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Sample records for impaired bone mineral

  1. Osteoprotective effect of hormone therapy on bone microarchitecture before impaired bone mineral density in ovariectomized rats

    PubMed Central

    Terzi, Hasan; Çırpan, Teksin; Terzi, Rabia; Yeniel, Ahmet Özgür; Aktuğ, Hüseyin; Bilgin, Onur

    2012-01-01

    Objective: We aimed to determine the effect of hormone replacement therapy on bone microarchitecture in ovariectomized rats. Material and Methods: In the Animal Ethics Committee approved-study, the effect of treatment with 17 β-estradiol 50 μg/kg and medroxyprogesterone 2.5 mg/kg on bone architecture and bone mineral density in rats versus ovariectomized control rats over the course of 20 days were evaluated. Femoral and lumbar bone mineral density levels and morphometric measurements were performed. Results: There were no significant differences in the femoral and lumbar bone mineral density levels between the groups. In the intact control group, the trabecular structures were significantly superior to those in the other groups. Additionally, the osteoblast count was significantly higher while the osteoclast count was significantly lower than in all other groups. Two parameters reflecting trabecular bone microarchitecture, which include the trabecular count and the trabecular area, demonstrated significant improvement in the hormone replacement group when compared to the ovariectomized control group. In the hormone replacement groups, the osteoblast count was significantly higher while the osteoclast count was significantly lower than in the ovariectomized control group. Conclusion: We suggest that offering estrogen alone or in combination with progestogen can be a beneficial approach in preventing early postmenopausal bone loss regardless of bone mineral density. PMID:24592053

  2. Impairment of mineralization by metavanadate and decavanadate solutions in a fish bone-derived cell line.

    PubMed

    Tiago, Daniel M; Laizé, Vincent; Cancela, M Leonor; Aureliano, Manuel

    2008-06-01

    Vanadium, a trace metal known to accumulate in bone and to mimic insulin, has been shown to regulate mammalian bone formation using in vitro and in vivo systems. In the present work, short- and long-term effects of metavanadate (containing monomeric, dimeric, tetrameric and pentameric vanadate species) and decavanadate (containing decameric vanadate species) solutions on the mineralization of a fish bone-derived cell line (VSa13) were studied and compared to that of insulin. After 2 h of incubation with vanadate (10 microM in monomeric vanadate), metavanadate exhibited higher accumulation rates than decavanadate (6.85 +/- 0.40 versus 3.95 +/- 0.10 microg V/g of protein, respectively) in fish VSa13 cells and was also shown to be less toxic when applied for short periods. In longer treatments with both metavanadate and decavanadate solutions, similar effects were promoted: stimulation of cell proliferation and strong impairment (75%) of extracellular matrix (ECM) mineralization. The effect of both vanadate solutions (5 microM in monomeric vanadate), on ECM mineralization was increased in the presence of insulin (10 nM). It is concluded that chronic treatment with both vanadate solutions stimulated fish VSa13 cells proliferation and prevented ECM mineralization. Newly developed VSa13 fish cells appeared to be appropriate in the characterization of vanadate effects on vertebrate bone formation, representing a good alternative to mammalian systems.

  3. Impaired Vestibular Function and Low Bone Mineral Density: Data from the Baltimore Longitudinal Study of Aging.

    PubMed

    Bigelow, Robin T; Semenov, Yevgeniy R; Anson, Eric; du Lac, Sascha; Ferrucci, Luigi; Agrawal, Yuri

    2016-10-01

    Animal studies have demonstrated that experimentally induced vestibular ablation leads to a decrease in bone mineral density, through mechanisms mediated by the sympathetic nervous system. Loss of bone mineral density is a common and potentially morbid condition that occurs with aging, and we sought to investigate whether vestibular loss is associated with low bone mineral density in older adults. We evaluated this question in a cross-sectional analysis of data from the Baltimore Longitudinal Study of Aging (BLSA), a large, prospective cohort study managed by the National Institute on Aging (N = 389). Vestibular function was assessed with cervical vestibular evoked myogenic potentials (cVEMPs), a measure of saccular function. Bone mineral density was assessed using dual-energy X-ray absorptiometry (DEXA). In two-way t test analysis, we observed that individuals with reduced vestibular physiologic function had significantly lower bone mineral density. In adjusted multivariate linear regression analyses, we observed that older individuals with reduced vestibular physiologic function had significantly lower bone mineral density, specifically in weight-bearing hip and lower extremity bones. These results suggest that the vestibular system may contribute to bone homeostasis in older adults, notably of the weight-bearing hip bones at greatest risk of osteoporotic fracture. Further longitudinal analysis of vestibular function and bone mineral density in humans is needed to characterize this relationship and investigate the potential confounding effect of physical activity.

  4. Multi-Generational Drinking of Bottled Low Mineral Water Impairs Bone Quality in Female Rats

    PubMed Central

    Zeng, Hui; Wang, Lingqiao; Wang, Dahua; Luo, Jiaohua; Zhang, Liang; Huang, Yujing; Chen, Ji-an; Shu, Weiqun

    2015-01-01

    Background Because of reproductions and hormone changes, females are more sensitive to bone mineral loss during their lifetime. Bottled water has become more popular in recent years, and a large number of products are low mineral water. However, research on the effects of drinking bottled low mineral water on bone health is sparse. Objective To elucidate the skeletal effects of multi-generational bottled water drinking in female rats. Methods Rats continuously drank tap water (TW), bottled natural water (bNW), bottled mineralized water (bMW), or bottled purified water (bPW) for three generations. Results The maximum deflection, elastic deflection, and ultimate strain of the femoral diaphysis in the bNW, bMW, and bPW groups and the fracture strain in the bNW and bMW groups were significantly decreased. The tibiae calcium levels in both the bNW and bPW groups were significantly lower than that in the TW group. The tibiae and teeth magnesium levels in both the bNW and bPW groups were significantly lower than those in the TW group. The collagen turnover markers PICP (in both bNW and bPW groups) were significantly lower than that in the TW group. In all three low mineral water groups, the 1,25-dihydroxy-vitamin D levels were significantly lower than those in the TW group. Conclusion Long-term drinking of low mineral water may disturb bone metabolism and biochemical properties and therefore weaken biomechanical bone properties in females. Drinking tap water, which contains adequate minerals, was found to be better for bone health. To our knowledge, this is the first report on drinking bottled low mineral water and female bone quality on three generation model. PMID:25803851

  5. Association of Bone Mineral Density With Hearing Impairment in Postmenopausal Women in Korea

    PubMed Central

    Jung, Da Jung; Cho, Hyun Ho; Lee, Kyu-Yup

    2016-01-01

    Objectives Previous studies examining the association between osteoporosis (OP) and hearing loss (HL) have shown conflicting results. The objective of the present study was to examine the association between hearing impairment and OP in postmenopausal women, using appropriate statistical analyses. Methods Total 1,009 participants were included in the current study. The propensity score matched (PSM) cohort was defined as the cohort including participants diagnosed with OP and participants without OP. Three statistical models were developed where model 1 was unadjusted, model 2 included age, and model 3 included age, body mass index, alcohol intake, smoking habit, diabetes mellitus, hypertension, high density lipoprotein cholesterol, triglyceride level, vitamin D, and alkaline phosphatase. Results There were 776 and 233 participants in the groups diagnosed without and with OP, respectively. For propensity score matching, 233 pairs were selected from the 776 participants without OP. In the total cohort, using statistical models 2 and 3, no significant difference in the four hearing thresholds was identified between the 2 groups. Logistic regression indicated that, in model 3, participants with OP had a 1.128 (P=0.323) increased risk HL. A significant HL risk was not observed in participants with OP. Using statistical model 3, there were no significant associations among lumbar spine or femoral neck T-scores and changes in the hearing thresholds. In the PSM cohort, statistical models also showed similar results. Conclusion The current study did not demonstrate and association between bone mineral density and hearing impairment in the study population of postmenopausal Korean women. PMID:27136368

  6. Bone mineral density test

    MedlinePlus

    ... density test; Bone densitometry; DEXA scan; DXA; Dual-energy x-ray absorptiometry; p-DEXA; Osteoporosis-BMD ... most common and accurate way uses a dual-energy x-ray absorptiometry (DEXA) scan. DEXA uses low- ...

  7. Regulation of bone mineral loss during lactation

    NASA Technical Reports Server (NTRS)

    Brommage, R.; Deluca, H. F.

    1985-01-01

    The effects of varyng dietary calcium and phosphorous levels, vitamin D deficiency, oophorectomy, adrenalectomy, and simultaneous pregnancy on bone mineral loss during lactation in rats are studied. The experimental procedures and evaluations are described. The femur ash weight of lactating and nonlactating rats are calculated. The data reveals that a decrease in dietary calcium of 0.02 percent results in an increased loss of bone mineral, an increase in calcium to 1.4 percent does not lessen bone mineral loss, and bone mineral loss in vitamin D deficient rats is independent of calcium levels. It is observed that changes in dietary phosphorous level, oophorectomy, adrenalectomy, and simultaneous pragnancy do not reduce bone mineral loss during lactation. The analysis of various hormones to determine the mechanism that triggers bone mineral loss during lactation is presented.

  8. Bone mineral measurement from Apollo experiment M-078. [derangement of bone mineral metabolism in spacecrews

    NASA Technical Reports Server (NTRS)

    Vogel, J. M.; Rambaut, P. C.; Smith, M. C., Jr.

    1974-01-01

    Loss of mineral from bone during periods of immobilization, recumbency, or weightlessness is examined. This report describes the instrumentation, technique, and bone mineral changes observed preflight and postflight for the Apollo 14, 15, and 16 missions. The bone mineral changes documented during the Apollo Program are reviewed, and their relevance to future missions is discussed.

  9. Mineralized Three-Dimensional Bone Constructs

    NASA Technical Reports Server (NTRS)

    Clarke, Mark S. F. (Inventor); Sundaresan, Alamelu (Inventor); Pellis, Neal R. (Inventor)

    2013-01-01

    The present disclosure provides ex vivo-derived mineralized three-dimensional bone constructs. The bone constructs are obtained by culturing osteoblasts and osteoclast precursors under randomized gravity vector conditions. Preferably, the randomized gravity vector conditions are obtained using a low shear stress rotating bioreactor, such as a High Aspect Ratio Vessel (HARV) culture system. The bone constructs of the disclosure have utility in physiological studies of bone formation and bone function, in drug discovery, and in orthopedics.

  10. Mineralized three-dimensional bone constructs

    NASA Technical Reports Server (NTRS)

    Clarke, Mark S. F. (Inventor); Sundaresan, Alamelu (Inventor); Pellis, Neal R. (Inventor)

    2011-01-01

    The present disclosure provides ex vivo-derived mineralized three-dimensional bone constructs. The bone constructs are obtained by culturing osteoblasts and osteoclast precursors under randomized gravity vector conditions. Preferably, the randomized gravity vector conditions are obtained using a low shear stress rotating bioreactor, such as a High Aspect Ratio Vessel (HARV) culture system. The bone constructs of the disclosure have utility in physiological studies of bone formation and bone function, in drug discovery, and in orthopedics.

  11. Citrate bridges between mineral platelets in bone.

    PubMed

    Davies, Erika; Müller, Karin H; Wong, Wai Ching; Pickard, Chris J; Reid, David G; Skepper, Jeremy N; Duer, Melinda J

    2014-04-08

    We provide evidence that citrate anions bridge between mineral platelets in bone and hypothesize that their presence acts to maintain separate platelets with disordered regions between them rather than gradual transformations into larger, more ordered blocks of mineral. To assess this hypothesis, we take as a model for a citrate bridging between layers of calcium phosphate mineral a double salt octacalcium phosphate citrate (OCP-citrate). We use a combination of multinuclear solid-state NMR spectroscopy, powder X-ray diffraction, and first principles electronic structure calculations to propose a quantitative structure for this material, in which citrate anions reside in a hydrated layer, bridging between apatitic layers. To assess the relevance of such a structure in native bone mineral, we present for the first time, to our knowledge, (17)O NMR data on bone and compare them with (17)O NMR data for OCP-citrate and other calcium phosphate minerals relevant to bone. The proposed structural model that we deduce from this work for bone mineral is a layered structure with thin apatitic platelets sandwiched between OCP-citrate-like hydrated layers. Such a structure can explain a number of known structural features of bone mineral: the thin, plate-like morphology of mature bone mineral crystals, the presence of significant quantities of strongly bound water molecules, and the relatively high concentration of hydrogen phosphate as well as the maintenance of a disordered region between mineral platelets.

  12. Vegetarian lifestyle and bone mineral density.

    PubMed

    Marsh, A G; Sanchez, T V; Michelsen, O; Chaffee, F L; Fagal, S M

    1988-09-01

    The amount and type of dietary protein affect bone mineral loss after the menopause. This observation was substantiated in 10 y of studies by direct photon absorptiometry, four results of which follow. 1) Studies of 1600 women in southwestern Michigan revealed that those who had followed the lactoovovegetarian diet for at least 20 y had only 18% less bone mineral by age 80 whereas closely paired omnivores had 35% less bone mineral. 2) A study of self-selected weighed food intake showed no statistical difference in nutrient intakes but a difference in Ca:P ratio and acid-base formation of diet, each significant to p less than 0.001. 3) When sulfur intake of a fixed diet was increased, the titratable acidity of the urine increased proportionately. 4) Bone mineral densities of 304 older women from the continental United States closely paralleled those from earlier Michigan studies.

  13. Bone impairment in oxalosis: An ultrastructural bone analysis.

    PubMed

    Bacchetta, Justine; Farlay, Delphine; Abelin-Genevois, Kariman; Lebourg, Ludivine; Cochat, Pierre; Boivin, Georges

    2015-12-01

    Deposition of calcium oxalate crystals in the kidney and bone is a hallmark of systemic oxalosis. Since the bone compartment can store massive amounts of oxalate, patients present with recurrent low-trauma fractures, bone deformations, severe bone pains and specific oxalate osteopathy on plain X-ray. Bone biopsy from the iliac crest displays specific features such as oxalate crystals surrounded by a granulomatous reaction due to an invasion of bone surface by macrophages. We present data obtained in 10 samples from 8 patients with oxalosis (16-68 years) who underwent iliac crest bone biopsy and bone quality analysis using modern methods (microradiography, microindentation, Fourier Transform InfraRed Microspectroscopy, transmission electron microscopy) in addition to histomorphometry. Disseminated calcium oxalate deposits (whewellite) were found in the bone marrow space (with a granulomatous reaction) but not in the bone matrix. Calcium oxalate deposits were totally surrounded by macrophages and multinucleated giant cells, and a phagocytosis activity was sometimes observed. Very few calcium oxalate crystals were directly in close contact with the mineral substance of the bone. Bone mineralization was not modified by the presence of calcium oxalate even in close vicinity. Bone quality analysis also revealed a harder bone than normal, perhaps in relationship with decreased carbonate content in the mineral. This increase in bone hardness could explain a more "brittle" bone. In patients with oxalosis, the formation and growth of calcium oxalate crystals in the bone appeared independent of apatite. The mechanisms leading to nucleation and growth of oxalate deposits are still unclear and deserve further studies.

  14. Bone mineral measurement: Experiment M078

    NASA Technical Reports Server (NTRS)

    Smith, M. C., Jr.; Rambaut, P. C.; Vogel, J. M.; Whittle, M. W.

    1977-01-01

    Gamma ray absorptiometric measurements on bone mineral content, in addition to calcium balance studies, were performed on male volunteers during bed rest periods of 24 to 36 weeks duration and compared to Skylab mission data. Results show that mineral losses occur from the bones of the lower extremities during missions of up to 84 days and that in general they follow the loss patterns of the bed rest situation. The level of loss observed in Spacelab crews are not of clinical concern.

  15. Baseline Bone Mineral Density Measurements Key to Future Testing Intervals

    MedlinePlus

    ... on Research 2012 May 2012 (historical) Baseline Bone Mineral Density Measurements Key to Future Testing Intervals How often a woman should have bone mineral density (BMD) tests to track bone mass is ...

  16. Anthropometric models of bone mineral content and areal bone mineral density based on the bone mineral density in childhood study

    PubMed Central

    Gilsanz, V.; Kalkwarf, H. J.; Lappe, J. M.; Oberfield, S.; Shepherd, J. A.; Winer, K. K.; Zemel, B. S.; Hangartner, T. N.

    2016-01-01

    Summary New models describing anthropometrically adjusted normal values of bone mineral density and content in children have been created for the various measurement sites. The inclusion of multiple explanatory variables in the models provides the opportunity to calculate Z-scores that are adjusted with respect to the relevant anthropometric parameters. Introduction Previous descriptions of children’s bone mineral measurements by age have focused on segmenting diverse populations by race and sex without adjusting for anthropometric variables or have included the effects of a single anthropometric variable. Methods We applied multivariate semi-metric smoothing to the various pediatric bone-measurement sites using data from the Bone Mineral Density in Childhood Study to evaluate which of sex, race, age, height, weight, percent body fat, and sexual maturity explain variations in the population’s bone mineral values. By balancing high adjusted R2 values with clinical needs, two models are examined. Results At the spine, whole body, whole body sub head, total hip, hip neck, and forearm sites, models were created using sex, race, age, height, and weight as well as an additional set of models containing these anthropometric variables and percent body fat. For bone mineral density, weight is more important than percent body fat, which is more important than height. For bone mineral content, the order varied by site with body fat being the weakest component. Including more anthropometrics in the model reduces the overlap of the critical groups, identified as those individuals with a Z-score below −2, from the standard sex, race, and age model. Conclusions If body fat is not available, the simpler model including height and weight should be used. The inclusion of multiple explanatory variables in the models provides the opportunity to calculate Z-scores that are adjusted with respect to the relevant anthropometric parameters. PMID:25311106

  17. High-strength mineralized collagen artificial bone

    NASA Astrophysics Data System (ADS)

    Qiu, Zhi-Ye; Tao, Chun-Sheng; Cui, Helen; Wang, Chang-Ming; Cui, Fu-Zhai

    2014-03-01

    Mineralized collagen (MC) is a biomimetic material that mimics natural bone matrix in terms of both chemical composition and microstructure. The biomimetic MC possesses good biocompatibility and osteogenic activity, and is capable of guiding bone regeneration as being used for bone defect repair. However, mechanical strength of existing MC artificial bone is too low to provide effective support at human load-bearing sites, so it can only be used for the repair at non-load-bearing sites, such as bone defect filling, bone graft augmentation, and so on. In the present study, a high strength MC artificial bone material was developed by using collagen as the template for the biomimetic mineralization of the calcium phosphate, and then followed by a cold compression molding process with a certain pressure. The appearance and density of the dense MC were similar to those of natural cortical bone, and the phase composition was in conformity with that of animal's cortical bone demonstrated by XRD. Mechanical properties were tested and results showed that the compressive strength was comparable to human cortical bone, while the compressive modulus was as low as human cancellous bone. Such high strength was able to provide effective mechanical support for bone defect repair at human load-bearing sites, and the low compressive modulus can help avoid stress shielding in the application of bone regeneration. Both in vitro cell experiments and in vivo implantation assay demonstrated good biocompatibility of the material, and in vivo stability evaluation indicated that this high-strength MC artificial bone could provide long-term effective mechanical support at human load-bearing sites.

  18. Bone Mineral Status in Children and Adolescents with Klinefelter Syndrome

    PubMed Central

    Stagi, Stefano; Di Tommaso, Mariarosaria; Manoni, Cristina; Scalini, Perla; Chiarelli, Francesco; Verrotti, Alberto; Lapi, Elisabetta; Giglio, Sabrina; Dosa, Laura; de Martino, Maurizio

    2016-01-01

    Objective. Klinefelter syndrome (KS) has long-term consequences on bone health. However, studies regarding bone status and metabolism during childhood and adolescence are very rare. Patients. This cross-sectional study involved 40 (mean age: 13.7 ± 3.8 years) KS children and adolescents and 80 age-matched healthy subjects. For both patient and control groups, we evaluated serum levels of ionised and total calcium, phosphate, total testosterone, luteinising hormone, follicle stimulating hormone, parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D, osteocalcin, bone alkaline phosphatase, and urinary deoxypyridinoline concentrations. We also calculated the z-scores of the phalangeal amplitude-dependent speed of sound (AD-SoS) and the bone transmission time (BTT). Results. KS children and adolescents showed significantly reduced AD-SoS (p < 0.005) and BTT (p < 0.0005) z-scores compared to the controls. However, KS patients presented significantly higher PTH (p < 0.0001) and significantly lower 25(OH)D (p < 0.0001), osteocalcin (p < 0.05), and bone alkaline phosphatase levels (p < 0.005). Interestingly, these metabolic bone disorders were already present in the prepubertal subjects. Conclusions. KS children and adolescents exhibited impaired bone mineral status and metabolism with higher PTH levels and a significant reduction of 25-OH-D and bone formation markers. Interestingly, this impairment was already evident in prepubertal KS patients. Follow-ups should be scheduled with KS patients to investigate and ameliorate bone mineral status and metabolism until the prepubertal ages. PMID:27413371

  19. Brief Report: HIV Infection Is Associated With Worse Bone Material Properties, Independently of Bone Mineral Density.

    PubMed

    Güerri-Fernández, Robert; Molina, Daniel; Villar-García, Judit; Prieto-Alhambra, Daniel; Mellibovsky, Leonardo; Nogués, Xavier; González-Mena, Alicia; Guelar, Ana; Trenchs-Rodríguez, Marta; Herrera-Fernández, Sabina; Horcajada, Juan Pablo; Díez-Pérez, Adolfo; Knobel, Hernando

    2016-07-01

    Low bone mineral density (BMD) in HIV-infected individuals has been documented in an increasing number of studies. However, it is not clear whether it is the infection itself or the treatment that causes bone impairment. Microindentation measures bone material strength (Bone Material Strength index) directly. We recruited 85 patients, 50 infected with HIV and 35 controls. Median Bone Material Strength index was 84.5 (interquartile range 83-87) in HIV-infected patients and 90 (88.5-93) in controls (P < 0.001). No significant differences in BMD between cases and controls at any of the sites examined (total hip, femoral neck, and lumbar spine). HIV infection is associated with bone damage, independently of BMD.

  20. Mathematical Model for the Mineralization of Bone

    NASA Technical Reports Server (NTRS)

    Martin, Bruce

    1994-01-01

    A mathematical model is presented for the transport and precipitation of mineral in refilling osteons. One goal of this model was to explain calcification 'halos,' in which the bone near the haversian canal is more highly mineralized than the more peripheral lamellae, which have been mineralizing longer. It was assumed that the precipitation rate of mineral is proportional to the difference between the local concentration of calcium ions and an equilibrium concentration and that the transport of ions is by either diffusion or some other concentration gradient-dependent process. Transport of ions was assumed to be slowed by the accumulation of mineral in the matrix along the transport path. ne model also mimics bone apposition, slowing of apposition during refilling, and mineralization lag time. It was found that simple diffusion cannot account for the transport of calcium ions into mineralizing bone, because the diffusion coefficient is two orders of magnitude too low. If a more rapid concentration gradient-driven means of transport exists, the model demonstrates that osteonal geometry and variable rate of refilling work together to produce calcification halos, as well as the primary and secondary calcification effect reported in the literature.

  1. Mathematical Model for the Mineralization of Bone

    NASA Technical Reports Server (NTRS)

    Martin, Bruce

    1994-01-01

    A mathematical model is presented for the transport and precipitation of mineral in refilling osteons. One goal of this model was to explain calcification 'halos,' in which the bone near the haversian canal is more highly mineralized than the more peripheral lamellae, which have been mineralizing longer. It was assumed that the precipitation rate of mineral is proportional to the difference between the local concentration of calcium ions and an equilibrium concentration and that the transport of ions is by either diffusion or some other concentration gradient-dependent process. Transport of ions was assumed to be slowed by the accumulation of mineral in the matrix along the transport path. The model also mimics bone apposition, slowing of apposition during refilling, and mineralization lag time. It was found that simple diffusion cannot account for the transport of calcium ions into mineralizing bone, because the diffusion coefficient is two orders of magnitude too low. If a more rapid concentration gradient-driven means of transport exists, the model demonstrates that osteonal geometry and variable rate of refilling work together to produce calcification halos, as well as the primary and secondary calcification effect reported in the literature.

  2. [Hyperprolactinaemia and bone mineral density].

    PubMed

    Kostrzak, Anna; Męczekalski, Błażej

    2015-08-01

    Hyperprolactinaemia is one of the most common endocrinological disorder at women at the reproductive age. Prolactin is produced by the anterior lobe of the pituitary.The main role of prolactin is associated with mamotrophic action and lactogenesis. Hyperprolactinaemia causes several symptoms such as menstrual disorders, infertility, decrease of sexual function, galactorrhea in women and gynecomasty, impotence and decrease of semen quality in men. Recent studies have presented prolactin as a homone involved in many metabolic processes. Long-term consequences of high prolactin serum concentration are related to higher risk of cardiovascular system disease, disturbances in lipid profile and immunological system. Hyperprolactiaemia causes decrease of bone mass density (BMD). High serum prolactin levels lead to increase of the risk of osteopenia or/and osteoporosis. Decrease of BMD results from hypoestrogenism induced by hyperprolactinaemia and also by the direct negative influence of prolactin on bone. Hyperprolactinaemia related to prolactinoma significantly (more than functional hyperprolactiaemia) increases the risk of osteopenia, osteoporosis and bone fractures. Important group of patients threatened by osteoporosis and bone fracture is constituted by women which use antipsychotic drugs (which induce hyperprolactinaemia). Hyperprolactinaemia diagnosed in patients should be treated as soon as possible. Hyperprolactinaemic patients should be diagnosed in the direction of osteopenia and osteoporosis. When diagnosis is confirmed proper treatment is indicated.

  3. Bone mineral content in normal US whites

    NASA Technical Reports Server (NTRS)

    Mazess, R. B.; Cameron, J. R.

    1974-01-01

    Photon absorptiometry with I-125 was used to measure the bone mineral content and the bone width on 763 children between the ages of 5 and 19 years, on 538 adults between the ages of 20 and 49 years, and on 550 adults over the age of 50 years. Measurements were made on the midshaft and the distal end of the radius and the ulna, and on the humerus midshaft. This has permitted analysis of annual bone growth in children, and the rate of change in elderly adults per decade. Male and female children grew at about the same rate until adolescence. After adolescence females grew at a slow rate until the mid-twenties, while males reached adult mineralization by age 20. Males remained relatively constant until the fifties, and females began their decline in the forties.

  4. Bone mineral measurement - Skylab experiment M-078

    NASA Technical Reports Server (NTRS)

    Vogel, J. M.

    1975-01-01

    Experimental observations of loss of bone mineral due to prolonged bedrest or weightlessness are reported. A new, precise method was employed that featured an essentially monoergetic photon source (125I) and a scintillation detector operating in a rectilinear scanning mode to measure bone mineral in the radius, ulna, and os calcis by the absorptiometric technique. Variable but small losses were found during 4-6 weeks of bedrest; losses of up to 40% were noted in the os calcis after 9 months. When the technique was used during the Apollo 14, 15, and 16 missions, only one crewmen showed significant losses in the os calcis and none in the radius or ulna. The variability recorded during bedrest was connected with the initial 24-hr urinary hydroxyproline excretion and the initial os calcis mineral content. The relevance of prediction terms based on bedrest data to Skylab and longer missions is discussed.

  5. Kinetic aspects of bone mineral metabolism

    NASA Technical Reports Server (NTRS)

    Palmer, H. E.

    1973-01-01

    Two techniques were studied for measuring changes in bone mass in rats. One technique measures the Ar-37 produced from calcium during neutron irradiation and the other measures the changes in the Na-22 content which has been incorporated within the rat bone. Both methods are performed in VIVO and cause no significant physiological damage. The Ar-37 leaves the body of a rat within an hour after being produced, and it can be quantitatively collected and measured with a precision of - or + 2% on the same rat. With appropriate irradiation conditions it appears that the absolute quantity of calcuim in any rat can be determined within - or + 3% regardless of animal size. The Na-22 when uniformly distributed in bone, can be used to monitor bone mineral turnover and this has been demonstrated in conditions of calcium deficiency during growth and also pregnancy coupled with calcium deficiency.

  6. High resolution bone mineral densitometry with a gamma camera

    NASA Technical Reports Server (NTRS)

    Leblanc, A.; Evans, H.; Jhingran, S.; Johnson, P.

    1983-01-01

    A technique by which the regional distribution of bone mineral can be determined in bone samples from small animals is described. The technique employs an Anger camera interfaced to a medical computer. High resolution imaging is possible by producing magnified images of the bone samples. Regional densitometry of femurs from oophorectomised and bone mineral loss.

  7. Bone and mineral metabolism in African Americans.

    PubMed

    Bell, N H

    1997-08-01

    Important differences exist in the metabolism of bone and mineral and the vitamin D endocrine system between whites and African Americans and include rate o f skeletal remodeling, bone mass, and vitamin D metabolism. A higher bone mineral density (BMD) in African Americans is associated with a diminished incidence o f osteoporosis and fractures. Serum 17beta-estradiol and the rate of GH secretion are higher in black than in white men, but there is no racial difference in women in this regard. The mechanisms for reduced rate o f skeletal remodeling and for greater BMD in blacks are not known, but diminished rate of skeletal remodeling could be a contributing factor for greater bone mass. Reduction in serum 25-hydroxyvitamin D in blacks is attributed to increased skin pigment and to diminished dermal production of vitamin D(3) and consequent decreased hepatic synthesis o f the metabolite. There is no evidence that alteration of the vitamin D endocrine system contributes to or is responsible for racial differences in skeletal remodeling and bone mass. Black infants, however, are at risk for developing vitamin D-deficient rickets, particularly when breast-fed.

  8. Bone mineral content and bone mineral density are lower in older than in younger females with Rett syndrome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although bone mineral deficits have been identified in Rett syndrome (RTT), the prevalence of low bone mineral density (BMD) and its association with skeletal fractures and scoliosis has not been characterized fully in girls and women with RTT. Accordingly, we measured total body bone mineral conten...

  9. Endochondral bone growth, bone calcium accretion, and bone mineral density: how are they related?

    PubMed

    Wongdee, Kannikar; Krishnamra, Nateetip; Charoenphandhu, Narattaphol

    2012-07-01

    Endochondral bone growth in young growing mammals or adult mammals with persistent growth plates progresses from proliferation, maturation and hypertrophy of growth plate chondrocytes to mineralization of cartilaginous matrix to form an osseous tissue. This complex process is tightly regulated by a number of factors with different impacts, such as genetics, endocrine/paracrine factors [e.g., PTHrP, 1,25(OH)(2)D(3), IGF-1, FGFs, and prolactin], and nutritional status (e.g., dietary calcium and vitamin D). Despite a strong link between growth plate function and elongation of the long bone, little is known whether endochondral bone growth indeed determines bone calcium accretion, bone mineral density (BMD), and/or peak bone mass. Since the process ends with cartilaginous matrix calcification, an increase in endochondral bone growth typically leads to more calcium accretion in the primary spongiosa and thus higher BMD. However, in lactating rats with enhanced trabecular bone resorption, bone elongation is inversely correlated with BMD. Although BMD can be increased by factors that enhance endochondral bone growth, the endochondral bone growth itself is unlikely to be an important determinant of peak bone mass since it is strongly determined by genetics. Therefore, endochondral bone growth and bone elongation are associated with calcium accretion only in a particular subregion of the long bone, but do not necessarily predict BMD and peak bone mass.

  10. Bone mineral density, Bone mineral contents, MMP-8 and MMP-9 levels in Human Mandible and alveolar bone: Simulated microgravity

    NASA Astrophysics Data System (ADS)

    Rai, Balwant; Kaur, Jasdeep; Catalina, Maria

    Exposure to microgravity has been associated with several physiological changes in astronauts and cosmonauts, including an osteoporosis-like loss of bone mass. It has been reported that head-down tilt bed-rest studies mimic many of the observations seen in flights. There is no study on the correlation on effects of mandibular bone and alveolar bone loss in both sex in simulating microgravity. This study was designed to determine the Bone mineral density and GCF MMP-8 MMP-9 in normal healthy subject of both sexes in simulated microgravity condition of -6 head-down-tilt (HDT) bed rest. The subjects of this investigation were 10 male and 10 female volunteers participated in three weeks 6 HDT bed-rest exposure. The Bone density and bone mineral contents were measured by dual energy X-ray absorptiometry before and in simulated microgravity. The GCF MMP-8 MMP-8 were measured by Enzyme-linked immunosorbent assays (Human Quantikine MMP-8,-9 ELISA kit). The bone mineral density and bone mineral contents levels were significantly decreased in simulated microgravity condition in both genders, although insignificantly loss was higher in females as compared to males. MMP-8 MMP-9 levels were significantly increased in simulated microgravity as compared to normal condition although insignificantly higher in females as compared to males. Further study is required on large samples size including all factors effecting in simulated microgravity and microgravity. Keys words-Simulated microgravity condition, head-down-tilt, Bone loss, MMP-8, MMP-9, Bone density, Bone mineral contents.

  11. Effects of Exercise on Bone Mineral Content in Postmenopausal Women.

    ERIC Educational Resources Information Center

    Rikli, Roberta E.; McManis, Beth G.

    1990-01-01

    Study tested the effect of exercise programs on bone mineral content (BMC) and BMC/bone width in 31 postmenopausal women. Subjects were placed in groups with aerobic exercise, aerobics plus upper-body weight training, or no exercise. Results indicate that regular exercise programs positively affect bone mineral maintenance in postmenopausal women.…

  12. Novel anatomic adaptation of cortical bone to meet increased mineral demands of reproduction.

    PubMed

    Macica, Carolyn M; King, Helen E; Wang, Meina; McEachon, Courtney L; Skinner, Catherine W; Tommasini, Steven M

    2016-04-01

    The goal of this study was to investigate the effects of reproductive adaptations to mineral homeostasis on the skeleton in a mouse model of compromised mineral homeostasis compared to adaptations in control, unaffected mice. During pregnancy, maternal adaptations to high mineral demand include more than doubling intestinal calcium absorption by increasing calcitriol production. However, calcitriol biosynthesis is impaired in HYP mice, a murine model of X-linked hypophosphatemia (XLH). In addition, there is a paucity of mineralized trabecular bone, a primary target of bone resorption during pregnancy and lactation. Because the highest density of mineral is in mature cortical bone, we hypothesized that mineral demand is met by utilizing intracortical mineral reserves. Indeed, analysis of HYP mice revealed dramatic increases in intracortical porosity characterized by elevated serum PTH and type-I collagen matrix-degrading enzyme MMP-13. We discovered an increase in carbonate ion substitution in the bone mineral matrix during pregnancy and lactation of HYP mice, suggesting an alternative mechanism of bone remodeling that maintains maternal bone mass during periods of high mineral demand. This phenomenon is not restricted to XLH, as increased carbonate in the mineral matrix also occurred in wild-type mice during lactation. Taken together, these data suggest that increased intracortical perilacunar mineral turnover also contributes to maintaining phosphate levels during periods of high mineral demand. Understanding the mechanisms of skeletal contribution to mineral homeostasis is important to improving the treatment and prevention of fracture risk and bone fragility for female patients with XLH, but also provides important insight into the role and unique adaptations of the maternal skeleton to the demands of fetal development and the needs of postnatal nutrition.

