deprivation Therapy

DTIC Science & Technology

2015-10-01

resulting from estrogen (E2) deprivation therapy. [20% complete] Percent Fat 0 2 4 6 8 -20 0 20 40 Weeks post-surgery OVX SHAM **p = 0.0050 by 2-way...increased body fat percentage as assessed by DXA, B. decreased bone mineral density (BMD) as assessed by DXA, and C. reduced forelimb grip strength in...e.g., glucocorticoids, GnRH inhibitors, radiation, fracture , osteoporosis, etc.) could increase the homing of dormant disseminated cancer cells to

A New Therapeutic Paradigm for Breast Cancer Exploiting Low Dose Estrogen-Induced Apoptosis

DTIC Science & Technology

2013-06-01

pulmonary embolism , colorectal cancer, hip fractures , and death from other causes. After a mean follow-up of 6.8 years, no signifi- cant effect of ET...20 The benefits of HT include a signifi- cantly decreased incidence of bone fractures .21 Seven hundred thirty-three women (8.6%) in the estrogen-plus...progestin group and 896 women (11.1%) in the placebo group developed a fracture (HR, 0.76; 95% CI, 0.69-0.83). Total hip bone mineral density increased

A numerical simulation of the effect of using porous superelastic Nitinol and stiff Titanium fixation hardware on the bone remodeling

NASA Astrophysics Data System (ADS)

Raad, Bahram; Shayesteh Moghaddam, Narges; Elahinia, Mohammad

2016-04-01

The aim of this article is to investigate the effect of two different fixation hardware materials on bone remodeling after a mandibular reconstruction surgery and to restore the mandible's function, healthy appearance, mastication, swallowing, breathing, and speech. The hypothesis is that using fixation hardware with stiffness close to that of the surrounding bone will result in a more successful healing process in the mandible bone. The finite element model includes the material properties and forces of the cancellous bone, cortical bone, ligaments, muscles, and teeth. The reconstruction surgery is modeled by including the fixation hardware and the grafted bone. In the sectioned mandible, to best mimic the geometry of the mandible, two single barrel grafts are placed at the top of each other to form a double barrel graft set. Two different materials were used as the mandibular fixation parts, stiff Ti-6Al-4V, and porous superelastic Nickel-Titanium (NiTi) alloys. A comparison of these two alloys demonstrates that using porous NiTi alloy as the fixation part results in a faster healing pace. Furthermore, the density distribution in the mandibular bone after the healing process is more similar to the normal mandible density distribution. The simulations results indicate that the porous superelastic NiTi fixation hardware transfers and distributes the existing forces on the mandible bone more favorably. The probability of stress shielding and/or stress concentration decrease. This type of fixation hardware, therefore, is more appropriate for mandible bone reconstruction surgery. These predictions are in agreement with the clinical observations.

Cancer treatment-induced bone loss in premenopausal women: a need for therapeutic intervention?

PubMed

Hadji, P; Gnant, M; Body, J J; Bundred, N J; Brufsky, A; Coleman, R E; Guise, T A; Lipton, A; Aapro, M S

2012-10-01

Current clinical treatment guidelines recommend cytotoxic chemotherapy, endocrine therapy, or both (with targeted therapy if indicated) for premenopausal women with early-stage breast cancer, depending on the biologic characteristics of the primary tumor. Some of these therapies can induce premature menopause or are specifically designed to suppress ovarian function and reduce circulating estrogen levels. In addition to bone loss associated with low estrogen levels, cytotoxic chemotherapy may have a direct negative effect on bone metabolism. As a result, cancer treatment-induced bone loss poses a significant threat to bone health in premenopausal women with breast cancer. Clinical trials of antiresorptive therapies, such as bisphosphonates, have demonstrated the ability to slow or prevent bone loss in this setting. Current fracture risk assessment tools are based on data from healthy postmenopausal women and do not adequately address the risks associated with breast cancer therapy, especially in younger premenopausal women. We therefore recommend that all premenopausal women with breast cancer be informed about the potential risk of bone loss prior to beginning anticancer therapy. Women who experience amenorrhea should have bone mineral density assessed by dual-energy X-ray absorptiometry and receive regular follow-up to monitor bone health. Regular exercise and daily calcium and vitamin D supplementation are recommended. Women with a Z-score <-2.0 or Z-score ≤-1.0 and/or a 5-10% annual decrease in bone mineral density should be considered for bisphosphonate therapy in addition to calcium and vitamin D supplements. Copyright © 2012 Elsevier Ltd. All rights reserved.

Safflower bud inhibits RANKL-induced osteoclast differentiation and prevents bone loss in ovariectomized mice.

PubMed

Choi, Joo-Hee; Lim, Seul-Ki; Kim, Dong-Il; Park, Min-Jung; Kim, Young-Kuk; Lee, An-Chul; Kim, Young-Min; Yang, Soo-Jin; Park, Jong-Hwan

2017-10-15

The powder and extract of safflower seeds are known to be effective in the prevention of bone loss in ovariectomized animals. However, the inhibitory effect and molecular mechanisms of safflower bud (SB), the germinated safflower, on bone destruction is unclear. The present study was designed to investigate the inhibitory effect and molecular mechanism of SB on osteoclastic differentiation and on bone loss in ovarietomized (OVX) mice. Osteoclastogenesis was determined by TRAP staining, F-actin ring formation, and bone resorption assay. NF-κB and MAPKs activation was analyzed by transfection assay and Western blot, respectively. Real-time PCR was performed to examine the expression of osteoclastogenesis-related genes. Histological changes, increases in TRAP-positive cells, and cathepsin K expression were examined in the metaphysis of OVX mice. Density of bone marrow was evaluated by µCT. SB inhibited the RANKL-induced differentiation of BMDMs into osteoclasts in a dose-dependent manner. F-actin ring formation and bone resorption were also reduced by SB in RANKL-treated BMDMs. In addition, SB decreased the activation of NF-κB and MAPKs and the expression of osteoclastogenesis-related genes in BMDMs treated with RANKL. Feeding of SB-included diet prevented bone loss in OVX mice. The number of TRAP-positive cells and level of protein expression of cathepsin K was reduced and bone mineral density was increased in the metaphysis of mice fed SB compared with OVX mice. These findings suggest that SB can be a preventive and therapeutic candidate for destructive bone diseases. Copyright © 2017. Published by Elsevier GmbH.

Influence of bone density on the cement fixation of femoral hip resurfacing components.

PubMed

Bitsch, Rudi G; Jäger, Sebastian; Lürssen, Marcus; Loidolt, Travis; Schmalzried, Thomas P; Clarius, Michael

2010-08-01

In clinical outcome studies, small component sizes, female gender, femoral shape, focal bone defects, bad bone quality, and biomechanics have been associated with failures of resurfacing arthroplasties. We used a well-established experimental setup and human bone specimens to analyze the effects of bone density on cement fixation of femoral hip resurfacing components. Thirty-one fresh frozen femora were prepared for resurfacing using the original instruments. ASR resurfacing prostheses were implanted after dual-energy X-ray densitometer scans. Real-time measurements of pressure and temperature during implantation, analyses of cement penetration, and measurements of micro motions under torque application were performed. The associations of bone density and measurement data were examined calculating regression lines and multiple correlation coefficients; acceptability was tested with ANOVA. We found significant relations between bone density and micro motion, cement penetration, cement mantle thickness, cement pressure, and interface temperature. Mean bone density of the femora was 0.82 +/- 0.13 g/cm(2), t-score was -0.7 +/- 1.0, and mean micro motion between bone and femoral resurfacing component was 17.5 +/- 9.1 microm/Nm. The regression line between bone density and micro motion was equal to -56.7 x bone density + 63.8, R = 0.815 (p < 0.001). Bone density scans are most helpful for patient selection in hip resurfacing, and a better bone quality leads to higher initial component stability. A sophisticated cementing technique is recommended to avoid vigorous impaction and incomplete seating, since increasing bone density also results in higher cement pressures, lower cement penetration, lower interface temperatures, and thicker cement mantles. Copyright 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Micro-computed tomography assessment of human alveolar bone: bone density and three-dimensional micro-architecture.

PubMed

Kim, Yoon Jeong; Henkin, Jeffrey

2015-04-01

Micro-computed tomography (micro-CT) is a valuable means to evaluate and secure information related to bone density and quality in human necropsy samples and small live animals. The aim of this study was to assess the bone density of the alveolar jaw bones in human cadaver, using micro-CT. The correlation between bone density and three-dimensional micro architecture of trabecular bone was evaluated. Thirty-four human cadaver jaw bone specimens were harvested. Each specimen was scanned with micro-CT at resolution of 10.5 μm. The bone volume fraction (BV/TV) and the bone mineral density (BMD) value within a volume of interest were measured. The three-dimensional micro architecture of trabecular bone was assessed. All the parameters in the maxilla and the mandible were subject to comparison. The variables for the bone density and the three-dimensional micro architecture were analyzed for nonparametric correlation using Spearman's rho at the significance level of p < .05. A wide range of bone density was observed. There was a significant difference between the maxilla and mandible. All micro architecture parameters were consistently higher in the mandible, up to 3.3 times greater than those in the maxilla. The most linear correlation was observed between BV/TV and BMD, with Spearman's rho = 0.99 (p = .01). Both BV/TV and BMD were highly correlated with all micro architecture parameters with Spearman's rho above 0.74 (p = .01). Two aspects of bone density using micro-CT, the BV/TV and BMD, are highly correlated with three-dimensional micro architecture parameters, which represent the quality of trabecular bone. This noninvasive method may adequately enhance evaluation of the alveolar bone. © 2013 Wiley Periodicals, Inc.

Proper Calcium Use: Vitamin K2 as a Promoter of Bone and Cardiovascular Health.

PubMed

Maresz, Katarzyna

2015-02-01

Inadequate calcium intake can lead to decreased bone mineral density, which can increase the risk of bone fractures. Supplemental calcium promotes bone mineral density and strength and can prevent osteoporosis. Recent scientific evidence, however, suggests that elevated consumption of calcium supplements may raise the risk for heart disease and can be connected with accelerated deposit of calcium in blood-vessel walls and soft tissues. In contrast, vitamin K2 is associated with the inhibition of arterial calcification and arterial stiffening. An adequate intake of vitamin K2 has been shown to lower the risk of vascular damage because it activates matrix GLA protein (MGP), which inhibits the deposits of calcium on the walls. Vitamin K, particularly as vitamin K2, is nearly nonexistent in junk food, with little being consumed even in a healthy Western diet. Vitamin K deficiency results in inadequate activation of MGP, which greatly impairs the process of calcium removal and increases the risk of calcification of the blood vessels. An increased intake of vitamin K2 could be a means of lowering calcium-associated health risks.