  13. Bone mineral density: testing for osteoporosis

    PubMed Central

    Sheu, Angela; Diamond, Terry

    2016-01-01

    Summary Primary osteoporosis is related to bone loss from ageing. Secondary osteoporosis results from specific conditions that may be reversible. A thoracolumbar X-ray is useful in identifying vertebral fractures, and dual energy X-ray absorptiometry is the preferred method of calculating bone mineral density. The density of the total hip is the best predictor for a hip fracture, while the lumbar spine is the best site for monitoring the effect of treatment. The T-score is a comparison of the patient’s bone density with healthy, young individuals of the same sex. A negative T-score of –2.5 or less at the femoral neck defines osteoporosis. The Z-score is a comparison with the bone density of people of the same age and sex as the patient. A negative Z-score of –2.5 or less should raise suspicion of a secondary cause of osteoporosis. Clinical risk calculators can be used to predict the 10-year probability of a hip or major osteoporotic fracture. A probability of more than 5% for the hip or more than 20% for any fracture is abnormal and treatment may be warranted. PMID:27340320

  14. Bone Mineral Density and Secondary Hyperparathyroidism in Pulmonary Hypertension

    PubMed Central

    Ulrich, Silvia; Hersberger, Martin; Fischler, Manuel; Huber, Lars C; Senn, Oliver; Treder, Ursula; Speich, Rudolf; Schmid, Christoph

    2009-01-01

    Background: Low bone mineral density (BMD) is common in chronic lung diseases and associated with reduced quality of life. Little is known about BMD in pulmonary hypertension (PH). Methods: Steroid-naïve patients with PH (n=34; 19 idiopathic, 15 chronic thromboembolic) had BMD measured by DXA at the time of diagnostic right heart catheterization. Exercise capacity, quality of life and various parameters related to PH severity and bone metabolism were also assessed. 24 patients with left heart failure (LHF) were similarly assessed as controls. Results: The prevalence of osteopenia was high both in PH (80%) and in controls with LHF (75%). Low BMD was associated with lean body mass, age, lower BMI, impaired exercise capacity and in PH with higher pulmonary vascular resistance. Serum parathyroid hormone (PTH) was elevated and considerably higher in PH than in LHF (above normal, in 55 vs 29%). Secondary hyperparathyroidism was not related to impaired renal function but possibly to low vitamin D status. Conclusions: Osteopenia is common in PH and in chronically ill patients with LHF. Osteopenia is associated with known risk factors but in PH also with disease severity. Preventive measures in an increasingly chronic ill PH population should be considered. Secondary hyperparathyroidism is highly prevalent in PH and might contribute to bone and possibly pulmonary vascular disease. Whether adequate vitamin D substitution could prevent low BMD in PH remains to be determined. PMID:19461899

  15. Serum leptin, bone mineral density and the healing of long bone fractures in men with spinal cord injury.

    PubMed

    Wang, Lei; Liu, Linjuan; Pan, Zhanpeng; Zeng, Yanjun

    2015-11-16

    Previously reported fracture rates in patients with spinal cord injury range from 1% to 20%. However, the exact role of spinal cord injury in bone metabolism has not yet been clarified. In order to investigate the effects of serum leptin and bone mineral density on the healing of long bone fractures in men with spinal cord injury, 15 male SCI patients and 15 matched controls were involved in our study. The outcome indicated that at 4 and 8 weeks after bone fracture, callus production in patients with spinal cord injury was lower than that in controls. Besides, bone mineral density was significantly reduced at 2, 4 and 8 weeks. In addition, it was found that at each time point, patients with spinal cord injury had significantly higher serum leptin levels than controls and no association was found between serum leptin level and bone mineral density of lumbar vertebrae. Moreover, bone mineral density was positively correlated with bone formation in both of the groups. These findings suggest that in early phases i.e. week 4 and 8, fracture healing was impaired in patients with spinal cord injury and that various factors participated in the complicated healing process, such as hormonal and mechanical factors.

  16. Skeletal development of mice lacking bone sialoprotein (BSP)--impairment of long bone growth and progressive establishment of high trabecular bone mass.

    PubMed

    Bouleftour, Wafa; Boudiffa, Maya; Wade-Gueye, Ndeye Marième; Bouët, Guénaëlle; Cardelli, Marco; Laroche, Norbert; Vanden-Bossche, Arnaud; Thomas, Mireille; Bonnelye, Edith; Aubin, Jane E; Vico, Laurence; Lafage-Proust, Marie Hélène; Malaval, Luc

    2014-01-01

    Adult Ibsp-knockout mice (BSP-/-) display shorter stature, lower bone turnover and higher trabecular bone mass than wild type, the latter resulting from impaired bone resorption. Unexpectedly, BSP knockout also affects reproductive behavior, as female mice do not construct a proper "nest" for their offsprings. Multiple crossing experiments nonetheless indicated that the shorter stature and lower weight of BSP-/- mice, since birth and throughout life, as well as their shorter femur and tibia bones are independent of the genotype of the mothers, and thus reflect genetic inheritance. In BSP-/- newborns, µCT analysis revealed a delay in membranous primary ossification, with wider cranial sutures, as well as thinner femoral cortical bone and lower tissue mineral density, reflected in lower expression of bone formation markers. However, trabecular bone volume and osteoclast parameters of long bones do not differ between genotypes. Three weeks after birth, osteoclast number and surface drop in the mutants, concomitant with trabecular bone accumulation. The growth plates present a thinner hypertrophic zone in newborns with lower whole bone expression of IGF-1 and higher IHH in 6 days old BSP-/- mice. At 3 weeks the proliferating zone is thinner and the hypertrophic zone thicker in BSP-/- than in BSP+/+ mice of either sex, maybe reflecting a combination of lower chondrocyte proliferation and impaired cartilage resorption. Six days old BSP-/- mice display lower osteoblast marker expression but higher MEPE and higher osteopontin(Opn)/Runx2 ratio. Serum Opn is higher in mutants at day 6 and in adults. Thus, lack of BSP alters long bone growth and membranous/cortical primary bone formation and mineralization. Endochondral development is however normal in mutant mice and the accumulation of trabecular bone observed in adults develops progressively in the weeks following birth. Compensatory high Opn may allow normal endochondral development in BSP-/- mice, while impairing

  17. Hypermineralized whale rostrum as the exemplar for bone mineral

    PubMed Central

    Li, Zhen; Pasteris, Jill D.; Novack, Deborah

    2013-01-01

    Although bone is a nanocomposite of mineral and collagen, mineral has been the more elusive component to study. A standard for bone mineral clearly is needed. We hypothesized that the most natural, least-processed bone mineral could be retrieved from the most highly mineralized bone. We therefore studied the rostrum of the toothed whale Mesoplodon densirostris, which has the densest recognized bone. Essential to establishment of a standard for bone mineral is documentation that the proposed tissue is bone-like in all properties except for its remarkably high concentration of mineral. Transmitted-light microscopy of unstained sections of rostral material shows normal bone morphology in osteon geometry, lacunae concentration, and vasculature development. Stained sections reveal extremely low density of thin collagen fibers throughout most of the bone, but enrichment in and thicker collagen fibers around vascular holes and in a minority of osteons. FE-SEM shows the rostrum to consist mostly of dense mineral prisms. Most rostral areas have the same chemical-structural features, Raman spectroscopically dominated by strong bands at ~962 Δcm−1 and weak bands at ~2940 Δcm−1. Spectral features indicate that the rostrum is composed mainly of the calcium phosphate mineral apatite and has only about 4 wt.% organic content. The degree of carbonate substitution (~8.5 wt.% carbonate) in the apatite is in the upper range found in most types of bone. We conclude that, despite its enamel-like extraordinarily high degree of mineralization, the rostrum is in all other features bone-like. Its mineral component is the long-sought uncontaminated, unaltered exemplar of bone mineral. PMID:23586370

  18. Tissue and cellular basis for impaired bone formation in aluminum-related osteomalacia in the pig.

    PubMed Central

    Sedman, A B; Alfrey, A C; Miller, N L; Goodman, W G

    1987-01-01

    Bone formation is impaired in aluminum-associated bone disease. Reductions in the number of osteoblasts or in the function of individual osteoblasts could account for this finding. Thus, quantitative bone histology and measurements of bone formation were done at three skeletal sites in piglets given aluminum (Al) parenterally, 1.5 mg/kg per d, for 8 wk (Al, n = 4) and in control animals (C, n = 4). Bone Al was 241 +/- 40 mg/kg per dry weight in Al and 1.6 +/- 0.9 in C, P less than 0.001. All Al-treated animals developed osteomalacia with increases in osteoid seam width, osteoid volume, and mineralization lag time at each skeletal site, P less than 0.05 vs. C for all values. Mineralized bone formation at the tissue level was lower in Al than in C, P less than 0.05 for each skeletal site, due to reductions in active bone forming surface. Bone formation at the cellular level was similar in each group, however, and total osteoid production by osteoblasts did not differ in C and Al. Aluminum impairs the formation of mineralized bone in vivo by decreasing the number of active osteoblasts, and this change can be distinguished from the effect of aluminum to inhibit, either directly or indirectly, the calcification of osteoid. PMID:3793934

  19. [Metabolic status and bone mineral density in patients with pseudarthrosis of long bones in hyperhomocysteinemia].

    PubMed

    Bezsmertnyĭ, Iu O

    2013-06-01

    In article described research of the metabolic status and bone mineral density in 153 patients with with pseudarthrosis of long bones, in individuals with consolidated fractures and healthy people. The violations of reparative osteogenesis at hyperhomocysteinemia are accompanied by disturbances of the functional state of bone tissue, inhibition of biosynthetic and increased destruction processes, reduced bone mineral density in the formation of osteopenia and osteoporosis. The degree and direction of change of bone depends on the type of violation of reparative osteogenesis.

  20. Tendon gradient mineralization for tendon to bone interface integration.

    PubMed

    Qu, Jin; Thoreson, Andrew R; Chen, Qingshan; An, Kai-Nan; Amadio, Peter C; Zhao, Chunfeng

    2013-11-01

    Tendon-to-bone integration is a great challenge for tendon or ligament reconstruction regardless of use of autograft or allograft tendons. We mineralized the tendon, thus transforming the tendon-to-bone into a "bone-to-bone" interface for healing. Sixty dog flexor digitorum profundus (FDP) tendons were divided randomly into five groups: (1) normal FDP tendon, (2) CaP (non-extraction and mineralization without fetuin), (3) CaPEXT (Extraction by Na2 HPO4 and mineralization without fetuin), (4) CaPFetuin (non-extraction and mineralization with fetuin), and (5) CaPEXTFetuin (extraction and mineralization with fetuin). The calcium and phosphate content significantly increased in tendons treated with combination of extraction and fetuin compared to the other treatments. Histology also revealed a dense mineral deposition throughout the tendon outer layers and penetrated into the tendon to a depth of 200 µm in a graded manner. Compressive moduli were significantly lower in the four mineralized groups compared with normal control group. No significant differences in maximum failure strength or stiffness were found in the suture pull-out test among all groups. Mineralization of tendon alters the interface from tendon to bone into mineralized tendon to bone, which may facilitate tendon-to-bone junction healing following tendon or ligament reconstruction.

  1. [Bone mineral density in pregnant women from Moscow: possible effects of pregnancy dynamics and nutrient intake].

    PubMed

    Kon, I Ya; Safronova, A I; Gmoshinskaya, M V; Shcheplyagina, L A; Korosteleva, M M; Toboleva, M A; Aleshina, I V; Kurkova, V I; Larionova, Z G

    2014-01-01

    Supporting of bone health is one of the main approaches to provide health in pregnant women considering intensive calcium and other mineral mobilization from mass bone that is necessary forforming fetus bone. This mobilization may lead to decrease of bone mineral density and development of osteopenia and osteoporosis. The important factors of development of bone impairment in pregnancy are nutrition and particular deficient consumption of protein, Ca, vitamin D. The possible role of reduced intake of pregnant women other nutrients remains unexplored. The aim of the research was estimating the prevalence of bone mineral density decrease in regard to the particular course of pregnancy and studying possible effects of key nutrients on bone mineral density in pregnant women. 131 women at different stages of pregnancy were involved in the survey. The bone density assessment was conducted using Bone Densitometer Omnisense 7000. As a criterion for bone density decrease in women used a Z-score, which was considered as normal to -1.0, as reduced from -1.0 to -2,0, and as significantly reduced when Z-score was less than -2,0. Analysis of the actual nutrition was performed by a 24-hour recording of 58 pregnant women. Normal bone mineral density was detected in 54 women or 41% of the total number of women surveyed. In 51 (39%) pregnant women reduced bone mineral density was discovered, and in 26 (20%) patients--significantly reduced bone density. There was a considerable deviation in pregnant patients' diet from the nutrition guidelines, which include, in particular, the high content of fat and saturated fatty acid, reduced intake of some micronutrients such as calcium, zinc, folic acid, β-carotene, vitamins A, B1, E. However, differences in the actual consumption of nutrients in women with varying bone mineral density have been identified only in case of consumption of fat and energy value of diets, also Mn and I. So, it may be suggested that the differences in bone mineral

  2. Derangements in bone mineral parameters and bone mineral density in south Indian subjects on antiepileptic medications

    PubMed Central

    Koshy, George; Varghese, Ron Thomas; Naik, Dukhabandhu; Asha, Hesargatta Shyamsunder; Thomas, Nihal; Seshadri, Mandalam Subramaniam; Alexander, Mathew; Thomas, Maya; Aaron, Sanjith; Paul, Thomas Vizhalil

    2014-01-01

    Background: Although there are reports describing the association of alternations of bone and mineral metabolism in epileptic patients with long-term anticonvulsant therapy, there are only limited Indian studies which have looked at this aspect. Objectives: This study was done to compare the prevalence of changes in bone mineral parameters and bone mineral density (BMD) in ambulant individuals on long-term anticonvulsant therapy with age- and body mass index (BMI)-matched healthy controls. Materials and Methods: There were 55 men (on medications for more than 6 months) and age- and BMI-matched 53 controls. Drug history, dietary calcium intake (DCI), and duration of sunlight exposure were recorded. Bone mineral parameters and BMD were measured. Results: The control group had a significantly higher daily DCI with mean ± SD of 396 ± 91 mg versus 326 ± 101 mg (P = 0.007) and more sunlight exposure of 234 ± 81 vs 167 ± 69 min (P = 0.05). BMD at the femoral neck was significantly lower in cases (0.783 ± 0.105 g/cm2) when compared to controls (0.819 ± 0.114 g/cm2). Majority of the patients (61%) had low femoral neck BMD (P = 0.04). There was no significant difference in the proportion of subjects with vitamin D deficiency (<20 ng/mL) between cases (n = 32) and controls (n = 37) (P = 0.234). Conclusions: Vitamin D deficiency was seen in both the groups in equal proportions, highlighting the existence of a high prevalence of this problem in India. Low femoral neck BMD found in cases may stress the need for supplementing calcium and treating vitamin D deficiency in this specific group. However, the benefit of such intervention has to be studied in a larger proportion of epileptic patients. PMID:25221394

  3. Low bone mineral density and decreased bone turnover in Duchenne muscular dystrophy.

    PubMed

    Söderpalm, Ann-Charlott; Magnusson, Per; Ahlander, Anne-Christine; Karlsson, Jón; Kroksmark, Anna-Karin; Tulinius, Már; Swolin-Eide, Diana

    2007-12-01

    This cross-sectional study examined bone mineral density, bone turnover, body composition and calciotropic hormones in 24 boys with Duchenne muscular dystrophy (DMD) (2.3-19.7 years), most of whom were being treated with prednisolone, and 24 age-matched healthy boys. Our study demonstrated lower bone mineral density in the DMD group for total body, spine, hip, heel and forearm measurements. These differences between DMD patients and controls increased with increasing age. Biochemical markers of both bone formation and resorption revealed reduced bone turnover in DMD patients. The fracture rate was not higher in DMD patients. The DMD group had low vitamin D levels but high leptin levels in comparison with the control group. Muscle strength correlated with bone mineral density assessed at the hip and heel in the DMD group. Interventions that increase bone formation should be considered, as DMD patients have reduced bone turnover in addition to their low bone mineral density.

  4. Assessing screening criteria for the radiocarbon dating of bone mineral

    NASA Astrophysics Data System (ADS)

    Fernandes, Ricardo; Hüls, Matthias; Nadeau, Marie-Josée; Grootes, Pieter M.; Garbe-Schönberg, C.-Dieter; Hollund, Hege I.; Lotnyk, Andriy; Kienle, Lorenz

    2013-01-01

    Radiocarbon dating of bone mineral (carbonate in the apatite lattice) has been the target of sporadic research for the last 40 years. Results obtained by different decontamination protocols have, however, failed to provide a consistent agreement with reference ages. In particular, quality criteria to assess bone mineral radiocarbon dating reliability are still lacking. Systematic research was undertaken to identify optimal preservation criteria for bone mineral in archeological bones. Six human long bones, originating from a single site, were radiocarbon-dated both for collagen and apatite, with the level of agreement between the dates providing an indication of exogenous carbon contamination. Several techniques (Histology, FTIR, TEM, LA-ICP-MS) were employed to determine the preservation status of each sample. Research results highlight the importance of a micro-scale approach in establishing bone preservation, in particular the use of trace element concentration profiles demonstrated its potential use as a viable sample selection criterion for bone carbonate radiocarbon dating.

  5. Minerals form a continuum phase in mature cancellous bone.

    PubMed

    Chen, Po-Yu; Toroian, Damon; Price, Paul A; McKittrick, Joanna

    2011-05-01

    Bone is a hierarchically structured composite consisting of a protein phase (type I collagen) and a mineral phase (carbonated apatite). The objective of this study was to investigate the hierarchical structure of mineral in mature bone. A method to completely deproteinize bone without altering the original structure is developed, and the completion is confirmed by protein analysis techniques. Stereoscopy and field emission electron microscopy are used to examine the structural features from submillimeter- to micrometer- to nanometer-length scales of bovine femur cancellous bone. Stereoscopic images of fully deproteinized and demineralized bovine femur cancellous bone samples show that fine trabecular architecture is unaltered and the microstructural features are preserved, indicating the structural integrity of mineral and protein constituents. SEM revealed that bone minerals are fused together and form a sheet-like structure in a coherent manner with collagen fibrils. Well-organized pore systems are observed at varying hierarchical levels. Mineral sheets are peeled off and folded after compressive deformation, implying strong connection between individual crystallites. Results were compared with commercially available heat-deproteinized bone (Bio-Oss(®)), and evidence showed consistency in bone mineral structure. A two-phase interpenetrating composite model of mature bone is proposed and discussed.

  6. Low bone mineral density among young healthy adult Saudi women

    PubMed Central

    Zeidan, Zeidan A.; Sultan, Intisar E.; Guraya, Shaista S.; Al-Zalabani, Abdulmohsen H.; Khoshhal, Khalid I.

    2016-01-01

    Objectives: To screen for low bone mineral density among young adult Saudi women using quantitative ultrasound (QUS) and exploring the high risk groups. Methods: A cross-sectional study was performed on 279, 20-36 years old female students and employees of Taibah University, Al Madinah Al Munawwarah, Kingdom of Saudi Arabia between January and May 2014. The study included bone status assessed using QUS, a structured self-reported questionnaire, anthropometric measurements, and evaluation of bone markers of bone metabolism. Results: The prevalence of low bone mineral density was 9%. Serum osteocalcin was found significantly higher in candidates with low bone mineral density, 20.67 ng/ml versus 10.7 ng/ml, and it was negatively correlated with T-scores. At any given point in time the exposed subjects to low calcium intake and inadequate sun exposure in the population were 11 times and 3 times more likely to have low bone mineral density, (adjusted odds ratio [OR], 11.0; 95%confidence interval [CI]=3.16, 38.34; p=0.001) and (adjusted OR, 3.32, 95%CI=1.27, 8.66, p<0.01). Conclusion: Early detection screening programs for low bone mineral density are needed in Saudi Arabia as it affects young Saudi women specially the high-risk group that includes young women with insufficient calcium intake and insufficient sun exposure. Serum osteocalcin as a biomarker for screening for low bone mineral density could be introduced. PMID:27761561

  7. Bone mineral density in children and young adults with neurofibromatosis type 1.

    PubMed

    Lodish, Maya B; Dagalakis, Urania; Sinaii, Ninet; Bornstein, Ethan; Kim, Aerang; Lokie, Kelsey B; Baldwin, Andrea M; Reynolds, James C; Dombi, Eva; Stratakis, Constantine A; Widemann, Brigitte C

    2012-12-01

    Concern for impaired bone health in children with neurofibromatosis type 1 (NF-1) has led to increased interest in bone densitometry in this population. Our study assessed bone mineral apparent density (BMAD) and whole-body bone mineral content (BMC)/height in pediatric patients with NF-1 with a high plexiform neurofibroma burden. Sixty-nine patients with NF-1 (age range 5.2-24.8; mean 13.7 ± 4.8 years) were studied. Hologic dual-energy X-ray absorptiometry scans (Hologic, Inc., Bedford, MA, USA) were performed on all patients. BMD was normalized to derive a reference volume by correcting for height through the use of the BMAD, as well as the BMC. BMAD of the lumbar spine (LS 2-4), femoral neck (FN), and total body BMC/height were measured and Z-scores were calculated. Impaired bone mineral density was defined as a Z-score ≤-2. Forty-seven percent of patients exhibited impaired bone mineral density at any bone site, with 36% at the LS, 18% at the FN, and 20% total BMC/height. BMAD Z-scores of the LS (-1.60 ± 1.26) were more impaired compared with both the FN (-0.54 ± 1.58; P=0.0003) and the whole-body BMC/height Z-scores (-1.16 ± 0.90; P=0.036). Plexiform neurofibroma burden was negatively correlated with LS BMAD (r(s)=-0.36, P=0.01). In pediatric and young adult patients with NF-1, LS BMAD was more severely affected than the FN BMAD or whole-body BMC/height.

  8. Deletion of the Intestinal Plasma Membrane Calcium Pump, Isoform 1, Atp2b1, in Mice is Associated with Decreased Bone Mineral Density and Impaired Responsiveness to 1, 25-Dihydroxyvitamin D3

    PubMed Central

    Ryan, Zachary C.; Craig, Theodore A.; Filoteo, Adelaida G.; Westendorf, Jennifer J.; Cartwright, Elizabeth J.; Neyses, Ludwig; Strehler, Emanuel E.; Kumar, Rajiv

    2016-01-01

    The physiological importance of the intestinal plasma membrane calcium pump, isoform 1, (Pmca1, Atp2b1), in calcium absorption and homeostasis has not been previously demonstrated in vivo. Since global germ-line deletion of the Pmca1 in mice is associated with embryonic lethality, we selectively deleted the Pmca1 in intestinal absorptive cells. Mice with loxP sites flanking exon 2 of the Pmca1 gene (Pmca1fl/fl) were crossed with mice expressing Cre recombinase in the intestine under control of the villin promoter to give mice in which the Pmca1 had been deleted in the intestine (Pmca1EKO mice). Pmca1EKO mice were born at a reduced frequency and were small at the time of birth when compared to wild-type (Wt) litter mates. At two months of age, Pmca1EKO mice fed a 0.81% calcium, 0.34% phosphorus, normal vitamin D diet had reduced whole body bone mineral density (P <0.037), and reduced femoral bone mineral density (P <0.015). There was a trend towards lower serum calcium and higher serum parathyroid hormone (PTH) and 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) concentrations in Pmca1EKO mice compared to Wt mice but the changes were not statistically significant. The urinary phosphorus/creatinine ratio was increased in Pmca1EKO mice (P <0.004). Following the administration of 200 ng of 1α,25(OH)2D3 intraperitoneally to Wt mice, active intestinal calcium transport increased ∼2-fold, whereas Pmca1EKO mice administered an equal amount of 1α,25(OH)2D3 failed to show an increase in active calcium transport. Deletion of the Pmca1 in the intestine is associated with reduced growth and bone mineralization, and a failure to up-regulate calcium absorption in response to 1α,25(OH)2D3. PMID:26392310

  9. Prebiotics, probiotics, and synbiotics affect mineral absorption, bone mineral content, and bone structure.

    PubMed

    Scholz-Ahrens, Katharina E; Ade, Peter; Marten, Berit; Weber, Petra; Timm, Wolfram; Açil, Yahya; Glüer, Claus-C; Schrezenmeir, Jürgen

    2007-03-01

    Several studies in animals and humans have shown positive effects of nondigestible oligosaccharides (NDO) on mineral absorption and metabolism and bone composition and architecture. These include inulin, oligofructose, fructooligosaccharides, galactooligosaccharides, soybean oligosaccharide, and also resistant starches, sugar alcohols, and difructose anhydride. A positive outcome of dietary prebiotics is promoted by a high dietary calcium content up to a threshold level and an optimum amount and composition of supplemented prebiotics. There might be an optimum composition of fructooligosaccharides with different chain lengths (synergy products). The efficacy of dietary prebiotics depends on chronological age, physiological age, menopausal status, and calcium absorption capacity. There is evidence for an independent probiotic effect on facilitating mineral absorption. Synbiotics, i.e., a combination of probiotics and prebiotics, can induce additional effects. Whether a low content of habitual NDO would augment the effect of dietary prebiotics or synbiotics remains to be studied. The underlying mechanisms are manifold: increased solubility of minerals because of increased bacterial production of short-chain fatty acids, which is promoted by the greater supply of substrate; an enlargement of the absorption surface by promoting proliferation of enterocytes mediated by bacterial fermentation products, predominantly lactate and butyrate; increased expression of calcium-binding proteins; improvement of gut health; degradation of mineral complexing phytic acid; release of bone-modulating factors such as phytoestrogens from foods; stabilization of the intestinal flora and ecology, also in the presence of antibiotics; stabilization of the intestinal mucus; and impact of modulating growth factors such as polyamines. In conclusion, prebiotics are the most promising but also best investigated substances with respect to a bone-health-promoting potential, compared with probiotics

  10. Bone mineral measurement using dual energy x ray densitometry

    NASA Technical Reports Server (NTRS)

    Smith, Steven W.

    1989-01-01

    Bone mineral measurements before and after space missions have shown that weightlessness greatly accelerates bone demineralization. Bone mineral losses as high as 1 to 3 percent per month were reported. Highly precise instrumentation is required to monitor this loss and thereby test the efficacy of treatment. During the last year, a significant improvement was made in Dual-Photon Absorptiometry by replacing the radioactive source with an x ray tube. Advantages of this system include: better precision, lower patient dose, better spacial resolution, and shorter scan times. The high precision and low radiation dose of this technique will allow detection of bone mineral changes of less than 1 percent with measurements conducted directly at the sites of interest. This will allow the required bone mineral studies to be completed in a shorter time with greater confidence.

  11. Localized tissue mineralization regulated by bone remodelling: A computational approach

    PubMed Central

    Decco, Oscar; Adams, George; Cook, Richard B.; García Aznar, José Manuel

    2017-01-01

    Bone is a living tissue whose main mechanical function is to provide stiffness, strength and protection to the body. Both stiffness and strength depend on the mineralization of the organic matrix, which is constantly being remodelled by the coordinated action of the bone multicellular units (BMUs). Due to the dynamics of both remodelling and mineralization, each sample of bone is composed of structural units (osteons in cortical and packets in cancellous bone) created at different times, therefore presenting different levels of mineral content. In this work, a computational model is used to understand the feedback between the remodelling and the mineralization processes under different load conditions and bone porosities. This model considers that osteoclasts primarily resorb those parts of bone closer to the surface, which are younger and less mineralized than older inner ones. Under equilibrium loads, results show that bone volumes with both the highest and the lowest levels of porosity (cancellous and cortical respectively) tend to develop higher levels of mineral content compared to volumes with intermediate porosity, thus presenting higher material densities. In good agreement with recent experimental measurements, a boomerang-like pattern emerges when plotting apparent density at the tissue level versus material density at the bone material level. Overload and disuse states are studied too, resulting in a translation of the apparent–material density curve. Numerical results are discussed pointing to potential clinical applications. PMID:28306746

  12. Localized tissue mineralization regulated by bone remodelling: A computational approach.

    PubMed

    Berli, Marcelo; Borau, Carlos; Decco, Oscar; Adams, George; Cook, Richard B; García Aznar, José Manuel; Zioupos, Peter

    2017-01-01

    Bone is a living tissue whose main mechanical function is to provide stiffness, strength and protection to the body. Both stiffness and strength depend on the mineralization of the organic matrix, which is constantly being remodelled by the coordinated action of the bone multicellular units (BMUs). Due to the dynamics of both remodelling and mineralization, each sample of bone is composed of structural units (osteons in cortical and packets in cancellous bone) created at different times, therefore presenting different levels of mineral content. In this work, a computational model is used to understand the feedback between the remodelling and the mineralization processes under different load conditions and bone porosities. This model considers that osteoclasts primarily resorb those parts of bone closer to the surface, which are younger and less mineralized than older inner ones. Under equilibrium loads, results show that bone volumes with both the highest and the lowest levels of porosity (cancellous and cortical respectively) tend to develop higher levels of mineral content compared to volumes with intermediate porosity, thus presenting higher material densities. In good agreement with recent experimental measurements, a boomerang-like pattern emerges when plotting apparent density at the tissue level versus material density at the bone material level. Overload and disuse states are studied too, resulting in a translation of the apparent-material density curve. Numerical results are discussed pointing to potential clinical applications.

  13. Molecular packing in bone collagen fibrils prior to mineralization

    NASA Astrophysics Data System (ADS)

    Hsiao, Benjamin; Zhou, Hong-Wen; Burger, Christian; Chu, Benjamin; Glimcher, Melvin J.

    2012-02-01

    The three-dimensional packing of collagen molecules in bone collagen fibrils has been largely unknown because even in moderately mineralized bone tissues, the organic matrix structure is severely perturbed by the deposition of mineral crystals. During the past decades, the structure of tendon collagen (e.g. rat tail) --- a tissue that cannot mineralize in vivo, has been assumed to be representative for bone collagen fibrils. Small-angle X-ray diffraction analysis of the native, uncalcified intramuscular fish bone has revealed a new molecular packing scheme, significantly different from the quasi-hexagonal arrangement often found in tendons. The deduced structure in bone collagen fibrils indicates the presence of spatially discrete microfibrils, and an arrangement of intrafibrillar space to form ``channels'', which could accommodate crystals with dimensions typically found in bone apatite.

  14. Bone mineral density, adiposity, and cognitive functions

    PubMed Central

    Sohrabi, Hamid R.; Bates, Kristyn A.; Weinborn, Michael; Bucks, Romola S.; Rainey-Smith, Stephanie R.; Rodrigues, Mark A.; Bird, Sabine M.; Brown, Belinda M.; Beilby, John; Howard, Matthew; Criddle, Arthur; Wraith, Megan; Taddei, Kevin; Martins, Georgia; Paton, Athena; Shah, Tejal; Dhaliwal, Satvinder S.; Mehta, Pankaj D.; Foster, Jonathan K.; Martins, Ian J.; Lautenschlager, Nicola T.; Mastaglia, Francis; Laws, Simon M.; Martins, Ralph N.

    2015-01-01

    Cognitive decline and dementia due to Alzheimer's disease (AD) have been associated with genetic, lifestyle, and environmental factors. A number of potentially modifiable risk factors should be taken into account when preventive or ameliorative interventions targeting dementia and its preclinical stages are investigated. Bone mineral density (BMD) and body composition are two such potentially modifiable risk factors, and their association with cognitive decline was investigated in this study. 164 participants, aged 34–87 years old (62.78 ± 9.27), were recruited for this longitudinal study and underwent cognitive and clinical examinations at baseline and after 3 years. Blood samples were collected for apolipoprotein E (APOE) genotyping and dual energy x-ray absorptiometry (DXA) was conducted at the same day as cognitive assessment. Using hierarchical regression analysis, we found that BMD and lean body mass, as measured using DXA were significant predictors of episodic memory. Age, gender, APOE status, and premorbid IQ were controlled for. Specifically, the List A learning from California Verbal Learning Test was significantly associated with BMD and lean mass both at baseline and at follow up assessment. Our findings indicate that there is a significant association between BMD and lean body mass and episodic verbal learning. While the involvement of modifiable lifestyle factors in human cognitive function has been examined in different studies, there is a need for further research to understand the potential underlying mechanisms. PMID:25741279

  15. Increased calcium content and inhomogeneity of mineralization render bone toughness in osteoporosis: mineralization, morphology and biomechanics of human single trabeculae.

    PubMed

    Busse, Björn; Hahn, Michael; Soltau, Markus; Zustin, Jozef; Püschel, Klaus; Duda, Georg N; Amling, Michael

    2009-12-01

    showed biomechanically beneficial properties due to a homogeneous mineralization configuration, whereas osteoporotic trabeculae predominantly demonstrated various mineralized bone packets, eroded surfaces, highly mineralized cement lines and microcracks. The Young's moduli of single trabeculae exhibited significantly negative linear correlations with trabecular thickness. Because of increased, but inhomogeneously distributed, calcium content, osteoporotic trabeculae may be subject to shear stresses that render bone fragile beyond structure impairment due to cracks and lacunae.

  16. Autophagy in osteoblasts is involved in mineralization and bone homeostasis

    PubMed Central

    Nollet, Marie; Santucci-Darmanin, Sabine; Breuil, Véronique; Al-Sahlanee, Rasha; Cros, Chantal; Topi, Majlinda; Momier, David; Samson, Michel; Pagnotta, Sophie; Cailleteau, Laurence; Battaglia, Séverine; Farlay, Delphine; Dacquin, Romain; Barois, Nicolas; Jurdic, Pierre; Boivin, Georges; Heymann, Dominique; Lafont, Frank; Lu, Shi Shou; Dempster, David W; Carle, Georges F; Pierrefite-Carle, Valérie

    2014-01-01

    Bone remodeling is a tightly controlled mechanism in which osteoblasts (OB), the cells responsible for bone formation, osteoclasts (OC), the cells specialized for bone resorption, and osteocytes, the multifunctional mechanosensing cells embedded in the bone matrix, are the main actors. Increased oxidative stress in OB, the cells producing and mineralizing bone matrix, has been associated with osteoporosis development but the role of autophagy in OB has not yet been addressed. This is the goal of the present study. We first show that the autophagic process is induced in OB during mineralization. Then, using knockdown of autophagy-essential genes and OB-specific autophagy-deficient mice, we demonstrate that autophagy deficiency reduces mineralization capacity. Moreover, our data suggest that autophagic vacuoles could be used as vehicles in OB to secrete apatite crystals. In addition, autophagy-deficient OB exhibit increased oxidative stress and secretion of the receptor activator of NFKB1 (TNFSF11/RANKL), favoring generation of OC, the cells specialized in bone resorption. In vivo, we observed a 50% reduction in trabecular bone mass in OB-specific autophagy-deficient mice. Taken together, our results show for the first time that autophagy in OB is involved both in the mineralization process and in bone homeostasis. These findings are of importance for mineralized tissues which extend from corals to vertebrates and uncover new therapeutic targets for calcified tissue-related metabolic pathologies. PMID:25484092

  17. Method for improved prediction of bone fracture risk using bone mineral density in structural analysis

    NASA Technical Reports Server (NTRS)

    Cann, Christopher E. (Inventor); Faulkner, Kenneth G. (Inventor)

    1992-01-01

    A non-invasive in-vivo method of analyzing a bone for fracture risk includes obtaining data from the bone such as by computed tomography or projection imaging which data represents a measure of bone material characteristics such as bone mineral density. The distribution of the bone material characteristics is used to generate a finite element method (FEM) mesh from which load capability of the bone can be determined. In determining load capability, the bone is mathematically compressed, and stress, strain force, force/area versus bone material characteristics are determined.

  18. Dependence of Long Bone Flexural Properties on Bone Mineral Distribution

    NASA Technical Reports Server (NTRS)

    Katz, BethAnn; Cleek, Tammy M.; Whalen, Robert T.; Connolly, James P. (Technical Monitor)

    1995-01-01

    The objective of this study is to assess whether a non-invasive determination of long bone cross-sectional areal properties using bone densitometry accurately estimates true long bone flexural properties. In this study, section properties of two pairs of human female embalmed tibiae were compared using two methods: special analysis of bone densitometry data, and experimental determination of flexural regidities from bone surface strain measurements during controlled loading.

  19. Analysis of bone protein and mineral composition in bone disease using synchrotron infrared microspectroscopy

    NASA Astrophysics Data System (ADS)

    Miller, Lisa M.; Hamerman, David; Chance, Mark R.; Carlson, Cathy S.

    1999-10-01

    Infrared (IR) microspectroscopy is an analytical technique that is highly sensitive to the chemical components in bone. The brightness of a synchrotron source permits the examination of individual regions of bone in situ at a spatial resolution superior to that of a conventional infrared source. At Beamlines U10B and U2B at the National Synchrotron Light Source, we are examining the role of bone chemical composition in bone disease. In osteoarthritis (OA), it has been demonstrated that the bone underlying the joint cartilage (subchondral bone) becomes thickened prior to cartilage breakdown. Using synchrotron infrared microspectroscopy, we have examined the chemical composition of the subchondral bone in histologically normal and OA monkeys. Results demonstrate that the subchondral bone of OA monkeys is significantly more mineralized than the normal bone, primarily due to an increase in carbonate concentration in the OA bone. High resolution analysis indicates that differences in carbonate content are uniform throughout the subchondral bone region, suggesting that high subchondral bone carbonate may be a marker for OA. Conversely, increases in phosphate content are more pronounced in the region near the marrow space, suggesting that, as the subchondral bone thickens, the bone also becomes more mineralized. Osteoporosis is a disease characterized by a reduction in bone mass and a skeleton that is more susceptible to fracture. To date, it is unclear whether bone remodeled after the onset of osteoporosis differs in chemical composition from older bone. Using fluorescence-assisted infrared microspectroscopy, we are comparing the composition of monkey bone remodeled at various time points after the onset of osteoporosis (induced by ovariectomy). We find that the chemical composition of bone remodeled one year after ovariectomy and one year prior to necropsy is similar to normal bone. On the other hand, bone remodeled two years after ovariectomy is less mature, indicated

  20. Molecular mechanics of mineralized collagen fibrils in bone

    NASA Astrophysics Data System (ADS)

    Nair, Arun K.; Gautieri, Alfonso; Chang, Shu-Wei; Buehler, Markus J.

    2013-04-01

    Bone is a natural composite of collagen protein and the mineral hydroxyapatite. The structure of bone is known to be important to its load-bearing characteristics, but relatively little is known about this structure or the mechanism that govern deformation at the molecular scale. Here we perform full-atomistic calculations of the three-dimensional molecular structure of a mineralized collagen protein matrix to try to better understand its mechanical characteristics under tensile loading at various mineral densities. We find that as the mineral density increases, the tensile modulus of the network increases monotonically and well beyond that of pure collagen fibrils. Our results suggest that the mineral crystals within this network bears up to four times the stress of the collagen fibrils, whereas the collagen is predominantly responsible for the material’s deformation response. These findings reveal the mechanism by which bone is able to achieve superior energy dissipation and fracture resistance characteristics beyond its individual constituents.

  1. Do metabolic syndrome and its components have an impact on bone mineral density in adolescents?

    PubMed

    da Silva, Valéria Nóbrega; Fiorelli, Luciana Nunes Mosca; da Silva, Carla Cristiane; Kurokawa, Cilmery Suemi; Goldberg, Tamara Beres Lederer

    2017-01-01

    In recent years, there has been growing concern about the occurrence of metabolic syndrome (MetS) at an early age and its effects on bone mass in adolescents. Adolescence is considered a critical period for bone mass gain. Impaired bone acquisition during this phase can lead to "suboptimal" peak bone mass and increase the risk of osteopenia/osteoporosis and fractures in old age. The objective of this review was to perform a critical analysis of articles that specifically focus on this age group, evaluating the influence of MetS and its components on bone mineral density in adolescents. A possible relationship between this syndrome and bone mass has been demonstrated, but the number of studies addressing this topic in adolescents is small. Despite the scarcity of evidence, the results of those studies show that Metabolic Syndrome is negatively correlated with bone mass and also that some components of MetS are negatively correlated with bone mineral density in adolescents. However, the associations between MetS and bone mass development need to be further explored in the age group corresponding to adolescence. Further good-quality studies are necessary to complement the understanding of this relationship.

  2. Bone mineral density testing after fragility fracture

    PubMed Central

    Posen, Joshua; Beaton, Dorcas E.; Sale, Joanna; Bogoch, Earl R.

    2013-01-01

    Abstract Objective To determine the proportion of patients with fragility fractures who can be expected to have low bone mineral density (BMD) at the time of fracture and to assist FPs in deciding whether to refer patients for BMD testing. Data sources MEDLINE, EMBASE, and CINAHL were searched from the earliest available dates through September 2009. Study selection English-language articles reporting BMD test results of patients with fragility fractures who were managed in an orthopedic environment (eg, fracture clinic, emergency management by orthopedic surgeons, inpatients) were eligible for review. While the orthopedic environment has been identified as an ideal point for case finding, FPs are often responsible for investigation and treatment. Factors that potentially influenced BMD test results (eg, selection of fracture types, exclusion criteria) were identified. Studies with 2 or more selection factors of potential influence were flagged, and rates of low BMD were calculated including and excluding these studies. Synthesis The distribution of the proportion of persons with low BMD was summarized across studies using descriptive statistics. We calculated lower boundaries on this distribution, using standard statistical thresholds, to determine a lower threshold of the expected rate of low BMD. Conclusion Family physicians evaluating patients with fragility fractures can expect that at least two-thirds of patients with fragility fractures who are older than 50 years of age will have low BMD (T score ≤ −1.0). With this a priori expectation, FPs might more readily conduct a fracture risk assessment and pursue warranted fracture risk reduction strategies following fragility fracture. PMID:24336562

  3. Bone mineral status in children with congenital adrenal hyperplasia.

    PubMed

    Fleischman, Amy; Ringelheim, Julie; Feldman, Henry A; Gordon, Catherine M

    2007-02-01

    Congenital adrenal hyperplasia (CAH) is caused by a deficiency in an adrenal enzyme resulting in alterations in cortisol and aldosterone production. Bone status is affected by chronic glucocorticoid therapy and excess androgen exposure in children with CAH. This cross-sectional study enrolled participants with 21-hydroxylase deficiency from a pediatric referral center. Bone mineral density in the participants was normal when compared to age, gender and ethnicity adjusted standards, with respect to chronological age or bone age. Lean body mass was positively correlated with bone mineral content (BMC), independent of fat mass (p < 0.001). There was no significant correlation between glucocorticoid dose or serum androgen levels and skeletal endpoints. In conclusion, lean body mass appears to be an important correlate of BMC in patients with CAH. The normal bone status may be explained by the differential effects of glucocorticoids on growing bone, beneficial androgen effects, or other disease specific factors.

  4. Osteocyte regulation of bone mineral: a little give and take.

    PubMed

    Atkins, G J; Findlay, D M

    2012-08-01

    Osteocytes actively participate in almost every phase of mineral handling by bone. They regulate the mineralisation of osteoid during bone formation, and they are also a major RANKL-producing cell. Osteocytes are thus able to liberate bone mineral by regulating osteoclast differentiation and activity in response to a range of stimuli, including bone matrix damage, bone disuse and mechanical unloading, oestrogen deficiency, high-dose glucocorticoid and chemotherapeutic agents. At least some of these activities may be regulated by the osteocyte-secreted product, sclerostin. There is also mounting evidence that in addition to regulating phosphate homeostasis systemically, osteocytes contribute directly to calcium homeostasis in the mature skeleton. Osteocyte cell death and the local loss of control of bone mineralisation may be the cause of focal hypermineralisation of bone and osteopetrosis, as seen in aging and pathology. The sheer number of osteocytes in bone means that "a little give and take" in terms of regulation of bone mineral content translates into a powerful whole organism effect.

  5. High dietary intake of retinol leads to bone marrow hypoxia and diaphyseal endosteal mineralization in rats.

    PubMed

    Lind, Thomas; Lind, P Monica; Jacobson, Annica; Hu, Lijuan; Sundqvist, Anders; Risteli, Juha; Yebra-Rodriguez, Africa; Larsson, Sune; Rodriguez-Navarro, Alejandro; Andersson, Göran; Melhus, Håkan

    2011-03-01

    Vitamin A (retinol) is the only molecule known to induce spontaneous fractures in laboratory animals and we have identified retinol as a risk factor for fracture in humans. Since subsequent observational studies in humans and old animal data both show that high retinol intake appears to only have small effects on bone mineral density (BMD) we undertook a mechanistic study of how excess retinol reduces bone diameter while leaving BMD essentially unaffected. We fed growing rats high doses of retinol for only 1 week. Bone analysis involved antibody-based methods, histology, pQCT, biomechanics and bone compartment-specific PCR together with Fourier Transform Infrared Spectroscopy of bone mineral. Excess dietary retinol induced weakening of bones with little apparent effect on BMD. Periosteal osteoclasts increased but unexpectedly endosteal osteoclasts disappeared and there was a reduction of osteoclastic serum markers. There was also a lack of capillary erythrocytes, endothelial cells and serum retinol transport protein in the endosteal/marrow compartment. A further indication of reduced endosteal/marrow blood flow was the increased expression of hypoxia-associated genes. Also, in contrast to the inhibitory effects in vitro, the marrow of retinol-treated rats showed increased expression of osteogenic genes. Finally, we show that hypervitaminotic bones have a higher degree of mineralization, which is in line with biomechanical data of preserved stiffness in spite of thinner bones. Together these novel findings suggest that a rapid primary effect of excess retinol on bone tissue is the impairment of endosteal/marrow blood flow leading to hypoxia and pathological endosteal mineralization.

  6. The pathogenesis of infantile malignant osteopetrosis: bone mineral metabolism and complications in five infants.

    PubMed

    Reeves, J; Arnaud, S; Gordon, S; Subryan, B; Block, M; Huffer, W; Arnaud, C; Mundy, G; Haussler, M

    1981-01-01

    Bone mineral metabolism was studied in five infants aged 8 to 22 months with severe osteopetrosis. There were findings consistent with biochemical osteomalacia. These included hypocalcemia, hypophosphatemia, high serum acid phosphatase and alkaline phosphatase activity, high levels of serum parathyroid hormone, and high urinary cyclic AMP. Serum 1,25(OH)2 vitamin D3 level was high in the one patient tested. Radiographs in all infants revealed rachitic changes in the metaphyses. However, dense bones on radiographs, calcium balance studies, and radio-calcium absorption studies demonstrated markedly positive calcium balance. Iliac crest bone biopsies showed increased quantity of woven bone with abundant numbers of osteoclasts, excessive amounts of osteoid, myelofibrosis, and a decreased number of Howship's lacunae. The wide bands of unmineralized osteoid did not take up tetracycline. In vitro bone resorbing activity due to osteoclast activating factor from cultured stimulated leukocytes was normal. Bone turnover however, was now as evidenced by low urinary hydroxyproline levels. We interpret these findings as indicating there is decreased bone remodeling and resorption in spite of increased humoral stimuli and osteoclasts. Since calcitonin levels were normal for age, the most likely cause of the impaired bone remodeling sequence was defective osteoclast function. We postulate that there may be a common genetic defect in phagocyte cells, including monocytes, neutrophils and osteoclasts, which accounts for the abnormalities of mineral metabolism and previously reported hematologic, neurologic, and infectious complications.

  7. Alterations to the Gut Microbiome Impair Bone Strength and Tissue Material Properties.

    PubMed

    Guss, Jason D; Horsfield, Michael W; Fontenele, Fernanda F; Sandoval, Taylor N; Luna, Marysol; Apoorva, Fnu; Lima, Svetlana F; Bicalho, Rodrigo C; Singh, Ankur; Ley, Ruth E; van der Meulen, Marjolein Ch; Goldring, Steven R; Hernandez, Christopher J

    2017-02-27

    Alterations in the gut microbiome have been associated with changes in bone mass and microstructure, but the effects of the microbiome on bone biomechanical properties are not known. Here we examined bone strength under two conditions of altered microbiota: (1) an inbred mouse strain known to develop an altered gut microbiome due to deficits in the immune system (the Toll-like receptor 5-deficient mouse [TLR5KO]); and (2) disruption of the gut microbiota (ΔMicrobiota) through chronic treatment with selected antibiotics (ampicillin and neomycin). The bone phenotypes of TLR5KO and WT (C57Bl/6) mice were examined after disruption of the microbiota from 4 weeks to 16 weeks of age as well as without treatment (n = 7 to 16/group, 39 animals total). Femur bending strength was less in ΔMicrobiota mice than in untreated animals and the reduction in strength was not fully explained by differences in bone cross-sectional geometry, implicating impaired bone tissue material properties. Small differences in whole-bone bending strength were observed between WT and TLR5KO mice after accounting for differences in bone morphology. No differences in trabecular bone volume fraction were associated with genotype or disruption of gut microbiota. Treatment altered the gut microbiota by depleting organisms from the phyla Bacteroidetes and enriching for Proteobacteria, as determined from sequencing of fecal 16S rRNA genes. Differences in splenic immune cell populations were also observed; B and T cell populations were depleted in TLR5KO mice and in ΔMicrobiota mice (p < 0.001), suggesting an association between alterations in bone tissue material properties and immune cell populations. We conclude that alterations in the gut microbiota for extended periods during growth may lead to impaired whole-bone mechanical properties in ways that are not explained by bone geometry. © 2017 American Society for Bone and Mineral Research.

  8. Contribution of mineral to bone structural behavior and tissue mechanical properties.

    PubMed

    Donnelly, Eve; Chen, Dan X; Boskey, Adele L; Baker, Shefford P; van der Meulen, Marjolein C H

    2010-11-01

    Bone geometry and tissue material properties jointly govern whole-bone structural behavior. While the role of geometry in structural behavior is well characterized, the contribution of the tissue material properties is less clear, partially due to the multiple tissue constituents and hierarchical levels at which these properties can be characterized. Our objective was to elucidate the contribution of the mineral phase to bone mechanical properties across multiple length scales, from the tissue material level to the structural level. Vitamin D and calcium deficiency in 6-week-old male rats was employed as a model of reduced mineral content with minimal collagen changes. The structural properties of the humeri were measured in three-point bending and related to the mineral content and geometry from microcomputed tomography. Whole-cortex and local bone tissue properties were examined with infrared (IR) spectroscopy, Raman spectroscopy, and nanoindentation to understand the role of altered mineral content on the constituent material behavior. Structural stiffness (-47%) and strength (-50%) were reduced in vitamin D-deficient (-D) humeri relative to controls. Moment of inertia (-38%), tissue mineral density (TMD, -9%), periosteal mineralization (-28%), and IR mineral:matrix ratio (-19%) were reduced in -D cortices. Thus, both decreased tissue mineral content and changes in cortical geometry contributed to impaired skeletal load-bearing function. In fact, 97% of the variability in humeral strength was explained by moment of inertia, TMD, and IR mineral:matrix ratio. The strong relationships between structural properties and cortical material composition demonstrate a critical role of the microscale material behavior in skeletal load-bearing performance.

  9. Effect of HIP/ribosomal protein L29 deficiency on mineral properties of murine bones and teeth.

    PubMed

    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

    2010-07-01

    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.

  10. Mechanical properties of nacre and highly mineralized bone.

    PubMed

    Currey, J D; Zioupos, P; Davies, P; Casino, A

    2001-01-07

    We compared the mechanical properties of 'ordinary' bovine bone, the highly mineralized bone of the rostrum of the whale Mesoplodon densirostris, and mother of pearl (nacre) of the pearl oyster Pinctada margaritifera. The rostrum and the nacre are similar in having very little organic material. However, the rostral bone is much weaker and more brittle than nacre, which in these properties is close to ordinary bone. The ability of nacre to outperform rostral bone is the result of its extremely well-ordered microstructure, with organic material forming a nearly continuous jacket round all the tiny aragonite plates, a design well adapted to produce toughness. In contrast, in the rostrum the organic material, mainly collagen, is poorly organized and discontinuous, allowing the mineral to join up to form, in effect, a brittle stony material.

  11. Mechanical properties of nacre and highly mineralized bone.

    PubMed Central

    Currey, J D; Zioupos, P; Davies, P; Casino, A

    2001-01-01

    We compared the mechanical properties of 'ordinary' bovine bone, the highly mineralized bone of the rostrum of the whale Mesoplodon densirostris, and mother of pearl (nacre) of the pearl oyster Pinctada margaritifera. The rostrum and the nacre are similar in having very little organic material. However, the rostral bone is much weaker and more brittle than nacre, which in these properties is close to ordinary bone. The ability of nacre to outperform rostral bone is the result of its extremely well-ordered microstructure, with organic material forming a nearly continuous jacket round all the tiny aragonite plates, a design well adapted to produce toughness. In contrast, in the rostrum the organic material, mainly collagen, is poorly organized and discontinuous, allowing the mineral to join up to form, in effect, a brittle stony material. PMID:12123292

  12. Weight Loss and Bone Mineral Density

    PubMed Central

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

    2014-01-01

    Purpose of the Review 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 BMD, fearing BMD will be decreased. Confusion exists concerning the effects weight loss has on bone health. Recent Findings Bone density is more closely associated with lean mass than total body mass and fat mass. Although rapid/large weight loss is often associated with loss of bone density, slower/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. While 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. Summary 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. PMID:25105997

  13. Minerals

    MedlinePlus

    Minerals are important for your body to stay healthy. Your body uses minerals for many different jobs, including keeping your bones, muscles, heart, and brain working properly. Minerals are also important for making enzymes and hormones. ...

  14. Bone mineral measurement, experiment M078. [space flight effects on human bone composition

    NASA Technical Reports Server (NTRS)

    Rambaut, P. C.; Vogel, J. M.; Ullmann, J.; Brown, S.; Kolb, F., III

    1973-01-01

    Measurement tests revealed few deviations from baseline bone mineral measurements after 56 days in a Skylab-type environment. No mineral change was observed in the right radius. One individual, however, showed a possible mineral loss in the left os calcis and another gained mineral in the right ulna. The cause of the gain is unclear but may be attributable to the heavy exercise routines engaged in by the crewmember in question. Equipment problems were identified during the experiment and rectified.

  15. Mineral metabolism in isolated mouse long bones: Opposite effects of microgravity on mineralization and resorption

    NASA Technical Reports Server (NTRS)

    Veldhuijzen, Jean Paul; Vanloon, Jack J. W. A.

    1994-01-01

    An experiment using isolated skeletal tissues under microgravity, is reported. Fetal mouse long bones (metatarsals) were cultured for 4 days in the Biorack facility of Spacelab during the IML-1 (International Microgravity Laboratory) mission of the Space Shuttle. Overall growth was not affected, however glucose consumption was significantly reduced under microgravity. Mineralization of the diaphysis was also strongly reduced under microgravity as compared to the on-board 1 g group. In contrast, mineral resorption by osteoclasts was signficantly increased. These results indicate that these fetal mouse long bones are a sensitive and useful model to further study the cellular mechanisms involved in the changed mineral metabolism of skeletal tissues under microgravity.

  16. Bone and mineral metabolism in adult celiac disease

    SciTech Connect

    Caraceni, M.P.; Molteni, N.; Bardella, M.T.; Ortolani, S.; Nogara, A.; Bianchi, P.A.

    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 significant 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.

  17. Can Dental Cone Beam Computed Tomography Assess Bone Mineral Density?

    PubMed Central

    2014-01-01

    Mineral density distribution of bone tissue is altered by active bone modeling and remodeling due to bone complications including bone disease and implantation surgery. Clinical cone beam computed tomography (CBCT) has been examined whether it can assess oral bone mineral density (BMD) in patient. It has been indicated that CBCT has disadvantages of higher noise and lower contrast than conventional medical computed tomography (CT) systems. On the other hand, it has advantages of a relatively lower cost and radiation dose but higher spatial resolution. However, the reliability of CBCT based mineral density measurement has not yet been fully validated. Thus, the objectives of this review are to discuss 1) why assessment of BMD distribution is important and 2) whether the clinical CBCT can be used as a potential tool to measure the BMD. Brief descriptions of image artefacts associated with assessment of gray value, which has been used to account for mineral density, in CBCT images are provided. Techniques to correct local and conversion errors in obtaining the gray values in CBCT images are also introduced. This review can be used as a quick reference for users who may encounter these errors during analysis of CBCT images. PMID:25006568

  18. Bone healing around nanocrystalline hydroxyapatite, deproteinized bovine bone mineral, biphasic calcium phosphate, and autogenous bone in mandibular bone defects.

    PubMed

    Broggini, Nina; Bosshardt, Dieter D; Jensen, Simon S; Bornstein, Michael M; Wang, Chun-Cheng; Buser, Daniel

    2015-10-01

    The individual healing profile of a given bone substitute with respect to osteogenic potential and substitution rate must be considered when selecting adjunctive grafting materials for bone regeneration procedures. In this study, standardized mandibular defects in minipigs were filled with nanocrystalline hydroxyapatite (HA-SiO), deproteinized bovine bone mineral (DBBM), biphasic calcium phosphate (BCP) with a 60/40% HA/β-TCP (BCP 60/40) ratio, or particulate autogenous bone (A) for histological and histomorphometric analysis. At 2 weeks, percent filler amongst the test groups (DBBM (35.65%), HA-SiO (34.47%), followed by BCP 60/40 (23.64%)) was significantly higher than the more rapidly substituted autogenous bone (17.1%). Autogenous bone yielded significantly more new bone (21.81%) over all test groups (4.91%-7.74%) and significantly more osteoid (5.53%) than BCP 60/40 (3%) and DBBM (2.25%). At 8 weeks, percent filler amongst the test groups (DBBM (31.6%), HA-SiO (31.23%), followed by BCP 60/40 (23.65%)) demonstrated a similar pattern and was again significantly higher as compared to autogenous bone (9.29%). Autogenous bone again exhibited statistically significantly greater new bone (55.13%) over HA-SiO (40.62%), BCP 60/40 (40.21%), and DBBM (36.35%). These results suggest that the osteogenic potential of HA-SiO and BCP is inferior when compared to autogenous bone. However, in instances where a low substitution rate is desired to maintain the volume stability of augmented sites, particularly in the esthetic zone, HA-SiO and DBBM may be favored.

  19. Computerized tomographic determination of spinal bone mineral content

    NASA Technical Reports Server (NTRS)

    Cann, C. E.; Genant, H. K.

    1980-01-01

    The aims of the study were three-fold: to determine the magnitude of vertebral cancellous mineral loss in normal subjects during bedrest, to compare this loss with calcium balance and mineral loss in peripheral bones, and to use the vertebral measurements as an evaluative criterion for the C12MDP treatment and compare it with other methods. The methods used are described and the results from 14 subjects are presented.

  20. Tooth dentin defects reflect genetic disorders affecting bone mineralization

    PubMed Central

    Vital, S. Opsahl; Gaucher, C.; Bardet, C.; Rowe, P.S.; George, A.; Linglart, A.; Chaussain, C.

    2012-01-01

    Several genetic disorders affecting bone mineralization may manifest during dentin mineralization. Dentin and bone are similar in several aspects, especially pertaining to the composition of the extracellular matrix (ECM) which is secreted by well-differentiated odontoblasts and osteoblasts, respectively. However, unlike bone, dentin is not remodelled and is not involved in the regulation of calcium and phosphate metabolism. In contrast to bone, teeth are accessible tissues with the shedding of deciduous teeth and the extractions of premolars and third molars for orthodontic treatment. The feasibility of obtaining dentin makes this a good model to study biomineralization in physiological and pathological conditions. In this review, we focus on two genetic diseases that disrupt both bone and dentin mineralization. Hypophosphatemic rickets is related to abnormal secretory proteins involved in the ECM organization of both bone and dentin, as well as in the calcium and phosphate metabolism. Osteogenesis imperfecta affects proteins involved in the local organization of the ECM. In addition, dentin examination permits evaluation of the effects of the systemic treatment prescribed to hypophosphatemic patients during growth. In conclusion, dentin constitutes a valuable tool for better understanding of the pathological processes affecting biomineralization. PMID:22296718

  1. Bone mineral imaging using a digital magnification mammography system

    NASA Astrophysics Data System (ADS)

    Toyofuku, Fukai; Tokumori, Kenji; Higashida, Yoshiharu; Arimura, Hidetaka; Morishita, Junji; Ohki, Masafumi

    2008-03-01

    The measurement of bone mineral content is important for diagnosis of demineralization diseases such as osteoporosis. A reliable method of obtaining bone mineral images using a digital magnification mammography system has been developed. The full-field digital phase contrast mammography (PCM) system, which has a molybdenum target of 0.1mm focal spot size, was used with 1.75 x magnification. We have performed several phantom experiments using aluminum step wedges (0.2 mm - 6.0 mm in thickness) and a bone mineral standard phantom composed of calcium carbonate and polyurethane (CaCO 3 concentration: 26.7 - 939.0 mg/cm 3) within a water or Lucite phantom. X-ray spectra on the exposure field are measured using a CdTe detector for evaluation of heel effect. From the equations of x-ray attenuation and the thickness of the subjects, quantitative images of both components were obtained. The quantitative images of the two components were obtained for different tube voltages of 24 kV to 39 kV. The relative accuracy was less than 2.5% for the entire aluminum thickness of 0.5 to 6.0 mm at 5 cm water thickness. Accuracy of bone mineral thickness was within 3.5% for 5cm water phantom. The magnified quantitative images of a hand phantom significantly increased the visibility of fine structures of bones. The digital magnification mammography system is useful not only for measurement of bone mineral content, but also high-resolution quantitative imaging of trabecular structure.

  2. Nonenzymatic Glycation and Degree of Mineralization Are Higher in Bone From Fractured Patients With Type 1 Diabetes Mellitus.

    PubMed

    Farlay, Delphine; Armas, Laura A G; Gineyts, Evelyne; Akhter, Mohammed P; Recker, Robert R; Boivin, Georges

    2016-01-01

    Low-energy fractures are frequent complications in type 1 diabetes mellitus patients (T1DM). Modifications of bone intrinsic composition might be a potential cause of fragility observed in diabetic subjects. Advanced glycation end products (AGEs) were found in numerous connective tissues from T1DM patients. However, whether AGEs are present at high levels in bone matrix from diabetic subjects is unknown. Moreover, whether elevated AGEs in the bone matrix impair mineralization has not been addressed in humans. The purposes of this study were 1) to determine whether bone matrix from fracturing and nonfracturing T1DM contained more AGEs than bone from healthy patients (CTL), and 2) to compare the degree of mineralization of bone and hardness between fracturing and nonfracturing T1DM versus CTL. We analyzed iliac crest bone biopsies from 5 fracturing T1DM patients, 5 nonfracturing T1DM patients, and 5 healthy subjects, all age- and sex-matched. AGEs (pentosidine) in bone matrix was measured by high-performance liquid chromatography separately in trabecular and cortical bone. The degree of mineralization of bone (DMB) was assessed by digitized microradiography, and mechanical properties by micro- and nanohardness tests. Trabecular bone from fracturing T1DM exhibited significantly higher levels of pentosidine than CTL (p = 0.04) and was more mineralized than nonfracturing T1DM (p = 0.04) and CTL (p = 0.04). Trabecular bone was not significantly different in pentosidine between nonfracturing T1DM and CTL. Cortical bone from nonfracturing T1DM was not significantly different from CTL. Positive correlations were found between HbA1c and pentosidine (r' = 0.79, p < 0.003) and between HbA1c and DMB (r' = 0.64, p < 0.02). Both modifications could lead to less flexible bone (reduced modulus of elasticity) and a tendency toward low-energy fractures in T1DM patients.

  3. Delayed bone regeneration and low bone mass in a rat model of insulin-resistant type 2 diabetes mellitus is due to impaired osteoblast function.

    PubMed

    Hamann, Christine; Goettsch, Claudia; Mettelsiefen, Jan; Henkenjohann, Veit; Rauner, Martina; Hempel, Ute; Bernhardt, Ricardo; Fratzl-Zelman, Nadja; Roschger, Paul; Rammelt, Stefan; Günther, Klaus-Peter; Hofbauer, Lorenz C

    2011-12-01

    Patients with diabetes mellitus have an impaired bone metabolism; however, the underlying mechanisms are poorly understood. Here, we analyzed the impact of type 2 diabetes mellitus on bone physiology and regeneration using Zucker diabetic fatty (ZDF) rats, an established rat model of insulin-resistant type 2 diabetes mellitus. ZDF rats develop diabetes with vascular complications when fed a Western diet. In 21-wk-old diabetic rats, bone mineral density (BMD) was 22.5% (total) and 54.6% (trabecular) lower at the distal femur and 17.2% (total) and 20.4% (trabecular) lower at the lumbar spine, respectively, compared with nondiabetic animals. BMD distribution measured by backscattered electron imaging postmortem was not different between diabetic and nondiabetic rats, but evaluation of histomorphometric indexes revealed lower mineralized bone volume/tissue volume, trabecular thickness, and trabecular number. Osteoblast differentiation of diabetic rats was impaired based on lower alkaline phosphatase activity (-20%) and mineralized matrix formation (-55%). In addition, the expression of the osteoblast-specific genes bone morphogenetic protein-2, RUNX2, osteocalcin, and osteopontin was reduced by 40-80%. Osteoclast biology was not affected based on tartrate-resistant acidic phosphatase staining, pit formation assay, and gene profiling. To validate the implications of these molecular and cellular findings in a clinically relevant model, a subcritical bone defect of 3 mm was created at the left femur after stabilization with a four-hole plate, and bone regeneration was monitored by X-ray and microcomputed tomography analyses over 12 wk. While nondiabetic rats filled the defects by 57%, diabetic rats showed delayed bone regeneration with only 21% defect filling. In conclusion, we identified suppressed osteoblastogenesis as a cause and mechanism for low bone mass and impaired bone regeneration in a rat model of type 2 diabetes mellitus.

  4. [Regulation of bone mineralization by parathyroid hormone].

    PubMed

    Shimizu, Masaru; Tamura, Tatsuya

    2004-06-01

    In randomized clinical trials, parathyroid hormone (PTH) showed potent anabolic effects on the lumbar spine and decreased the risk of incident vertebral fractures dramatically. Although the anabolic effect of PTH on cortical bone in the femoral neck is still unclear, it should be demonstrated in further clinical studies. Concurrent or sequential therapies of PTH and anti-resorptive agents will be one of the major issues of treatment for osteoporosis in the future.

  5. Probing carbonate in bone forming minerals on the nanometre scale.

    PubMed

    Kłosowski, Michał M; Friederichs, Robert J; Nichol, Robert; Antolin, Nikolas; Carzaniga, Raffaella; Windl, Wolfgang; Best, Serena M; Shefelbine, Sandra J; McComb, David W; Porter, Alexandra E

    2015-07-01

    To devise new strategies to treat bone disease in an ageing society, a more detailed characterisation of the process by which bone mineralises is needed. In vitro studies have suggested that carbonated mineral might be a precursor for deposition of bone apatite. Increased carbonate content in bone may also have significant implications in altering the mechanical properties, for example in diseased bone. However, information about the chemistry and coordination environment of bone mineral, and their spatial distribution within healthy and diseased tissues, is lacking. Spatially resolved analytical transmission electron microscopy is the only method available to probe this information at the length scale of the collagen fibrils in bone. In this study, scanning transmission electron microscopy combined with electron energy-loss spectroscopy (STEM-EELS) was used to differentiate between calcium-containing biominerals (hydroxyapatite, carbonated hydroxyapatite, beta-tricalcium phosphate and calcite). A carbon K-edge peak at 290 eV is a direct marker of the presence of carbonate. We found that the oxygen K-edge structure changed most significantly between minerals allowing discrimination between calcium phosphates and calcium carbonates. The presence of carbonate in carbonated HA (CHA) was confirmed by the formation of peak at 533 eV in the oxygen K-edge. These observations were confirmed by simulations using density functional theory. Finally, we show that this method can be utilised to map carbonate from the crystallites in bone. We propose that our calibration library of EELS spectra could be extended to provide spatially resolved information about the coordination environment within bioceramic implants to stimulate the development of structural biomaterials.

  6. Relationship of bone mineral density to progression of knee osteoarthritis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective. To evaluate the longitudinal relationship between bone mineral density (BMD) and BMD changes and the progression of knee osteoarthritis (OA), as measured by cartilage outcomes. Methods. We used observational cohort data from the Vitamin D for Knee Osteoarthritis trial. Bilateral femoral ...

  7. 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…

  8. Bone-composition imaging using coherent-scatter computed tomography: Assessing bone health beyond bone mineral density

    SciTech Connect

    Batchelar, Deidre L.; Davidson, Melanie T.M.; Dabrowski, Waldemar; Cunningham, Ian A.

    2006-04-15

    Quantitative analysis of bone composition is necessary for the accurate diagnosis and monitoring of metabolic bone diseases. Accurate assessment of the bone mineralization state is the first requirement for a comprehensive analysis. In diagnostic imaging, x-ray coherent scatter depends upon the molecular structure of tissues. Coherent-scatter computed tomography (CSCT) exploits this feature to identify tissue types in composite biological specimens. We have used CSCT to map the distributions of tissues relevant to bone disease (fat, soft tissue, collagen, and mineral) within bone-tissue phantoms and an excised cadaveric bone sample. Using a purpose-built scanner, we have measured hydroxyapatite (bone mineral) concentrations based on coherent-scatter patterns from a series of samples with varying hydroxyapatite content. The measured scatter intensity is proportional to mineral density in true g/cm{sup 3}. Repeated measurements of the hydroxyapatite concentration in each sample were within, at most, 2% of each other, revealing an excellent precision in determining hydroxyapatite concentration. All measurements were also found to be accurate to within 3% of the known values. Phantoms simulating normal, over-, and under-mineralized bone were created by mixing known masses of pure collagen and hydroxyapatite. An analysis of the composite scatter patterns gave the density of each material. For each composite, the densities were within 2% of the known values. Collagen and hydroxyapatite concentrations were also examined in a bone-mimicking phantom, incorporating other bone constituents (fat, soft tissue). Tomographic maps of the coherent-scatter properties of each specimen were reconstructed, from which material-specific images were generated. Each tissue was clearly distinguished and the collagen-mineral ratio determined from this phantom was also within 2% of the known value. Existing bone analysis techniques cannot determine the collagen-mineral ratio in intact

  9. Hake fish bone as a calcium source for efficient bone mineralization.

    PubMed

    Flammini, Lisa; Martuzzi, Francesca; Vivo, Valentina; Ghirri, Alessia; Salomi, Enrico; Bignetti, Enrico; Barocelli, Elisabetta

    2016-01-01

    Calcium is recognized as an essential nutritional factor for bone health. An adequate intake is important to achieve or maintain optimal bone mass in particular during growth and old age. The aim of the present study was to evaluate the efficiency of hake fish bone (HBF) as a calcium source for bone mineralization: in vitro on osteosarcoma SaOS-2 cells, cultured in Ca-free osteogenic medium (OM) and in vivo on young growing rats fed a low-calcium diet. Lithotame (L), a Ca supplement derived from Lithothamnium calcareum, was used as control. In vitro experiments showed that HBF supplementation provided bone mineralization similar to standard OM, whereas L supplementation showed lower activity. In vivo low-Ca HBF-added and L-added diet similarly affected bone deposition. Physico-chemical parameters concerning bone mineralization, such as femur breaking force, tibia density and calcium/phosphorus mineral content, had beneficial effects from both Ca supplementations, in the absence of any evident adverse effect. We conclude HBF derived from by-product from the fish industry is a good calcium supplier with comparable efficacy to L.

  10. [Effect of vitamin D on bone mineral density; bone strength and fracture prevention].

    PubMed

    Okuizumi, Hiroyasu; Harada, Atsushi

    2006-07-01

    Although vitamin D improves bone mineral density 0.66% per year at spine site and 1.23% per year at femoral neck site, respectively, vitamin D is useful for preventing osteoporotic fractures, especially hip fractures in the elderly. Vitamin D affects microstructure and bone turnover for osteoporotic bone to become strong bone. And vitamin D improves muscle function to prevent falls in the elderly. Moreover the appropriate amount and treatment target of vitamin D must be considered for the elderly with many different diseases.