Mechanisms Inducing Low Bone Density in Duchenne Muscular Dystrophy in Mice and Humans

PubMed Central

Rufo, Anna; Del Fattore, Andrea; Capulli, Mattia; Carvello, Francesco; De Pasquale, Loredana; Ferrari, Serge; Pierroz, Dominique; Morandi, Lucia; De Simone, Michele; Rucci, Nadia; Bertini, Enrico; Bianchi, Maria Luisa; De Benedetti, Fabrizio; Teti, Anna

2011-01-01

Patients affected by Duchenne muscular dystrophy (DMD) and dystrophic MDX mice were investigated in this study for their bone phenotype and systemic regulators of bone turnover. Micro–computed tomographic (µCT) and histomorphometric analyses showed reduced bone mass and higher osteoclast and bone resorption parameters in MDX mice compared with wild-type mice, whereas osteoblast parameters and mineral apposition rate were lower. In a panel of circulating pro-osteoclastogenic cytokines evaluated in the MDX sera, interleukin 6 (IL-6) was increased compared with wild-type mice. Likewise, DMD patients showed low bone mineral density (BMD) Z-scores and high bone-resorption marker and serum IL-6. Human primary osteoblasts from healthy donors incubated with 10% sera from DMD patients showed decreased nodule mineralization. Many osteogenic genes were downregulated in these cultures, including osterix and osteocalcin, by a mechanism blunted by an IL-6-neutralizing antibody. In contrast, the mRNAs of osteoclastogenic cytokines IL6, IL11, inhibin-βA, and TGFβ2 were increased, although only IL-6 was found to be high in the circulation. Consistently, enhancement of osteoclastogenesis was noted in cultures of circulating mononuclear precursors from DMD patients or from healthy donors cultured in the presence of DMD sera or IL-6. Circulating IL-6 also played a dominant role in osteoclast formation because ex vivo wild-type calvarial bones cultured with 10% sera of MDX mice showed increase osteoclast and bone-resorption parameters that were dampen by treatment with an IL-6 antibody. These results point to IL-6 as an important mediator of bone loss in DMD and suggest that targeted anti-IL-6 therapy may have a positive impact on the bone phenotype in these patients. © 2011 American Society for Bone and Mineral Research PMID:21509823

Extracellular post-translational modifications of collagen are major determinants of biomechanical properties of fetal bovine cortical bone.

PubMed

Garnero, Patrick; Borel, Olivier; Gineyts, Evelyne; Duboeuf, Francois; Solberg, Helene; Bouxsein, Mary L; Christiansen, Claus; Delmas, Pierre D

2006-03-01

Mechanical behavior of bone depends on its mass and architecture, and on the material properties of the matrix, which is composed of a mineral phase and an organic component mainly constituted of type I collagen. Mineral accounts largely for the stiffness of bone, whereas type I collagen provides bone its ductility and toughness, i.e., its ability to undergo deformation and absorb energy after it begins to yield. The molecular mechanisms underlying the effect of alterations in type I collagen on bone mechanical properties are unclear. We used an in vitro model of fetal bovine cortical bone specimens (n = 44), where the extent of type I collagen cross-linking was modified by incubation at 37 degrees C for 0, 60, 90 and 120 days, keeping constant the architecture and the mineral content. At each incubation time, the following parameters were determined: (1) the bone concentration of enzymatic (pyridinoline; PYD and deoxypyridinoline, DPD) and non-enzymatic (pentosidine) crosslinks by HPLC, (2) the extent of aspartic acid isomerization of the type I collagen C-telopeptide (CTX) by ELISA of native (alpha CTX) and isomerized (beta CTX) forms, (3) the mineral density by DXA, (4) the porosity by micro-computed tomography and (5) the bending and compressive mechanical properties. Incubation of bone specimens at 37 degrees C for 60 days increased the level (per molecule of collagen) of PYD (+98%, P = 0.005), DPD (+42%, P = 0.013), pentosidine (+55-fold, P = 0.005), and the degree of type I collagen C-telopeptide isomerization (+4.9-fold, P = 0.005). These biochemical changes of collagen were associated with a 30% decrease in bending and compressive yield stress and a 2.5-fold increase in compressive post-yield energy absorption (P < 0.02 for all), with no significant change of bone stiffness. In multivariate analyses, the level of collagen cross-linking was associated with yield stress and post-yield energy absorption independently of bone mineral density, explaining up to 25% of their variance. We conclude that the extent and nature of collagen cross-linking contribute to the mechanical properties of fetal bovine cortical bone independently of bone mineral density.

Microgravity promotes osteoclast activity in medaka fish reared at the international space station.

PubMed

Chatani, Masahiro; Mantoku, Akiko; Takeyama, Kazuhiro; Abduweli, Dawud; Sugamori, Yasutaka; Aoki, Kazuhiro; Ohya, Keiichi; Suzuki, Hiromi; Uchida, Satoko; Sakimura, Toru; Kono, Yasushi; Tanigaki, Fumiaki; Shirakawa, Masaki; Takano, Yoshiro; Kudo, Akira

2015-09-21

The bone mineral density (BMD) of astronauts decreases specifically in the weight-bearing sites during spaceflight. It seems that osteoclasts would be affected by a change in gravity; however, the molecular mechanism involved remains unclear. Here, we show that the mineral density of the pharyngeal bone and teeth region of TRAP-GFP/Osterix-DsRed double transgenic medaka fish was decreased and that osteoclasts were activated when the fish were reared for 56 days at the international space station. In addition, electron microscopy observation revealed a low degree of roundness of mitochondria in osteoclasts. In the whole transcriptome analysis, fkbp5 and ddit4 genes were strongly up-regulated in the flight group. The fish were filmed for abnormal behavior; and, interestingly, the medaka tended to become motionless in the late stage of exposure. These results reveal impaired physiological function with a change in mechanical force under microgravity, which impairment was accompanied by osteoclast activation.

Microgravity promotes osteoclast activity in medaka fish reared at the international space station

PubMed Central

Chatani, Masahiro; Mantoku, Akiko; Takeyama, Kazuhiro; Abduweli, Dawud; Sugamori, Yasutaka; Aoki, Kazuhiro; Ohya, Keiichi; Suzuki, Hiromi; Uchida, Satoko; Sakimura, Toru; Kono, Yasushi; Tanigaki, Fumiaki; Shirakawa, Masaki; Takano, Yoshiro; Kudo, Akira

2015-01-01

The bone mineral density (BMD) of astronauts decreases specifically in the weight-bearing sites during spaceflight. It seems that osteoclasts would be affected by a change in gravity; however, the molecular mechanism involved remains unclear. Here, we show that the mineral density of the pharyngeal bone and teeth region of TRAP-GFP/Osterix-DsRed double transgenic medaka fish was decreased and that osteoclasts were activated when the fish were reared for 56 days at the international space station. In addition, electron microscopy observation revealed a low degree of roundness of mitochondria in osteoclasts. In the whole transcriptome analysis, fkbp5 and ddit4 genes were strongly up-regulated in the flight group. The fish were filmed for abnormal behavior; and, interestingly, the medaka tended to become motionless in the late stage of exposure. These results reveal impaired physiological function with a change in mechanical force under microgravity, which impairment was accompanied by osteoclast activation. PMID:26387549

Bone Density and Cortical Structure after Pediatric Renal Transplantation

PubMed Central

Terpstra, Anniek M.; Kalkwarf, Heidi J.; Shults, Justine; Zemel, Babette S.; Wetzsteon, Rachel J.; Foster, Bethany J.; Strife, C. Frederic; Foerster, Debbie L.

2012-01-01

The impact of renal transplantation on trabecular and cortical bone mineral density (BMD) and cortical structure is unknown. We obtained quantitative computed tomography scans of the tibia in pediatric renal transplant recipients at transplantation and 3, 6, and 12 months; 58 recipients completed at least two visits. We used more than 700 reference participants to generate Z-scores for trabecular BMD, cortical BMD, section modulus (a summary measure of cortical dimensions and strength), and muscle and fat area. At baseline, compared with reference participants, renal transplant recipients had significantly lower mean section modulus and muscle area; trabecular BMD was significantly greater than reference participants only in transplant recipients younger than 13 years. After transplantation, trabecular BMD decreased significantly in association with greater glucocorticoid exposure. Cortical BMD increased significantly in association with greater glucocorticoid exposure and greater decreases in parathyroid hormone levels. Muscle and fat area both increased significantly, but section modulus did not improve. At 12 months, transplantation associated with significantly lower section modulus and greater fat area compared with reference participants. Muscle area and cortical BMD did not differ significantly between transplant recipients and reference participants. Trabecular BMD was no longer significantly elevated in younger recipients and was low in older recipients. Pediatric renal transplant associated with persistent deficits in section modulus, despite recovery of muscle, and low trabecular BMD in older recipients. Future studies should determine the implications of these data on fracture risk and identify strategies to improve bone density and structure. PMID:22282589

Successful operative rib fixation of traumatic flail chest in a patient with osteogenesis imperfecta.

PubMed

Kulaylat, Afif N; Chesnut, Charles H; Santos, Ariel P; Armen, Scott B

2014-09-01

Increasing attention has been directed towards operative rib fixation of traumatic flail chest; reported benefits include more rapid weaning from the ventilator, decreased intensive care unit stays, decreased complications and improved functional results. The outcomes of this surgical intervention in patients with osteogenesis imperfecta, a rare condition characterized by low bone density and bone fragility, are unknown. This case demonstrates that, in the management of traumatic flail chest in a patient with osteogenesis imperfecta, surgical fixation can be successful and should be considered early. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Repeated administration of mazindol reduces spontaneous pain-related behaviors without modifying bone density and microarchitecture in a mouse model of complete Freund’s adjuvant-induced knee arthritis

PubMed Central

Robledo-González, LE; Martínez-Martínez, A; Vargas-Muñoz, VM; Acosta-González, RI; Plancarte-Sánchez, R; Anaya-Reyes, M; Fernández del Valle-Laisequilla, C; Reyes-García, JG; Jiménez-Andrade, JM

2017-01-01

Background The role of dopaminergic system in the development of rheumatoid arthritis-related pain, a major symptom in this disease, has not been explored. Therefore, the anti-nociceptive effect of mazindol, a dopamine uptake inhibitor, was evaluated in a model of complete Freund’s adjuvant (CFA)-induced arthritis. Furthermore, as studies have shown that the dopaminergic system regulates bone metabolism, the effect of mazindol on bone mass and microarchitecture was determined. Methods Adult ICR male mice received intra-articular injections of either CFA or saline into the right knee joint every week. Spontaneous pain-like behaviors (flinching and guarding) and locomotor activity were assessed at day 26 post-first CFA, following which, a single intraperitoneally (i.p.) administered dose of mazindol was given (1, 3 and 10 mg/kg). Then, the antinociceptive effect of a repeated administration of 3 mg/kg mazindol (daily, i.p.; day 15–day 26) was evaluated. Additionally, at day 26, the participation of D1-like, D2-like or opioid receptors in the antinociceptive effect of mazindol was evaluated. The effect of mazindol on bone density and microarchitecture was evaluated by micro-computed tomography. Results Acute administration of mazindol decreased the spontaneous pain-like behaviors in a dose-dependent manner without reducing the knee edema. However, mazindol at 10 mg/kg significantly increased the locomotor activity; therefore, 3 mg/kg mazindol was used for further studies. Repeated administration of 3 mg/kg mazindol significantly decreased the pain-like behaviors without modifying locomotor activity. The antinociceptive effect of mazindol was blocked by administration of a D2-like receptor antagonist (haloperidol), but not by administration of D1-like receptor antagonist (SCH 23390) or an opioid receptor antagonist (naloxone). Repeated administration of mazindol did not significantly modify the density and microarchitecture of periarticular bone of the arthritic and nonarthritic knee joints. Conclusion Results suggest that mazindol via D2-like receptors has an antinociceptive role in mice with CFA-induced knee arthritis without modifying the bone health negatively. PMID:28794657

Repeated administration of mazindol reduces spontaneous pain-related behaviors without modifying bone density and microarchitecture in a mouse model of complete Freund's adjuvant-induced knee arthritis.

PubMed

Robledo-González, L E; Martínez-Martínez, A; Vargas-Muñoz, V M; Acosta-González, R I; Plancarte-Sánchez, R; Anaya-Reyes, M; Fernández Del Valle-Laisequilla, C; Reyes-García, J G; Jiménez-Andrade, J M

2017-01-01

The role of dopaminergic system in the development of rheumatoid arthritis-related pain, a major symptom in this disease, has not been explored. Therefore, the anti-nociceptive effect of mazindol, a dopamine uptake inhibitor, was evaluated in a model of complete Freund's adjuvant (CFA)-induced arthritis. Furthermore, as studies have shown that the dopaminergic system regulates bone metabolism, the effect of mazindol on bone mass and microarchitecture was determined. Adult ICR male mice received intra-articular injections of either CFA or saline into the right knee joint every week. Spontaneous pain-like behaviors (flinching and guarding) and locomotor activity were assessed at day 26 post-first CFA, following which, a single intraperitoneally (i.p.) administered dose of mazindol was given (1, 3 and 10 mg/kg). Then, the antinociceptive effect of a repeated administration of 3 mg/kg mazindol (daily, i.p.; day 15-day 26) was evaluated. Additionally, at day 26, the participation of D1-like, D2-like or opioid receptors in the antinociceptive effect of mazindol was evaluated. The effect of mazindol on bone density and microarchitecture was evaluated by micro-computed tomography. Acute administration of mazindol decreased the spontaneous pain-like behaviors in a dose-dependent manner without reducing the knee edema. However, mazindol at 10 mg/kg significantly increased the locomotor activity; therefore, 3 mg/kg mazindol was used for further studies. Repeated administration of 3 mg/kg mazindol significantly decreased the pain-like behaviors without modifying locomotor activity. The antinociceptive effect of mazindol was blocked by administration of a D2-like receptor antagonist (haloperidol), but not by administration of D1-like receptor antagonist (SCH 23390) or an opioid receptor antagonist (naloxone). Repeated administration of mazindol did not significantly modify the density and microarchitecture of periarticular bone of the arthritic and nonarthritic knee joints. Results suggest that mazindol via D2-like receptors has an antinociceptive role in mice with CFA-induced knee arthritis without modifying the bone health negatively.

Intake of Novel Red Clover Supplementation for 12 Weeks Improves Bone Status in Healthy Menopausal Women

PubMed Central

Thorup, Anne Cathrine; Lambert, Max Norman; Kahr, Henriette Strøm; Bjerre, Mette; Jeppesen, Per Bendix

2015-01-01

Objective. To investigate the effect by which daily consumption of a novel red clover (RC) extract influences bone health, inflammatory status, and cardiovascular health in healthy menopausal women. Design. A 12-week randomized, double-blinded, placebo-controlled trial involving 60 menopausal women receiving a daily dose of 150 mL RC extract containing 37.1 mg isoflavones (33.8 mg as aglycones) or placebo. Methods. Bone parameters were changes in bone mineral density (BMD), bone mineral content (BMC), and T-score at the lumbar spine and femoral neck. Bone turnover (CTx) and inflammatory markers were measured in plasma and finally blood pressure (BP) was evaluated. Results. RC extract had positive effect on bone health, and only the women receiving the placebo experienced a decline in BMD (p < 0.01) at the lumbar spine. T-score at the lumbar spine only decreased in the placebo group (p < 0.01). CTx decreased in the RC group with −9.94 (±4.93)%, although not significant. Conclusion. Daily consumption of RC extract over a 12-week period was found to have a beneficial effect on bone health in menopausal women based on BMD and T-score at the lumbar spine and plasma CTx levels. No changes in BP or inflammation markers were found and no side effects were observed. PMID:26265926

Effect of HIP/Ribosomal Protein L29 Deficiency on Mineral Properties of Murine Bones and Teeth

PubMed Central

Sloofman, Laura G.; Verdelis, Kostas; Spevak, Lyudmila; Zayzafoon, Majd; Yamauchi, Mistuo; Opdenaker, Lynn M.; Farach-Carson, Mary C.; Boskey, Adele L.; Kirn-Safran, Catherine B.

2010-01-01

Mice lacking HIP/RPL29, a component of the ribosomal machinery, display increased bone fragility. To understand the effect of sub-efficient protein synthetic rates on mineralized tissue quality, we performed dynamic and static histomorphometry and examined the mineral properties of both bones and teeth in HIP/RPL29 knock-out mice using Fourier transform infrared imaging (FTIRI). While loss of HIP/RPL29 consistently reduced total bone size, decreased mineral apposition rates were not significant, indicating that short stature is not primarily due to impaired osteoblast function. Interestingly, our microspectroscopic studies showed that a significant decrease in collagen crosslinking during maturation of HIP/RPL29-null bone precedes an overall enhancement in the relative extent of mineralization of both trabecular and cortical adult bones. This report provides strong genetic evidence that ribosomal insufficiency induces subtle organic matrix deficiencies which elevates calcification. Consistent with the HIP/RPL29-null bone phenotype, HIP/RPL29-deficient teeth also showed reduced geometric properties accompanied with relative increased mineral densities of both dentin and enamel. Increased mineralization associated with enhanced tissue fragility related to imperfection in organic phase microstructure evokes defects seen in matrix protein-related bone and tooth diseases. Thus, HIP/RPL29 mice constitute a new genetic model for studying the contribution of global protein synthesis in the establishment of organic and inorganic phases in mineral tissues. PMID:20362701

Determinants of bone density among athletes engaged in weight-bearing and non-weight-bearing activity

NASA Technical Reports Server (NTRS)

Block, Jon E.; Friedlander, Anne L.; Brooks, George A.; Steiger, Peter; Stubbs, Harrison A.

1989-01-01

The effect of weight bearing activity on the bone density was investigated in athletes by comparing the measures of bone density of athletes engaged in weight-training programs with those of polo players and nonexercising subjects. All subjects had measurements of spinal trabecular and integral bone density by quantitative tomography, as well as determinations of hip bone density by dual photon absorptiometry. Results confirmed previous findings by Block et al. (1987) of significantly greater bone density among highly trained athletes compared with nonexercising subjects of similar age. Results also indicated that athletes engaged in non-weight-bearing forms of rigorous exercise had greater levels of bone density. However, as the participants in this study were exceptional athletes, engaged in a strenuous sport with both aerobic and heavy resistance components, a confirmation of these data is needed, using larger samples of individuals.

Outcomes of bone density measurements in coeliac disease.

PubMed

Bolland, Mark J; Grey, Andrew; Rowbotham, David S

2016-01-29

Some guidelines recommend that patients with newly diagnosed coeliac disease undergo bone density scanning. We assessed the bone density results in a cohort of patients with coeliac disease. We searched bone density reports over two 5-year periods in all patients from Auckland District Health Board (2008-12) and in patients under 65 years from Counties Manukau District Health Board (2009-13) for the term 'coeliac.' Reports for 137 adults listed coeliac disease as an indication for bone densitometry. The average age was 47 years, body mass index (BMI) 25 kg/m(2), and 77% were female. The median time between coeliac disease diagnosis and bone densitometry was 261 days. The average bone density Z-score was slightly lower than expected (Z-score -0.3 to 0.4) at the lumbar spine, total hip and femoral neck, but 88-93% of Z-scores at each site lay within the normal range. Low bone density was strongly related to BMI: the proportions with Z-score <-2 for BMI <20, 20-25, 25-30, and >30 kg/m(2) were 28%, 15%, 6% and 0% respectively. Average bone density was normal, suggesting that bone density measurement is not indicated routinely in coeliac disease, but could be considered on a case-by-case basis for individuals with strong risk factors for fracture.

Whole Body Vibration Reduces Inflammatory Bone Loss in a Lipopolysaccharide Murine Model.

PubMed

Kim, I S; Lee, B; Yoo, S J; Hwang, S J

2014-07-01

Whole body vibration (WBV) stimulation has a beneficial effect on the recovery of osteoporotic bone. We aimed to investigate the immediate effect of WBV on lipopolysaccharide (LPS)-mediated inflammatory bone loss by varying the exposure timing. Balb/C mice were divided into the following groups: control, LPS (L), and LPS with vibration (LV). The L and LV groups received LPS (5 mg/kg) by 2 intraperitoneal injections on days 0 and 4. The LV group was exposed to WBV (0.4 g, 45 Hz) either during LPS treatment (LV1) or after cessation of LPS injection (LV2) and then continued WBV treatment for 10 min/d for 3 d. Evaluation based on micro-computed tomography was performed 7 d after the first injection, when the L group showed a significant decrease in bone volume (-25.8%) and bone mineral density (-33.5%) compared with the control group. The LV2 group recovered bone volume (35%) and bone mineral density (19.9%) compared with the L group, whereas the LV1 group showed no improvement. This vibratory signal showed a suppressive effect on the LPS-mediated induction of inflammatory cytokines such as IL-1β or TNF-α in human mesenchymal stem cells in vitro. These findings suggest that immediate exposure to WBV after the conclusion of LPS treatment efficiently reduces trabecular bone loss, but WBV might be less effective during the course of treatment with inflammatory factor. © International & American Associations for Dental Research.

Whole Body Vibration Reduces Inflammatory Bone Loss in a Lipopolysaccharide Murine Model

PubMed Central

Kim, I.S.; Lee, B.; Yoo, S.J.; Hwang, S.J.

2014-01-01

Whole body vibration (WBV) stimulation has a beneficial effect on the recovery of osteoporotic bone. We aimed to investigate the immediate effect of WBV on lipopolysaccharide (LPS)–mediated inflammatory bone loss by varying the exposure timing. Balb/C mice were divided into the following groups: control, LPS (L), and LPS with vibration (LV). The L and LV groups received LPS (5 mg/kg) by 2 intraperitoneal injections on days 0 and 4. The LV group was exposed to WBV (0.4 g, 45 Hz) either during LPS treatment (LV1) or after cessation of LPS injection (LV2) and then continued WBV treatment for 10 min/d for 3 d. Evaluation based on micro–computed tomography was performed 7 d after the first injection, when the L group showed a significant decrease in bone volume (−25.8%) and bone mineral density (−33.5%) compared with the control group. The LV2 group recovered bone volume (35%) and bone mineral density (19.9%) compared with the L group, whereas the LV1 group showed no improvement. This vibratory signal showed a suppressive effect on the LPS-mediated induction of inflammatory cytokines such as IL-1β or TNF-α in human mesenchymal stem cells in vitro. These findings suggest that immediate exposure to WBV after the conclusion of LPS treatment efficiently reduces trabecular bone loss, but WBV might be less effective during the course of treatment with inflammatory factor. PMID:24810275

Trapezium Bone Density-A Comparison of Measurements by DXA and CT.