  11. Effect of probiotics supplementation on bone mineral content and bone mass density.

    PubMed

    Parvaneh, Kolsoom; Jamaluddin, Rosita; Karimi, Golgis; Erfani, Reza

    2014-01-01

    A few studies in animals and a study in humans showed a positive effect of probiotic on bone metabolism and bone mass density. Most of the investigated bacteria were Lactobacillus and Bifidobacterium. The positive results of the probiotics were supported by the high content of dietary calcium and the high amounts of supplemented probiotics. Some of the principal mechanisms include (1) increasing mineral solubility due to production of short chain fatty acids; (2) producing phytase enzyme by bacteria to overcome the effect of mineral depressed by phytate; (3) reducing intestinal inflammation followed by increasing bone mass density; (4) hydrolysing glycoside bond food in the intestines by Lactobacillus and Bifidobacteria. These mechanisms lead to increase bioavailability of the minerals. In conclusion, probiotics showed potential effects on bone metabolism through different mechanisms with outstanding results in the animal model. The results also showed that postmenopausal women who suffered from low bone mass density are potential targets to consume probiotics for increasing mineral bioavailability including calcium and consequently increasing bone mass density.

  12. Effect of Probiotics Supplementation on Bone Mineral Content and Bone Mass Density

    PubMed Central

    Parvaneh, Kolsoom; Jamaluddin, Rosita; Karimi, Golgis; Erfani, Reza

    2014-01-01

    A few studies in animals and a study in humans showed a positive effect of probiotic on bone metabolism and bone mass density. Most of the investigated bacteria were Lactobacillus and Bifidobacterium . The positive results of the probiotics were supported by the high content of dietary calcium and the high amounts of supplemented probiotics. Some of the principal mechanisms include (1) increasing mineral solubility due to production of short chain fatty acids; (2) producing phytase enzyme by bacteria to overcome the effect of mineral depressed by phytate; (3) reducing intestinal inflammation followed by increasing bone mass density; (4) hydrolysing glycoside bond food in the intestines by Lactobacillus and Bifidobacteria. These mechanisms lead to increase bioavailability of the minerals. In conclusion, probiotics showed potential effects on bone metabolism through different mechanisms with outstanding results in the animal model. The results also showed that postmenopausal women who suffered from low bone mass density are potential targets to consume probiotics for increasing mineral bioavailability including calcium and consequently increasing bone mass density. PMID:24587733

  13. Kinetic measurements of bone mineral metabolism: The use of Na-22 as a tracer for long-term bone mineral turnover studies

    NASA Technical Reports Server (NTRS)

    Palmer, H. E.

    1978-01-01

    Sodium-22 was studied as a tracer for bone mineral metabolism in rats and dogs. When incorporated into bone during growth from birth to adulthood, the bone becomes uniformly tagged with (22)Na which is released through the metabolic turnover of the bone. The (22)Na which is not incorporated in the bone matrix is rapidly excreted within a few days when animals are fed high but nontoxic levels of NaCl. The (22)Na tracer can be used to measure bone mineral loss in animals during space flight and in research on bone disease.

  14. International longitudinal pediatric reference standards for bone mineral content.

    PubMed

    Baxter-Jones, Adam D G; Burrows, Melonie; Bachrach, Laura K; Lloyd, Tom; Petit, Moira; Macdonald, Heather; Mirwald, Robert L; Bailey, Don; McKay, Heather

    2010-01-01

    To render a diagnosis pediatricians rely upon reference standards for bone mineral density or bone mineral content, which are based on cross-sectional data from a relatively small sample of children. These standards are unable to adequately represent growth in a diverse pediatric population. Thus, the goal of this study was to develop sex and site-specific standards for BMC using longitudinal data collected from four international sites in Canada and the United States. Data from four studies were combined; Saskatchewan Paediatric Bone Mineral Accrual Study (n=251), UBC Healthy Bones Study (n=382); Penn State Young Women's Health Study (n=112) and Stanford's Bone Mineral Accretion study (n=423). Males and females (8 to 25 years) were measured for whole body (WB), total proximal femur (PF), femoral neck (FN) and lumbar spine (LS) BMC (g). Data were analyzed using random effects models. Bland-Altman was used to investigate agreement between predicted and actual data. Age, height, weight and ethnicity independently predicted BMC accrual across sites (P<0.05). Compared to White males, Asian males had 31.8 (6.8) g less WB BMC accrual; Hispanic 75.4 (28.2) g less BMC accrual; Blacks 82.8 (26.3) g more BMC accrual with confounders of age, height and weight controlled. We report similar findings for the PF and FN. Models for females for all sites were similar with age, height and weight as independent significant predictors of BMC accrual (P<0.05). We provide a tool to calculate a child's BMC Z-score, accounting for age, size, sex and ethnicity. In conclusion, when interpreting BMC in pediatrics we recommend standards that are sex, age, size and ethnic specific.

  15. Unique biochemical and mineral composition of whale ear bones.

    PubMed

    Kim, Sora L; Thewissen, J G M; Churchill, Morgan M; Suydam, Robert S; Ketten, Darlene R; Clementz, Mark T

    2014-01-01

    Abstract Cetaceans are obligate aquatic mammals derived from terrestrial artiodactyls. The defining characteristic of cetaceans is a thick and dense lip (pachyosteosclerotic involucrum) of an ear bone (the tympanic). This unique feature is absent in modern terrestrial artiodactyls and is suggested to be important in underwater hearing. Here, we investigate the mineralogical and biochemical properties of the involucrum, as these may hold clues to the aquatic adaptations of cetaceans. We compared bioapatites (enamel, dentine, cementum, and skeletal bone) of cetaceans with those of terrestrial artiodactyls and pachyosteosclerotic ribs of manatees (Sirenia). We investigated organic, carbonate, and mineral composition as well as crystal size and crystallinity index. In all studied variables, bioapatites of the cetacean involucrum were intermediate in composition and structure between those of tooth enamel on the one hand and those of dentine, cementum, and skeletal bone on the other. We also studied the amino acid composition of the cetacean involucrum relative to that of other skeletal bone. The central involucrum had low glycine and hydroxyproline concentrations but high concentrations of nonessential amino acids, unlike most bone samples but similar to the tympanic of hippos and the (pachyosteosclerotic) ribs of manatees. These amino acid results are evidence of rapid bone development. We hypothesize that the mineralogical and amino acid composition of cetacean bullae differs from that of other bone because of (1) functional modifications for underwater sound reception and (2) structural adaptations related to rapid ossification.

  16. Socket preservation using deproteinized horse-derived bone mineral

    PubMed Central

    Park, Jang-Yeol; Koo, Ki-Tae; Kim, Tae-Il; Seol, Yang-Jo; Lee, Yong-Moo; Ku, Young; Rhyu, In-Chul

    2010-01-01

    Purpose The healing process following tooth extraction apparently results in a pronounced resorption of the alveolar ridge. As a result, the width of alveolar ridge is reduced and severe alveolar bone resorption occurs. The purpose of this experiment is to clinically and histologically evaluate the results of using horse-derived bone mineral for socket preservation. Methods The study comprised 4 patients who were scheduled for extraction as a consequence of severe chronic periodontitis or apical lesion. The extraction was followed by socket preservation using horse-derived bone minerals. Clinical parameters included buccal-palatal width, mid-buccal crest height, and mid-palatal crest height. A histologic examination was conducted. Results The surgical sites healed uneventfully. The mean ridge width was 7.75 ± 2.75 mm at baseline and 7.00 ± 2.45 mm at 6 months. The ridge width exhibited no significant difference between baseline and 6 months. The mean buccal crest height at baseline was 7.5 ± 5.20 mm, and at 6 months, 3.50 ± 0.58 mm. The mean palatal crest height at baseline was 7.75 ± 3.10 mm, and at 6 months, 5.00 ± 0.82 mm. There were no significant differences between baseline and 6 months regarding buccal and palatal crest heights. The amount of newly formed bone was 9.88 ± 2.90%, the amount of graft particles was 42.62 ± 6.57%, and the amount of soft tissue was 47.50 ± 9.28%. Conclusions Socket preservation using horse-derived bone mineral can effectively maintain ridge dimensions following tooth extraction and can promote new bone formation through osteoconductive activities. PMID:21072219

  17. Body Composition and Bone Mineral Density in Patients With Heart Failure.

    PubMed

    Abshire, Demetrius A; Moser, Debra K; Clasey, Jody L; Chung, Misook L; Pressler, Susan J; Dunbar, Sandra B; Heo, Seongkum; Lennie, Terry A

    2016-07-10

    The purpose of this study was to examine associations among bone mineral density, osteopenia/osteoporosis, body mass index (BMI), and body composition in patients with heart failure (HF). A total of 119 patients (age = 61 ± 12 years, 65% male) underwent dual-energy X-ray absorptiometry scans to determine bone mineral density and body composition. In multivariable linear regressions, BMI, relative skeletal muscle index (RSMI), and mineral-free lean mass were positively associated with total body bone mineral density. Mineral-free lean mass was most strongly associated with bone mineral density (β = .398). In multivariable logistic regressions, higher BMI, RSMI, and mineral-free lean mass were associated with lower odds for osteopenia/osteoporosis. Fat mass was not associated with total body bone mineral density or osteopenia/osteoporosis. These results suggest that muscle mass may be the important component of body mass associated with bone mineral density in patients with HF.

  18. Preliminary report: effect of adrenal androgen and estrogen on bone maturation and bone mineral density.

    PubMed

    Arisaka, O; Hoshi, M; Kanazawa, S; Numata, M; Nakajima, D; Kanno, S; Negishi, M; Nishikura, K; Nitta, A; Imataka, M; Kuribayashi, T; Kano, K

    2001-04-01

    To clarify the independent physiological roles of adrenal androgen and estrogen on bone growth, we compared the lumbar spine bone mineral density (BMD) in prepubertal girls with virilizing congenital adrenal hyperplasia (CAH) (n = 17) and girls with central precocious puberty (CPP) (n = 18). When BMD was analyzed according to chronologic age, no significant differences were found between CPP and CAH patients. However, when adjusted to bone age, BMD was statistically higher in CAH than in CPP subjects. This finding suggests that adrenal androgen, as well as estrogen, plays an important role in increasing BMD. Adrenal androgen may act on bone not only as androgen, but as estrogen after having been metabolized into an aromatized bone-active compound in peripheral tissues, such as bone and fat. Therefore, adrenal androgen may have a more important role in increasing BMD than previously realized.

  19. Modification of os calcis bone mineral profiles during bedrest

    NASA Technical Reports Server (NTRS)

    Vogel, J. M.

    1977-01-01

    The mineral content of the left central os calcis was determined using the photon absorptiometric technique modified for the space missions to permit area scanning, and was compared with total body calcium balance changes. The instrument consists of a rectilinear scanner that is programmed by a specially designed control module to move a low energy X-ray emitting radionuclide placed in opposition to a detector to scan the foot which is places between them. The foot is placed in a plexiglas box filled with water to provide tissue equivalence and to compensate for irregularities in thickness of tissue cover that surrounds the bone. The mineral content is obtained from basic attenuation equation.

  20. CALCOSPHERULITES* ISOLATED FROM THE MINERALIZATION FRONT OF BONE INDUCE THE MINERALIZATION OF TYPE I COLLAGEN

    PubMed Central

    Midura, Ronald J.; Vasanji, Amit; Su, Xiaowei; Wang, Aimin; Midura, Sharon B.; Gorski, Jeff P.

    2007-01-01

    Previous work has suggested that “calcospherulites” actively participate in the mineralization of developing and healing bone. This study sought to directly test this hypothesis by developing a method to isolate calcospherulites and analyzing their capacity to seed mineralization of fibrillar collagen. The periosteal surface of juvenile rat tibial diaphysis was enriched in spherulites of ~0.5-micron diameter exhibiting a Ca/P ratio of 1.3. Their identity as calcospherulites was confirmed by their uptake of calcein at the tibial mineralization front 24 h following in vivo injection. Periosteum was dissected and unmineralized osteoid removed by collagenase in order to expose calcospherulites. Calcein-labeled calcospherulites were then released from the mineralization front by dispase digestion and isolated via fluorescence flow sorting. X-ray diffraction analysis revealed they contained apatite crystals (c-axis length of 17.5 ± 0.2 nm), though their Ca/P ratio of 1.3 is lower than that of hydroxyapatite. Much of their non-mineral phosphorous content was removed by ice-cold ethanol, elevating their Ca/P ratio to 1.6, suggesting the presence of phospholipids. Western blot analyses showed the presence of bone matrix proteins and type I collagen in these preparations. Incubating isolated calcospherulites in collagen hydrogels demonstrated that they could seed a mineralization reaction on type I collagen fibers in vitro. Ultrastructural analyses revealed crystals on the collagen fibers that were distributed rather uniformly along the fiber lengths. Furthermore, crystals were observed at distances well away from the observed calcospherulites. Our results directly support an active role for calcospherulites in inducing the mineralization of type I collagen fibers at the mineralization front of bone. PMID:17936099

  1. WNT16 influences bone mineral density, cortical bone thickness, bone strength, and osteoporotic fracture risk.

    PubMed

    Zheng, Hou-Feng; Tobias, Jon H; Duncan, Emma; Evans, David M; Eriksson, Joel; Paternoster, Lavinia; Yerges-Armstrong, Laura M; Lehtimäki, Terho; Bergström, Ulrica; Kähönen, Mika; Leo, Paul J; Raitakari, Olli; Laaksonen, Marika; Nicholson, Geoffrey C; Viikari, Jorma; Ladouceur, Martin; Lyytikäinen, Leo-Pekka; Medina-Gomez, Carolina; Rivadeneira, Fernando; Prince, Richard L; Sievanen, Harri; Leslie, William D; Mellström, Dan; Eisman, John A; Movérare-Skrtic, Sofia; Goltzman, David; Hanley, David A; Jones, Graeme; St Pourcain, Beate; Xiao, Yongjun; Timpson, Nicholas J; Smith, George Davey; Reid, Ian R; Ring, Susan M; Sambrook, Philip N; Karlsson, Magnus; Dennison, Elaine M; Kemp, John P; Danoy, Patrick; Sayers, Adrian; Wilson, Scott G; Nethander, Maria; McCloskey, Eugene; Vandenput, Liesbeth; Eastell, Richard; Liu, Jeff; Spector, Tim; Mitchell, Braxton D; Streeten, Elizabeth A; Brommage, Robert; Pettersson-Kymmer, Ulrika; Brown, Matthew A; Ohlsson, Claes; Richards, J Brent; Lorentzon, Mattias

    2012-07-01

    We aimed to identify genetic variants associated with cortical bone thickness (CBT) and bone mineral density (BMD) by performing two separate genome-wide association study (GWAS) meta-analyses for CBT in 3 cohorts comprising 5,878 European subjects and for BMD in 5 cohorts comprising 5,672 individuals. We then assessed selected single-nucleotide polymorphisms (SNPs) for osteoporotic fracture in 2,023 cases and 3,740 controls. Association with CBT and forearm BMD was tested for ∼2.5 million SNPs in each cohort separately, and results were meta-analyzed using fixed effect meta-analysis. We identified a missense SNP (Thr>Ile; rs2707466) located in the WNT16 gene (7q31), associated with CBT (effect size of -0.11 standard deviations [SD] per C allele, P = 6.2 × 10(-9)). This SNP, as well as another nonsynonymous SNP rs2908004 (Gly>Arg), also had genome-wide significant association with forearm BMD (-0.14 SD per C allele, P = 2.3 × 10(-12), and -0.16 SD per G allele, P = 1.2 × 10(-15), respectively). Four genome-wide significant SNPs arising from BMD meta-analysis were tested for association with forearm fracture. SNP rs7776725 in FAM3C, a gene adjacent to WNT16, was associated with a genome-wide significant increased risk of forearm fracture (OR = 1.33, P = 7.3 × 10(-9)), with genome-wide suggestive signals from the two missense variants in WNT16 (rs2908004: OR = 1.22, P = 4.9 × 10(-6) and rs2707466: OR = 1.22, P = 7.2 × 10(-6)). We next generated a homozygous mouse with targeted disruption of Wnt16. Female Wnt16(-/-) mice had 27% (P<0.001) thinner cortical bones at the femur midshaft, and bone strength measures were reduced between 43%-61% (6.5 × 10(-13)bone strength, and risk of fracture.

  2. Artemisia capillaris Alleviates Bone Loss by Stimulating Osteoblast Mineralization and Suppressing Osteoclast Differentiation and Bone Resorption.

    PubMed

    Lee, Chung-Jo; Shim, Ki-Shuk; Ma, Jin Yeul

    2016-01-01

    Artemisia capillaris has been used to treat jaundice and relieve high liver-heat in traditional medicine. In this study, we found that the administration of a water extract from A. capillaris (WEAC) to the receptor activator of nuclear factor kappa-B ligand (RANKL)-induced bone loss model significantly prevents osteoporotic bone loss, increasing bone volume/trabecular volume by 22% and trabecular number by 24%, and decreasing trabecular separation by 29%. WEAC stimulated in vitro osteoblast mineralization from primary osteoblasts in association with increasing expression of osterix, nuclear factor of activated T cells cytoplasmic 1, and activator protein-1, as well as phosphorylation of extracellular signal-regulated kinase. In contrast to the anabolic effect of WEAC, WEAC significantly suppressed in vitro osteoclast formation from bone marrow macrophages by inhibiting the RANKL signaling pathways and bone resorption by downregulating the expression of resorption markers. Therefore, this study demonstrated that WEAC has a beneficial effect on bone loss through the regulation of osteoblast mineralization, as well as osteoclast formation and bone resorption. These results suggest that A. capillaris may be a promising herbal candidate for therapeutic agents to treat or prevent osteoporotic bone diseases.

  3. The pleiotropic effects of paricalcitol: Beyond bone-mineral metabolism.

    PubMed

    Egido, Jesús; Martínez-Castelao, Alberto; Bover, Jordi; Praga, Manuel; Torregrosa, José Vicente; Fernández-Giráldez, Elvira; Solozábal, Carlos

    2016-01-01

    Secondary hyperparathyroidism (SHPT) is a common complication in patients with chronic kidney disease (CKD) that is characterised by elevated parathyroid hormone (PTH) levels and a series of bone-mineral metabolism anomalies. In patients with SHPT, treatment with paricalcitol, a selective vitamin D receptor activator, has been shown to reduce PTH levels with minimal serum calcium and phosphorus variations. The classic effect of paricalcitol is that of a mediator in mineral and bone homeostasis. However, recent studies have suggested that the benefits of treatment with paricalcitol go beyond PTH reduction and, for instance, it has a positive effect on cardiovascular disease and survival. The objective of this study is to review the most significant studies on the so-called pleiotropic effects of paricalcitol treatment in patients with CKD.

  4. Quantification of bone mineral density to define osteoporosis in rat.

    PubMed

    Srivastava, M; Mandal, S K; Sengupta, S; Arshad, M; Singh, M M

    2008-05-01

    The diagnosis of osteoporosis centers on assessment of bone mass and quality. In the absence of evidence-based guidelines to assess bone status in laboratory animals and unsuitability of use of T-/Z-scores meant for clinical application in animal studies, most investigators involved in new drug research and development employ clinical biomarkers and kits to assess bone turnover rate and portray change in bone mineral density (BMD) as percentage of increase/decrease, making comparative assessment of the effect highly impractical. This study proposes threshold boundaries of BMD (rT-score) in colony-bred Sprague-Dawley rats, distinct from those used clinically. Boundaries were obtained keeping fixed Type-I error (alpha=0.025). Femur neck was considered best for defining bone status using BMD measured by dual-energy X-ray absorptiometry. Findings demonstrate that BMD-1.96 and <-0.80 rT-score as osteopenia. Performance of boundaries to ascertain bone status was examined through simulation under different physiological/ hormonal states viz. estrogen deficiency, ageing, estrus cycle, pregnancy, and lactation. The Area Under the Receiver Operating Characteristic curve of 0.98 obtained using BMD of femur neck, being close to unity, shows excellent ability of the proposed rT-score to effectively identify osteoporosis. Further studies using certain hierarchical measures of bone quality such as histomorphometry, mechanical testing etc. could supplement these findings. Since, unlike humans, most laboratory animals including rats only exhibit osteopenia and do not fracture their bones, the proposed thresholds are intended to serve as categorical tools to define bone quality and not to predict fracture risk.

  5. Bone Mineral Density in Elite DanceSport Athletes.

    PubMed

    Kruusamäe, Helena; Maasalu, Katre; Jürimäe, Jaak

    2016-03-01

    This study compared bone mineral density (BMD) variables of female and male elite dancesport athletes with untrained control subjects of the same gender. Sixty-six elite dancesport athletes (M 33, F 33) and 64 untrained controls (M 34, F 31) participated in this study. Elite dancesport athletes were dancing couples competing at the international level. Whole-body bone mineral content and whole-body, forearm, lumbar-spine, and femoral-neck BMD, as well as whole-body fat mass and fat free mass, were measured by dual-energy X-ray absorptiometry. There were no differences (p>0.05) in height and body mass between dancers and controls of the same gender, but percent body fat was lower (p<0.05) in dancers of both genders than in untrained controls. Elite dancesport athletes had significantly higher femoral-neck BMD, and male dancers also higher whole-body BMD values when compared with controls of the same gender. All other measured bone mineral values did not differ between the groups of the same gender. In addition, training experience was positively correlated with whole-body BMD (r=0.27; p<0.05) in dancesport athletes. Based on this study, it can be concluded that elite dancesport athletes have higher BMD values at the weight-bearing site (femoral-neck BMD), while other measured areas and whole-body bone mineral values do not differ from the corresponding values of healthy sedentary controls of the same gender. According to our results, low BMD is not an issue for elite female dancesport athletes, despite their lower percent body fat values.

  6. 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

  7. Bone mineral density in premenopausal women receiving levothyroxine suppressive therapy.

    PubMed

    Nuzzo, V; Lupoli, G; Esposito Del Puente, A; Rampone, E; Carpinelli, A; Del Puente, A E; Oriente, P

    1998-10-01

    Osteoporosis is a well-known complication of thyrotoxicosis. Prolonged subclinical hyperthyroidism due to L-thyroxine treatment has been associated with reduced bone mass and thus with the potential risk of premature development of osteoporosis. The aim of this study was to assess the effect of a chronic L-thyroxine suppressive treatment on bone mineral density (BMD) in a group of premenopausal women. Forty consecutive patients (mean age +/- SE = 40.95 +/- 1.56 years) affected by non-toxic goiter underwent bone mineral densitometry (dual energy X-ray absorptiometry; DEXA) of the lumbar spine (L1-L4) and right femoral neck. At the time of the study the patients had been under thyroid stimulating hormone (TSH) suppressive therapy for 74.95 +/- 10.34 months (range 17-168 months). Baseline levels of free thyroxine (fT4), free triiodothyronine (fT3), TSH, calcium and phosphorus were measured and correlated with BMD. The age of starting, duration of treatment, main daily dose, cumulative dose of treatment and body mass index (BMI) were also correlated with BMD. Statistical analysis was performed by multiple linear regression. BMD among female patients was not significantly different from that of the general population matched for age and sex. With the use of the regression model, no significant correlation was found between BMD and the variables considered. In conclusion, our data suggest that L-thyroxine suppressive therapy, if carefully carried out and monitored, has no significant effect on bone mass.

  8. Mineralized polymer composites as biogenic bone substitute material

    NASA Astrophysics Data System (ADS)

    Shah, Rushita; Saha, Nabanita; Kitano, Takeshi; Saha, Petr

    2015-05-01

    Mineralized polymer composites (MPC) are recognized as potential fillers of bone defects. Though bioceramics exhibits quite a good bone-bonding and vascularization, it is considered to be too stiff and brittle for using alone. Thus, the use of polymer scaffold instead of bioceramics has several advantages including combining the osteoconductivity and bone-bonding potential of the inorganic phase with the porosity and interconnectivity of the three-dimensional construction. Aiming the advantages of ceramic-polymer composite scaffolds, the calcium carbonate (CaCO3) based biomineralized scaffold was prepared, where the PVP-CMC hydrogel was used as an extracellular matrix. This paper is reported about the morphology, swelling trend (in physiological solution) and viscoelastic behavior of (90 min mineralized) MPC. The dry MPC are off-white, coarse in texture, comparatively less flexible than the original PVP-CMC based hydrogel film, and the deposition of granular structures on the surface of the hydrogel film confirms about the development of biomineralized scaffold/polymer composites. Irrespective of thickness, the dry MPC shows higher values of swelling ratio within 30 min, which varies between 200-250 approximately. The dynamic viscoelastic nature of freshly prepared MPC was investigated applying 1% and 10% strain. At higher strain the viscoelastic moduli (G' and G") show significant change, and the nature of MPC turns from elastic to viscous. Based on the observed basic properties, the MPC (calcite based polymer composites) can be recommended for the treatment of adyanamic bone disorder.

  9. Loss of transcription factor early growth response gene 1 results in impaired endochondral bone repair.

    PubMed

    Reumann, Marie K; Strachna, Olga; Yagerman, Sarah; Torrecilla, Daniel; Kim, Jihye; Doty, Stephen B; Lukashova, Lyudmila; Boskey, Adele L; Mayer-Kuckuk, Philipp

    2011-10-01

    Transcription factors that play a role in ossification during development are expected to participate in postnatal fracture repair since the endochondral bone formation that occurs in embryos is recapitulated during fracture repair. However, inherent differences exist between bone development and fracture repair, including a sudden disruption of tissue integrity followed by an inflammatory response. This raises the possibility that repair-specific transcription factors participate in bone healing. Here, we assessed the consequence of loss of early growth response gene 1 (EGR-1) on endochondral bone healing because this transcription factor has been shown to modulate repair in vascularized tissues. Model fractures were created in ribs of wild type (wt) and EGR-1(-/-) mice. Differences in tissue morphology and composition between these two animal groups were followed over 28 post fracture days (PFDs). In wt mice, bone healing occurred in healing phases characteristic of endochondral bone repair. A similar healing sequence was observed in EGR-1(-/-) mice but was impaired by alterations. A persistent accumulation of fibrin between the disconnected bones was observed on PFD7 and remained pronounced in the callus on PFD14. Additionally, the PFD14 callus was abnormally enlarged and showed increased deposition of mineralized tissue. Cartilage ossification in the callus was associated with hyper-vascularity and -proliferation. Moreover, cell deposits located in proximity to the callus within skeletal muscle were detected on PFD14. Despite these impairments, repair in EGR-1(-/-) callus advanced on PFD28, suggesting EGR-1 is not essential for healing. Together, this study provides genetic evidence that EGR-1 is a pleiotropic regulator of endochondral fracture repair.

  10. Bone mineral density in children and adolescents with juvenile diabetes: selective measurement of bone mineral density of trabecular and cortical bone using peripheral quantitative computed tomography.

    PubMed

    Lettgen, B; Hauffa, B; Möhlmann, C; Jeken, C; Reiners, C

    1995-01-01

    Bone mineral density (BMD) was studied in 21 children and adolescents with type I diabetes and in age- and sex-matched healthy controls. BMD was selectively measured in trabecular and total bone using peripheral quantitative computed tomography (pQCT). Cortical bone density was calculated. There was a decrease of trabecular bone density (-18.9%, p < 0.01), total bone density (-9.0%, NS) and cortical bone density (-5.1%, NS) in diabetes. Trabecular bone density was inversely correlated with the duration of diabetes and the concentration of glycosylated hemoglobin (HbA1) (r = -0.48, p = 0.027 and r = -0.63, p = 0.002, respectively). Total BMD correlated inversely with HbA1 (r = -0.52, p = 0.017). pQCT allows the selective measurement of metabolically active trabecular bone where changes of mineralization first occur. We conclude that pQCT is a useful method for investigating BMD in diabetes.

  11. Fitting of bone mineral density with consideration of anthropometric parameters

    PubMed Central

    Short, D. F.; Zemel, B. S.; Gilsanz, V.; Kalkwarf, H. J.; Lappe, J. M.; Mahboubi, S.; Oberfield, S. E.; Shepherd, J. A.; Winer, K. K.

    2010-01-01

    Summary A new model describing normal values of bone mineral density in children has been evaluated, which includes not only the traditional parameters of age, gender, and race, but also weight, height, percent body fat, and sexual maturity. This model may constitute a better comparative norm for a specific child with given anthropometric values. Introduction Previous descriptions of children's bone mineral density (BMD) by age have focused on segmenting diverse populations by race and gender without adjusting for anthropometric variables or have included the effects of anthropometric variables over a relatively homogeneous population. Methods Multivariate semi-metric smoothing (MS2) provides a way to describe a diverse population using a model that includes multiple effects and their interactions while producing a result that can be smoothed with respect to age in order to provide connected percentiles. We applied MS2 to spine BMD data from the Bone Mineral Density in Childhood Study to evaluate which of gender, race, age, height, weight, percent body fat, and sexual maturity explain variations in the population's BMD values. By balancing high adjusted R2 values and low mean square errors with clinical needs, a model using age, gender, race, weight, and percent body fat is proposed and examined. Results This model provides narrower distributions and slight shifts of BMD values compared to the traditional model, which includes only age, gender, and race. Thus, the proposed model might constitute a better comparative standard for a specific child with given anthropometric values and should be less dependent on the anthropometric characteristics of the cohort used to devise the model. Conclusions The inclusion of multiple explanatory variables in the model, while creating smooth output curves, makes the MS2 method attractive in modeling practically sized data sets. The clinical use of this model by the bone research community has yet to be fully established. PMID

  12. Optical studies of changes in bone mineral density

    NASA Astrophysics Data System (ADS)

    Ugryumova, Nadya; Matcher, Stephen J.; Attenburrow, Don P.

    2003-07-01

    The ability to measure changes in bone-mineral-density (BMD) in-vivo has potential applications in monitoring stress-induced bone remodelling in, for example, competition race horses. In this study we have begun to investigate the potential of optical techniques to monitor such changes via changes in bone optical scattering. Using integrating spheres, we have investigated the optical properties of bone samples taken from the leg of the horse. Since our samples have stable characteristics over the time, we are able to use a single integrating-sphere technique. Diffuse reflection and transmission coefficients have been measured over the wavelength range 520 to 960 nm. Measurements were made on samples immersed in formic acid solution for different lengths of time; this was to investigate the effect of reduction in BMD on the optical properties. The experimental results and a Monte-Carlo based inversion method were used to extract the absorption coefficient and unmodified scattering coefficient of the samples. After full demineralisation scattering coefficient fell by a factor 4. This shows that the calcium-content in bone influences its optical properties considerably. Our experiments confirm the possibility of using optical techniques to determine changes in the BMD of samples.

  13. Bone mineral disorders in pediatric and adolescent renal transplant recipients.

    PubMed

    Derakhshan, Ali; Behbahan, Afshin G; Lotfi, Mehrzad; Omrani, Gholam-Hossein; Fallahzadeh, Mohammad-Hossein; Basiratnia, Mitra; Al-Hashemi, Ghamar H

    2011-06-01

    Incomplete resolution of abnormalities of mineral metabolism associated with CRF results in the relatively high prevalence of ROD in pediatric kidney recipients. This non-randomized, cross-sectional, and analytic-descriptive study on bone density, vitamin D, and mineral metabolism was performed in 57 children and adolescents who had received a total of 60 renal allografts in Shiraz, Iran. The height and weight of the patients were measured; their serum calcium (Ca), phosphorus (P), Alk-P, PTH, 25(OH)-vitamin D(3), BUN, creatinine, and electrolyte levels were analyzed, and a complete blood count was performed. In addition, standard radiologic bone assessments, which included conventional left hand-wrist radiography and bone mineral densitometry by the DXA technique, were carried out. Special pediatric software was used for age-related interpretation of the Z-scores of BMD. SPSS(®) software (version 15) was used for statistical analyses. We studied 57 patients (27 males [47.4%]) with a mean age of 18.7 ± 4.25 (9-27) yr and a mean age at transplantation of 13.1 ± 3.46 (4.5-20) yr. They had a post-transplantation follow-up of 67.1 ± 33.8 (6-132) months, and all had well-functioning allografts at enrollment. The mean height age of the patients was 11.9 ± 1.8 (6-15.5), and the mean bone age was 15.6 ± 3.3 (7-19) yr, which corresponded to mean height-age and bone-age retardations of 5.7 ± 2.3 (0.5-10.5) and 1.22 ± 1.47 (0-7) yr, respectively. Hyperphosphatemia and hypercalcemia were each found in nine patients (15.8%), hypophosphatemia in five (8.8%), and hypocalcemia in none of the patients. Seven out of 57 patients (12.3%) had a (Ca×P) product of more than 55 mg(2)/dL(2). Hyperparathyroidism was found in 27 (47.3%) and vitamin D(3) deficiency in four (7%) of the cases. The serum level of Alk-P was higher than the age-related normal range in 20 patients (35%). Left hand-wrist radiography showed no radiologic sign of ROD in any patient. The mean BMD Z-score was

  14. Bone Mineral Density in Healthy Female Adolescents According to Age, Bone Age and Pubertal Breast Stage

    PubMed Central

    Moretto, M.R; Silva, C.C; Kurokawa, C.S; Fortes, C.M; Capela, R.C; Teixeira, A.S; Dalmas, J.C; Goldberg, T.B

    2011-01-01

    Objectives: This study was designed to evaluate bone mineral density (BMD) in healthy female Brazilian adolescents in five groups looking at chronological age, bone age, and pubertal breast stage, and determining BMD behavior for each classification. Methods: Seventy-two healthy female adolescents aged between 10 to 20 incomplete years were divided into five groups and evaluated for calcium intake, weight, height, body mass index (BMI), pubertal breast stage, bone age, and BMD. Bone mass was measured by bone densitometry (DXA) in lumbar spine and proximal femur regions, and the total body. BMI was estimated by Quetelet index. Breast development was assessed by Tanner’s criteria and skeletal maturity by bone age. BMD comparison according to chronologic and bone age, and breast development were analyzed by Anova, with Scheffe’s test used to find significant differences between groups at P≤0.05. Results: BMD (g·cm-2) increased in all studied regions as age advanced, indicating differences from the ages of 13 to 14 years. This group differed to the 10 and 11 to 12 years old groups for lumbar spine BMD (0.865±0.127 vs 0.672±0.082 and 0.689±0.083, respectively) and in girls at pubertal development stage B3, lumbar spine BMD differed from B5 (0.709±0.073 vs 0.936±0.130) and whole body BMD differed from B4 and B5 (0.867±0.056 vs 0.977±0.086 and 1.040±0.080, respectively). Conclusion: Bone mineralization increased in the B3 breast maturity group, and the critical years for bone mass acquisition were between 13 and 14 years of age for all sites evaluated by densitometry. PMID:21966336

  15. Distal radius bone mineral density estimation using the filling factor of trabecular bone in the x-ray image.

    PubMed

    Lee, Sooyeul; Jeong, Ji-Wook; Lee, Jeong Won; Yoo, Done-Sik; Kim, Seunghwan

    2006-01-01

    Osteoporosis is characterized by an abnormal loss of bone mineral content, which leads to a tendency to non-traumatic bone fractures or to structural deformations of bone. Thus, bone density measurement has been considered as a most reliable method to assess bone fracture risk due to osteoporosis. In past decades, X-ray images have been studied in connection with the bone mineral density estimation. However, the estimated bone mineral density from the X-ray image can undergo a relatively large accuracy or precision error. The most relevant origin of the accuracy or precision error may be unstable X-ray image acquisition condition. Thus, we focus our attentions on finding a bone mineral density estimation method that is relatively insensitive to the X-ray image acquisition condition. In this paper, we develop a simple technique for distal radius bone mineral density estimation using the trabecular bone filling factor in the X-ray image and apply the technique to the wrist X-ray images of 20 women. Estimated bone mineral density shows a high linear correlation with a dual-energy X-ray absorptiometry (r=0.87).