PubMed

Breddam Mosegaard, Sebastian; Breddam Mosegaard, Kamille; Bouteldja, Nadia; Bæk Hansen, Torben; Stilling, Maiken

2018-01-18

Bone density may influence the primary fixation of cementless implants, and poor bone density may increase the risk of implant failure. Before deciding on using total joint replacement as treatment in osteoarthritis of the trapeziometacarpal joint, it is valuable to determine the trapezium bone density. The aim of this study was to: (1) determine the correlation between measurements of bone mineral density of the trapezium obtained by dual-energy X-ray absorptiometry (DXA) scans by a circumference method and a new inner-ellipse method; and (2) to compare those to measurements of bone density obtained by computerized tomography (CT)-scans in Hounsfield units (HU). We included 71 hands from 59 patients with a mean age of 59 years (43-77). All patients had Eaton-Glickel stage II-IV trapeziometacarpal (TM) joint osteoarthritis, were under evaluation for trapeziometacarpal total joint replacement, and underwent DXA and CT wrist scans. There was an excellent correlation (r = 0.94) between DXA bone mineral density measures using the circumference and the inner-ellipse method. There was a moderate correlation between bone density measures obtained by DXA- and CT-scans with (r = 0.49) for the circumference method, and (r = 0.55) for the inner-ellipse method. DXA may be used in pre-operative evaluation of the trapezium bone quality, and the simpler DXA inner-ellipse measurement method can replace the DXA circumference method in estimation of bone density of the trapezium.

The skeletal consequences of thyrotoxicosis.

PubMed

Nicholls, Jonathan J; Brassill, Mary Jane; Williams, Graham R; Bassett, J H Duncan

2012-06-01

Euthyroid status is essential for normal skeletal development and the maintenance of adult bone structure and strength. Established thyrotoxicosis has long been recognised as a cause of high bone turnover osteoporosis and fracture but more recent studies have suggested that subclinical hyperthyroidism and long-term suppressive doses of thyroxine (T4) may also result in decreased bone mineral density (BMD) and an increased risk of fragility fracture, particularly in postmenopausal women. Furthermore, large population studies of euthyroid individuals have demonstrated that a hypothalamic-pituitary-thyroid axis set point at the upper end of the normal reference range is associated with reduced BMD and increased fracture susceptibility. Despite these findings, the cellular and molecular mechanisms of thyroid hormone action in bone remain controversial and incompletely understood. In this review, we discuss the role of thyroid hormones in bone and the skeletal consequences of hyperthyroidism.

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

Increased serum cartilage oligomeric matrix protein levels and decreased patellar bone mineral density in patients with chondromalacia patellae

PubMed Central

Murphy, E; FitzGerald, O; Saxne, T; Bresnihan, B

2002-01-01

Background: Chondromalacia patellae is a potentially disabling disorder characterised by features of patellar cartilage degradation. Objective: To evaluate markers of cartilage and bone turnover in patients with chondromalacia patellae. Methods: 18 patients with chondromalacia patellae were studied. Serum cartilage oligomeric matrix protein (s-COMP) and bone sialoprotein (s-BSP) levels were measured by enzyme linked immunosorbent assay (ELISA) and compared with those of age and sex matched healthy control subjects. Periarticular bone mineral density (BMD) of both knee joints was assessed by dual energy x ray absorptiometry (DXA). Results: s-COMP levels were significantly raised in all patients with chondromalacia patellae compared with healthy control subjects (p=0.0001). s-BSP levels did not differ significantly between the groups (p=0.41). BMD of the patella was significantly reduced in patients with chondromalacia patellae compared with the control subjects (p=0.016). In patients with bilateral chondromalacia patellae, BMD of the patella was lower in the more symptomatic knee joint (p=0.005). Changes in periarticular BMD were localised to the patella and were not present in femoral regions. Neither s-COMP (p=0.18) nor s-BSP (p=0.40) levels correlated with patellar BMD. Conclusions: Increased s-COMP levels, reflecting cartilage degradation, and reduced BMD localised to the patella may represent clinically useful markers in the diagnosis and monitoring of patients with chondromalacia patellae. Measures of cartilage degradation did not correlate with loss of patellar bone density, suggesting dissociated pathophysiological mechanisms. PMID:12379520

Increased serum cartilage oligomeric matrix protein levels and decreased patellar bone mineral density in patients with chondromalacia patellae.

PubMed

Murphy, E; FitzGerald, O; Saxne, T; Bresnihan, B

2002-11-01

Chondromalacia patellae is a potentially disabling disorder characterised by features of patellar cartilage degradation. To evaluate markers of cartilage and bone turnover in patients with chondromalacia patellae. 18 patients with chondromalacia patellae were studied. Serum cartilage oligomeric matrix protein (s-COMP) and bone sialoprotein (s-BSP) levels were measured by enzyme linked immunosorbent assay (ELISA) and compared with those of age and sex matched healthy control subjects. Periarticular bone mineral density (BMD) of both knee joints was assessed by dual energy x ray absorptiometry (DXA). s-COMP levels were significantly raised in all patients with chondromalacia patellae compared with healthy control subjects (p=0.0001). s-BSP levels did not differ significantly between the groups (p=0.41). BMD of the patella was significantly reduced in patients with chondromalacia patellae compared with the control subjects (p=0.016). In patients with bilateral chondromalacia patellae, BMD of the patella was lower in the more symptomatic knee joint (p=0.005). Changes in periarticular BMD were localised to the patella and were not present in femoral regions. Neither s-COMP (p=0.18) nor s-BSP (p=0.40) levels correlated with patellar BMD. Increased s-COMP levels, reflecting cartilage degradation, and reduced BMD localised to the patella may represent clinically useful markers in the diagnosis and monitoring of patients with chondromalacia patellae. Measures of cartilage degradation did not correlate with loss of patellar bone density, suggesting dissociated pathophysiological mechanisms.

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

Bolus administration of steroid therapy is more favorable than the conventional use in preventing decrease of bone density and the increase of body fat percentage in patients with inflammatory bowel disease.

PubMed

Farkas, Klaudia; Bálint, Anita; Valkusz, Zsuzsanna; Szepes, Zoltán; Nagy, Ferenc; Szűcs, Mónika; Bor, Renáta; Wittmann, Tibor; Molnár, Tamás

2014-09-01

The effects of short course of corticosteroids on the metabolic processes and bone formation has not been well studied. Our aim was to compare the efficacy, the side effects and the bone and lipid metabolisms in IBD patients using bolus or conventional tapering of methylprednisolone for 12 weeks. Nineteen IBD patients received intravenous methylprednisolone of 1mg/kg for 5 days tapered by 4 mg per week. Patients were prospectively randomized in two groups. In "conventional" group (I) steroids were given daily. In "pulse" group (II) weekly doses of steroids were given on special days of the week. The body mass index (BMI) was measured before and after the corticosteroid therapy. Blood samples were collected to assess glucose level, electrolytes, cholesterol and triglyceride levels, inflammatory parameters, cortisol, osteocalcin and crosslaps values. Total body composition analysis was performed at the beginning and at the end of the steroid therapy. In Group I, BMI increased, total body bone density decreased significantly at the end of the steroid therapy. Body fat percent showed a tendency to be higher at the end of steroid therapy in Group I. Cholesterol level increased significantly in Group I patients. The decrease in serum cortisol level was more remarkable in Group I vs. Group II after steroid therapy. Less side-effect occurred in Group II vs. Group I. Our results suggest that bolus tapering of corticosteroids may have more favorable short term outcome than conventional tapering that may revolutionize steroid therapy in IBD. Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

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.

Correlation of Bone Mineral Density on Quality of Life in Patients with Osteogenesis Imperfecta during Treatment with Denosumab.

PubMed

Hoyer-Kuhn, Heike; Stark, Christina; Franklin, Jeremy; Schoenau, Eckhard; Semler, Oliver

2017-11-01

Osteogenesis imperfecta (OI) is a rare hereditary skeletal disease leading to recurrent fractures, short stature and impaired mobility. The phenotype varies from mildly affected patients to perinatal lethal forms. In most cases an impaired collagen production due to mutations in COL1A1 or COL1A2 cause this hereditary bone fragility syndrome with an autosomal dominant inheritance. Currently an interdisciplinary therapeutic approach with antiresorptive drugs, physiotherapy and surgical procedures is the state of the art therapy. The effect of such a therapy is evaluated by measuring different surrogate parameters like areal bone mineral density or by using different mobility tests or questionnaires. Up till now the impact of these parameters on quality of life of the patients is not evaluated. Currently pharmacological strategies are based on antiresorptive treatment with bisphosphonates. In this trial we investigated the effect of an antiresorptive therapy with the monoclonal antibody denosumab decreasing the activity of osteoclasts. Denosumab was administered subcutaneously in a dose of 1mg/kg body weight in 10 children with OI (5-10 years of age) every 12 weeks for 48 weeks. Areal bone mineral density, mobility, pain scores and quality of life were measured. The results showed a good effect of the treatment on bone mineral density but this improvement showed no correlation to pain and quality of life. In conclusion further trials have to define parameters to assess interventions which influence activities of daily life of the patients. An interdisciplinary approach including physicians, basic researchers and patient organisation is needed to focus research on topics improving quality of life of patients with severe skeletal diseases. Copyright© of YS Medical Media ltd.

Calcium, vitamin D, and your bones

MedlinePlus

Osteoporosis - calcium; Osteoporosis - low bone density ... Your body needs calcium to keep your bones dense and strong. Low bone density can cause your bones to become brittle and fragile. These weak bones can break easily, even without ...

Integrating micro CT indices, CT imaging and computational modelling to assess the mechanical performance of fluoride treated bone.