  16. Bone mineral density-affecting genes in Africans.

    PubMed Central

    Gong, Gordon; Haynatzki, Gleb; Haynatzka, Vera; Howell, Ryan; Kosoko-Lasaki, Sade; Fu, Yun-Xin; Yu, Fei; Gallagher, John C.; Wilson, M. Roy

    2006-01-01

    BACKGROUND: We have recently reported the role of environmental exposure in the ethnic diversity of bone mineral density (BMD). Potential genetic difference has not been adequately assessed. PURPOSE: To determine allele frequencies of BMD-affecting genes and their association with BMD in Africans. METHODS: Allele frequencies at 18 polymorphic sites in 13 genes that affect BMD in Asians and/or Caucasians were determined in 143 recent immigrants (55 men and 88 women, 18-51 years of age) from sub-Saharan Sudan to the United States. Genetic association studies were performed. RESULTS: Among the 14 single-nucleotide polymorphisms (SNPs), 10 were significantly different in allele frequency between Sudanese and Asians, and 10 between Sudanese and Caucasians. Only the osteocalcin gene was not significantly different in allele frequency among Sudanese, Asians and Caucasians. Allele frequencies in the TGFB, COL1A1 and CSR genes were extremely low (<0.04) in the Sudanese. Frequencies of microsatellite alleles in four genes were significantly different among Sudanese, Asians and Caucasians. SNPs in the VDR and ERalpha genes were associated with BMD and/or BMC (bone mineral content) at several bone sites. CONCLUSIONS: Genetic difference may play a role in the ethnic diversity in BMD and/or BMC. PMID:16895279

  17. Preservation of bone structure and function by Lithothamnion sp. derived minerals.

    PubMed

    Aslam, Muhammad Nadeem; Bergin, Ingrid; Jepsen, Karl; Kreider, Jaclynn M; Graf, Kristin H; Naik, Madhav; Goldstein, Steven A; Varani, James

    2013-12-01

    Progressive bone mineral loss and increasing bone fragility are hallmarks of osteoporosis. A combination of minerals isolated from the red marine algae, Lithothamnion sp. was examined for ability to inhibit bone mineral loss in female mice maintained on either a standard rodent chow (control) diet or a high-fat western diet (HFWD) for 5, 12, and 18 months. At each time point, femora were subjected to μ-CT analysis and biomechanical testing. A subset of caudal vertebrae was also analyzed. Following this, individual elements were assessed in bones. Serum levels of the 5b isoform of tartrate-resistant acid phosphatase (TRAP) and procollagen type I propeptide (P1NP) were also measured. Trabecular bone loss occurred in both diets (evident as early as 5 months). Cortical bone increased through month 5 and then declined. Cortical bone loss was primarily in mice on the HFWD. Inclusion of the minerals in the diet reduced bone mineral loss in both diets and improved bone strength. Bone mineral density was also enhanced by these minerals. Of several cationic minerals known to be important to bone health, only strontium was significantly increased in bone tissue from animals fed the mineral diets, but the increase was large (5-10 fold). Serum levels of TRAP were consistently higher in mice receiving the minerals, but levels of P1NP were not. These data suggest that trace minerals derived from marine red algae may be used to prevent progressive bone mineral loss in conjunction with calcium. Mineral supplementation could find use as part of an osteoporosis-prevention strategy.

  18. Bone mineral density and metabolism in familial dysautonomia.

    PubMed

    Maayan, C; Bar-On, E; Foldes, A J; Gesundheit, B; Pollak, R Dresner

    2002-05-01

    Familial dysautonomia (FD) patients suffer from multiple fractures and have reduced bone pain, which defers the diagnosis. The pathogenesis of bone fragility in FD is unknown. This study aimed to characterize bone mineral metabolism and density in FD. Seventy-nine FD patients aged 8 months to 48 years (mean age 13.9 +/- 10.4 years, median 12.3) were studied. Clinical data included weight, height, bone age, weekly physical activity and history of fractures. Bone mineral density (BMD) of the lumbar spine (n = 43), femoral neck (n = 26), total hip (n = 22) and whole body (n = 15) were determined by dual-energy X-ray absorptiometry. Serum 25-hydroxyvitamin D3, osteocalcin, bone alkaline phosphatase (B-ALP), parathyroid hormone and urinary N-telopeptide cross-linked type 1 collagen (NTx) were determined in 68 patients and age- and sex-matched controls. Forty-two of 79 patients (53%) sustained 75 fractures. Twenty-four of 43 patients had a spine Z-score < -2.0, and 13 of 26 had a femoral neck Z-score < -2.0. Mean femoral neck BMD Z-score was lower in patients with fractures compared with those without (-2.5 +/- 0.9 vs -1.5 +/- 1.0, p = 0.01). Mean body mass index (BMI) was 16 kg/m2 in prepubertal patients and 18.4 kg/m2 in postpubertal patients. Bone age was significantly lower than chronological age (75.5 vs 99.3 months in prepubertal patients, p < 0.001; 151 vs 174 in postpubertal patients, p < 0.05). NTx and osteocalcin levels were higher in FD patients compared with controls (400 +/- 338 vs 303 +/- 308, BCE/mM creatinine p < 0.02; 90 +/- 59.5 vs 61.8 +/- 36.9 ng/ml, p < 0.001, respectively). B-ALP was lower in FD patients compared with controls (44.66 +/- 21.8 vs 55.36 +/- 36.6 ng/ml, p < 0.04). Mean spine Z-score was significantly lower in physically inactive compared with active patients (-3.00 +/- 1.70 vs -1.77 +/- 1.3, respectively, p = 0.05). We conclude that fractures in FD patients are associated with reduced BMD. FD patients have increased NTx and osteocalcin

  19. Periprosthetic tibial bone mineral density changes after total knee arthroplasty

    PubMed Central

    Jaroma, Antti; Soininvaara, Tarja; Kröger, Heikki

    2016-01-01

    Background and purpose Total knee arthroplasty (TKA) may cause postoperative periprosthetic bone loss due to stress shielding. Bone also adapts to mechanical alterations such as correction of malalignment. We investigated medium-term changes in bone mineral density (BMD) in tibial periprosthetic bone after TKA. Patients and methods 86 TKA patients were prospectively measured with dual-energy X-ray absorptiometry (DXA), the baseline measurement being within 1 week after TKA and the follow-up measurements being at 3 and 6 months, and at 1, 2, 4, and 7 years postoperatively. Long standing radiographs were taken and clinical evaluation was done with the American Knee Society (AKS) score. Results The baseline BMD of the medial tibial metaphyseal region of interest (ROI) was higher in the varus aligned knees (25%; p < 0.001). Medial metaphyseal BMD decreased in subjects with preoperatively varus aligned knees (13%, p < 0.001) and in those with preoperatively valgus aligned knees (12%, p = 0.02) between the baseline and 7-year measurements. No statistically significant changes in BMD were detected in lateral metaphyseal ROIs. No implant failures or revision surgery due to tibial problems occurred. Interpretation Tibial metaphyseal periprosthetic bone is remodeled after TKA due to mechanical axis correction, resulting in more balanced bone stock below the tibial tray. The diaphyseal BMD remains unchanged after the initial drop, within 3–6 months. This remodeling process was related to good component survival, as there were no implant failures or revision operations due to tibial problems in this medium-term follow-up. PMID:27120266

  20. Mechanisms of Bone Mineralization and Effects of Mechanical Loading

    NASA Technical Reports Server (NTRS)

    Babich, Michael

    1996-01-01

    The data suggest that PTH and PKC inhibit nodule formation, and that alternative energy sources are utilized by osteoblasts in the process of mineralization. The conditions and techniques to grow, fix, photograph, and measure bone mineralization in vitro were defined. The results are presently in preliminary form and require further assessment as follows; quantitate the surface area of nodules + treatments via computer-aided image analysis; use PTH + inhibitors of signaling pathways to determine the mechanism of nodule formation; determine how protein kinase C is involved as a promotor of nodule formation; cell proliferation vs. cell death affected by modulation of signal transduction (i.e., PTH, enzyme inhibitors and activators); identify mRNA induced or decreased in response to PTH and signaling modulators that encode proteins that regulate cell morphology, proliferation, and nodule formation. Therefore, several follow-up studies between the laboratories at NASA-Ames Research Center and my laboratory at the University of Illinois have been initiated.

  1. Updated association of tea consumption and bone mineral density

    PubMed Central

    Zhang, Zhao-Fei; Yang, Jun-Long; Jiang, Huan-Chang; Lai, Zheng; Wu, Feng; Liu, Zhi-Xiang

    2017-01-01

    Abstract Background: Current studies evaluating the association of tea consumption and bone mineral density (BMD) have yielded inconsistent findings. Therefore, we conducted a meta-analysis to assess the relationship between tea consumption and BMD. Methods: The PubMed, Embase, and Cochrane Library databases were comprehensively searched, and a meta-analysis performed of all observational studies assessing the association of tea consumption and BMD. Forest plots were used to illustrate the results graphically. The Q-test and I2 statistic were employed to evaluate between-study heterogeneity. Potential publication bias was assessed by the funnel plot. Results: Four cohort, 1 case–control, and 8 cross-sectional studies including a total of 12,635 cases were included. Tea consumption was shown to prevent bone loss [odds ratio (OR): 0.66; 95% confidence interval (CI), 0.47–0.94; P = 0.02], yielding higher mineral densities in several bones, including the lumbar spine [standardized mean difference (SMD): 0.19; 95% CI, 0.08–0.31; P = 0.001], hip (SMD: 0.19; 95% CI, 0.05–0.34; P = 0.01), femoral neck [mean difference (MD): 0.01; 95% CI, 0.00–0.02; P = 0.04], Ward triangle (MD: 0.02; 95% CI, 0.01–0.04; P = 0.001), and greater trochanter (MD: 0.03; 95% CI, 0.02–0.04; P < 0.00001), than the non-tea consumption group. Conclusion: This meta-analysis provided a potential trend that tea consumption might be beneficial for BMD, especially in the lumbar spine, hip, femoral neck, Ward triangle, and greater trochanter, which might help prevent bone loss. PMID:28328853

  2. Pycnogenol® treatment inhibits bone mineral density loss and trabecular deterioration in ovariectomized rats

    PubMed Central

    Huang, Gangyong; Wu, Jianguo; Wang, Siqun; Wei, Yibing; Chen, Feiyan; Chen, Jie; Shi, Jingsheng; Xia, Jun

    2015-01-01

    Context: Pycnogenol® extracted from French maritime pine bark (Pinus pinaster Ait. subsp. atlantica) is functional for its antioxidant activity. Objective: To investigate the effects of Pycnogenol® on bone mineral density (BMD), trabecular microarchitecture and bone metabolism in ovariectomized (OVX) rats. Materials and methods: Thirty Sprague-Dawley rats were randomized into 3 groups: SHAM group (sham-operated rats), OVX group (OVX rats), and treatment group (OVX rats supplemented with 40 mg/kg Pycnogenol® by oral gavage). Serum levels of procollagen type I N-terminal propeptide (PINP), alkaline phosphatase (ALP) and minerals were detected at the end of 9 weeks of gavage. Deoxypyridinoline/creatinine (DPYD/Cr) and N-telopeptide of type I collagen/creatinine (NTX/Cr) rate in urine were also calculated. Left femora were collected for BMD determination, and the right distal femora were made into undecalcified specimens for histomorphometry analysis. Results: At the end of study, PINP level, DPYD/Cr and NTX/Cr rate were significantly increased, and femoral BMD were dramatically decreased in OVX group compared with SHAM group (P < 0.01) while serum minerals and ALP concentrations showed no significant difference. The treatment group had dramatically decreased biomarkers and increased BMD than OVX group (P < 0.01). Histomorphometry analysis showed worse bone microarchitecture parameters in the OVX group compared with the SHAM group which were significantly improved in the treatment group compared with the OVX group (P < 0.01). Discussion and conclusion: Pycnogenol® (40 mg/kg) can inhibit aggravated bone resorption, prevent BMD loss, and restore the impaired trabecular microarchitecture in OVX rats after 9-week-intervention. PMID:26379883

  3. The vitamin D analog ZK191784 normalizes decreased bone matrix mineralization in mice lacking the calcium channel TRPV5.

    PubMed

    van der Eerden, Bram C J; Fratzl-Zelman, Nadja; Nijenhuis, Tom; Roschger, Paul; Zügel, Ulrich; Steinmeyer, Andreas; Hoenderop, Joost G J; Bindels, René J M; Klaushofer, Klaus; van Leeuwen, Johannes P T M

    2013-02-01

    Mice lacking the renal epithelial Ca(2+) channel TRPV5 (TRPV5(-/-)) display impaired renal Ca(2+) reabsorption, hypercalciuria, and intestinal Ca(2+) hyperabsorption, due to secondary hypervitaminosis D. Using these mice, we previously demonstrated that ZK191784 acts as an intestine-specific 1,25(OH)(2) D(3) antagonist without affecting serum calcium levels. On the other hand, it acted as an agonist in the kidney and the effects of ZK191784 on bone were ambiguous. The present study was undertaken to further evaluate the effect of the vitamin D receptor antagonist on murine bone in mice lacking TRPV5. Eight-week-old female Trpv5(+/+) and Trpv5(-/-) mice were treated for 4 weeks with or without 50 µg/kg/day ZK191784. Quantitative backscattered electron imaging showed that the reduced bone matrix mineralization found in femoral bones of Trpv5(-/-) mice was partially but significantly restored upon ZK191784 treatment, just as we observed for trabecular bone thickness. This supports the significance of 1,25(OH)(2) D(3) and optimal control of Ca(2+) homeostasis for bone formation and matrix mineralization. Restoration also took place at the bone gene expression level, where 1α-hydroxylase (Cyp27b1) mRNA in femurs from ZK-treated Trpv5(-/-) mice was upregulated compared to control levels. The downregulated 24-hydroxylase (Cyp24a1) gene expression in femoral bone indicated local vitamin D resistance in the mice treated with ZK191784. Phosphate homeostasis was unaffected between the groups as shown by unaltered serum PO(4)(3-) and fibroblast growth factor (FGF) 23 as well as Fgf23 mRNA expression in bone. In conclusion, circulating 1,25(OH)(2) D(3) is important for optimal control of Ca(2+) homeostasis but also for controlled bone formation and matrix mineralization.

  4. The use of Na-22 as a tracer for long-term bone mineral turnover studies.

    NASA Technical Reports Server (NTRS)

    Palmer, H. E.; Rieksts, G. A.; Palmer, R. F.; Gillis, M. F.

    1979-01-01

    Sodium-22 has been studied as a tracer for bone mineral metabolism in rats and dogs. When incorporated into bone during growth from birth to adulthood, the bone becomes uniformly tagged with Na-22, which is released through the metabolic turnover of the bone. The Na-22 not incorporated in the bone matrix is rapidly excreted within a few days when animals are fed high, but nontoxic levels of NaCl. The Na-22 tracer can be used to measure bone mineral loss in animals during space flight and in research on bone disease.

  5. The Formation of Calcified Nanospherites during Micropetrosis Represents a Unique Mineralization Mechanism in Aged Human Bone.

    PubMed

    Milovanovic, Petar; Zimmermann, Elizabeth A; Vom Scheidt, Annika; Hoffmann, Björn; Sarau, George; Yorgan, Timur; Schweizer, Michaela; Amling, Michael; Christiansen, Silke; Busse, Björn

    2017-01-01

    Osteocytes-the central regulators of bone remodeling-are enclosed in a network of microcavities (lacunae) and nanocanals (canaliculi) pervading the mineralized bone. In a hitherto obscure process related to aging and disease, local plugs in the lacuno-canalicular network disrupt cellular communication and impede bone homeostasis. By utilizing a suite of high-resolution imaging and physics-based techniques, it is shown here that the local plugs develop by accumulation and fusion of calcified nanospherites in lacunae and canaliculi (micropetrosis). Two distinctive nanospherites phenotypes are found to originate from different osteocytic elements. A substantial deviation in the spherites' composition in comparison to mineralized bone further suggests a mineralization process unlike regular bone mineralization. Clearly, mineralization of osteocyte lacunae qualifies as a strong marker for degrading bone material quality in skeletal aging. The understanding of micropetrosis may guide future therapeutics toward preserving osteocyte viability to maintain mechanical competence and fracture resistance of bone in elderly individuals.

  6. The impact of sex hormone changes on bone mineral deficit in chronic renal failure.

    PubMed

    Doumouchtsis, Konstantinos K; Perrea, Despoina N; Doumouchtsis, Stergios K

    2009-01-01

    In chronic renal failure several factors affect bone homeostasis leading to the development of renal osteodystrophy. Common calcitropic hormone derangements in renal failure play a central role in bone structure and mineral defects, which in turn accompany osteodystrophy frequently resulting in low bone mineral density (BMD) values. However, patients with end-stage renal disease (ESRD) suffer from several comorbidities, which may partly account for renal bone disease lesions. Hypogonadism in particular accompanies chronic renal failure frequently and exerts an additive effect on bone loss potential. Sex hormones contribute to the equilibrium of osteotropic hormones and cytokines, exerting a protective action on bone tissue. Estrogens have a regulatory effect on bone metabolism in women with renal failure as well. Hypogonadal ESRD women experience a higher bone turnover and more significant bone mass decrements than ESRD women with relatively normal hormone profile and menstrual habits. Female hemodialysis patients have lower BMD values than male patients on average, probably because of menstrual cycle irregularities. However, hypogonadal ESRD men may also experience bone mineral deficits and the severity of hypogonadism may correlate to their bone mineral status. Hormone replacement therapy (HRT) appears to reverse bone mineral loss to some extent in both sexes. In conclusion hypogonadism in renal failure contributes to the bone structure and mineral defects as well as the low-energy fracture risk, reflected in BMD measurements. HRT in ESRD patients should therefore not be overlooked in these patients in the face of their significant comorbidities.

  7. Tensile properties of rat femoral bone as functions of bone volume fraction, apparent density and volumetric bone mineral density.

    PubMed

    Nazarian, Ara; Araiza Arroyo, Francisco J; Rosso, Claudio; Aran, Shima; Snyder, Brian D

    2011-09-02

    Mechanical testing has been regarded as the gold standard to investigate the effects of pathologies on the structure-function properties of the skeleton. Tensile properties of cancellous and cortical bone have been reported previously; however, no relationships describing these properties for rat bone as a function of volumetric bone mineral density (ρ(MIN)), apparent density or bone volume fraction (BV/TV) have been reported in the literature. We have shown that at macro level, compression and torsion properties of rat cortical and cancellous bone can be well described as a function of BV/TV, apparent density or ρ(MIN) using non-destructive micro-computed tomographic imaging and mechanical testing to failure. Therefore, the aim of this study is to derive a relationship expressing the tensile properties of rat cortical bone as a function of BV/TV, apparent density or ρ(MIN) over a range of normal and pathologic bones. We used bones from normal, ovariectomized and osteomalacic animals. All specimens underwent micro-computed tomographic imaging to assess bone morphometric and densitometric indices and uniaxial tension to failure. We obtained univariate relationships describing 74-77% of the tensile properties of rat cortical bone as a function of BV/TV, apparent density or ρ(MIN) over a range of density and common skeletal pathologies. The relationships reported in this study can be used in the structural rigidity to provide a non-invasive method to assess the tensile behavior of bones affected by pathology and/or treatment options.

  8. Effects of Rubus coreanus-Cheonggukjang on Bone Mineral Density and Bone Mineral Content in Growing Rats

    PubMed Central

    Jung, Yun-Jung; Choi, Mi-Ja

    2015-01-01

    The purpose of the present study was to investigate the bone-conserving effects of Rubus coreanus-Cheonggukjang (RC-CGJ) supplemented with more intensified phytochemicals compared to general Cheonggukjang (CGJ) in growing rats. Eighteen rats were divided into 3 treatment groups (Control, CGJ, and RC-CGJ) and were given experimental diets for 9 weeks. All of the rats in this study were fed a AIN-93G-based diet. Both CGJ groups were fed with 33.1% CGJ and RC-CGJ powder, respectively. The results of this study indicate that weight gain, mean food intake, and food efficiency ratio were not significantly different by the experimental diets among all groups. Spine bone mineral density (BMD) and femur BMD were not significantly different by the experimental diets. Spine bone mineral content (BMC) was significantly higher in the RC-CGJ and CGJ groups than in the control group, regardless of CGJ type. The femur BMC of the CGJ supplemented group was significantly higher compared with the control group and the RC-CGJ group. Compared with the control group, spine BMD and femur BMD per weight were markedly increased in the RC-CGJ and CGJ group regardless of CGJ type. Also, spine BMC per weight was significantly higher in the RC-CGJ group than in the CGJ group. However, femur BMC per weight was significantly higher in the CGJ group than in the RC-CGJ group. It can be concluded that RC-CGJ and CGJ supplemented diets have more beneficial effects on spine and femur peak bone mass in growing rats. PMID:26770913

  9. Vascular calcification, bone and mineral metabolism after kidney transplantation

    PubMed Central

    D’Marco, Luis; Bellasi, Antonio; Mazzaferro, Sandro; Raggi, Paolo

    2015-01-01

    The development of end stage renal failure can be seen as a catastrophic health event and patients with this condition are considered at the highest risk of cardiovascular disease among any other patient groups and risk categories. Although kidney transplantation was hailed as an optimal solution to such devastating disease, many issues related to immune-suppressive drugs soon emerged and it became evident that cardiovascular disease would remain a vexing problem. Progression of chronic kidney disease is accompanied by profound alterations of mineral and bone metabolism that are believed to have an impact on the cardiovascular health of patients with advanced degrees of renal failure. Cardiovascular risk factors remain highly prevalent after kidney transplantation, some immune-suppression drugs worsen the risk profile of graft recipients and the alterations of mineral and bone metabolism seen in end stage renal failure are not completely resolved. Whether this complex situation promotes progression of vascular calcification, a hall-mark of advanced chronic kidney disease, and whether vascular calcifications contribute to the poor cardiovascular outcome of post-transplant patients is reviewed in this article. PMID:26722649

  10. Accelerated growth plate mineralization and foreshortened proximal limb bones in fetuin-A knockout mice.

    PubMed

    Seto, Jong; Busse, Björn; Gupta, Himadri S; Schäfer, Cora; Krauss, Stefanie; Dunlop, John W C; Masic, Admir; Kerschnitzki, Michael; Zaslansky, Paul; Boesecke, Peter; Catalá-Lehnen, Philip; Schinke, Thorsten; Fratzl, Peter; Jahnen-Dechent, Willi

    2012-01-01

    The plasma protein fetuin-A/alpha2-HS-glycoprotein (genetic symbol Ahsg) is a systemic inhibitor of extraskeletal mineralization, which is best underscored by the excessive mineral deposition found in various tissues of fetuin-A deficient mice on the calcification-prone genetic background DBA/2. Fetuin-A is known to accumulate in the bone matrix thus an effect of fetuin-A on skeletal mineralization is expected. We examined the bones of fetuin-A deficient mice maintained on a C57BL/6 genetic background to avoid bone disease secondary to renal calcification. Here, we show that fetuin-A deficient mice display normal trabecular bone mass in the spine, but increased cortical thickness in the femur. Bone material properties, as well as mineral and collagen characteristics of cortical bone were unaffected by the absence of fetuin-A. In contrast, the long bones especially proximal limb bones were severely stunted in fetuin-A deficient mice compared to wildtype littermates, resulting in increased biomechanical stability of fetuin-A deficient femora in three-point-bending tests. Elevated backscattered electron signal intensities reflected an increased mineral content in the growth plates of fetuin-A deficient long bones, corroborating its physiological role as an inhibitor of excessive mineralization in the growth plate cartilage matrix--a site of vigorous physiological mineralization. We show that in the case of fetuin-A deficiency, active mineralization inhibition is a necessity for proper long bone growth.

  11. Accelerated Growth Plate Mineralization and Foreshortened Proximal Limb Bones in Fetuin-A Knockout Mice

    PubMed Central

    Gupta, Himadri S.; Schäfer, Cora; Krauss, Stefanie; Dunlop, John W. C.; Masic, Admir; Kerschnitzki, Michael; Zaslansky, Paul; Boesecke, Peter; Catalá-Lehnen, Philip; Schinke, Thorsten; Fratzl, Peter; Jahnen-Dechent, Willi

    2012-01-01

    The plasma protein fetuin-A/alpha2-HS-glycoprotein (genetic symbol Ahsg) is a systemic inhibitor of extraskeletal mineralization, which is best underscored by the excessive mineral deposition found in various tissues of fetuin-A deficient mice on the calcification-prone genetic background DBA/2. Fetuin-A is known to accumulate in the bone matrix thus an effect of fetuin-A on skeletal mineralization is expected. We examined the bones of fetuin-A deficient mice maintained on a C57BL/6 genetic background to avoid bone disease secondary to renal calcification. Here, we show that fetuin-A deficient mice display normal trabecular bone mass in the spine, but increased cortical thickness in the femur. Bone material properties, as well as mineral and collagen characteristics of cortical bone were unaffected by the absence of fetuin-A. In contrast, the long bones especially proximal limb bones were severely stunted in fetuin-A deficient mice compared to wildtype littermates, resulting in increased biomechanical stability of fetuin-A deficient femora in three-point-bending tests. Elevated backscattered electron signal intensities reflected an increased mineral content in the growth plates of fetuin-A deficient long bones, corroborating its physiological role as an inhibitor of excessive mineralization in the growth plate cartilage matrix - a site of vigorous physiological mineralization. We show that in the case of fetuin-A deficiency, active mineralization inhibition is a necessity for proper long bone growth. PMID:23091616

  12. Impairment of osteoclastic bone resorption in rapidly growing female p47phox knockout mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bone formation is dependent on the activity and differentiation of osteoblasts; whereas resorption of preexisting mineralized bone matrix by osteoclasts is necessary not only for bone development but also for regeneration and remodeling. Bone remodeling is a process in which osteoblasts and osteocla...

  13. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women.

    PubMed

    Wensel, Terri M; Iranikhah, Maryam M; Wilborn, Teresa W

    2011-05-01

    Osteoporosis is a degenerative bone disease affecting approximately 10 million American adults. Several options are available to prevent development of the disease or slow and even stop its progression. Nonpharmacologic measures include adequate intake of calcium and vitamin D, exercise, fall prevention, and avoidance of tobacco and excessive alcohol intake. Current drug therapy includes bisphosphonates, calcitonin, estrogen or hormone therapy, selective estrogen receptor modulators, and teriparatide. Denosumab, a receptor activator of nuclear factor-K B ligand (RANKL) inhibitor, was recently approved by the United States Food and Drug Administration for treatment of postmenopausal osteoporosis. Patients treated with denosumab experienced significant gains in bone mineral density, rapid reductions in markers of bone turnover, and a reduced risk for new vertebral fracture. Compared with placebo, patients receiving denosumab 60 mg subcutaneously once every 6 months experienced gains in bone mineral density of 6.5-11% when treated for 24-48 months. One trial demonstrated the superiority of denosumab compared with alendronate, but the differences were small. The most common adverse reactions to denosumab include back pain, pain in extremities, musculoskeletal pain, and cystitis. Serious, but rare, adverse reactions include the development of serious infections, dermatologic changes, and hypocalcemia. The recommended dosing of denosumab is 60 mg every 6 months as a subcutaneous injection in the upper arm, upper thigh, or abdomen. Although beneficial effects on bone mineral density and fracture rate have been established in clinical trials, the risks associated with denosumab must be evaluated before therapy initiation. Of concern is the risk of infection, and denosumab should likely be avoided in patients taking immunosuppressive therapy or at high risk for infection. Therefore, bisphosphonates will likely remain as first-line therapy. Denosumab should be considered in

  14. Gemstone spectral imaging for measuring adult bone mineral density

    PubMed Central

    Shao, Wei-Guang; Liu, Dian-Mei

    2016-01-01

    The present study aimed to detect the bone Ca2+ content of L3 vertebrae in adults by gemstone spectral computed tomography. In total, 235 patients were selected and divided into age groups of 10 years each. The scanning data were used to detect the water-based and Ca2+-based substance levels on the L3 vertebral cancellous bone images. The results indicated that there were significant differences in vertebral Ca2+-water and water-Ca2+ densities determined by gemstone spectral imaging (GSI) between males and females in subjects aged 50–59 years, 60–69 years, 70–79 years and ≥80 years (P<0.05). The ages of male and female participants were negatively correlated with vertebral Ca2+-water density (P<0.01) and water-Ca2+ density (P<0.01). In conclusion, GSI may be used as a novel method of measuring the vertebral adult bone mineral density. PMID:27703518

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

    PubMed Central

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

    2015-01-01

    Purpose of Review To update the reader's knowledge about the factors that influence bone mineral accrual and to review the advances in the assessment of bone health and treatment of bone disorders. Recent Findings Maternal vitamin D status influences neonatal calcium levels, bone mineral density and bone size. In turn, bone mineral density z-score tends to track in childhood. These factors highlight the importance of bone health as early as fetal life. Dual-energy x-ray absorptiometry is the mainstay of clinical bone health assessment in this population due to the availability of appropriate reference data. Recently, more information has become available about assessment and treatment of bone disease in chronically ill pediatric patients. Summary Bone health must become a health focus starting prenatally in order to maximize peak bone mass and to prevent osteoporosis-related bone disease in adulthood. Vitamin D, calcium and weight-bearing activity are factors of key importance throughout childhood in achieving optimal bone health as bone mineral density z-score tracks through childhood and into adulthood. Recent updates of the International Society for Clinical Densitometry focus on the appropriate use of dual-energy x-ray absorptiometry in children of all ages, including children with chronic disease, and on the treatment of pediatric bone disease. PMID:25517023

  16. Longitudinal evolution of bone mineral density and bone markers in human immunodeficiency virus-infected individuals.

    PubMed

    Mondy, Kristin; Yarasheski, Kevin; Powderly, William G; Whyte, Michael; Claxton, Sherry; DeMarco, Debra; Hoffmann, Mary; Tebas, Pablo

    2003-02-15

    The underlying mechanisms of several bone disorders in human immunodeficiency virus (HIV)-infected persons and any relation to antiretroviral therapy have yet to be defined. A longitudinal study was conducted to estimate the prevalence of osteopenia or osteoporosis in HIV-infected persons; to assess bone mineralization, metabolism, and histomorphometry over time; and to evaluate predisposing factors. A total of 128 patients enrolled the study, and 93 were observed for 72 weeks. "Classic" risk factors (low body mass index, history of weight loss, steroid use, and smoking) for low bone mineral density (BMD) and duration of HIV infection were strongly associated with osteopenia. There was a weak association between low BMD and receipt of treatment with protease inhibitors; this association disappeared after controlling for the above factors. Markers of bone turnover tended to be elevated in the whole cohort but were not associated with low BMD. BMD increased slightly during follow-up. Traditional risk factors and advanced HIV infection play a more significant pathogenic role in the development of osteopenia and osteoporosis associated with HIV infection than do treatment-associated factors.

  17. Serum Bone Markers Levels and Bone Mineral Density in Familial Mediterranean Fever

    PubMed Central

    Aydın, Teoman; Taspınar, Ozgur; Akbal, Yildiz; Peru, Celaleddin; Guler, Mustafa; Uysal, Omer; Yakıcıer, M. Cengiz

    2014-01-01

    [Purpose] The aim of this study was to measure bone mineral density, serum and urinary bone turnover parameters, and to evaluate the influence of demographic and genetic factors on these parameters in FMF patients. [Subjects and Methods] Twenty-seven attack-free patients who were diagnosed with FMF (in accordance with Tel Hashomer criteria) were recruited at outpatient rheumatology clinics. We investigated whether there were any differences between the FMF patients and a control group in terms of lumbar and femur bone mineral density (BMD), standard deviation scores (Z scores and T scores) and bone markers. [Results] In terms of the median values of lumbar BMD (p = 0.21), lumbar T (p = 0.098) and Z (p = 0.109) scores, femoral neck BMD, femoral T and Z scores and total femur BMD, T (p = 0.788) and Z scores, there were no significant differences. [Conclusion] In our study, no statistically significant differences were found between FMF patients and a control group in terms of osteoporosis. The 25-OH vitamin D was found to be significantly lower in FMF patients than in the control group. PMID:25276036

  18. No change detected by DEXA in bone mineral density after periacetabular osteotomy.

    PubMed

    Mechlenburg, Inger; Kold, Søren; Søballe, Kjeld

    2009-12-01

    The purpose of this study was to assess acetabular bone mineral density after periacetabular osteotomy and to examine whether bone mineral density correlates with postoperative migration of the osteotomised acetabular fragment. Twenty-five female and three male patients scheduled for periacetabular osteotomy were consecutively included. The patients were scanned by dual energy X-ray absorptiometry (DEXA) at 1 week, 1 year, and 2 1/2 years after surgery. Radiostereometric analyses (RSA) were done at 1, 4, 8, and 24 weeks after surgery. Two and a half years after periacetabular osteotomy, no significant changes in bone mineral density or any biological effect on bone remodelling due a changed loading pattern in the acetabulum could be detected. There was no significant correlation between bone mineral density and migration of the acetabulum. Dual energy X-ray absorptiometry is not an appropriate method to demonstrate the changes in bone mineral density after periacetabular osteotomy or to predict postoperative acetabular migration.

  19. Agave fructans: their effect on mineral absorption and bone mineral content.

    PubMed

    García-Vieyra, María Isabel; Del Real, Alicia; López, Mercedes G

    2014-11-01

    In this study we investigate the effect that Agave fructans as new prebiotics have on mineral absorption improvement. Forty-eight 12-week-old C57BL/6J mice were used in this study. Forty mice were ovariectomized and eight were sham-operated controls. Mice were fed standard diets or diets supplemented with 10% Agave fructans or 10% inulin fructans. Calcium and magnesium were evaluated as well as their excretion in feces. Osteocalcin levels were also measured; femur structure was studied by scanning electron microscopy. Other parameters, such as food intake, body weight, glucose, and short-chain fatty acid content, were recorded. Calcium in plasma and bone increased in Agave fructan groups (from 53.1 to 56 and 85 mg/L and from 0.402 to 0.474 and 0.478 g/g, respectively) and osteocalcin increased in all fructan groups (>50%). Scanning electron microscopy showed that fructans were able to mitigate bone loss. In conclusion, we demonstrated that supplementation with Agave fructans prevents bone loss and improves bone formation.

  20. Gonadal steroid–dependent effects on bone turnover and bone mineral density in men

    PubMed Central

    Finkelstein, Joel S.; Lee, Hang; Leder, Benjamin Z.; Goldstein, David W.; Hahn, Christopher W.; Hirsch, Sarah C.; Linker, Alex; Perros, Nicholas; Servais, Andrew B.; Taylor, Alexander P.; Webb, Matthew L.; Youngner, Jonathan M.; Yu, Elaine W.