PubMed

Sreenivasan, D; Watson, M; Callon, K; Dray, M; Das, R; Grey, A; Cornish, J; Fernandez, J

2013-12-01

In this study we evaluate the influence of low-dose fluoride treatment on 23 patient biopsies. Computational finite element (FE) models of each biopsy were subjected to a range of loads including compression, shear and torsion. The modelling framework was validated against three 3D printed models with known material properties subjected to compression till failure using an Instron machine. The primary outcomes from this study were that mechanical strength was not significantly correlated to low-dose (<10 mg/day) of fluoride levels (one-way ANOVA, P-values of 0.78, 0.69 and 0.62 for compression, shear and torsion, respectively). However, when bulk bone material properties were derived from DXA bone mineral density (BMD) from each patient's proximal femur a non-significant linear decline in mechanical strength with increase in fluoride was predicted. When the same material property was used for all bones (to evaluate bone architecture influence) then mechanical strength showed a characteristic concave upwards trend, consistent with the variation of micro CT derived percentage bone volume (BV/TV). The secondary outcomes from this study were that in compression, BV/TV was observed to be a strong surrogate measure for mechanical strength (R(2) = 0.83), while bone surface density (R(2)=0.6), trabecular thickness (R(2) = 0.5) and intersection surface (R(2) = 0.6) also explained the variation of mechanical strength well. However, trabecular separation and trabecular number were mildly correlated with mechanical strength (R(2) of 0.31 and 0.35, respectively). Compression was the loading mode most strongly correlated to micro CT indices. Material properties adapted from the proximal femur reduced the CT index correlations by up to 58% indicating that bulk density from a near proximity is a poor representation of specific localised density. Substituting the 3D micro CT indices with 2D histomorphometric data decreased correlations by at least 33% indicating that structural identification on a plane is not representative of the full 3D architecture necessary for a complete bone strength analysis. The presented computational framework may be used to assess the roles that bone architecture and loading modes play in bone quality, and which micro CT indices are good surrogate measures for mechanical strength. Copyright © 2013 IPEM. Published by Elsevier Ltd. All rights reserved.

Obstacles in the optimization of bone health outcomes in the female athlete triad.

PubMed

Ducher, Gaele; Turner, Anne I; Kukuljan, Sonja; Pantano, Kathleen J; Carlson, Jennifer L; Williams, Nancy I; De Souza, Mary Jane

2011-07-01

Maintaining low body weight for the sake of performance and aesthetic purposes is a common feature among young girls and women who exercise on a regular basis, including elite, college and high-school athletes, members of fitness centres, and recreational exercisers. High energy expenditure without adequate compensation in energy intake leads to an energy deficiency, which may ultimately affect reproductive function and bone health. The combination of low energy availability, menstrual disturbances and low bone mineral density is referred to as the 'female athlete triad'. Not all athletes seek medical assistance in response to the absence of menstruation for 3 or more months as some believe that long-term amenorrhoea is not harmful. Indeed, many women may not seek medical attention until they sustain a stress fracture. This review investigates current issues, controversies and strategies in the clinical management of bone health concerns related to the female athlete triad. Current recommendations focus on either increasing energy intake or decreasing energy expenditure, as this approach remains the most efficient strategy to prevent further bone health complications. However, convincing the athlete to increase energy availability can be extremely challenging. Oral contraceptive therapy seems to be a common strategy chosen by many physicians to address bone health issues in young women with amenorrhoea, although there is little evidence that this strategy improves bone mineral density in this population. Assessment of bone health itself is difficult due to the limitations of dual-energy X-ray absorptiometry (DXA) to estimate bone strength. Understanding how bone strength is affected by low energy availability, weight gain and resumption of menses requires further investigations using 3-dimensional bone imaging techniques in order to improve the clinical management of the female athlete triad.

One year soy protein supplementation has positive effects on bone formation markers but not bone density in postmenopausal women.

PubMed

Arjmandi, Bahram H; Lucas, Edralin A; Khalil, Dania A; Devareddy, Latha; Smith, Brenda J; McDonald, Jennifer; Arquitt, Andrea B; Payton, Mark E; Mason, Claudia

2005-02-23

Although soy protein and its isoflavones have been reported to reduce the risk of osteoporosis in peri- and post-menopausal women, most of these studies are of short duration (i.e. six months). The objective of this study was to examine if one year consumption of soy-containing foods (providing 25 g protein and 60 mg isoflavones) exerts beneficial effects on bone in postmenopausal women. Eighty-seven eligible postmenopausal women were randomly assigned to consume soy or control foods daily for one year. Bone mineral density (BMD) and bone mineral content (BMC) of the whole body, lumbar (L1-L4), and total hip were measured using dual energy x-ray absorptiometry at baseline and after one year. Blood and urine markers of bone metabolism were also assessed. Sixty-two subjects completed the one-year long study. Whole body and lumbar BMD and BMC were significantly decreased in both the soy and control groups. However, there were no significant changes in total hip BMD and BMC irrespective of treatment. Both treatments positively affected markers of bone formation as indicated by increased serum bone-specific alkaline phosphatase (BSAP) activity, insulin-like growth factor-I (IGF-I), and osteocalcin (BSAP: 27.8 and 25.8%, IGF-I: 12.8 and 26.3%, osteocalcin: 95.2 and 103.4% for control and soy groups, respectively). Neither of the protein supplements had any effect on urinary deoxypyridinoline excretion, a marker of bone resorption. Our findings suggest that although one year supplementation of 25 g protein per se positively modulated markers of bone formation, this amount of protein was unable to prevent lumbar and whole body bone loss in postmenopausal women.

ATOMIC ENERGY COMMISSION PROGRESS REPORT ON BONE RESEARCH , 1960-1961

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

None

1962-10-31

A review of osteoporosis concepts is presented. Activities in an experimental program to study osteoporosis by examining mineral metabolism in bone and by examining bone composition and density are reported. Sr/sup 85/ was administered to seven osteoporotic patients as a tracer for skeletal mineral metabolism. The activity levels in the blood and the excretion rate were measured. From these data the accretion rate and the diffusible component volume were calculated. It was found that the accretion rate was not increased in any case. The size of the diffusible component was normal in six patients and reduced in one. Concurrent experimentsmore » with estrogen administration were conducted. Over-all results indicate that in osteoporosis, the rate of bone accretion is never elevated and an effect of estrogen administration was the decrease of bone resorption rather than stimulation of bone formation. In studies of skeletal metabolism, the kinetics of Sr/sup 85/ metabolism was compared in normal subjects and patients with skeletal disorders. Various aspects of the results are analyzed and it is concluded that values obtained by kinetic studies appear to be quantitative, reproducible, and to correlate with presently established information on alterations of bone metabolism in systemic deseases. In studies of peripheral circulation and bone growth, I/sup 131tagged human serum albumin was injected in animals. The investigation was conducted to determine blood volumne turnover rate in extremities, to correlate changes in this rate with fractures and bone disorders, and to examine the method for use in evaluation of circulation under certain pathological conditions. Data and findings are included. Data are also included on in vitro mobilization of Sr/ sup 85/ during bone formation and bone density studies. (J.R.D.)« less

Nano-structural, compositional and micro-architectural signs of cortical bone fragility at the superolateral femoral neck in elderly hip fracture patients vs. healthy aged controls.

PubMed

Milovanovic, Petar; Rakocevic, Zlatko; Djonic, Danijela; Zivkovic, Vladimir; Hahn, Michael; Nikolic, Slobodan; Amling, Michael; Busse, Bjoern; Djuric, Marija

2014-07-01

To unravel the origins of decreased bone strength in the superolateral femoral neck, we assessed bone structural features across multiple length scales at this cortical fracture initiating region in postmenopausal women with hip fracture and in aged-matched controls. Our combined methodological approach encompassed atomic force microscopy (AFM) characterization of cortical bone nano-structure, assessment of mineral content/distribution via quantitative backscattered electron imaging (qBEI), measurement of bone material properties by reference point indentation, as well as evaluation of cortical micro-architecture and osteocyte lacunar density. Our findings revealed a wide range of differences between the fracture group and the controls, suggesting a number of detrimental changes at various levels of cortical bone hierarchical organization that may render bone fragile. Namely, mineral crystals at external cortical bone surfaces of the fracture group were larger (65.22nm±41.21nm vs. 36.75nm±18.49nm, p<0.001), and a shift to a higher mineral content and more homogenous mineralization profile as revealed via qBEI were found in the bone matrix of the fracture group. Fracture cases showed nearly 35% higher cortical porosity and showed significantly reduced osteocyte lacunar density compared to controls (226±27 vs. 247±32#/mm(2), p=0.05). Along with increased crystal size, a shift towards higher mineralization and a tendency to increased cortical porosity and reduced osteocyte lacunar number delineate that cortical bone of the superolateral femoral neck bears distinct signs of fragility at various levels of its structural organization. These results contribute to the understanding of hierarchical bone structure changes in age-related fragility. Copyright © 2014 Elsevier Inc. All rights reserved.

Influence of External Beam Radiotherapy on the Properties of Polymethyl Methacrylate-Versus Silicone-Induced Membranes in a Bilateral Segmental Bone Defect in Rats.

PubMed

Sagardoy, Thomas; Ehret, Camille; Bareille, Reine; Benoit, Jérôme; Amedee, Joëlle; De Mones, Erwan

2018-05-01

Standard care for malignant tumors arising next to a bone structure is surgical removal with safety margins, followed by external beam radiotherapy (EBRT). Complete tumor removal can result in large bone defects. A two-step bone reconstruction technique using the induced membrane (IM) technique has proven its efficacy to bridge gap nonunion. During the first step, a spacer is placed in the bone gap. The spacer then is removed and the IM around it is filled with autologous cancellous bone graft. However, the feasibility of this technique with the addition of adjuvant EBRT between the two reconstruction steps has not yet been studied. Polymethyl methacrylate (PMMA) used to be the standard spacer material for the first step. Silicone spacers could replace them owing to their good behavior when submitted to EBRT and their easier removal from the surgical site during the second step. The aim of this study was to evaluate the influence of EBRT on the histological and biochemical properties of IM induced using PMMA or silicone as spacer. The analyses were performed on PMMA- or silicone-IM with and without EBRT in a 6-mm bilateral femoral defect in 32 rats. Thickness and vessel content were measured in both groups. Bone morphogenetic protein 2 (BMP2) and vascular endothelial growth factor (VEGF) content in lysates of the crushed membranes were measured by enzyme immunoassay. Finally, alkaline phosphatase activity was analyzed in human bone marrow stromal cell cultures in contact with the same lysates. EBRT did not change the histological structure of the cellular internal layer or the fibrous outer layer. The nature of the spacer only influenced IM thickness, PMMA-IM with external radiotherapy being significantly thicker. EBRT decreased the vascular density of IM but was less effective on VEGF/BMP2 production. In vitro, IM could have an osteoinductive potential on human bone marrow stem cells. EBRT did not modify the histological properties of IMs but decreased their vascular density. VEGF and BMP2 production within IMs was not affected by EBRT. Silicone spacers are able to induce membranes with similar histological characteristics to PMMA-IM.

Measurement of hard tissue density based on image density of intraoral radiograph

NASA Astrophysics Data System (ADS)

Katsumata, Akitoshi; Fukui, Tatsumasa; Shimoda, Shinji; Kobayashi, Kaoru; Hayashi, Tatsuro

2018-02-01

We developed a DentalSCOPE computer program to measure the bone mineral density (BMD) of the alveolar bone. Mineral density measurement of alveolar bone may be useful to predict possible patients who will occur medication-related osteonecrosis of the jaw (MRONJ). Because these osteoporosis medicines affect the mineral density of alveolar bone significantly. The BMD of alveolar bone was compared between dual-energy X-ray absorptiometry (DEXA) and the DentalSCOPE program. A high correlation coefficient was revealed between the DentalSCOPE measurement and the DEXA measurement.

Differential Adaptations of the Musculoskeletal System after Spinal Cord Contusion and Transection in Rats.

PubMed

Lin, Ching-Yi; Androjna, Charlie; Rozic, Richard; Nguyen, Bichtram; Parsons, Brett; Midura, Ronald J; Lee, Yu-Shang

2018-04-05

Spinal cord injury (SCI) causes impaired neuronal function with associated deficits in the musculoskeletal system, which can lead to permanent disability. Here, the impact of SCI on in vivo musculoskeletal adaptation was determined by studying deficits in locomotor function and analyzing changes that occur in the muscle and bone compartments within the rat hindlimb after contusion or transection SCI. Analyses of locomotor patterns, as assessed via the Basso, Beattie, and Bresnahan (BBB) rating scale, revealed that transection animals showed significant deficits, while the contusion group had moderate deficits, compared with naïve groups. Muscle myofiber cross-sectional areas (CSA) of both the soleus and tibialis anterior muscles were significantly decreased three months after contusion SCI. Such decreases in CSA were even more dramatic in the transection SCI group, suggesting a dependence on muscle activity, which is further validated by the correlation analyses between BBB score and myofiber CSA. Bone compartment analyses, however, revealed that transection animals showed the most significant deficits, while contusion animals showed no significant differences in the trabecular bone content within the proximal tibia compartment. In general, values of bone volume per total bone volume (BV/TV) were similar across the SCI groups. Significant decreases were observed, however, in the transection animals for bone mineral content, bone mineral density, and three-dimensional trabecular structure parameters (trabecular number, thickness, and spacing) compared with the naïve and contusion groups. Together, these findings suggest an altered musculoskeletal system can be correlated directly to motor dysfunctions seen after SCI.

Effects of vitamin K2 (menatetrenone) and alendronate on bone mineral density and bone strength in rats fed a low-magnesium diet.

PubMed

Kobayashi, M; Hara, K; Akiyama, Y

2004-11-01

In this study, we examined changes in bone parameters and bone strength in rats fed low-Mg diets (experiment 1) and the effects of vitamin K2 (MK-4, experiment 3) and alendronate (ALN, experiment 2) in this model. In experiment 1, 5-week-old male Wistar rats were fed three low-Mg diets (Mg 9, 6, 3 mg/100 g diet) for 4 weeks. Although the cortical bone mineral content (CtBMC) and cortical thickness (CtTh) of the femoral diaphysis in all low-Mg-diet groups were the same as or greater than those in the intact group (Mg: 90 mg/100 g diet), the maximum load and elastic modulus were significantly reduced in the 3-mg-Mg group. In experiment 2, 4-week-old Wistar rats were fed a 6-mg-Mg diet for 8 weeks, and the effect of ALN (2, 20, and 200 microg/kg twice a week) was evaluated. The administration of ALN at 200 microg/kg increased the cortical bone mineral content (CtBMC), CtTh, and maximum load, but had no effect on the elastic modulus, as compared with the low-Mg-control group. In experiment 3, the effect of MK-4 was evaluated under the same conditions as in experiment 2. The administration of MK-4 had no effect on CtBMC, CtTh, or bone components of the femoral diaphysis. However, MK-4 inhibited the decreases in maximum load and elastic modulus due to the low-Mg diet. Since there is no other experimental model in which there is a decrease in bone mechanical properties without a decrease in bone mineral content, the low-Mg diet model is considered to be an excellent model for examining bone quality. Our results from this model suggest that MK-4 and ALN affect bone mechanical properties by different mechanisms.

Sex-related differences of bone properties of pelvic limb and bone metabolism indices in 14-month-old ostriches (Struthio camelus).

PubMed

Krupski, W; Tatara, M R; Charuta, A; Brodzki, A; Szpetnar, M; Jóźwik, A; Strzałkowska, N; Poławska, E; Łuszczewska-Sierakowska, I

2018-06-01

1. Sex-related differences of long pelvic limb bones and serum bone metabolism indices were evaluated in 14-month-old female (N = 7) and male (N = 7) ostriches of similar body weights. 2. Densitometric parameters of femur, tibia and tarsometatarsus were determined using quantitative computed tomography (volumetric bone mineral density, calcium hydroxyapatite density and mean volumetric bone mineral density) and dual energy X-ray absorptiometry (bone mineral density and bone mineral content) methods. Geometrical parameters such as cortical bone area, cross-sectional area, second moment of inertia, mean relative wall thickness and cortical index were determined in the midshaft of bones. Mechanical properties of bones (maximum elastic strength and ultimate strength) were evaluated using three-point bending test. Serum concentrations of free amino acids, osteocalcin, N-terminal propeptide of type I procollagen, C-terminal telopeptides of type II collagen and total antioxidative capacity were also determined. 3. Bone weight and relative bone weight of all bones were significantly higher in males than in females. Significantly lower values of trabecular bone mineral density and calcium hydroxyapatite density were found in the trabecular bone of tibia in males. The highest number of the sex-related differences was observed in the tarsometatarsus where bone length, bone mineral content, cortical bone area, cross-sectional area and ultimate strength were higher in males. Serum concentrations of taurine, hydroxyproline, valine and isoleucine were significantly higher in males. 4. Higher loading of the tarsometatarsus in comparison to femur and tibia may be an important factor interacting with sex hormones in regulation of bone formation and mineralisation processes. Sex-related differences of bone properties were associated with increased serum concentration of selected amino acids in males.

Quantitative, Structural and Image-based Mechanical Analysis of Nonunion Fracture Repaired by Genetically Engineered Mesenchymal Stem Cells

PubMed Central

Kallai, Ilan; van Lenthe, G. Harry; Ruffoni, Davide; Zilberman, Yoram; Müller, Ralph; Pelled, Gadi; Gazit, Dan

2010-01-01

Stem cell-mediated gene therapy for fracture repair, utilizes genetically engineered mesenchymal stem cells (MSCs) for the induction of bone growth and is considered a promising approach in skeletal tissue regeneration. Previous studies have shown that murine nonunion fractures can be repaired by implanting MSCs over-expressing recombinant human bone morphogenetic protein-2 (rhBMP-2). Nanoindentation studies of bone tissue induced by MSCs in a radius fracture site indicated similar elastic modulus compared to intact murine bone, eight weeks post treatment. In the present study we sought to investigate temporal changes in microarchitecture and biomechanical properties of repaired murine radius bones, following the implantation of MSCs. High resolution micro computed tomography (Micro-CT) was performed 10 and 35 weeks post MSC implantation, followed by micro finite element (Micro-FE) analysis. The results have shown that the regenerated bone tissue remodels over time, as indicated by a significant decrease in bone volume, total volume and connectivity density combined with an increase in mineral density. In addition, the axial stiffness of limbs repaired with MSCs was 2 to 1.5 times higher compared to the contralateral intact limbs, at 10 and 35 weeks post treatment. These results could be attributed to the fusion that occurred between in the ulna and radius bones. In conclusion, although MSCs induce bone formation, which exceeds the fracture site, significant remodeling of the repair callus occurs over time. In addition, limbs treated with an MSC graft demonstrated superior biomechanical properties, which could indicate the clinical benefit of future MSC application in nonunion fracture repair. PMID:20471652

Second hand tobacco smoke adversely affects the bone of immature rats.

PubMed

Rosa, Rodrigo César; Pereira, Sângela Cunha; Cardoso, Fabrizio Antônio Gomide; Caetano, Abadio Gonçalves; Santiago, Hildemberg Agostinho Rocha de; Volpon, José Batista

2017-12-01

To evaluate the influence of secondhand cigarette smoke exposure on longitudinal growth of the tibia of growing rats and some parameters of bone quality. Forty female rats were randomly divided into four groups: control: rats were sham exposed; 30 days: rats were exposed to tobacco smoke for 30 days; 45 days: rats were exposed to tobacco smoke for 45 days; and 60 days: rats were exposed to tobacco smoke for 60 days. Blood samples were collected to evaluate the levels of cotinine and alkaline phosphatase. Both tibias were dissected and weighed; the lengths were measured, and the bones were then stored in a freezer for analysis of bone mineral content and mechanical resistance (maximal load and stiffness). Exposure of rats to tobacco smoke significantly compromised bone health, suggesting that the harmful effects may be time dependent. Harmful effects on bone growth were detected and were more pronounced at 60-day follow-ups with a 41.8% reduction in alkaline phosphatase levels (p<0.01) and a decrease of 11.25% in tibia length (p<0.001). Furthermore, a 41.5% decrease in bone mineral density was observed (p<0.001), leading to a 42.8% reduction in maximum strength (p<0.001) and a 56.7% reduction in stiffness (p<0.001). Second hand cigarette smoke exposure in rats affected bones that were weaker, deforming them and making them osteopenic. Additionally, the long bone was shorter, suggesting interference with growth. Such events seem to be related to time of exposure.

Alterations of collagen matrix in weight-bearing bones during skeletal unloading

NASA Technical Reports Server (NTRS)

Shiiba, M.; Arnaud, S. B.; Tanzawa, H.; Uzawa, K.; Yamauchi, M.

2001-01-01

Skeletal unloading induces loss of bone mineral density in weight-bearing bones. The objectives of this study were to characterize the post-translational modifications of collagen of weight-bearing bones subjected to hindlimb unloading for 8 weeks. In unloaded bones, tibiae and femurs, while the overall amino acid composition was essentially identical in the unloaded and control tibiae and femurs, the collagen cross-link profile showed significant differences. Two major reducible cross-links (analyzed as dihydroxylysinonorleucine and hydroxylysinonorleucine) were increased in the unloaded bones. In addition, the ratios of the former to the latter as well as pyridinoline to deoxypyridinoline were significantly decreased in the unloaded bones indicating a difference in the extent of lysine hydroxylation at the cross-linking sites between these two groups. These results indicate that upon skeletal unloading the relative pool of newly synthesized collagen is increased and it is post-translationally altered. The alteration could be associated with impaired osteoblastic differentiation induced by skeletal unloading that results in a mineralization defect.

Effects of habitual chitosan intake on bone mass, bone-related metabolic markers and duodenum CaBP D9K mRNA in ovariectomized SHRSP rats.