    2016-01-01

    BACKGROUND. Severe gonadal steroid deficiency induces bone loss in adult men; however, the specific roles of androgen and estrogen deficiency in hypogonadal bone loss are unclear. Additionally, the threshold levels of testosterone and estradiol that initiate bone loss are uncertain. METHODS. One hundred ninety-eight healthy men, ages 20–50, received goserelin acetate, which suppresses endogenous gonadal steroid production, and were randomized to treatment with 0, 1.25, 2.5, 5, or 10 grams of testosterone gel daily for 16 weeks. An additional cohort of 202 men was randomized to receive these treatments plus anastrozole, which suppresses conversion of androgens to estrogens. Thirty-seven men served as controls and received placebos for goserelin and testosterone. Changes in bone turnover markers, bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA), and BMD by quantitative computed tomography (QCT) were assessed in all men. Bone microarchitecture was assessed in 100 men. RESULTS. As testosterone dosage decreased, the percent change in C-telopeptide increased. These increases were considerably greater when aromatization of testosterone to estradiol was also suppressed, suggesting effects of both testosterone and estradiol deficiency. Decreases in DXA BMD were observed when aromatization was suppressed but were modest in most groups. QCT spine BMD fell substantially in all testosterone-dose groups in which aromatization was also suppressed, and this decline was independent of testosterone dose. Estradiol deficiency disrupted cortical microarchitecture at peripheral sites. Estradiol levels above 10 pg/ml and testosterone levels above 200 ng/dl were generally sufficient to prevent increases in bone resorption and decreases in BMD in men. CONCLUSIONS. Estrogens primarily regulate bone homeostasis in adult men, and testosterone and estradiol levels must decline substantially to impact the skeleton. TRIAL REGISTRATION. ClinicalTrials.gov, NCT00114114

  1. Effect of intravenous pamidronate on bone markers and local bone mineral density in fibrous dysplasia.

    PubMed

    Parisi, Muriel S; Oliveri, Beatriz; Mautalen, Carlos A

    2003-10-01

    Bisphosphonates have proven to be effective in patients with fibrous dysplasia of the bone (FD) as shown by their effect on bone pain, markers of bone turnover, or radiological changes. The aim of this study was to evaluate the usefulness of measuring bone mineral density (BMD) of affected bones to assess the efficacy of bisphosphonate treatment. Seven patients (mean age 26 years) received courses of 180 mg intravenous infusion of pamidronate every 6 months (60 mg/day during 3 days). Clinical symptoms, serum alkaline phosphatase, and urinary C-terminal cross-linking telopeptide of type I collagen were assessed every 3 months. BMD of total skeleton and X-rays of FD areas (FDa) were performed at baseline and at 12 months. BMD of FDa was compared with the contralateral side (CL) using the region of interest program on the total skeleton scan. BMD of total skeleton was normal at baseline. Average BMD of FDa was -11.4% compared with CL, a significantly greater difference than that observed between the left and right sides in healthy controls, -0.7% (P < 0.02). At 12 months bone pain diminished in all patients. Bone turnover markers decreased. Mean total skeleton BMD increased 3.3% (P < 0.02). Subregions of the total skeleton scan presenting FD lesions augmented: arms +9.6% (P < 0.02), legs +4.2%, and pelvis +3.5% (P < 0.05). The increase in mean BMD of FDa was +6.8% compared with +2.6% in CL. No changes were observed on the X-ray. These results indicate that simultaneous determination of markers of bone turnover and BMD of FDa is useful in short-term follow-up to determine the efficacy of intravenous pamidronate.

  2. Influence of the mineral staggering on the elastic properties of the mineralized collagen fibril in lamellar bone.

    PubMed

    Vercher-Martínez, Ana; Giner, Eugenio; Arango, Camila; Fuenmayor, F Javier

    2015-02-01

    In this work, a three-dimensional finite element model of the staggered distribution of the mineral within the mineralized collagen fibril has been developed to characterize the lamellar bone elastic behavior at the sub-micro length scale. Minerals have been assumed to be embedded in a collagen matrix, and different degrees of mineralization have been considered allowing the growth of platelet-shaped minerals both in the axial and the transverse directions of the fibril, through the variation of the lateral space between platelets. We provide numerical values and trends for all the elastic constants of the mineralized collagen fibril as a function of the volume fraction of mineral. In our results, we verify the high influence of the mineral overlapping on the mechanical response of the fibril and we highlight that the lateral distance between crystals is relevant to the mechanical behavior of the fibril and not only the mineral overlapping in the axial direction.

  3. Differences by sex and handedness in right and left femur bone mineral densities.

    PubMed

    Sahin, Ali; Dane, Senol; Seven, Bedri; Akar, Sedat; Yildirim, Serap

    2009-12-01

    Left-handedness was reported to be a risk factor for accident-related injuries, head injuries, traumatic brain injuries, sport-related injuries, and bone breaks and fractures. As decreased bone mineral density is a good marker of bone fractures, the femoral bone mineral densities of normal left-handed university students were compared with those of right-handed students. Hand preference of 66 men and 47 women was assessed using the Edinburgh Handedness Inventory. Measures of bone mineral density with a Hologic QDR-4500W (S/N 48403) densitometer showed bone mineral densities of both right and left proximal femur regions were higher in right-handed than in left-handed students. These results are consistent with the claim that left-handed participants had higher trauma and injury risk. Also, these results may explain the sex-related differences by handedness for susceptibility in accident-related injuries such as bone fractures.

  4. Paracetamol (acetaminophen) use, fracture and bone mineral density.

    PubMed

    Williams, Lana J; Pasco, Julie A; Henry, Margaret J; Sanders, Kerrie M; Nicholson, Geoffrey C; Kotowicz, Mark A; Berk, Michael

    2011-06-01

    Paracetamol is the most widely prescribed simple analgesic and antipyretic. It exerts its effects via cyclooxygenase and endocannabinoid pathways, which may affect signalling in bone cells and hence influence bone metabolism. Given the high rates of paracetamol use in the community and the evidence linking its mechanism of action to bone metabolism, we aimed to investigate the association between paracetamol use, fracture, and bone mineral density (BMD) in women participating in the Geelong Osteoporosis Study (GOS). Cases (n = 569) were women aged ≥ 50 years identified from radiological reports as having sustained a fracture between 1994 and 1996. Controls (n = 775) were women without fracture recruited from the same region during this period. BMD was measured at the spine, hip, total body and forearm using dual energy absorptiometry. Medication use, medical history and lifestyle factors were self-reported. There were 69 (12.1%) paracetamol users among the cases and 63 (8.1%) among the controls. Paracetamol use increased the odds for fracture (OR = 1.56, 95%CI 1.09-2.24, p = 0.02). Adjustment for BMD at the spine, total hip and forearm did not confound the association. However, incorporating total body BMD into the model attenuated the association (adjusted OR = 1.46, 95%CI 1.00-2.14, p = 0.051). Further adjustment for age, weight, physical activity, smoking, alcohol, calcium intake, medication use, medical conditions, falls and previous fracture did not explain the association. These data suggest that paracetamol use is a risk factor for fracture, although the mechanism of action remains unclear.

  5. Bone morphometry and mineral density measurement using quantitative computed tomography

    SciTech Connect

    Jacobson, D.R.

    1991-01-01

    Application of computed tomography (CT) to the study of bone structure and density was explored and developed. A review of bone mineral densitometry (BMD) methodology and general principles of quantitative CT (QCT) are presented. A method for QCT of the spine was developed using a flexible tissue equivalent reference placed adjacent to the patient. A methodology for the development and production of tissue equivalent materials is also presented. Patient equivalent phantoms were used to characterize the method, and phantom studies were performed at five clinical sites. A protocol is defined for measuring the inside diameter of the lumbar pedicular canal. Data generated from this study has proven invaluable in the planning for lumbar fusion surgery when screws are to be used for immobilization. Pedicular canal data from 33 patients is presented. QCT was also used to quantify several parameters of the femoral shaft for use in hip replacement surgical planning. Parameters studied include inside diameter, BMD, endosteal BMD and proximal shaft morphology. The structure and trabecular BMD of the proximal femur was extensively studied using QCT. A large variation was found in the fat content of marrow within the proximal femur, and phantom studies were performed to quantify the effect of fat on trabecular QCT BMD. Cadaveric trabecular bone samples with marrow were analyzed physically to determine water, fat, non-fat soft tissue, and ash content. Multiple thin-slice CT studies were performed on cadaveric femurs. A structural model of the proximal femur was developed in which the structural support is provided primarily by trabecular bone. This model may have profound implications in the study of femoral fractures and prosthetic hardware design.

  6. Risk factors for developing mineral bone disease in phenylketonuric patients.

    PubMed

    Mirás, Alicia; Bóveda, M Dolores; Leis, María R; Mera, Antonio; Aldámiz-Echevarría, Luís; Fernández-Lorenzo, José R; Fraga, José M; Couce, María L

    2013-03-01

    There is a compromised bone mass in phenylketonuria patients compared with normal population, but the mechanisms responsible are still a matter of investigation. In addition, tetrahydrobiopterin therapy is a new option for a significant proportion of these patients and the prevalence of mineral bone disease (MBD) in these patients is unknown. We conducted a cross-sectional observational study including 43 phenylketonuric patients. Bone densitometry, nutritional assessment, physical activity questionnaire, biochemical parameters, and molecular study were performed in all patients. Patients were stratified by phenotype, age and type of treatment. The MBD prevalence in phenylketonuria was 14%. Osteopenic and osteoporotic (n=6 patients) had an average daily natural protein intake significantly lower than the remaining (n=37) patients with PKU (14.33 ± 8.95 g vs 21.25 ± 20.85 g). Besides, a lower body mass index was found. There were no statistical differences in physical activity level, calcium, phosphorus and fat intake, and in phenylalanine, vitamin D, paratohormone, docosahexaenoic and eicosapentaenoic acid blood levels. Mutational spectrum was found in up to 30 different PAH genotypes and no relationship was established among genotype and development of MBD. None of the twelve phenylketonuric patients treated with tetrahydrobiopterin (27.9%), for an average of 7.1 years, developed MBD. Natural protein intake and blood levels of eicosapentaenoic acid were significantly higher while calcium intake was lower in these patients. This study shows that the decrease in natural protein intake can play an important role in MBD development in phenylketonuric patients. Therapy with tetrahydrobiopterin allows a more relaxed protein diet, which is associated with better bone mass.

  7. Bone Mineral Density in Sheehan's Syndrome; Prevalence of Low Bone Mass and Associated Factors.

    PubMed

    Chihaoui, Melika; Yazidi, Meriem; Chaker, Fatma; Belouidhnine, Manel; Kanoun, Faouzi; Lamine, Faiza; Ftouhi, Bochra; Sahli, Hela; Slimane, Hedia

    2016-10-01

    Hypopituitarism is a known cause of bone mineral loss. This study aimed to evaluate the frequency of osteopenia and osteoporosis in patients with Sheehan's syndrome (SS) and to determine the risk factors. This is a retrospective study of 60 cases of SS that have had a bone mineral density (BMD) measurement. Clinical, biological, and therapeutic data were collected. The parameters of osteodensitometry at the femoral neck and the lumbar spine of 60 patients with SS were compared with those of 60 age-, height-, and weight-matched control women. The mean age at BMD measurement was 49.4 ± 9.9 yr (range: 25-76 yr). The mean duration of SS was 19.3 ± 8.5 yr (range: 3-41 yr). All patients had corticotropin deficiency and were treated with hydrocortisone at a mean daily dose of 26.3 ± 4.1 mg. Fifty-seven patients (95%) had thyrotropin deficiency and were treated with thyroxine at a mean daily dose of 124.3 ± 47.4 µg. Thirty-five of the 49 patients, aged less than 50 yr at diagnosis and having gonadotropin deficiency (71.4%), had estrogen-progesterone substitution. Osteopenia was present in 25 patients (41.7%) and osteoporosis in 21 (35.0%). The BMD was significantly lower in the group with SS than in the control group (p < 0.001). The odds ratio of osteopenia-osteoporosis was 3.1 (95% confidence interval: 1.4-6.8) at the femoral neck and 3.7 (95% confidence interval: 1.7-7.8) at the lumbar spine. The lumbar spine was more frequently affected by low bone mineral mass (p < 0.05). The duration of the disease and the daily dose of hydrocortisone were independently and inversely associated with BMD at the femoral neck. The daily dose of thyroxine was independently and inversely associated with BMD at the lumbar spine. Estrogen-progesterone replacement therapy was not associated with BMD. Low bone mineral mass was very common in patients with SS. The lumbar spine was more frequently affected. The duration of the disease and the doses of

  8. Preoperative Periarticular Knee Bone Mineral Density in Osteoarthritic Patients Undergoing TKA

    PubMed Central

    Ishii, Yoshinori; Noguchi, Hideo; Sato, Junko; Todoroki, Koji; Ezawa, Nobukazu; Toyabe, Shin-ichi

    2016-01-01

    Background: Preoperative periarticular bone quality is affected by joint loading. The purpose of this study was to determine the periarticular bone mineral density of the knee joint of patients undergoing total knee arthroplasty, and whether the location of the load-bearing axis correlates with the measured bone mineral density. Materials and Methods: The bone mineral densities of the medial and lateral femoral condyles and the medial and lateral tibial condyles were analyzed in consecutive 116 osteoarthritic patients (130 knees) by dual energy x-ray absorptiometry. Results: The median bone mineral density values in the condyles were 1.138 in femoral medial, 0.767 in femoral lateral, 1.056 in tibial medial, and 0.714 in tibial lateral. The medial condyles showed significantly higher bone mineral densities than the lateral condyles in both the femur and tibia. In addition, the femoral medial showed significantly higher bone mineral density levels than the tibial medial, and the femoral lateral condyle had higher bone mineral density levels than the tibial lateral. The bone mineral density Medial/Lateral ratio was significantly negatively correlated with the location (tibial medial edge 0%, lateral edge 100%) of the load-bearing axis in the femur and tibia. Conclusion: Preoperative bone mineral density values may provide against the changes in bone mineral density after total knee arthroplasty by reflecting the correlation with joint loading axis. These results help explain why total knee arthroplasty has such good long-term clinical outcomes with a low frequency of component loosening and periarticular fractures despite a high degree of postoperative bone loss. PMID:27583058

  9. Nonalcoholic Fatty Liver Disease is Associated with Low Bone Mineral Density in Obese Children

    PubMed Central

    Pardee, Perrie E.; Dunn, Winston; Schwimmer, Jeffrey B.

    2015-01-01

    SUMMARY BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children. Liver disease can be a cause of low bone mineral density. Whether NAFLD influences bone health is unknown. AIM To evaluate bone mineral density in obese children with and without NAFLD. METHODS Thirty-eight children with biopsy-proven NAFLD were matched for age, sex, race, ethnicity, height, and weight to children without evidence of liver disease from the National Health and Nutrition Examination Survey. Bone mineral density was measured by dual energy x-ray absorptiometry. Age and sex-specific bone mineral density Z-scores were calculated and compared between children with and without NAFLD. After controlling for age, sex, race, ethnicity, and total percent body fat, the relationship between bone mineral density and the severity of histology was analyzed in children with NAFLD. RESULTS Obese children with NAFLD had significantly (p<0.0001) lower bone mineral density Z-scores (−1.98) than obese children without NAFLD (0.48). Forty-five percent of children with NAFLD had low bone mineral density for age, compared to none of the children without NAFLD (p < 0.0001). Among those children with NAFLD, children with NASH had a significantly (p< 0.05) lower bone mineral density Z-score (−2.37) than children with NAFLD who did not have NASH (−1.58). CONCLUSIONS NAFLD was associated with poor bone health in obese children. More severe disease was associated with lower bone mineralization. Further studies are needed to evaluate the underlying mechanisms and consequences of poor bone mineralization in children with NAFLD. PMID:22111971

  10. Mineralization defects in cementum and craniofacial bone from loss of bone sialoprotein

    PubMed Central

    Foster, B.L.; Ao, M.; Willoughby, C.; Soenjaya, Y.; Holm, E.; Lukashova, L.; Tran, A. B.; Wimer, H.F.; Zerfas, P.M.; Nociti, F.H.; Kantovitz, K.R.; Quan, B.D.; Sone, E.D.; Goldberg, H.A.; Somerman, M.J.

    2015-01-01

    Bone sialoprotein (BSP) is a multifunctional extracellular matrix protein found in mineralized tissues, including bone, cartilage, tooth root cementum (both acellular and cellular types), and dentin. In order to define the role BSP plays in the process of biomineralization of these tissues, we analyzed cementogenesis, dentinogenesis, and osteogenesis (intramembranous and endochondral) in craniofacial bone in Bsp null mice and wild-type (WT) controls over a developmental period (1-60 days post natal; dpn) by histology, immunohistochemistry, undecalcified histochemistry, microcomputed tomography (microCT), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and quantitative PCR (qPCR). Regions of intramembranous ossification in the alveolus, mandible, and calvaria presented delayed mineralization and osteoid accumulation, assessed by von Kossa and Goldner's trichrome stains at 1 and 14 dpn. Moreover, Bsp−/− mice featured increased cranial suture size at the early time point, 1 dpn. Immunostaining and PCR demonstrated that osteoblast markers, osterix, alkaline phosphatase, and osteopontin were unchanged in Bsp null mandibles compared to WT. Bsp−/− mouse molars featured a lack of functional acellular cementum formation by histology, SEM, and TEM, and subsequent loss of Sharpey's collagen fiber insertion into the tooth root structure. Bsp−/− mouse alveolar and mandibular bone featured equivalent or fewer osteoclasts at early ages (1 and 14 dpn), however, increased RANKL immunostaining and mRNA, and significantly increased number of osteoclast-like cells (2-5 fold) were found at later ages (26 and 60 dpn), corresponding to periodontal breakdown and severe alveolar bone resorption observed following molar teeth entering occlusion. Dentin formation was unperturbed in Bsp−/− mouse molars, with no delay in mineralization, no alteration in dentin dimensions, and no differences in odontoblast markers analyzed. No defects were identified

  11. Autologous implantation of BMP2-expressing dermal fibroblasts to improve bone mineral density and architecture in rabbit long bones.

    PubMed

    Ishihara, Akikazu; Weisbrode, Steve E; Bertone, Alicia L

    2015-10-01

    Cell-mediated gene therapy may treat bone fragility disorders. Dermal fibroblasts (DFb) may be an alternative cell source to stem cells for orthopedic gene therapy because of their rapid cell yield and excellent plasticity with bone morphogenetic protein-2 (BMP2) gene transduction. Autologous DFb or BMP2-expressing autologous DFb were administered in twelve rabbits by two delivery routes; a transcortical intra-medullar infusion into tibiae and delayed intra-osseous injection into femoral drill defects. Both delivery methods of DFb-BMP2 resulted in a successful cell engraftment, increased bone volume, bone mineral density, improved trabecular bone microarchitecture, greater bone defect filling, external callus formation, and trabecular surface area, compared to non-transduced DFb or no cells. Cell engraftment within trabecular bone and bone marrow tissue was most efficiently achieved by intra-osseous injection of DFb-BMP2. Our results suggested that BMP2-expressing autologous DFb have enhanced efficiency of engraftment in target bones resulting in a measurable biologic response by the bone of improved bone mineral density and bone microarchitecture. These results support that autologous implantation of DFb-BMP2 warrants further study on animal models of bone fragility disorders, such as osteogenesis imperfecta and osteoporosis to potentially enhance bone quality, particularly along with other gene modification of these diseases.

  12. Bone Mineral Density in Children and Adolescents with Congenital Adrenal Hyperplasia

    PubMed Central

    Garcia Alves Junior, Paulo Alonso; Schueftan, Daniel Luis Gilban; de Mendonça, Laura Maria Carvalho; Farias, Maria Lucia Fleiuss; Beserra, Izabel Calland Ricarte

    2014-01-01

    Chronic glucocorticoid therapy is associated with reduced bone mineral density. In paediatric patients with congenital adrenal hyperplasia, increased levels of androgens could not only counteract this effect, but could also advance bone age, with interference in the evaluation of densitometry. We evaluate bone mineral density in paediatric patients with classic congenital adrenal hyperplasia taking into account chronological and bone ages at the time of the measurement. Patients aged between 5 and 19 years underwent radiography of the hand and wrist followed by total body and lumbar spine densitometry. Chronological and bone ages were used in the scans interpretation. In fourteen patients, mean bone mineral density Z-score of total body to bone age was −0.76 and of lumbar spine to bone age was −0.26, lower than those related to chronological age (+0.03 and +0.62, resp.). Mean Z-score differences were statistically significant (P = 0.004 for total body and P = 0.003 for lumbar spine). One patient was classified as having low bone mineral density only when assessed by bone age. We conclude that there was a reduction in the bone mineral density Z-score in classic congenital adrenal hyperplasia paediatric patients when bone age was taken into account instead of chronological age. PMID:24734045

  13. Bone mineral density in children and adolescents with congenital adrenal hyperplasia.

    PubMed

    Garcia Alves Junior, Paulo Alonso; Schueftan, Daniel Luis Gilban; de Mendonça, Laura Maria Carvalho; Farias, Maria Lucia Fleiuss; Beserra, Izabel Calland Ricarte

    2014-01-01

    Chronic glucocorticoid therapy is associated with reduced bone mineral density. In paediatric patients with congenital adrenal hyperplasia, increased levels of androgens could not only counteract this effect, but could also advance bone age, with interference in the evaluation of densitometry. We evaluate bone mineral density in paediatric patients with classic congenital adrenal hyperplasia taking into account chronological and bone ages at the time of the measurement. Patients aged between 5 and 19 years underwent radiography of the hand and wrist followed by total body and lumbar spine densitometry. Chronological and bone ages were used in the scans interpretation. In fourteen patients, mean bone mineral density Z-score of total body to bone age was -0.76 and of lumbar spine to bone age was -0.26, lower than those related to chronological age (+0.03 and +0.62, resp.). Mean Z-score differences were statistically significant (P = 0.004 for total body and P = 0.003 for lumbar spine). One patient was classified as having low bone mineral density only when assessed by bone age. We conclude that there was a reduction in the bone mineral density Z-score in classic congenital adrenal hyperplasia paediatric patients when bone age was taken into account instead of chronological age.

  14. Bisphosphonate Treatment Modifies Canine Bone Mineral and Matrix Properties and their Heterogeneity

    PubMed Central

    Gourion-Arsiquaud, Samuel; Allen, Matthew R.; Burr, David B.; Vashishth, Deepak; Tang, Simon Y.; Boskey, Adele L.

    2009-01-01

    Bone loss and alterations in bone quality are major causes leading to bone fragility in postmenopausal women. Although bisphosphonates are well known to reduce bone turnover and prevent bone loss in postmenopausal osteoporosis, their effects on other bone properties are not fully characterized. Changes in bone mineral and matrix properties may contribute to the anti-fracture efficacy observed with bisphosphonate treatments. The aim of this work was to analyze the effect of a one-year treatment with either alendronate or risedronate, at low and high doses, on spatially resolved bone material and compositional properties that could contribute to the fracture efficacy of these agents. Distal tibias from thirty normal beagles that had been treated daily for one year with oral doses of vehicle (Veh), alendronate (Aln) at 0.2 or 1 mg/kg, and risedronate (Ris) at 0.1 or 0.5 mg/kg were analyzed by Fourier Transform Infrared imaging (FTIRI) to assess the changes in both mineral and matrix properties in discrete bone areas. The widths at half maximum of the pixel histograms for each FTIRI parameter were used to assess the heterogeneity of the bone tissue. Aln and Ris increased the mineral content and the collagen maturity mainly in cancellous bone and at the endocortical surface. Significant differences were observed in the mineral content and in the hydroxyapatite crystallinity distribution in bone tissue, which can contribute to reduced ductility and micro-crack accumulation. No significant differences were observed between low and high dose nor between Aln and Ris treatments. These results show that pharmacologic suppression of bone turnover increases the mineral and matrix bone tissue maturity in normal cancellous and endocortical bone areas where bone turnover is higher. These positive effects for decreased fracture risk are also associated with a loss of bone heterogeneity that could be one factor contributing to increased bone tissue brittleness and micro

  15. 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

  16. Competitive season of triathlon does not alter bone metabolism and bone mineral status in male triathletes.

    PubMed

    Maïmoun, L; Galy, O; Manetta, J; Coste, O; Peruchon, E; Micallef, J P; Mariano-Goulart, D; Couret, I; Sultan, C; Rossi, M

    2004-04-01

    This longitudinal study evaluated the effects of a triathlon season on bone metabolism and hormonal status. Seven male competitive triathletes (mean age 19.3 years, range 18 - 20) with 5.0 +/- 0.3 years of competition experience were tested twice during the season: at the beginning of training and 32 weeks later. Total and regional bone mineral density (BMD) was determined by dual-energy X-ray absorptiometry, while bone turnover was evaluated by specific biochemical markers: bone-specific alkaline phosphatase (B-ALP), osteocalcin, and urinary type I collagen C-telopeptide. In addition, sexual, calciotropic and somatotropic hormones were also analyzed. After 32 weeks, a BMD increase was found at the lumbar spine (1.9 %; p = 0.031) and skull (3.1 %; p = 0.048), while no variation was observed for total body or at the proximal femur. The B-ALP level decreased (-23.2 %; p = 0.031), but no variation was found for the other bone markers. 1.25 (OH) (2)D3, IGF-1 and the bioavailability IGF-1 index (IGF-1/IGFBP-3) increased by 18.3 % (p = 0.047), 29 % (p = 0.048), 33 % (p = 0.011), respectively, while PTH, testosterone, IGFBP-3 and cortisol concentrations were unchanged. In conclusion, the triathlon season had a moderately favourable effect on BMD, although a slowing down of bone formation activity was observed. No variation in hormonal levels was observed that could have limited the effects of exercise on bone tissue.

  17. Comparison of bone mineral density in the jaws of patients with and without chronic periodontitis

    PubMed Central

    Öztürk Tonguç, M; Ş Büyükkaplan, U; Fentoğlu, Ö; A Gümüş, B; S Çerçi, S; Y Kırzıoğlu, F

    2012-01-01

    Objectives Although several studies have addressed the relationship between systemic bone mineral status and the severity of periodontitis, there is little knowledge of the relationship between periodontal disease and locally detected bone mineral density. The aim of this study was to compare the mandibular bone mineral density of patients with chronic periodontitis with that of periodontally healthy subjects. Methods 48 systemically healthy subjects were included in the study and underwent a periodontal examination to determine their status. 24 subjects were periodontally healthy and the other 24 had moderate or severe chronic periodontitis. The mandibular bone mineral density of the subjects was determined by dual energy X-ray absorptiometry. The region of interest on the body of the mandible was independently determined on the dual energy absorptiometry radiographs, and a computer calculated the bone mineral density of these regions. Results The mandibular bone mineral density of the subjects with periodontitis was significantly lower than that of the periodontally healthy subjects (p < 0.01). There were significant negative correlations between the mandibular bone mineral density values and parameters related to the amount of periodontal destruction. Conclusions Low bone mineral density in the jaw may be associated with chronic periodontitis. PMID:22241867

  18. The Development of Bone Mineral Lateralization in the Arms

    PubMed Central

    Siminoski, Kerry; Lee, Kwok-Choy; Abish, Sharon; Alos, Nathalie; Bell, Lorraine; Blydt-Hansen, Tom; Couch, Robert; Cummings, Elizabeth A.; Ellsworth, Janet; Feber, Janusz; Fernandez, Conrad V.; Halton, Jacqueline; Huber, Adam M.; Israels, Sara; Jurencak, Roman; Lang, Bianca; Laverdière, Caroline; LeBlanc., Claire; Lewis, Victor; Midgley, Julian; Miettunen, Paivi M.; Oen, Kiem; Phan, Veronique; Pinsk, Maury; Rauch, Frank; Rodd, Celia; Roth, Johannes; Saint-Cyr, Claire; Scuccimarri, Rosie; Stephure, David; Taback, Shayne; Wilson, Beverly; Ward, Leanne M.

    2014-01-01

    Purpose Bone mineral content (BMC) exhibits sidedness in the arms after the age of 8 years, but it is not known whether BMC is greater in the dominant arm from birth or whether lateralization develops in early childhood. To address this, we examined bone mineral status in relation to handedness and age. Methods Subjects (n = 158) were children recently initiating glucocorticoid for underlying disease (leukemia 43%, rheumatic conditions 39%, nephrotic syndrome 18%). Handedness was determined by questionnaire and BMC by dual-energy x-ray absorptiometry. Results Median age was 7.2 years (range, 1.5 to 17.0 years), 49% were male, and the spine BMD Z-score was −0.9 (SD, 1.3). By linear regression, BMC sidedness in the arms was significantly related to age (r = 0.294, p = 0.0005). Breakpoint analysis revealed two lines with a knot at 6.0 years (95% CI, 4.5–7.5 years). The formula for the first line was: dominant:nondominant arm BMC ratio = 0.029 × age [in years] + 0.850 (r = 0.323, p = 0.017). The slope of the second line was not different from 0 (p = 0.332), while the slopes for the two lines were significantly different (p = 0.027). Conclusions These results show that arm BMC sidedness in this patient group develops up to age six years and then remains stable into late adolescence. This temporal profile is consistent with mechanical stimulation of the skeleton in response to asymmetrical muscle use as handedness becomes manifest. PMID:22744715

  19. Quantitative (31)P NMR spectroscopy and (1)H MRI measurements of bone mineral and matrix density differentiate metabolic bone diseases in rat models.

    PubMed

    Cao, Haihui; Nazarian, Ara; Ackerman, Jerome L; Snyder, Brian D; Rosenberg, Andrew E; Nazarian, Rosalynn M; Hrovat, Mirko I; Dai, Guangping; Mintzopoulos, Dionyssios; Wu, Yaotang

    2010-06-01

    In this study, bone mineral density (BMD) of normal (CON), ovariectomized (OVX), and partially nephrectomized (NFR) rats was measured by (31)P NMR spectroscopy; bone matrix density was measured by (1)H water- and fat-suppressed projection imaging (WASPI); and the extent of bone mineralization (EBM) was obtained by the ratio of BMD/bone matrix density. The capability of these MR methods to distinguish the bone composition of the CON, OVX, and NFR groups was evaluated against chemical analysis (gravimetry). For cortical bone specimens, BMD of the CON and OVX groups was not significantly different; BMD of the NFR group was 22.1% (by (31)P NMR) and 17.5% (by gravimetry) lower than CON. For trabecular bone specimens, BMD of the OVX group was 40.5% (by (31)P NMR) and 24.6% (by gravimetry) lower than CON; BMD of the NFR group was 26.8% (by (31)P NMR) and 21.5% (by gravimetry) lower than CON. No significant change of cortical bone matrix density between CON and OVX was observed by WASPI or gravimetry; NFR cortical bone matrix density was 10.3% (by WASPI) and 13.9% (by gravimetry) lower than CON. OVX trabecular bone matrix density was 38.0% (by WASPI) and 30.8% (by gravimetry) lower than CON, while no significant change in NFR trabecular bone matrix density was observed by either method. The EBMs of OVX cortical and trabecular specimens were slightly higher than CON but not significantly different from CON. Importantly, EBMs of NFR cortical and trabecular specimens were 12.4% and 26.3% lower than CON by (31)P NMR/WASPI, respectively, and 4.0% and 11.9% lower by gravimetry. Histopathology showed evidence of osteoporosis in the OVX group and severe secondary hyperparathyroidism (renal osteodystrophy) in the NFR group. These results demonstrate that the combined (31)P NMR/WASPI method is capable of discerning the difference in EBM between animals with osteoporosis and those with impaired bone mineralization.

  20. Photon absorptiometry for non-invasive measurement of bone mineral content

    SciTech Connect

    Gupta, S.; Luna, E.; Belsky, J.; Gelfman, N.; Miller, K.; Davies, T.

    1984-08-01

    Bone mineral content of the distal radius was determined in 106 patients by single photon absorptiometry using iodine-125 monochromatic source. The technique provided a reliable means to assess the degree of mineral loss in conditions such as osteoporosis, renal osteodystrophy in patients on chronic maintenance dialysis, subjects on long-term steroid therapy, and those with diabetes mellitus. It is more sensitive than conventional radiography and completely noninvasive compared to bone biopsy. It is suggested that photon absorptiometry is a simple, sensitive, and reliable technique for assessment and follow-up of the bone mineral content in a host of disorders associated with bone demineralization.

  1. Determinants of bone mineral density in Chinese men.

    PubMed

    Cheung, E Y N; Ho, A Y Y; Lam, K F; Tam, S; Kung, A W C

    2005-12-01

    Osteoporotic fractures are increasing among Asian populations in both genders, but the risk factors for low bone mineral density (BMD) in Asian men is unclear. To determine the hormonal and lifestyle risk factors for low BMD in Asian men, we studied 407 community-dwelling southern Chinese men aged 50 years and above. Medical history and lifestyle habits were obtained with a structured questionnaire. Dietary calcium and phytoestrogen intake were assessed by a semi-quantitative questionnaire. BMD at the spine and hip were measured by dual-energy X-ray absorptiometry (DXA). Fasting blood was analyzed for 25(OH)D, parathyroid hormone (PTH), total and bioavailable estradiol (bio-E) and testosterone (bio-T). The mean age of the cohort was 68.42+/-10.4 (50-96) years. In the linear regression model, weight, age, body mass index (BMI), bio-E, PTH, cigarette smoking and weight-bearing exercise were significant determinants of total hip BMD. Together they explained 55% of the total variance of hip BMD, with body weight being the most important determining factor. With age and weight adjustment, height, bio-T and flavonoid intake were identified as additional determinants of total hip BMD. Strategies to prevent bone loss and osteoporosis in Asian men should include lifestyle modification and maintenance of hormonal sufficiency.

  2. Age-related differences in the bone mineralization pattern of rats following exercise

    SciTech Connect

    McDonald, R.; Hegenauer, J.; Saltman, P.

    1986-07-01

    The effect of 12 weeks of treadmill exercise on the mineralization of trabecular and cortical bone was studied in rats 7, 14, and 19 months of age. Bone mineralization was evaluated by measuring concentrations of Ca, Mg, and hydroxyproline as well as uptake of 45Ca concentration in the femur, humerus, rib and calvaria. The 7- and 14-month-old rats increased mineralization in those cortical bones directly involved in exercise. The 19-month animal responded to exercise by increasing mineralization in all bones examined, including the nonweight bearing trabecular calvaria and cortical rib. From these data, it is apparent that the older animals undergo a total skeletal mineralization in response to exercise compared with local adaptation in the younger animal. Further, we provide evidence to support the use of the rat as a model in which to study mammalian bone physiology during the aging process.

  3. Bone mineral density and blood metals in premenopausal women

    SciTech Connect

    Pollack, A.Z.; Mumford, S.L.; Wactawski-Wende, J.; Yeung, E.; Mendola, P.; Mattison, D.R.; Schisterman, E.F.

    2013-01-15

    Exposure to metals, specifically cadmium, lead, and mercury, is widespread and is associated with reduced bone mineral density (BMD) in older populations, but the associations among premenopausal women are unclear. Therefore, we evaluated the relationship between these metals in blood and BMD (whole body, total hip, lumbar spine, and non-dominant wrist) quantified by dual energy X-ray absorptiometry in 248 premenopausal women, aged 18-44. Participants were of normal body mass index (mean BMI 24.1), young (mean age 27.4), 60% were white, 20% non-Hispanic black, 15% Asian, and 6% other race group, and were from the Buffalo, New York region. The median (interquartile range) level of cadmium was 0.30 {mu}g/l (0.19-0.43), of lead was 0.86 {mu}g/dl (0.68-1.20), and of mercury was 1.10 {mu}g/l (0.58-2.00). BMD was treated both as a continuous variable in linear regression and dichotomized at the 10th percentile for logistic regression analyses. Mercury was associated with reduced odds of decreased lumbar spine BMD (0.66, 95% confidence interval: 0.44, 0.99), but overall, metals at environmentally relevant levels of exposure were not associated with reduced BMD in this population of healthy, reproductive-aged women. Further research is needed to determine if the blood levels of cadmium, lead, and mercury in this population are sufficiently low that there is no substantive impact on bone, or if effects on bone can be expected only at older ages.

  4. Ubiquitin C-terminal hydrolase L1 deficiency decreases bone mineralization.

    PubMed

    Shim, Sehwan; Kwon, Young-Bae; Yoshikawa, Yasuhiro; Kwon, Jungkee

    2008-06-01

    Ubiquitin C-terminal hydrolase L1 is a component of the ubiquitin proteasome system, which evidences unique biological activities. In this study, we report the pattern of UCH-L1 expression, and show that it regulates bone mineralization in osteogenesis. UCH-L1 was expressed in osteoblasts, osteoclasts, and hematopoietic precursor cells of bone marrow in the metaphysis and diaphysis of the femora. To further assess the involvement of UCH-L1 in the regulation of bone mineralization, we evaluated the bone mineral density (BMD) rate of gad mice, using the Latheta computed tomography system. Male gad mice evidenced a significantly decreased BMD rate in the metaphysis and diaphysis of the femora. These findings of decreased BMD rate in the bones of gad mice may suggest that UCH-L1 function regulates bone mineralization during osteogenesis.