PubMed

Yang, Chu-Ya; Oh, Tae-Woong; Nakajima, Daito; Maeda, Atsuko; Naka, Tatsuki; Kim, Chang-Sun; Igawa, Shoji; Ohta, Fukio

2002-10-01

We have demonstrated that the habitual intake of chitosan can decrease bone mass in ovariectomized (OVX) SHRSP rats fed a low-Ca diet (0.1%). In the present study, we examined both the etiology of bone loss induced by dietary chitosan and the preventive effect of vitamin C supplementation. Rats were OVX and maintained on one of the following diets for 6 wk: 10% cellulose (CE). 10% chitosan (CH) or 10% chitosan with sodium ascorbate (CHVC). CH caused a significant reduction in bone mineral density (BMD) and stiffness in femurs and the fourth lumbar vertebrae (L4). There was no significant difference in intestinal Ca absorption between CH and CE, whereas CH intake significantly reduced intestinal P absorption. The bone loss in CH rats was accompanied with an increase in urinary Ca excretion and a decrease in serum Ca as well as a significant increment In serum PTH and 1,25(OH)2D3. The vitamin D receptor and calcium binding protein D9K mRNAs were also significantly increased in the duodenum of CH rats. Vitamin C supplementation to CH caused an increase in the Ca and P contents of femurs as well as BMD of the L4, with a decrease in urinary Ca excretion. These results indicate that dietary chitosan with low Ca intake possibly induces the loss of bone mass by enhancing urinary Ca excretion rather than by inhibiting Ca absorption, and that vitamin C supplementation could prevent bone loss caused by chitosan through the increment of retained Ca followed by suppression of urinary Ca excretion.

Effect of swimming exercise on three-dimensional trabecular bone microarchitecture in ovariectomized rats.

PubMed

Ju, Yong-In; Sone, Teruki; Ohnaru, Kazuhiro; Tanaka, Kensuke; Fukunaga, Masao

2015-11-01

Swimming is generally considered ineffective for increasing bone mass in humans, at least compared with weight-bearing sports. However, swimming exercise has sometimes been shown to have a strong positive effect on bone mass in small animals. This study investigated the effects of swimming on bone mass, strength, and microarchitecture in ovariectomized (OVX) rats. OVX or sham operations were performed on 18-wk-old female Fisher 344 rats. Rats were randomly divided into four groups: sham sedentary (Sham-CON), sham swimming exercised (Sham-SWI), OVX sedentary (OVX-CON), and OVX swimming exercised (OVX-SWI). Rats in exercise groups performed swimming in a water bath for 60 min/day, 5 days/wk, for 12 wk. Bone mineral density (BMD) in right femurs was analyzed using dual-energy X-ray absorptiometry. Three-dimensional trabecular architecture at the distal femoral metaphysis was analyzed using microcomputed tomography (μCT). Geometrical properties of diaphyseal cortical bone were evaluated in the midfemoral region using μCT. The biomechanical properties of femurs were analyzed using three-point bending. Femoral BMD was significantly decreased following ovariectomy. This change was suppressed by swimming. Trabecular bone thickness, number, and connectivity were decreased by ovariectomy, whereas structure model index (i.e., ratio of rod-like to plate-like trabeculae) increased. These changes were also suppressed by swimming exercise. Femurs displayed greater cortical width and maximum load in SWI groups than in CON groups. Together, these results demonstrate that swimming exercise drastically alleviated both OVX-induced decreases in bone mass and mechanical strength and the deterioration of trabecular microarchitecture in rat models of osteoporosis. Copyright © 2015 the American Physiological Society.

Low bone mineral density in ambulatory persons with cerebral palsy? A systematic review.

PubMed

Mus-Peters, Cindy T R; Huisstede, Bionka M A; Noten, Suzie; Hitters, Minou W M G C; van der Slot, Wilma M A; van den Berg-Emons, Rita J G

2018-05-22

Non-ambulatory persons with cerebral palsy are prone to low bone mineral density. In ambulatory persons with cerebral palsy, bone mineral density deficits are expected to be small or absent, but a consensus conclusion is lacking. In this systematic review bone mineral density in ambulatory persons with cerebral palsy (Gross Motor Function Classification Scales I-III) was studied. Medline, Embase, and Web of Science were searched. According to international guidelines, low bone mineral density was defined as Z-score ≤ -2.0. In addition, we focused on Z-score ≤ -1.0 because this may indicate a tendency towards low bone mineral density. We included 16 studies, comprising 465 patients aged 1-65 years. Moderate and conflicting evidence for low bone mineral density (Z-score ≤ -2.0) was found for several body parts (total proximal femur, total body, distal femur, lumbar spine) in children with Gross Motor Function Classification Scales II and III. We found no evidence for low bone mineral density in children with Gross Motor Function Classification Scale I or adults, although there was a tendency towards low bone mineral density (Z-score ≤ -1.0) for several body parts. Although more high-quality research is needed, results indicate that deficits in bone mineral density are not restricted to non-ambulatory people with cerebral palsy. Implications for Rehabilitation Although more high-quality research is needed, including adults and fracture risk assessment, the current study indicates that deficits in bone mineral density are not restricted to non-ambulatory people with CP. Health care professionals should be aware that optimal nutrition, supplements on indication, and an active lifestyle, preferably with weight-bearing activities, are important in ambulatory people with CP, also from a bone quality point-of-view. If indicated, medication and fall prevention training should be prescribed.

Alterations in TNF- and IL-related gene expression in space-flown WI38 human fibroblasts

NASA Technical Reports Server (NTRS)

Semov, Alexandre; Semova, Nathalia; Lacelle, Chantale; Marcotte, Richard; Petroulakis, Emmanuel; Proestou, Gregory; Wang, Eugenia

2002-01-01

Spaceflight, just like aging, causes profound changes in musculoskeletal parameters, which result in decreased bone density and muscular weakness. As these conditions decrease our ability to conduct long-term manned space missions, and increase bone frailty in the elderly, the identification of genes responsible for the apparition of these physiological changes will be of great benefit. Thus, we developed and implemented a new microarray approach to investigate the changes in normal WI38 human fibroblast gene expression that arise as a consequence of space flight. Using our microarray, we identified changes in the level of expression of 10 genes, belonging to either the tumor necrosis factor- (TNF) or interleukin- (IL) related gene families in fibroblasts when WI38 cells exposed to microgravity during the STS-93 Space Shuttle mission were compared with ground controls. The genes included two ligands from the TNF superfamily, TWEAK and TNFSF15; two TNF receptor-associated proteins, NSMAF and PTPN13; three TNF-inducible genes, ABC50, PTX3, and SCYA13; TNF-alpha converting enzyme, IL-1 receptor antagonist, and IL-15 receptor alpha chain. Most of these are involved in either the regulation of bone density, and as such the development of spaceflight osteopenia, or in the development of proinflammatory status.

Loss of lean body mass affects low bone mineral density in patients with rheumatoid arthritis - results from the TOMORROW study.

PubMed

Okano, Tadashi; Inui, Kentaro; Tada, Masahiro; Sugioka, Yuko; Mamoto, Kenji; Wakitani, Shigeyuki; Koike, Tatsuya; Nakamura, Hiroaki

2017-11-01

Osteoporosis is one of the complications for patients with rheumatoid arthritis (RA). Rheumatoid cachexia, the loss of lean body mass, is another. However, the relationship between decreased lean body mass and reduced bone mineral density (BMD) in patients with RA has not been well studied. This study included 413 participants, comprising 208 patients with RA and 205 age- and sex-matched healthy volunteers. Clinical data, BMD, bone metabolic markers (BMM) and body composition, such as lean body mass and percent fat, were collected. Risk factors for osteoporosis in patients with RA including the relationship BMD and body composition were analyzed. Patients with RA showed low BMD and high BMM compared with controls. Moreover, lean body mass was lower and percent fat was higher in patients with RA. Lean body mass correlated positively and percent fat negatively with BMD. Lean body mass was a positive and disease duration was a negative independent factor for BMD in multivariate statistical analysis. BMD and lean body mass were significantly lower in patients with RA compared to healthy controls. Lean body mass correlated positively with BMD and decreased lean body mass and disease duration affected low BMD in patients with RA. [UMIN Clinical Trials Registry, http://www.umin.ac.jp/ctr/ , UMIN000003876].

Changes in bone mineral density and body composition during pregnancy and postpartum. A controlled cohort study.

PubMed

Møller, U K; Við Streym, S; Mosekilde, L; Rejnmark, L

2012-04-01

In a controlled cohort study, bone mineral density (BMD) was measured in 153 women pre-pregnancy; during pregnancy; and 0.5, 4, 9, and 19 months postpartum. Seventy-five age-matched controls, without pregnancy plans, were followed in parallel. Pregnancy and breastfeeding cause a reversible bone loss, which, initially, is most pronounced at trabecular sites but also involves cortical sites during prolonged breastfeeding. Conflicting results have been reported on effects of pregnancy and breastfeeding on BMD and body composition (BC). In a controlled cohort study, we elucidate changes in BMD and BC during and following a pregnancy. We measured BMD and BC in 153 women planning pregnancy (n = 92 conceived), once in each trimester during pregnancy and 15, 129, and 280 days postpartum. Moreover, BMD was measured 19 months postpartum (n = 31). Seventy-five age-matched controls, without pregnancy plans, were followed in parallel. Compared with controls, BMD decreased significantly during pregnancy by 1.8 ± 0.5% at the lumbar spine, 3.2 ± 0.5% at the total hip, 2.4 ± 0.3% at the whole body, and 4.2 ± 0.7% at the ultra distal forearm. Postpartum, BMD decreased further with an effect of breastfeeding. At 9 months postpartum, women who had breastfed for <9 months had a BMD similar to that of the controls, whereas BMD at the lumbar spine and hip was decreased in women who were still breastfeeding. During prolonged breastfeeding, BMD at sites which consist of mostly trabecular bone started to be regained, whereas BMD at sites rich in cortical bone decreased further. At 19 months postpartum, BMD did not differ from baseline at any site. During pregnancy, fat- and lean-tissue mass increased by 19 ± 22% and 5 ± 6% (p < 0.001), respectively. Postpartum, changes in fat mass differed according to breastfeeding status with a slower decline in women who continued breastfeeding. Calcium and vitamin D intake was not associated with BMD changes. Pregnancy and breastfeeding cause a reversible bone loss. At 19 months postpartum, BMD has returned to pre-pregnancy level independently of breastfeeding length. Reversal of changes in fat mass depends on breastfeeding status.

Reliability of analysis of the bone mineral density of the second and fifth metatarsals using dual-energy x-ray absorptiometry (DXA).

PubMed

Pritchard, N Stewart; Smoliga, James M; Nguyen, Anh-Dung; Branscomb, Micah C; Sinacore, David R; Taylor, Jeffrey B; Ford, Kevin R

2017-01-01

Metatarsal fractures, especially of the fifth metatarsal, are common injuries of the foot in a young athletic population, but the risk factors for this injury are not well understood. Dual-energy x-ray absorptiometry (DXA) provides reliable measures of regional bone mineral density to predict fracture risk in the hip and lumbar spine. Recently, sub-regional metatarsal reliability was established in fresh cadaveric specimens and associated with ultimate fracture force. The purpose of this study was to assess the reliability of DXA bone mineral density measurements of sub-regions of the second and fifth metatarsals in a young, active population. Thirty two recreationally active individuals participated in the study, and the bone density of the second (2MT) and fifth (5MT) metatarsals of each subject was measured using a Hologic QDR x-ray bone densitometer. Scans were analyzed separately by two raters, and regional bone mineral density, bone mineral content, and area measurements were calculated for the proximal, shaft, and distal regions of the bone. Intra-rater, inter-rater, and scan-rescan reliability were then determined for each region. Proximal and shaft bone mineral density measurements of the second and fifth metatarsal were reliable. ICC's were variable across regions and metatarsals, with the distal region being the poorest. Bone mineral density measurements of the metatarsals may be a better indicator of fracture risk of the metatarsals than whole body measurements. A reliable method for measuring the regional bone mineral densities of the metatarsals was found. However, inter-rater reliability and scan-rescan reliability for the distal regions were poor. Future research should examine the relationship between DXA bone mineral density measurements and fracture risk at the metatarsals.