  5. Variations in Urine Calcium Isotope: Composition Reflect Changes in Bone Mineral Balance in Humans

    NASA Technical Reports Server (NTRS)

    Skulan, Joseph; Anbar, Ariel; Bullen, Thomas; Puzas, J. Edward; Shackelford, Linda; Smith, Scott M.

    2004-01-01

    Changes in bone mineral balance cause rapid and systematic changes in the calcium isotope composition of human urine. Urine from subjects in a 17 week bed rest study was analyzed for calcium isotopic composition. Comparison of isotopic data with measurements of bone mineral density and metabolic markers of bone metabolism indicates the calcium isotope composition of urine reflects changes in bone mineral balance. Urine calcium isotope composition probably is affected by both bone metabolism and renal processes. Calcium isotope. analysis of urine and other tissues may provide information on bone mineral balance that is in important respects better than that available from other techniques, and illustrates the usefulness of applying geochemical techniques to biomedical problems.

  6. Dental malocclusion is associated with reduced systemic bone mineral density in adolescents.

    PubMed

    Konstantynowicz, Jerzy; Sierpinska, Teresa; Kaczmarski, Maciej; Piotrowska-Jastrzebska, Janina; Golebiewska, Maria

    2007-01-01

    There is no published data about associations between the state of dentition and bone mass in adolescents. The objective of this study was to investigate whether the prevalence of caries and dental malocclusion is associated with bone mass during growth. In 123 healthy Caucasian subjects (72 males, 51 females) aged 14-18 yr, DMFT figures (decayed teeth, missing teeth, filled teeth) and presence of malocclusion, according to Angle classification, were determined. Participants completed a questionnaire regarding dental hygiene, physical activity level, and consumption of sweets. Anthropometry and pubertal stages were examined. Bone mineral density (BMD) was examined using dual energy X-ray absorptiometry (DXA) in the total body, head, and lumbar spine. No association was found between DMFT (mean+/-SD: 8.33+/-3.9) and BMD or Z-scores for BMD. Malocclusion was found in 49 subjects (39.8%) and was more prevalent in females than males. Malocclusion was associated with lower total BMD independently of body size (p=0.001; Z-scores: -0.21+/-0.27 vs +0.33+/-0.17; p=0.1) in males (but not females), producing odds ratio 1.6 (95% confidence interval: 1.09-2.34%; p=0.02). Head BMD was also lower in the males with malocclusion than in those without (p=0.004). Neither caries nor the tooth loss appear to be associated with BMD during growth. Boys with malocclusion are at higher risk of reduced BMD. This suggests that inadequate bone mass accrual in males coexists with impaired growth of the masticatory system in childhood and adolescence, however, the causal pathway is unknown. Factors that produce malocclusion may also affect bone mass or size but further prospective studies are needed to evaluate the relationship.

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

    PubMed Central

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

    2009-01-01

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

  8. Bone geometry, structure and mineral distribution using Dual energy X ray Absorptiometry (DXA)

    NASA Technical Reports Server (NTRS)

    Whalen, Robert; Cleek, Tammy

    1993-01-01

    Dual energy x-ray absorptiometry (DXA) is currently the most widely used method of analyzing regional and whole body changes in bone mineral content (BMC) and areal (g/sq cm) bone mineral density (BMD). However, BMC and BMD do not provide direct measures of long bone geometry, structure, or strength nor do regional measurements detect localized changes in other regions of the same bone. The capabilities of DXA can be enhanced significantly by special processing of pixel BMC data which yields cross-sectional geometric and structural information. We have extended this method of analysis in order to develop non-uniform structural beam models of long bones.

  9. Association between bone mineralization, body composition, and cardiorespiratory fitness level in young Australian men.

    PubMed

    Liberato, Selma Coelho; Maple-Brown, Louise; Bressan, Josefina

    2015-01-01

    The critical age for attainment of peak bone mineralization is however 20-30 yr, but few studies have investigated bone mineralization and its association with body composition and cardiorespiratory fitness level in young men. This study aimed to investigate relationships between age, bone mineral measurements, body composition measurements, and cardiorespiratory fitness level in a group of young healthy Australian men. Thirty-five healthy men aged 18-25 yr had anthropometric measures, body composition, and cardiorespiratory fitness level assessed. Bone mineral content was significantly associated with height, body mass and lean mass, and bone mineral density positively correlated with lean mass and body mass. Bone mineral measurements did not correlate with fat mass, percentage of fat mass, or cardiorespiratory fitness level. Age was directly correlated with total body mass, body fat, and percentage of fat mass. Body mineral measurements correlated with lean mass but not with fat mass or with cardiorespiratory fitness in this group of young healthy men. Positive association between body fat and age in such young group suggests that more studies with young men are warranted and may help inform strategies to optimize increase in bone mineral measurements.

  10. FLUORIDE EFFECTS ON BONE FORMATION AND MINERALIZATION ARE INFLUENCED BY GENETICS

    PubMed Central

    Mousny, M.; Omelon, S.; Wise, L.; Everett, E. T.; Dumitriu, M.; Holmyard, D. P.; Banse, X.; Devogelaer, J. P.; Grynpas, M. D

    2008-01-01

    Introduction A variation in bone response to fluoride (F−) exposure has been attributed to genetic factors. Increasing fluoride doses (0ppm, 25ppm, 50ppm, 100ppm) for three inbred mouse strains with different susceptibilities to developing dental enamel fluorosis (A/J, a “susceptible” strain; SWR/J, an “intermediate” strain; 129P3/J, a “resistant” strain) had different effects on their cortical and trabecular bone mechanical properties. In this paper, the structural and material properties of the bone were evaluated to explain the previously observed changes in mechanical properties. Materials and Methods This study assessed the effect of increasing fluoride doses on the bone formation, microarchitecture, mineralization and microhardness of the A/J, SWR/J and 129P3/J mouse strains. Bone microarchitecture was quantified with microcomputed tomography and strut analysis. Bone formation was evaluated by static histomorphometry. Bone mineralization was quantified with backscattered electron (BSE) imaging and powder x-ray diffraction. Microhardness measurements were taken from the vertebral bodies (cortical and trabecular bone) and the cortex of the distal femur. Results Fluoride treatment had no significant effect on bone microarchitecture for any of the strains. All three strains demonstrated a significant increase in osteoid formation at the largest fluoride dose. Vertebral body trabecular bone BSE imaging revealed significantly decreased mineralization heterogeneity in the SWR/J strain at 50ppm and 100ppm F−. The trabecular and cortical bone mineralization profiles showed a non-significant shift towards higher mineralization with increasing F− dose in the three strains. Powder x-ray diffraction showed significantly smaller crystals for the 129P3/J strain, and increased crystal width with increasing F− dose for all strains. There was no effect of F− on trabecular and cortical bone microhardness. Conclusion Fluoride treatment had no significant

  11. Rapidly assessing changes in bone mineral balance using natural stable calcium isotopes

    NASA Astrophysics Data System (ADS)

    Morgan, Jennifer L. L.; Skulan, Joseph L.; Gordon, Gwyneth W.; Romaniello, Stephen J.; Smith, Scott M.; Anbar, Ariel D.

    2012-06-01

    The ability to rapidly detect changes in bone mineral balance (BMB) would be of great value in the early diagnosis and evaluation of therapies for metabolic bone diseases such as osteoporosis and some cancers. However, measurements of BMB are hampered by difficulties with using biochemical markers to quantify the relative rates of bone resorption and formation and the need to wait months to years for altered BMB to produce changes in bone mineral density large enough to resolve by X-ray densitometry. We show here that, in humans, the natural abundances of Ca isotopes in urine change rapidly in response to changes in BMB. In a bed rest experiment, use of high-precision isotope ratio MS allowed the onset of bone loss to be detected in Ca isotope data after about 1 wk, long before bone mineral density has changed enough to be detectable with densitometry. The physiological basis of the relationship between Ca isotopes and BMB is sufficiently understood to allow quantitative translation of changes in Ca isotope abundances to changes in bone mineral density using a simple model. The rate of change of bone mineral density inferred from Ca isotopes is consistent with the rate observed by densitometry in long-term bed rest studies. Ca isotopic analysis provides a powerful way to monitor bone loss, potentially making it possible to diagnose metabolic bone disease and track the impact of treatments more effectively than is currently possible.

  12. Bone geometry, bone mineral density, and micro-architecture in patients with myelofibrosis: a cross-sectional study using DXA, HR-pQCT, and bone turnover markers.

    PubMed

    Farmer, Sarah; Vestergaard, Hanne; Hansen, Stinus; Shanbhogue, Vikram Vinod; Shanbhoque, Vikram Vinod; Stahlberg, Claudia Irene; Hermann, Anne Pernille; Frederiksen, Henrik

    2015-07-01

    Primary myelofibrosis (MF) is a severe chronic myeloproliferative neoplasm, progressing towards a terminal stage with insufficient haematopoiesis and osteosclerotic manifestations. Whilst densitometry studies have showed MF patients to have elevated bone mineral density, data on bone geometry and micro-structure assessed with non-invasive methods are lacking. We measured areal bone mineral density (aBMD) using dual-energy X-ray absorptiometry (DXA). Bone geometry, volumetric BMD, and micro-architecture were measured using high-resolution peripheral quantitative computed tomography (HR-pQCT). We compared the structural parameters of bones by comparing 18 patients with MF and healthy controls matched for age, sex, and height. Blood was analysed for biochemical markers of bone turnover in patients with MF. There were no significant differences in measurements of bone geometry, volumetric bone mineral density, and micro-structure between MF patients and matched controls. Estimated bone stiffness and bone strength were similar between MF patients and controls. The level of pro-collagen type 1 N-terminal pro-peptide (P1NP) was significantly increased in MF, which may indicate extensive collagen synthesis, one of the major diagnostic criteria in MF. We conclude that bone mineral density, geometry, and micro-architecture in this cohort of MF patients are comparable with those in healthy individuals.

  13. A network modeling approach for the spatial distribution and structure of bone mineral content.

    PubMed

    Li, Hui; Zhang, Aidong; Bone, Lawrence; Buyea, Cathy; Ramanathan, Murali

    2014-05-01

    This study aims to develop a spatial model of bone for quantitative assessments of bone mineral density and microarchitecture. A spatially structured network model for bone microarchitecture was systematically investigated. Bone mineral-forming foci were distributed radially according to the cumulative normal distribution, and Voronoi tessellation was used to obtain edges representing bone mineral lattice. Methods to simulate X-ray images were developed. The network model recapitulated key features of real bone and contained spongy interior regions resembling trabecular bone that transitioned seamlessly to densely mineralized, compact cortical bone-like microarchitecture. Model-simulated imaging profiles were similar to patients' X-ray images. The morphometric metrics were concordant with microcomputed tomography results for real bone. Simulations comparing normal and diseased bone of 20-30 to 70-80 year-olds demonstrated the method's effectiveness for modeling osteoporosis. The novel spatial model may be useful for pharmacodynamic simulations of bone drugs and for modeling imaging data in clinical trials.

  14. The effects of strontium on bone mineral: A review on current knowledge and microanalytical approaches.

    PubMed

    Querido, William; Rossi, Andre L; Farina, Marcos

    2016-01-01

    The interest in effects of strontium (Sr) on bone has greatly increased in the last decade due to the development of the promising drug strontium ranelate. This drug is used for treating osteoporosis, a major bone disease affecting hundreds of millions of people worldwide, especially postmenopausal women. The novelty of strontium ranelate compared to other treatments for osteoporosis is its unique effect on bone: it simultaneously promotes bone formation by osteoblasts and inhibits bone resorption by osteoclasts. Besides affecting bone cells, treatment with strontium ranelate also has a direct effect on the mineralized bone matrix. Due to the chemical similarities between Sr and Ca, a topic that has long been of particular interest is the incorporation of Sr into bones replacing Ca from the mineral phase, which is composed by carbonated hydroxyapatite nanocrystals. Several groups have analyzed the mineral produced during treatment; however, most analysis were done with relatively large samples containing numerous nanocrystals, resulting thus on data that represents an average of many crystalline domains. The nanoscale analysis of the bone apatite crystals containing Sr has only been described in a few studies. In this study, we review the current knowledge on the effects of Sr on bone mineral and discuss the methodological approaches that have been used in the field. In particular, we focus on the great potential that advanced microscopy and microanalytical techniques may have on the detailed analysis of the nanostructure and composition of bone apatite nanocrystals produced during treatment with strontium ranelate.

  15. Effects of ethnicity and vitamin D supplementation on vitamin D status and changes in bone mineral content in infants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To evaluate the effects on serum 25(OH)D and bone mineralization of supplementation of breast-fed Hispanic and non-Hispanic Caucasian infants with vitamin D in infants in Houston, Texas. We measured cord serum 25(OH)D levels, bone mineral content (BMC), bone mineral density (BMD) and their changes o...

  16. Transport of membrane-bound mineral particles in blood vessels during chicken embryonic bone development.

    PubMed

    Kerschnitzki, Michael; Akiva, Anat; Ben Shoham, Adi; Koifman, Naama; Shimoni, Eyal; Rechav, Katya; Arraf, Alaa A; Schultheiss, Thomas M; Talmon, Yeshayahu; Zelzer, Elazar; Weiner, Stephen; Addadi, Lia

    2016-02-01

    During bone formation in embryos, large amounts of calcium and phosphate are taken up and transported to the site where solid mineral is first deposited. The initial mineral forms in vesicles inside osteoblasts and is deposited as a highly disordered calcium phosphate phase. The mineral is then translocated to the extracellular space where it penetrates the collagen matrix and crystallizes. To date little is known about the transport mechanisms of calcium and phosphate in the vascular system, especially when high transport rates are needed and the concentrations of these ions in the blood serum may exceed the solubility product of the mineral phase. Here we used a rapidly growing biological model, the chick embryo, to study the bone mineralization pathway taking advantage of the fact that large amounts of bone mineral constituents are transported. Cryo scanning electron microscopy together with cryo energy dispersive X-ray spectroscopy and focused-ion beam imaging in the serial surface view mode surprisingly reveal the presence of abundant vesicles containing small mineral particles in the lumen of the blood vessels. Morphologically similar vesicles are also found in the cells associated with bone formation. This observation directly implicates the vascular system in solid mineral distribution, as opposed to the transport of ions in solution. Mineral particle transport inside vesicles implies that far larger amounts of the bone mineral constituents can be transported through the vasculature, without the danger of ectopic precipitation. This introduces a new stage into the bone mineral formation pathway, with the first mineral being formed far from the bone itself.

  17. Improved accuracy of cortical bone mineralization measured by polychromatic microcomputed tomography using a novel high mineral density composite calibration phantom

    SciTech Connect

    Deuerling, Justin M.; Rudy, David J.; Niebur, Glen L.; Roeder, Ryan K.

    2010-09-15

    Purpose: Microcomputed tomography (micro-CT) is increasingly used as a nondestructive alternative to ashing for measuring bone mineral content. Phantoms are utilized to calibrate the measured x-ray attenuation to discrete levels of mineral density, typically including levels up to 1000 mg HA/cm{sup 3}, which encompasses levels of bone mineral density (BMD) observed in trabecular bone. However, levels of BMD observed in cortical bone and levels of tissue mineral density (TMD) in both cortical and trabecular bone typically exceed 1000 mg HA/cm{sup 3}, requiring extrapolation of the calibration regression, which may result in error. Therefore, the objectives of this study were to investigate (1) the relationship between x-ray attenuation and an expanded range of hydroxyapatite (HA) density in a less attenuating polymer matrix and (2) the effects of the calibration on the accuracy of subsequent measurements of mineralization in human cortical bone specimens. Methods: A novel HA-polymer composite phantom was prepared comprising a less attenuating polymer phase (polyethylene) and an expanded range of HA density (0-1860 mg HA/cm{sup 3}) inclusive of characteristic levels of BMD in cortical bone or TMD in cortical and trabecular bone. The BMD and TMD of cortical bone specimens measured using the new HA-polymer calibration phantom were compared to measurements using a conventional HA-polymer phantom comprising 0-800 mg HA/cm{sup 3} and the corresponding ash density measurements on the same specimens. Results: The HA-polymer composite phantom exhibited a nonlinear relationship between x-ray attenuation and HA density, rather than the linear relationship typically employed a priori, and obviated the need for extrapolation, when calibrating the measured x-ray attenuation to high levels of mineral density. The BMD and TMD of cortical bone specimens measured using the conventional phantom was significantly lower than the measured ash density by 19% (p<0.001, ANCOVA) and 33% (p<0

  18. Modulation of Vitamin D Status and Dietary Calcium Affects Bone Mineral Density and Mineral Metabolism in Göttingen Minipigs

    PubMed Central

    Scholz-Ahrens, Katharina E.; Glüer, Claus-Christian; Bronner, Felix; Delling, Günter; Açil, Yahya; Hahne, Hans-Jürgen; Hassenpflug, Joachim; Timm, Wolfram; Schrezenmeir, Jürgen

    2013-01-01

    Calcium and vitamin D deficiency impairs bone health and may cause rickets in children and osteomalacia in adults. Large animal models are useful to study experimental osteopathies and associated metabolic changes. We intended to modulate vitamin D status and induce nutritional osteomalacia in minipigs. The control group (n = 9) was fed a semisynthetic reference diet with 6 g calcium and 6,500 IU vitamin D3/kg and the experimental group (n = 10) the same diet but with only 2 g calcium/kg and without vitamin D. After 15 months, the deficient animals were in negative calcium balance, having lost bone mineral density significantly (means ± SEM) with −51.2 ± 14.7 mg/cm3 in contrast to controls (−2.3 ± 11.8 mg/cm3), whose calcium balance remained positive. Their osteoid surface was significantly higher, typical of osteomalacia. Their plasma 25(OH)D dropped significantly from 60.1 ± 11.4 nmol/L to 15.3 ± 3.4 nmol/L within 10 months, whereas that of the control group on the reference diet rose. Urinary phosphorus excretion and plasma 1,25-dihydroxyvitamin D concentrations were significantly higher and final plasma calcium significantly lower than in controls. We conclude that the minipig is a promising large animal model to induce nutritional osteomalacia and to study the time course of hypovitaminosis D and associated functional effects. PMID:24062955

  19. Assessing Bone Mineral Density Following Acute Hip Fractures

    PubMed Central

    Wiggin, Molly; Hemmati, Pouya; Switzer, Julie

    2015-01-01

    Objectives: In older patients, bone mineral density (BMD) diminishes with age, increasing susceptibility to femoral neck fractures. Evidence has emerged that patients who should have dual x-ray absorptiometry scans to evaluate their bone health are not doing so. Because computed tomography (CT) attenuation has now been correlated with BMD thresholds relating to osteoporosis, virtually any existing CT scan that includes the L1 vertebra can be used to assess BMD. This study evaluates the utility of CT attenuation in characterizing BMD in patients after femoral neck fractures. Methods: The electronic medical records of adults who presented to a level I trauma center with hip fractures were evaluated for eligibility. Those with a CT scan of the abdomen or other CT scan with a complete view of the L1 vertebra were included. To measure attenuation, a region of interest was selected to include the body of the L1 vertebra in the axial plane and exclude the cortices and posterior venous complex. Results: Of the 589 patients reviewed, 217 met inclusion criteria; 112 were aged 18 to 64, while 105 were ≥65. Eight (7.1%) patients in the younger cohort had a mean CT attenuation below the 110-HU threshold set for 90% specificity, whereas 31 (29.5%) patients in the older cohort had a mean CT attenuation below this threshold. Using the 160-HU threshold set for 90% sensitivity, 39 (34.8%) patients of the younger cohort and 74 (70%) patients of the older cohort were osteoporotic; all differences in CT attenuation by age were strongly significant (P < .0001). Conclusions: A significantly larger proportion of older patients with hip fractures had osteoporosis, helping validate the utility of CT attenuation in this context. In addition, a large proportion of these patients already had these images available, thus potentially helping limit cost and unnecessary medical investigations. PMID:26246948

  20. Bone mineral density predicts fractures in chronic kidney disease.

    PubMed

    West, Sarah L; Lok, Charmaine E; Langsetmo, Lisa; Cheung, Angela M; Szabo, Eva; Pearce, Dawn; Fusaro, Maria; Wald, Ron; Weinstein, Jordan; Jamal, Sophie A

    2015-05-01

    Fractures are common in chronic kidney disease (CKD). The optimal methods by which to assess fracture risk are unknown, in part, due to a lack of prospective studies. We determined if bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA), and/or high-resolution peripheral quantitative computed tomography (HRpQCT) could predict fractures in men and women ≥18 years old with stages 3 to 5 CKD. BMD was measured by DXA (at the total hip, lumbar spine, ultradistal, and 1/3 radius) and by HRpQCT (at the radius), and subjects were followed for 2 years for incident morphometric spine fractures and low-trauma clinical fractures. The mean age of the subjects was 62 years with equal numbers having stages 3, 4, and 5 CKD. Over 2 years there were 51 fractures in 35 subjects. BMD by DXA at baseline was significantly lower at all sites among those with incident fractures versus those without. For example, the mean BMD at the total hip in those with incident fractures was 0.77 g/cm2 (95% confidence interval [CI], 0.73 to 0.80) and in those without fracture was 0.95 g/cm2 (95% CI, 0.92 to 0.98). Almost all baseline HRpQCT measures were lower in those with incident fracture versus those without. For example, volumetric BMD in those with incident fractures was 232 mg HA/cm3 (95% CI, 213 to 251) and in those without fracture was 317.6 mg HA/cm3 (95% CI, 306 to 329.1). Bone loss occurred in all subjects, but was significantly greater among those with incident fractures. Our data demonstrate that low BMD (by DXA and HRpQCT) and a greater annualized percent decrease in BMD are risk factors for subsequent fracture in men and women with predialysis CKD.

  1. Body composition and bone mineral status in patients with Turner syndrome

    PubMed Central

    Shi, Kun; Liu, Li; He, Yao-Juan; Li, Duan; Yuan, Lian-Xiong; Lash, Gendie E.; Li, Li

    2016-01-01

    Turner syndrome (TS) is associated with decreased bone mineral density and increased fracture rate. However, the developmental trajectory of bone density or body composition in patients with TS is still unclear. The present study tested the hypothesis that different karyotypes and/or age contributes to abnormal body composition and decreased bone mineral status parameters in patients with TS. This study included 24 girls with TS, in which 13 girls exhibited X0 karyotype and 11 had mosaicism. Quantitative ultrasound (QUS) assessed the bone mineral status of the calcaneus, including bone mineral density (BMD), amplitude-dependent speed of sound (AD-SOS), broadband ultrasound attenuation (BUA) and InBody 770 assessed body composition. Pearson’s test was performed to correlate measured parameters with patient age. The body composition and bone mineral status parameters were not significantly influenced by patient karyotype. There was a correlation between patient age and AD-SOS (r = −0.61, P = 0.002) and BUA (r = 0.50, P = 0.013) but not BMD (r = −0.19, P = 0.379). In conclusion, there was no effect of karyotype on body composition or body mineral status. Bone mineral status, as evidenced by changes in AD-SOS and BUA, alters with age regardless of karyotype. The developmental trajectory demonstrated in the current study warrants further validation in a longitudinal study. PMID:27901060

  2. Bio-inspired mineralization of hydroxyapatite in 3D silk fibroin hydrogel for bone tissue engineering.

    PubMed

    Jin, Yashi; Kundu, Banani; Cai, Yurong; Kundu, Subhas C; Yao, Juming

    2015-10-01

    To fabricate hard tissue implants with bone-like structure using a biomimetic mineralization method is drawing much more attentions in bone tissue engineering. The present work focuses in designing 3D silk fibroin hydrogel to modulate the nucleation and growth of hydroxyapatite crystals via a simple ion diffusion method. The study indicates that Ca(2+) incorporation within the hydrogel provides the nucleation sites for hydroxyapatite crystals and subsequently regulates their oriented growth. The mineralization process is regulated in a Ca(2+) concentration- and minerlization time-dependent way. Further, the compressive strength of the mineralized hydrogels is directly proportional with the mineral content in hydrogel. The orchestrated organic/inorganic composite supports well the viability and proliferation of human osteoblast cells; improved cyto-compatibility with increased mineral content. Together, the present investigation reports a simple and biomimetic process to fabricate 3D bone-like biomaterial with desired efficacy to repair bone defects.

  3. High insulin levels in KK-Ay diabetic mice cause increased cortical bone mass and impaired trabecular micro-structure.

    PubMed

    Fu, Cen; Zhang, Xiaolin; Ye, Fei; Yang, Jianhong

    2015-04-13

    Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by hyperglycemia, hyperinsulinemia and complications, including obesity and osteoporosis. Rodents have been widely used to model human T2DM and investigate its effect on the skeleton. We aimed to investigate skeletal alterations in Yellow Kuo Kondo (KK-Ay) diabetic mice displaying high insulin and glucose levels. Bone mineral density (BMD), micro-architecture and bone metabolism-related genes were analyzed. The total femoral areal BMD (aBMD), cortical volumetric BMD (vBMD) and thickness were significantly increased in KK-Ay mice, while the trabecular vBMD and mineralized bone volume/tissue volume (BV/TV), trabecular thickness and number were decreased compared to C57BL mice. The expression of both osteoblast-related genes, such as osteocalcin (OC), bone sialoprotein, Type I Collagen, osteonectin, RUNX2 and OSX, and osteoclast-related genes, such as TRAP and TCIRG, were up-regulated in KK-Ay mice. Correlation analyses showed that serum insulin levels were positively associated with aBMD, cortical vBMD and thickness and negatively associated with trabecular vBMD and micro-architecture. In addition, serum insulin levels were positively related to osteoblast-related and osteoclast-related gene expression. Our data suggest that high insulin levels in KK-Ay diabetic mice may increase cortical bone mass and impair trabecular micro-structure by up-regulating osteoblast-and osteoclast-related gene expression.

  4. Determinants of ovine compact bone viscoelastic properties: effects of architecture, mineralization, and remodeling.

    PubMed

    Les, C M; Spence, C A; Vance, J L; Christopherson, G T; Patel, B; Turner, A S; Divine, G W; Fyhrie, D P

    2004-09-01

    Significant decreases in ovine compact bone viscoelastic properties (specifically, stress-rate sensitivity, and damping efficiency) are associated with three years of ovariectomy and are particularly evident at higher frequencies [Proc. Orthop. Res. Soc. 27 (2002) 89]. It is unclear what materials or architectural features of bone are responsible for either the viscoelastic properties themselves, or for the changes in those properties that were observed with estrogen depletion. In this study, we examined the relationship between these viscoelastic mechanical properties and features involving bone architecture (BV/TV), materials parameters (ash density, %mineralization), and histologic evidence of remodeling (%remodeled, cement line interface). The extent of mineralization was inversely proportional to the material's efficiency in damping stress oscillations. The damping characteristics of bone material from ovariectomized animals were significantly more sensitive to variation in mineralization than was bone from control animals. At low frequencies (6 Hz or less), increased histologic evidence of remodeling was positively correlated with increased damping efficiency. However, the dramatic decreases in stress-rate sensitivity that accompanied 3-year ovariectomy were seen throughout the bone structure and occurred even in areas with little or no secondary Haversian remodeling as well as in areas of complete remodeling. Taken together, these data suggest that, while the mineral component may modify the viscoelastic behavior of bone, the basic mechanism underlying bone viscoelastic behavior, and of the changes in that behavior with estrogen depletion, reside in a non-mineral component of the bone that can be significantly altered in the absence of secondary remodeling.

  5. Bone mineral density in glycogen storage disease type Ia and Ib.

    PubMed

    Minarich, Laurie A; Kirpich, Alexander; Fiske, Laurie M; Weinstein, David A

    2012-04-05

    Purpose:The aim of this study was to characterize the pathogenesis of low bone mineral density in glycogen storage disease type Ia and Ib.Methods:A retrospective chart review performed at the University of Florida Glycogen Storage Disease Program included patients with glycogen storage disease type Ia and Ib for whom dual-energy X-ray absorptiometry analysis was performed. A Z-score less than -2 SD was considered low. Analysis for association of bone mineral density with age, gender, presence of complications, mean triglyceride and 25-hydroxyvitamin D concentrations, erythrocyte sedimentation rate, duration of granulocyte colony-stimulating factor therapy, and history of corticosteroid use was performed.Results:In glycogen storage disease Ia, 23/42 patients (55%) had low bone mineral density. Low bone mineral density was associated with other disease complications (P = 0.02) and lower mean serum 25-hydroxyvitamin D concentration (P = 0.03). There was a nonsignificant trend toward lower mean triglyceride concentration in the normal bone mineral density group (P = 0.1).In patients with glycogen storage disease type Ib, 8/12 (66.7%) had low bone mineral density. We did not detect an association with duration of granulocyte colony-stimulating factor therapy (P = 0.68), mean triglyceride level (P = 0.267), erythrocyte sedimentation rate (P = 0.3), or 25-hydroxyvitamin D (P = 0.63) concentration, and there was no evidence that corticosteroid therapy was associated with lower bone mineral density (P = 1).Conclusion:In glycogen storage disease type Ia, bone mineral density is associated with other complications and 25-hydroxyvitamin D status. In glycogen storage disease type Ib, bone mineral density was not associated with any covariates analyzed, suggesting multifactorial etiology or reflecting a small sample.Genet Med advance online publication 5 April 2012.

  6. Utilization of DXA Bone Mineral Densitometry in Ontario

    PubMed Central

    2006-01-01

    Executive Summary Issue Systematic reviews and analyses of administrative data were performed to determine the appropriate use of bone mineral density (BMD) assessments using dual energy x-ray absorptiometry (DXA), and the associated trends in wrist and hip fractures in Ontario. Background Dual Energy X-ray Absorptiometry Bone Mineral Density Assessment Dual energy x-ray absorptiometry bone densitometers measure bone density based on differential absorption of 2 x-ray beams by bone and soft tissues. It is the gold standard for detecting and diagnosing osteoporosis, a systemic disease characterized by low bone density and altered bone structure, resulting in low bone strength and increased risk of fractures. The test is fast (approximately 10 minutes) and accurate (exceeds 90% at the hip), with low radiation (1/3 to 1/5 of that from a chest x-ray). DXA densitometers are licensed as Class 3 medical devices in Canada. The World Health Organization has established criteria for osteoporosis and osteopenia based on DXA BMD measurements: osteoporosis is defined as a BMD that is >2.5 standard deviations below the mean BMD for normal young adults (i.e. T-score <–2.5), while osteopenia is defined as BMD that is more than 1 standard deviation but less than 2.5 standard deviation below the mean for normal young adults (i.e. T-score< –1 & ≥–2.5). DXA densitometry is presently an insured health service in Ontario. Clinical Need   Burden of Disease The Canadian Multicenter Osteoporosis Study (CaMos) found that 16% of Canadian women and 6.6% of Canadian men have osteoporosis based on the WHO criteria, with prevalence increasing with age. Osteopenia was found in 49.6% of Canadian women and 39% of Canadian men. In Ontario, it is estimated that nearly 530,000 Ontarians have some degrees of osteoporosis. Osteoporosis-related fragility fractures occur most often in the wrist, femur and pelvis. These fractures, particularly those in the hip, are associated with increased

  7. A comparative study of zwitterionic ligands-mediated mineralization and the potential of mineralized zwitterionic matrices for bone tissue engineering

    PubMed Central

    Liu, Pingsheng; Emmons, Erin

    2014-01-01

    Cationic and anionic residues of the extracellular matrices (ECM) of bone play synergistic roles in recruiting precursor ions and templating the nucleation, growth and crystalline transformations of calcium apatite in natural biomineralization. We previously reported that zwitterionic sulfobetaine ligands can template extensive 3-dimensional (3-D) hydroxyapaptite (HA)-mineralization of photo-crosslinked polymethacrylatehydrogels. Here, we compared the potency of two other major zwitterionic ligands, phosphobetaine and carboxybetaine, with that of the sulfobetaine in mediating 3-D mineralization using the crosslinked polymethacrylate hydrogel platform. We confirmed that all three zwitterionic hydrogels were able to effectively template 3-D mineralization, supporting the general ability of zwitterions to mediate templated mineralization. Among them, however, sulfobetaine and phosphobetaine hydrogels templated denser 3-D mineralizationthan the carboxybetaine hydrogel, likely due to their higher free water fractions and better maintenance of zwitterionic nature throughout the pH-changes during the in vitro mineralization process. We further demonstrated that the extensively mineralized zwitterionic hydrogels could be exploited for efficient retention (e.g. 99% retention after 24-h incubation in PBS) of osteogenic growth factor recombinant bone morphogenetic protein-2 (rhBMP-2) and subsequent sustained local release with retained bioactivity. Combined with the excellent cytocompatibility of all three zwitterionic hydrogels and the significantly improved cell adhesive properties of their mineralized matrices, these materials could find promising applications in bone tissue engineering. PMID:25558374

  8. Effects of genistein on vertebral trabecular bone microstructure, bone mineral density, microcracks, osteocyte density, and bone strength in ovariectomized rats.

    PubMed

    Dai, Ruchun; Ma, Yulin; Sheng, Zhifeng; Jin, Yan; Zhang, Yuhai; Fang, Lingna; Fan, Huijie; Liao, Eryuan

    2008-01-01

    Until now, the effects of phytoestrogen on bone in both women and ovarian hormone-deficient animal models of osteoporosis have remained uncertain. We have aimed here to investigate the effect of genistein (GEN) on trabecular bone quality in ovariectomized (OVX) rats. Forty 7-month-old female Sprague-Dawley rats were randomly divided into the following four groups: OVX, sham-operated (SHAM), treated with 17beta-estradiol (EST, 10 microg x kg(-1) x day(-1)), and GEN (5 mg x kg(-1) x day(-1)). At 15 weeks postoperation, the compressive test was performed on the L5 vertebral body; additionally, microcomputed tomography (micro-CT) assessment was performed to estimate the bone mineral density (BMD) and microstructure parameters of the L6 vertebral body. After fatigue damage testing, the L6 vertebral body was bulk-stained in 1% basic fuchsin and embedded in methylmethacrylate. The L4 vertebral body was embedded in methylmethacrylate for dynamic histomorphometry analysis without staining. Mounted bone slices were used to measure microcrack parameters, empty osteocyte lacuna density (e.Lc.Dn), and osteocyte density (Ot.N/T.Ar). Maximum loading (ML) and Ot.N/T.Ar were significantly lower in the OVX group than in the other groups. E.Lc.Dn was significantly decreased in GEN and EST groups compared to the OVX group. ML was significantly decreased in the GEN group compared to the SHAM group. Microcrack density, microcrack surface density, and microcrack length were significantly increased in the OVX group compared to the other groups. Mineral apposition rate was significantly decreased in the OVX group compared to the SHAM and GEN groups. Bone formation rate was significantly decreased in the OVX group compared to other groups. There were no significant differences with regard to mineralizing surface among the four groups. Volumetric BMD at organ was significantly lower in OVX, EST, and GEN groups than in the SHAM group. Bone mineral content was significantly lower in the OVX

  9. FRAX and fracture prediction without bone mineral density.

    PubMed

    Kanis, J A; Harvey, N C; Johansson, H; Odén, A; Leslie, W D; McCloskey, E V

    2015-01-01

    The major application of FRAX in osteoporosis is to direct pharmacological interventions to those at high risk of fracture. Whereas the efficacy of osteoporosis treatment, with the possible exception of alendronate, is largely independent of baseline bone mineral density (BMD), it remains a widely held perception that osteoporosis therapies are only effective in the presence of low BMD. Thus, the use of FRAX in the absence of BMD to identify individuals requiring therapy remains the subject of some debate and is the focus of this review. The clinical risk factors used in FRAX have high evidence-based validity to identify a risk responsive to intervention. The selection of high-risk individuals with FRAX, without knowledge of BMD, preferentially selects for low BMD and thus identifies a risk that is responsive to pharmacological intervention. The prediction of fractures with the use of clinical risk factors alone in FRAX is comparable to the use of BMD alone to predict fractures and is suitable, therefore, in the many countries where facilities for BMD testing are sparse. In countries where access to BMD is greater, FRAX can be used without BMD in the majority of cases and BMD tests reserved for those close to a probability-based intervention threshold. Thus concerns surrounding the use of FRAX in clinical practice without information on BMD are largely misplaced.