Deregulation of arginase induces bone complications in high-fat/high-sucrose diet diabetic mouse model

PubMed Central

Bhatta, Anil; Sangani, Rajnikumar; Kolhe, Ravindra; Toque, Haroldo A.; Cain, Michael; Wong, Abby; Howie, Nicole; Shinde, Rahul; Elsalanty, Mohammed; Yao, Lin; Chutkan, Norman; Hunter, Monty; Caldwell, Ruth B.; Isales, Carlos; Caldwell, R. William; Fulzele, Sadanand

2016-01-01

A balanced diet is crucial for healthy development and prevention of musculoskeletal related diseases. Diets high in fat content are known to cause obesity, diabetes and a number of other disease states. Our group and others have previously reported that activity of the urea cycle enzyme arginase is involved in diabetes-induced dysregulation of vascular function due to decreases in nitric oxide formation. We hypothesized that diabetes may also elevate arginase activity in bone and bone marrow, which could lead to bone-related complications. To test this we determined the effects of diabetes on expression and activity of arginase, in bone and bone marrow stromal cells (BMSCs). We demonstrated that arginase 1 is abundantly present in the bone and BMSCs. We also demonstrated that arginase activity and expression in bone and bone marrow is up-regulated in models of diabetes induced by HFHS diet and streptozotocin (STZ). HFHS diet down-regulated expression of healthy bone metabolism markers (BMP2, COL-1, ALP, and RUNX2) and reduced bone mineral density, bone volume and trabecular thickness. However, treatment with an arginase inhibitor (ABH) prevented these bone-related complications of diabetes. In-vitro study of BMSCs showed that high glucose treatment increased arginase activity and decreased nitric oxide production. These effects were reversed by treatment with an arginase inhibitor (ABH). Our study provides evidence that deregulation of L-arginine metabolism plays a vital role in HFHS diet-induced diabetic complications and that these complications can be prevented by treatment with arginase inhibitors. The modulation of L-arginine metabolism in disease could offer a novel therapeutic approach for osteoporosis and other musculoskeletal related diseases. PMID:26704078

Association of unipedal standing time and bone mineral density in community-dwelling Japanese women.

PubMed

Sakai, A; Toba, N; Takeda, M; Suzuki, M; Abe, Y; Aoyagi, K; Nakamura, T

2009-05-01

Bone mineral density (BMD) and physical performance of the lower extremities decrease with age. In community-dwelling Japanese women, unipedal standing time, timed up and go test, and age are associated with BMD while in women aged 70 years and over, unipedal standing time is associated with BMD. The aim of this study was to clarify whether unipedal standing time is significantly associated with BMD in community-dwelling women. The subjects were 90 community-dwelling Japanese women aged 54.7 years. BMD of the second metacarpal bone was measured by computed X-ray densitometry. We measured unipedal standing time as well as timed up and go test to assess physical performance of the lower extremities. Unipedal standing time decreased with increased age. Timed up and go test significantly correlated with age. Low BMD was significantly associated with old age, short unipedal standing time, and long timed up and go test. Stepwise regression analysis revealed that age, unipedal standing time, and timed up and go test were significant factors associated with BMD. In 21 participants aged 70 years and over, body weight and unipedal standing time, but not age, were significantly associated with BMD. BMD and physical performance of the lower extremities decrease with older age. Unipedal standing time, timed up and go test, and age are associated with BMD in community-dwelling Japanese women. In women aged 70 years and over, unipedal standing time is significantly associated with BMD.

The Effect of Rosiglitazone on Bone Quality in a Rat Model of Insulin Resistance and Osteoporosis

NASA Astrophysics Data System (ADS)

Sardone, Laura Donata

Rosiglitazone (RSG) is an insulin-sensitizing drug used to treat Type 2 Diabetes Mellitus (T2DM). Clinical trials show that women taking RSG experience more limb fractures than patients taking other T2DM drugs. The purpose of this study is to understand how RSG (3mg/kg/day and 10mg/kg/day) and the bisphosphonate alendronate (0.7mg/kg/week) alter bone quality in the male, female and female ovariectomized (OVX) Zucker fatty rat model over a 12 week period. Bone quality was evaluated by mechanical testing of cortical and trabecular bone. Microarchitecture, bone mineral density (BMD), cortical bone porosity, bone formation/resorption and mineralization were also measured. Female OVX RSG10mg/kg rats had significantly lower vertebral BMD and compromised trabecular architecture versus OVX controls. Increased cortical porosity and decreased mechanical properties occurred in these rats. ALN treatment prevented these negative effects in the OVX RSG model. Evidence of reduced bone formation and excess bone resorption was detected in female RSG-treated rats.

Bone Mineral 31P and Matrix-Bound Water Densities Measured by Solid-State 1H and 31P MRI

PubMed Central

Seifert, Alan C.; Li, Cheng; Rajapakse, Chamith S.; Bashoor- Zadeh, Mahdieh; Bhagat, Yusuf A.; Wright, Alexander C.; Zemel, Babette S.; Zavaliangos, Antonios; Wehrli, Felix W.

2014-01-01

Bone is a composite material consisting of mineral and hydrated collagen fractions. MRI of bone is challenging due to extremely short transverse relaxation times, but solid-state imaging sequences exist that can acquire the short-lived signal from bone tissue. Previous work to quantify bone density via MRI used powerful experimental scanners. This work seeks to establish the feasibility of MRI-based measurement on clinical scanners of bone mineral and collagen-bound water densities, the latter as a surrogate of matrix density, and to examine the associations of these parameters with porosity and donors’ age. Mineral and matrix-bound water images of reference phantoms and cortical bone from 16 human donors, ages 27-97 years, were acquired by zero-echo-time 31P and 1H MRI on whole body 7T and 3T scanners, respectively. Images were corrected for relaxation and RF inhomogeneity to obtain density maps. Cortical porosity was measured by micro-CT, and apparent mineral density by pQCT. MRI-derived densities were compared to x-ray-based measurements by least-squares regression. Mean bone mineral 31P density was 6.74±1.22 mol/L (corresponding to 1129±204 mg/cc mineral), and mean bound water 1H density was 31.3±4.2 mol/L (corresponding to 28.3±3.7 %v/v). Both 31P and bound water (BW) densities were correlated negatively with porosity (31P: R2 = 0.32, p < 0.005; BW: R2 = 0.63, p < 0.0005) and age (31P: R2 = 0.39, p < 0.05; BW: R2 = 0.70, p < 0.0001), and positively with pQCT density (31P: R2 = 0.46, p < 0.05; BW: R2 = 0.50, p < 0.005). In contrast, the bone mineralization ratio (expressed here as the ratio of 31P density to bound water density), which is proportional to true bone mineralization, was found to be uncorrelated with porosity, age, or pQCT density. This work establishes the feasibility of image-based quantification of bone mineral and bound water densities using clinical hardware. PMID:24846186

Assessment of Cortical and Trabecular Bone Changes in Two Models of Post-Traumatic Osteoarthritis

PubMed Central

Pauly, Hannah M; Larson, Blair E; Coatney, Garrett A; Button, Keith D.; DeCamp, Charlie E; Fajardo, Ryan S; Haut, Roger C; Donahue, Tammy L Haut

2015-01-01

Subchondral bone is thought to play a significant role in the initiation and progression of the post-traumatic osteoarthritis. The goal of this study was to document changes in tibial and femoral subchondral bone that occur as a result of two lapine models of anterior cruciate ligament injury, a modified ACL transection model and a closed-joint traumatic compressive impact model. Twelve weeks post-injury bones were scanned via micro-computed tomography. The subchondral bone of injured limbs from both models showed decreases in bone volume and bone mineral density. Surgical transection animals showed significant bone changes primarily in the medial hemijoint of femurs and tibias, while significant changes were noted in both the medial and lateral hemijoints of both bones for traumatic impact animals. It is believed that subchondral bone changes in the medial hemijoint were likely caused by compromised soft tissue structures seen in both models. Subchondral bone changes in the lateral hemijoint of traumatic impact animals are thought to be due to transmission of the compressive impact force through the joint. The joint-wide bone changes shown in the traumatic impact model were similar to clinical findings from studies investigating the progression of osteoarthritis in humans. PMID:26147652

In peripubertal girls, artistic gymnastics improves areal bone mineral density and femoral bone geometry without affecting serum OPG/RANKL levels.

PubMed

Maïmoun, L; Coste, O; Mariano-Goulart, D; Galtier, F; Mura, T; Philibert, P; Briot, K; Paris, F; Sultan, C

2011-12-01

Peripubertal artistic gymnasts display elevated areal bone mineral density at various bone sites, despite delayed menarche and a high frequency of menstrual disorders, factors that may compromise bone health. The concomitant improvement in femoral bone geometry and strength suggested that this type of physical activity might have favourable clinical impact. The purpose of this study is to evaluate the effect of artistic gymnastics (GYM) on areal bone mineral density (aBMD), femoral bone geometry and bone markers and its relationship with the osteoprotegerin (OPG)/rank-ligand (RANKL) system in peripubertal girls. Forty-six girls (age 10-17.2 years) were recruited for this study: 23 elite athletes in the GYM group (training 12-30 h/week, age at start of training 5.3 years) and 23 age-matched (± 6 months; leisure physical activity ≤ 3 h/week) controls (CON). The aBMD at whole body, total proximal femur, lumbar spine, mid-radius and skull was determined using dual-X-ray absorptiometry. Hip structural analysis (HSA software) was applied at the femur to evaluate cross-sectional area (CSA, cm(2)), cross-sectional moment of inertia (CSMI, cm(4)), and the section modulus (Z, cm(3)) and buckling ratio at neck, intertrochanteric region and shaft. Markers of bone turnover and OPG/RANKL levels were also analysed. GYM had higher (5.5-16.4%) non-adjusted aBMD and adjusted aBMD for age, fat-free soft tissue and fat mass at all bone sites, skull excepted and the difference increased with age. In the three femoral regions adjusted for body weight and height, CSA (12.5-18%), CSMI (14-18%), Z (15.5-18.6%) and mean cortical thickness (13.6-21%) were higher in GYM than CON, while the buckling ratio (21-27.1%) was lower. Bone markers decreased with age in both groups and GYM presented higher values than CON only in the postmenarchal period. A similar increase in RANKL with age without OPG variation was observed for both groups. GYM is associated not only with an increase in aBMD but also an improvement in bone geometry associated with an increase in bone remodelling. These adaptations seem to be independent of the OPG/RANKL system.