  10. Effect of Clothing on Measurement of Bone Mineral Density.

    PubMed

    McNamara, Elizabeth A; Feldman, Anna Z; Malabanan, Alan O; Abate, Ejigayehu G; Whittaker, LaTarsha G; Yano-Litwin, Amanda; Dorazio, Jolene; Rosen, Harold N

    2016-01-01

    It is unknown whether allowing patients to have BMD (bone mineral density) studies acquired while wearing radiolucent clothing adlib contributes appreciably to the measurement error seen. To examine this question, a spine phantom was scanned 30 times without any clothing, while draped with a gown, and while draped with heavy winter clothing. The effect on mean BMD and on SD (standard deviation) was assessed. The effect of clothing on mean or SD of the area was not significant. The effect of clothing on mean and SD for BMD was small but significant and was around 1.6% for the mean. However, the effect on BMD precision was much more clinically important. Without clothing the spine phantom had an least significant change of 0.0077 gm/cm(2), while when introducing variability of clothing the least significant change rose as high as 0.0305 gm/cm(2). We conclude that, adding clothing to the spine phantom had a small but statistically significant effect on the mean BMD and on variance of the measurement. It is unlikely that the effect on mean BMD has any clinical significance, but the effect on the reproducibility (precision) of the result is likely clinically significant.

  11. Effect of Multiparity and Prolonged Lactation on Bone Mineral Density

    PubMed Central

    Natung, Tanie; Barooah, Rituparna; Ahanthem, Santa Singh

    2016-01-01

    Objectives This study was done to determine the effect of multiparity and prolonged lactation on bone mineral density (BMD). Methods This cross-sectional study included 196 perimenopausal and postmenopausal women aged 40 to 60 years old. Age, body mass index (BMI), menopausal status, duration of menopause, parity and total duration of lactation, nutritional history were recorded. Lumbar spine (LS; L2-L4) and femur neck (FN) BMD were measured using dual energy X-ray absorptiometry. Correlation of parity and lactation with BMD were investigated using multiple regression analysis. Results Parity was inversely correlated to BMD for LS (β = −0.266, P = 0.001) and FN (β = −0.380, P = 0.000). This relation remained significant even after adjusting for age, BMI and duration of menopause. Duration of lactation was inversely correlated with BMD for LS (β = −0.271, P = 0.001) but no for FN (β = −0.124, P = 0.130). Conclusions Multiparity and prolonged lactation have negative impact on BMD especially with in a socioeconomic group whose nutritional intake is borderline. Our data support that parity and duration of lactation can be associated with future osteoporosis. PMID:28119896

  12. Inhibition of PHOSPHO1 activity results in impaired skeletal mineralization during limb development of the chick.

    PubMed

    Macrae, Vicky E; Davey, Megan G; McTeir, Lynn; Narisawa, Sonoko; Yadav, Manisha C; Millan, Jose Luis; Farquharson, Colin

    2010-04-01

    PHOSPHO1 is a bone-specific phosphatase implicated in the initiation of inorganic phosphate generation for matrix mineralization. The control of mineralization is attributed to the actions of tissue-nonspecific alkaline phosphatase (TNAP). However, matrix vesicles (MVs) containing apatite crystals are present in patients with hypophosphatasia as well as TNAP null (Akp2(-/-)) mice. It is therefore likely that other phosphatases work with TNAP to regulate matrix mineralization. Although PHOSPHO1 and TNAP expression is associated with MVs, it is not known if PHOSPHO1 and TNAP are coexpressed during the early stages of limb development. Furthermore, the functional in vivo role of PHOSPHO1 in matrix mineralization has yet to be established. Here, we studied the temporal expression and functional role of PHOSPHO1 within chick limb bud mesenchymal micromass cultures and also in wild-type and talpid(3) chick mutants. These mutants are characterized by defective hedgehog signalling and the absence of endochondral mineralization. The ability of in vitro micromass cultures to differentiate and mineralize their matrix was temporally associated with increased expression of PHOSPHO1 and TNAP. Comparable changes in expression were noted in developing embryonic legs (developmental stages 23-36HH). Micromass cultures treated with lansoprazole, a small-molecule inhibitor of PHOSPHO1 activity, or FGF2, an inhibitor of chondrocyte differentiation, resulted in reduced alizarin red staining (P<0.05). FGF2 treatment also caused a reduction in PHOSPHO1 (P<0.001) and TNAP (P<0.001) expression. Expression analysis by whole-mount RNA in situ hybridization correlated with qPCR micromass data and demonstrated the existence of a tightly regulated pattern of Phospho1 and Tnap expression which precedes mineralization. Treatment of developing embryos for 5 days with lansoprazole completely inhibited mineralization of all leg and wing long bones as assessed by alcian blue/alizarin red staining

  13. High Salt Diets, Bone Strength and Mineral Content of Mature Femur After Skeletal Unloading

    NASA Technical Reports Server (NTRS)

    Liang, Michael T. C.

    1998-01-01

    It is known that high salt diets increase urinary calcium (Ca) loss, but it is not known whether this effect weakens bone during space flight. The Bone Hormone Lab has studied the effect of high salt diets on Ca balance and whole body Ca in a space flight model (2,8). Neither the strength nor mineral content of the femurs from these studies has been evaluated. The purpose of this study was to determine the effect of high salt diets (HiNa) and skeletal unloading on femoral bone strength and bone mineral content (BMC) in mature rats.

  14. Biomimetic mineralization of woven bone-like nanocomposites: role of collagen cross-links.

    PubMed

    Li, Yuping; Thula, Taili T; Jee, Sangsoo; Perkins, Sasha L; Aparicio, Conrado; Douglas, Elliot P; Gower, Laurie B

    2012-01-09

    Ideal biomaterials for bone grafts must be biocompatible, osteoconductive, osteoinductive and have appropriate mechanical properties. For this, the development of synthetic bone substitutes mimicking natural bone is desirable, but this requires controllable mineralization of the collagen matrix. In this study, densified collagen films (up to 100 μm thick) were fabricated by a plastic compression technique and cross-linked using carbodiimide. Then, collagen-hydroxyapatite composites were prepared by using a polymer-induced liquid-precursor (PILP) mineralization process. Compared to traditional methods that produce only extrafibrillar hydroxyapatite (HA) clusters on the surface of collagen scaffolds, by using the PILP mineralization process, homogeneous intra- and extrafibrillar minerals were achieved on densified collagen films, leading to a similar nanostructure as bone, and a woven microstructure analogous to woven bone. The role of collagen cross-links on mineralization was examined and it was found that the cross-linked collagen films stimulated the mineralization reaction, which in turn enhanced the mechanical properties (hardness and modulus). The highest value of hardness and elastic modulus was 0.7 ± 0.1 and 9.1 ± 1.4 GPa in the dry state, respectively, which is comparable to that of woven bone. In the wet state, the values were much lower (177 ± 31 and 8 ± 3 MPa) due to inherent microporosity in the films, but still comparable to those of woven bone in the same conditions. Mineralization of collagen films with controllable mineral content and good mechanical properties provide a biomimetic route toward the development of bone substitutes for the next generation of biomaterials. This work also provides insight into understanding the role of collagen fibrils on mineralization.

  15. Single x-ray transmission system for bone mineral density determination

    SciTech Connect

    Jimenez-Mendoza, Daniel; Vargas-Vazquez, Damian; Giraldo-Betancur, Astrid L.; Hernandez-Urbiola, Margarita I.; Rodriguez-Garcia, Mario E.

    2011-12-15

    Bones are the support of the body. They are composed of many inorganic compounds and other organic materials that all together can be used to determine the mineral density of the bones. The bone mineral density is a measure index that is widely used as an indicator of the health of the bone. A typical manner to evaluate the quality of the bone is a densitometry study; a dual x-ray absorptiometry system based study that has been widely used to assess the mineral density of some animals' bones. However, despite the success stories of utilizing these systems in many different applications, it is a very expensive method that requires frequent calibration processes to work properly. Moreover, its usage in small species applications (e.g., rodents) has not been quite demonstrated yet. Following this argument, it is suggested that there is a need for an instrument that would perform such a task in a more reliable and economical manner. Therefore, in this paper we explore the possibility to develop a new, affordable, and reliable single x-ray absorptiometry system. The method consists of utilizing a single x-ray source, an x-ray image sensor, and a computer platform that all together, as a whole, will allow us to calculate the mineral density of the bone. Utilizing an x-ray transmission theory modified through a version of the Lambert-Beer law equation, a law that expresses the relationship among the energy absorbed, the thickness, and the absorption coefficient of the sample at the x-rays wavelength to calculate the mineral density of the bone can be advantageous. Having determined the parameter equation that defines the ratio of the pixels in radiographies and the bone mineral density [measured in mass per unit of area (g/cm{sup 2})], we demonstrated the utility of our novel methodology by calculating the mineral density of Wistar rats' femur bones.

  16. Single x-ray transmission system for bone mineral density determination

    NASA Astrophysics Data System (ADS)

    Jimenez-Mendoza, Daniel; Espinosa-Arbelaez, Diego G.; Giraldo-Betancur, Astrid L.; Hernandez-Urbiola, Margarita I.; Vargas-Vazquez, Damian; Rodriguez-Garcia, Mario E.

    2011-12-01

    Bones are the support of the body. They are composed of many inorganic compounds and other organic materials that all together can be used to determine the mineral density of the bones. The bone mineral density is a measure index that is widely used as an indicator of the health of the bone. A typical manner to evaluate the quality of the bone is a densitometry study; a dual x-ray absorptiometry system based study that has been widely used to assess the mineral density of some animals' bones. However, despite the success stories of utilizing these systems in many different applications, it is a very expensive method that requires frequent calibration processes to work properly. Moreover, its usage in small species applications (e.g., rodents) has not been quite demonstrated yet. Following this argument, it is suggested that there is a need for an instrument that would perform such a task in a more reliable and economical manner. Therefore, in this paper we explore the possibility to develop a new, affordable, and reliable single x-ray absorptiometry system. The method consists of utilizing a single x-ray source, an x-ray image sensor, and a computer platform that all together, as a whole, will allow us to calculate the mineral density of the bone. Utilizing an x-ray transmission theory modified through a version of the Lambert-Beer law equation, a law that expresses the relationship among the energy absorbed, the thickness, and the absorption coefficient of the sample at the x-rays wavelength to calculate the mineral density of the bone can be advantageous. Having determined the parameter equation that defines the ratio of the pixels in radiographies and the bone mineral density [measured in mass per unit of area (g/cm2)], we demonstrated the utility of our novel methodology by calculating the mineral density of Wistar rats' femur bones.

  17. Poor Compliance to Hormone Therapy and Decreased Bone Mineral Density in Women with Premature Ovarian Insufficiency

    PubMed Central

    Bachelot, Anne; Nicolas, Carole; Gricourt, Solenne; Dulon, Jérôme; Leban, Monique; Golmard, Jean Louis; Touraine, Philippe

    2016-01-01

    Premature ovarian insufficiency leads to through infertility and estrogen deficiency. Optimal management encompasses estrogen replacement therapy. Long-term outcome of women with POI is not known. We design a study to evaluate the medical care, hormone replacement therapy compliance and bone mineral density (BMD) in POI women with at least a five-year follow-up after the first evaluation. One hundred and sixty-two patients (37.3±8.0 years) were evaluated (follow-up 7.9±2.8 years). Sixty-nine patients (42.6%) had stopped their hormone replacement therapy (HRT) for at least one year during the follow up period. BMD determination at initial evaluation and at follow-up visit was completed in 92 patients. At first evaluation, 28 patients (30%) had osteopenia and 7 (8%) had osteoporosis. At follow up, 31 women (34%) had BMD impairment with osteopenia in 61% and osteoporosis in 5%. In univariate analysis and multivariate analysis, there was a significant loss of femoral BMD in women who had stopped their HRT for over a year. In conclusion, this first study concerning long-term follow-up of POI patients shows the poor compliance to their HRT, despite its importance in the prevention of bone demineralization. This study reinforces the need for follow up and specific care for POI women. PMID:27906970

  18. Natural variations in calcium isotope composition as a monitor of bone mineral balance in humans.

    NASA Astrophysics Data System (ADS)

    Skulan, J.; Anbar, A.; Thomas, B.; Smith, S.

    2004-12-01

    The skeleton is the largest reservoir of calcium in the human body and is responsible for the short term control of blood levels of this element. Accurate measurement of changes in bone calcium balance is critical to understanding how calcium metabolism responds to physiological and environmental changes and, more specifically, to diagnosing and evaluating the effectiveness of treatments for osteoporosis and other serious calcium-related disorders. It is very difficult to measure bone calcium balance using current techniques, however, because these techniques rely either on separate estimates of bone resorption and formation that are not quantitatively comparable, or on complex and expensive studies of calcium kinetics using administered isotopic tracers. This difficulty is even more apparent and more severe for measurements of short-term changes in bone calcium balance that do not produce detectable changes in bone mineral density. Calcium isotopes may provide a novel means of addressing this problem. The foundation of this isotope application is the ca. 1.3 per mil fractionation of calcium during bone formation, favoring light calcium in the bone. This fractionation results in a steady-state isotopic offset between calcium in bone and calcium in soft tissues, blood and urine. Perturbations to this steady state due to changes in the net formation or resorption of bone should be reflected in changes in the isotopic composition of soft tissues and fluids. Here we present evidence that easily detectable shifts in the natural calcium isotope composition of human urine rapidly reflect changes in bone calcium balance. Urine from subjects in a 17-week bed rest study was analyzed for calcium isotopic composition. Bed rest promotes net resorption of bone, shifting calcium from bone to soft tissues, blood and urine. The calcium isotope composition of patients in this study shifted toward lighter values during bed rest, consistent with net resorption of isotopically

  19. 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.

  20. Genetic variants in adult bone mineral density and fracture risk genes are associated with the rate of bone mineral density acquisition in adolescence

    PubMed Central

    Warrington, Nicole M.; Kemp, John P.; Tilling, Kate; Tobias, Jonathan H.; Evans, David M.

    2015-01-01

    Previous studies have identified 63 single-nucleotide polymorphisms (SNPs) associated with bone mineral density (BMD) in adults. These SNPs are thought to reflect variants that influence bone maintenance and/or loss in adults. It is unclear whether they affect the rate of bone acquisition during adolescence. Bone measurements and genetic data were available on 6397 individuals from the Avon Longitudinal Study of Parents and Children at up to five follow-up clinics. Linear mixed effects models with smoothing splines were used for longitudinal modelling of BMD and its components bone mineral content (BMC) and bone area (BA), from 9 to 17 years. Genotype data from the 63 adult BMD associated SNPs were investigated individually and as a genetic risk score in the longitudinal model. Each additional BMD lowering allele of the genetic risk score was associated with lower BMD at age 13 [per allele effect size, 0.002 g/cm2 (SE = 0.0001, P = 1.24 × 10−38)] and decreased BMD acquisition from 9 to 17 years (P = 9.17 × 10−7). This association was driven by changes in BMC rather than BA. The genetic risk score explained ∼2% of the variation in BMD at 9 and 17 years, a third of that explained in adults (6%). Genetic variants that putatively affect bone maintenance and/or loss in adults appear to have a small influence on the rate of bone acquisition through adolescence. PMID:25941325

  1. Muscle strength is a determinant of bone mineral content in the hemiparetic upper extremity: implications for stroke rehabilitation.

    PubMed

    Pang, Marco Y C; Eng, Janice J

    2005-07-01

    Individuals with stroke have a high incidence of bone fractures and approximately 30% of these fractures occur in the upper extremity. The high risk of falls and the decline in bone and muscle health make the chronic stroke population particularly prone to upper extremity fractures. This was the first study to investigate the bone mineral content (BMC), bone mineral density (BMD), and soft tissue composition of the upper extremities and their relationship to stroke-related impairments in ambulatory individuals with chronic stroke (onset >1 year). Dual-energy X-ray absorptiometry (DXA) was used to acquire total body scans on 56 (22 women) community-dwelling individuals (>or=50 years of age) with chronic stroke. BMC (g) and BMD (g/cm2), lean mass (g), and fat mass (g) for each arm were derived from the total body scans. The paretic upper extremity was evaluated for muscle strength (hand-held dynamometry), impairment of motor function (Fugl-Meyer motor assessment), spasticity (Modified Ashworth Scale), and amount of use of the paretic arm in daily activities (Motor Activity Log). Results showed that the paretic arm had significantly lower BMC (13.8%, P<0.001), BMD (4.5%, P<0.001), and lean mass (9.0%, P<0.001) but higher fat mass (6.3%, P=0.028) than the non-paretic arm. Multiple regression analysis showed that lean mass in the paretic arm, height, and muscle strength were significant predictors (R2=0.810, P<0.001) of the paretic arm BMC. Height, muscle strength, and gender were significant predictors (R2=0.822, P<0.001) of lean mass in the paretic arm. These results highlight the potential of muscle strengthening to promote bone health of the paretic arm in individuals with chronic stroke.

  2. Muscle strength is a determinant of bone mineral content in the hemiparetic upper extremity: Implications for stroke rehabilitation

    PubMed Central

    Pang, Marco YC; Eng, Janice J

    2011-01-01

    Individuals with stroke have a high incidence of bone fractures and approximately 30% of these fractures occur in the upper extremity. The high risk of falls and the decline in bone and muscle health make the chronic stroke population particularly prone to upper extremity fractures. This was the first study to investigate the bone mineral content (BMC), bone mineral density (BMD) and soft tissue composition of the upper extremities and their relationship to stroke-related impairments in ambulatory individuals with chronic stroke (onset >1 year). Dual-energy X-ray absorptiometry (DXA) was used to acquire total body scans on 56 (22 women) community-dwelling individuals (≥50 years of age) with chronic stroke. BMC (g) and BMD (g/cm2), lean mass (g) and fat mass (g) for each arm were derived from the total body scans. The paretic upper extremity was evaluated for muscle strength (hand-held dynamometry), spasticity (Modified Ashworth Scale), impairment of motor function (Fugl-Meyer Motor Assessment) and amount of use of the paretic arm in daily activities (Motor Activity Log). Results showed that the paretic arm had significantly lower BMC (13.8%, p<0.001), BMD (4.5%, p<0.001) and lean mass (9.0%, p<0.001) but higher fat mass (6.3%, p=0.028) than the non-paretic arm. Multiple regression analysis showed that lean mass in the paretic arm, height and muscle strength were significant predictors (R2=0.810, p<0.001) of the paretic arm BMC. Height, muscle strength and gender were significant predictors (R2=0.822, p<0.001) of lean mass in the paretic arm. These results highlight the potential of muscle strengthening to promote bone health of the paretic arm in individuals with chronic stroke. PMID:15869927

  3. Physiology of bone: Mineral compartment proteins as candidates for environmental perturbation by lead

    SciTech Connect

    Sauk, J.J.; Somerman, M.J. )

    1991-02-01

    Termine et al. first demonstrated that sequential dissociative extraction and fractionation procedures with protease inhibitors could provide a convenient approach for the study of mineral compartment constituents. The primary extraction regimen used 4 M guanidine HCl to remove most of the protein from the nonmineralized phase of bone. Subsequently, EDTA-guanidine was used to remove the mineral-phase components. These methods discriminate on the basis of physical-chemical association with a mineral phase rather than on the specific gene products of a particular cell. In the present discussion emphasis is directed at a group of divalent cation binding proteins isolated from the mineral compartment of bone. The localization, synthesis, and chemical characteristics of osteonectin, bone sialoproteins I and II, and bone acidic glycoprotein-75 are discussed and offered as possible sites for perturbation by the environment with lead exposure.

  4. Physiology of bone: mineral compartment proteins as candidates for environmental perturbation by lead.

    PubMed Central

    Sauk, J J; Somerman, M J

    1991-01-01

    Termine et al. first demonstrated that sequential dissociative extraction and fractionation procedures with protease inhibitors could provide a convenient approach for the study of mineral compartment constituents. The primary extraction regimen used 4 M guanidine HCl to remove most of the protein from the nonmineralized phase of bone. Subsequently, EDTA-guanidine was used to remove the mineral-phase components. These methods discriminate on the basis of physical-chemical association with a mineral phase rather than on the specific gene products of a particular cell. In the present discussion emphasis is directed at a group of divalent cation binding proteins isolated from the mineral compartment of bone. The localization, synthesis, and chemical characteristics of osteonectin, bone sialoproteins I and II, and bone acidic glycoprotein-75 are discussed and offered as possible sites for perturbation by the environment with lead exposure. Images FIGURE 1. FIGURE 2. FIGURE 2. FIGURE 2. FIGURE 3. FIGURE 3. FIGURE 3. FIGURE 3. PMID:2040255

  5. Mineralization of Synthetic Polymer Scaffolds: A Bottom-upApproach for the Development of Artificial Bone

    SciTech Connect

    Song, Jie; Viengkham, Malathong; Bertozzi, Carolyn R.

    2004-09-27

    The controlled integration of organic and inorganic components confers natural bone with superior mechanical properties. Bone biogenesis is thought to occur by templated mineralization of hard apatite crystals by an elastic protein scaffold, a process we sought to emulate with synthetic biomimetic hydrogel polymers. Crosslinked polymethacrylamide and polymethacrylate hydrogels were functionalized with mineral-binding ligands and used to template the formation of hydroxyapatite. Strong adhesion between the organic and inorganic materials was achieved for hydrogels functionalized with either carboxylate or hydroxy ligands. The mineral-nucleating potential of hydroxyl groups identified here broadens the design parameters for synthetic bone-like composites and suggests a potential role for hydroxylated collagen proteins in bone mineralization.

  6. Giemsa as a fluorescent dye for mineralizing bone-like nodules in vitro.

    PubMed

    Querido, W; Farina, M; Balduino, A

    2012-02-01

    Giemsa was first used as a fluorescent dye for mineralized bone and cartilage in tissue sections. The aim of this study was to establish the use of Giemsa as a fluorescent dye for mineralizing bone-like nodules produced in cell cultures. Osteoblasts were grown under mineralizing conditions for 14 days, producing typical bone-like nodules. Upon staining with Giemsa stock solution for 1 min, the mineralizing nodules could be selectively visualized emitting intense green and red fluorescence when observed under blue and green illumination, respectively. The textural details of the nodules were clearly observed under fluorescence microscopy, allowing to identify regions with different degrees of mineralization. The mineralized nature of the nodules was confirmed using von Kossa's method, Alizarin Red S staining and x-ray mapping for Ca and P in a scanning electron microscope, showing a strong correlation between the mineralizing and the fluorescent nodules. The selective fluorescence was related to the mineral phase, being absent in decalcified samples. The use of Giemsa as a fluorescent dye for mineralizing bone-like nodules presents a simple alternative method to quickly analyze biomineralization assays in vitro under fluorescence microscopy, particularly in the biological evaluation of biomaterials.

  7. Moderate chronic kidney disease impairs bone quality in C57Bl/6J mice.

    PubMed

    Heveran, Chelsea M; Ortega, Alicia M; Cureton, Andrew; Clark, Ryan; Livingston, Eric W; Bateman, Ted A; Levi, Moshe; King, Karen B; Ferguson, Virginia L

    2016-05-01

    Chronic kidney disease (CKD) increases bone fracture risk. While the causes of bone fragility in CKD are not clear, the disrupted mineral homeostasis inherent to CKD may cause material quality changes to bone tissue. In this study, 11-week-old male C57Bl/6J mice underwent either 5/6th nephrectomy (5/6 Nx) or sham surgeries. Mice were fed a normal chow diet and euthanized 11weeks post-surgery. Moderate CKD with high bone turnover was established in the 5/6 Nx group as determined through serum chemistry and bone gene expression assays. We compared nanoindentation modulus and mineral volume fraction (assessed through quantitative backscattered scanning electron microscopy) at matched sites in arrays placed on the cortical bone of the tibia mid-diaphysis. Trabecular and cortical bone microarchitecture and whole bone strength were also evaluated. We found that moderate CKD minimally affected bone microarchitecture and did not influence whole bone strength. Meanwhile, bone material quality decreased with CKD; a pattern of altered tissue maturation was observed with 5/6 Nx whereby the newest 60μm of bone tissue adjacent to the periosteal surface had lower indentation modulus and mineral volume fraction than more interior, older bone. The variance of modulus and mineral volume fraction was also altered following 5/6 Nx, implying that tissue-scale heterogeneity may be negatively affected by CKD. The observed lower bone material quality may play a role in the decreased fracture resistance that is clinically associated with human CKD.

  8. Mineralization of bone-related SaOS-2 cells under physiological hypoxic conditions.

    PubMed

    Müller, Werner E G; Schröder, Heinz C; Tolba, Emad; Diehl-Seifert, Bärbel; Wang, Xiaohong

    2016-01-01

    Inorganic polyphosphate (polyP) is a physiological energy-rich polymer with multiple phosphoric anhydride bonds. In cells such as bone-forming osteoblasts, glycolysis is the main pathway generating metabolic energy in the form of ATP. In the present study, we show that, under hypoxic culture conditions, the growth/viability of osteoblast-like SaOS-2 cells is not impaired. The addition of polyP to those cells, administered as amorphous calcium polyP nanoparticles (aCa-polyP-NP; approximate size 100 nm), significantly increased the proliferation of the cells. In the presence of polyP, the cells produce significant levels of lactate, the end product of anaerobic glycolysis. Under those conditions, an eight-fold increase in the steady-state level of the membrane-associated carbonic anhydrase IX is found, as well as a six-fold induction of the hypoxia-inducible factor 1. Consequently, biomineral formation onto the SaOS-2 cells decreases under low oxygen tension. If the polyP nanoparticles are added to the cells, the degree of mineralization is enhanced. These changes had been measured also in human mesenchymal stem cells. The assumption that the bicarbonate, generated by the carbonic anhydrase in the presence of polyP under low oxygen, is deposited as a constituent of the bioseeds formed during initial hydroxyapatite formation is corroborated by the identification of carbon besides of calcium, oxygen and phosphorus in the initial biomineral deposit onto the cells using the sensitive technology of high-resolution energy dispersive spectrometry mapping. Based on these data, we conclude that polyP is required for the supply of metabolic energy during bone mineral formation under physiological, hypoxic conditions, acting as a 'metabolic fuel' for the cells to grow.

  9. Local calibrated bone mineral density in the mandible presented using a color coding scheme.

    PubMed

    Homolka, P; Beer, A; Birkfellner, W; Gahleitner, A; Nowotny, R; Bergmann, H

    2001-11-01

    Calibrated information on bone mineral density (BMD) may be used in dental implantology to measure "bone quality". It can be used to estimate the expected primary implant stability preoperatively and to guide the surgeon in selecting optimum implant types and operation techniques. Using a preoperative dental computed tomography (Dental-CT) scan, all of this information can be obtained without additional examinations and thus without additional X-ray exposure of the patient. In contrast to bone mineral determination in other body regions, local BMD values are important in the jaw bone. Therefore, a regimen where color-coded information on local bone mineralization is superimposed on Dental-CT images is proposed using the original CT volumes as well as reformatted views.

  10. Effect of hydrazine based deproteination protocol on bone mineral crystal structure.

    PubMed

    Karampas, I A; Orkoula, M G; Kontoyannis, C G

    2012-05-01

    In several bone deproteination protocols the chemical agent used for protein cleavage is hydrazine. The effect of hydrazine deproteination method on the crystal size and crystallinity of the bone mineral was studied. Bovine bones were subjected to this protocol and the crystal size and crystallinity of the remaining bone mineral were determined by X-ray Diffraction (XRD), by measuring the width at the half of the maximum intensity of the (002) reflection. It was found that hydrazine deproteination induces noteworthy increase of crystal size and crystallinity. The effect was enhanced by increasing hydrazine temperature from 25 to 55°C. Furthermore, infrared spectroscopy revealed that hydrazine facilitates the removal of carbonate and acid phosphate ions from bone mineral. It is proposed that the mechanism of modification of crystal size and crystallinity lies on the removal of these ions thus, resulting in crystal re-organization.

  11. Europium-Doped Gd2O3 Nanotubes Increase Bone Mineral Density in Vivo and Promote Mineralization in Vitro.

    PubMed

    Liu, Huifang; Jin, Yi; Ge, Kun; Jia, Guang; Li, Zhenhua; Yang, Xinjian; Chen, Shizhu; Ge, Min; Sun, Wentong; Liu, Dandan; Zhang, Jinchao

    2017-02-22

    Europium-doped Gd2O3 nanotubes (Gd2O3:Eu(3+) NTs) have been extensively applied in the field of bioscience for their photostability and magnetic properties. Nevertheless, the distribution and interaction between Gd2O3:Eu(3+) NTs and metabolism of bone are not yet sufficiently understood. In this study, a systematic study of the toxicity and distribution of Gd2O3:Eu(3+) NTs in mice after oral administration was carried out. The results showed that a small number of the Gd2O3:Eu(3+) NTs could pass through biological barriers into the lung, liver, and spleen, but a high concentration was observed in bone. Furthermore, the effects of Gd2O3:Eu(3+) NTs on bone metabolism were systematically studied in vitro and in vivo when accumulating in bone. After being administered to mice, the Gd2O3:Eu(3+) NTs extremely enhanced the bone mineral density and bone biomechanics. In vitro the Gd2O3:Eu(3+) NTs increased the alkaline phosphatase (ALP) activity and mineralization and promoted the expression of osteogenesis genes in preosteoblasts MC3T3-E1 through activation of the BMP signaling pathway. This study will be significant for appropriate application of Gd2O3:Eu(3+) NTs in the biomedical field and expounding the molecular mechanism of bone metabolism.

  12. Bone mineral disorder in chronic kidney disease: Klotho and FGF23; cardiovascular implications.

    PubMed

    Salanova Villanueva, Laura; Sánchez González, Carmen; Sánchez Tomero, José Antonio; Aguilera, Abelardo; Ortega Junco, Esther

    2016-01-01

    Cardiovascular factors are one of the main causes of morbidity and mortality in patients with chronic kidney disease. Bone mineral metabolism disorders and inflammation are pathological conditions that involve increased cardiovascular risk in chronic kidney disease. The cardiovascular risk involvement of bone mineral metabolism classical biochemical parameters such as phosphorus, calcium, vitamin D and PTH is well known. The newest markers, FGF23 and klotho, could also be implicated in cardiovascular disease.

  13. Management of mineral and bone disorders in patients on dialysis: a team approach to improving outcomes.

    PubMed

    Carver, Michelle; Carder, Jacqueline; Hartwell, Lori; Arjomand, Mahiyar

    2008-01-01

    Most patients with mineral and bone disorders do not simultaneously achieve KDOQI target goals for parathyroid hormone, calcium, phosphorus, and the calcium-phosphorus product. A multidisciplinary team composed of the patient, nephrologists, nephrology nurses, renal dietitians, social workers, patient care technicians, clinical pharmacists, and physical therapists can help improve the coordination of care for mineral and bone disorders. The roles of team members are reviewed, with emphasis on nephrology nurses.

  14. Practice of martial arts and bone mineral density in adolescents of both sexes

    PubMed Central

    Ito, Igor Hideki; Mantovani, Alessandra Madia; Agostinete, Ricardo Ribeiro; Costa, Paulo; Zanuto, Edner Fernando; Christofaro, Diego Giulliano Destro; Ribeiro, Luis Pedro; Fernandes, Rômulo Araújo

    2016-01-01

    Abstract Objective: The purpose of this study was to analyze the relationship between martial arts practice (judo, karate and kung-fu) and bone mineral density in adolescents. Methods: The study was composed of 138 (48 martial arts practitioners and 90 non-practitioners) adolescents of both sexes, with an average age of 12.6 years. Bone mineral density was measured using Dual-Energy X-ray Absorptiometry in arms, legs, spine, trunk, pelvis and total. Weekly training load and previous time of engagement in the sport modality were reported by the coach. Partial correlation tested the association between weekly training load and bone mineral density, controlled by sex, chronological age, previous practice and somatic maturation. Analysis of covariance was used to compare bone mineral density values according to control and martial arts groups, controlled by sex, chronological age, previous practice and somatic maturation. Significant relationships between bone mineral density and muscle mass were inserted into a multivariate model and the slopes of the models were compared using the Student t test (control versus martial art). Results: Adolescents engaged in judo practice presented higher values of bone mineral density than the control individuals (p-value=0.042; Medium Effect size [Eta-squared=0.063]), while the relationship between quantity of weekly training and bone mineral density was significant among adolescents engaged in judo (arms [r=0.308] and legs [r=0.223]) and kung-fu (arms [r=0.248] and spine [r=0.228]). Conclusions: Different modalities of martial arts are related to higher bone mineral density in different body regions among adolescents. PMID:27017002

  15. Jumping exercise preserves bone mineral density and mechanical properties in osteopenic ovariectomized rats even following established osteopenia.

    PubMed

    Okubo, R; Sanada, L S; Castania, V A; Louzada, M J Q; de Paula, F J A; Maffulli, N; Shimano, A C

    2017-04-01

    The effects of jump training on bone structure before and after ovariectomy-induced osteopenia in rats were investigated. Jumping exercise induced favorable changes in bone mineral density, bone mechanical properties, and bone formation/resorption markers. This exercise is effective to prevent bone loss after ovariectomy even when osteopenia is already established.

  16. Bone mineral density in cystic fibrosis: benefit of exercise capacity.

    PubMed

    Dodd, Jonathan D; Barry, Sinead C; Barry, Rupert B M; Cawood, Tom J; McKenna, Malachi J; Gallagher, Charles G

    2008-01-01

    The aim of this study was to evaluate the association between bone mineral density (BMD) and objective maximal exercise measurements in adults with cystic fibrosis (CF). Twenty-five CF patients (19 males, 6 females, mean age 25.5 yr, range: 17-52) underwent BMD assessment and maximal-cycle ergometer exercise testing. We examined the relationship between gas exchange (% peak-predicted O(2) uptake, CO(2) output, O(2) saturation), exercise performance (maximum power, exercise duration), and respiratory mechanics (tidal volume, rate) with lumbar spine and total proximal femur BMD. The strongest clinical correlate with BMD was forced expiratory volume at 1s (lumbar spine Z-score, r=0.36; total proximal femur Z-score, r=0.68, p<0.01). The strongest exercise correlate was % peak-predicted O(2) uptake (lumbar spine Z-score, r=0.44, p<0.01; total proximal femur Z-score, r=0.59, p<0.01). There was a closer association between exercise parameters and total proximal femur BMD (r=0.43-0.60) than with lumbar spine BMD (r=0.04-0.45). Multiple regression analysis revealed VO(2) to be the strongest independent predictor of BMD (R(2)=0.86, p<0.001) followed by petCO(2) and body mass index (R(2)=0.7 and 0.5, respectively, p<0.01). Exercise appears to influence total proximal femur BMD more than lumbar spine BMD in CF. Exercise rehabilitation programs focusing on peripheral strength training may benefit those CF patients with low total proximal femur BMD.

  17. Bone mineral density, muscle strength, and recreational exercise in men

    NASA Technical Reports Server (NTRS)

    Snow-Harter, C.; Whalen, R.; Myburgh, K.; Arnaud, S.; Marcus, R.

    1992-01-01

    Muscle strength has been shown to predict bone mineral density (BMD) in women. We examined this relationship in 50 healthy men who ranged in age from 28 to 51 years (average 38.3 years). BMD of the lumbar spine, proximal femur, whole body, and tibia were measured by dual-energy x-ray absorptiometry (Hologic QDR 1000W). Dynamic strength using one repetition maximum was assessed for the biceps, quadriceps, and back extensors and for the hip abductors, adductors, and flexors. Isometric grip strength was measured by dynamometry. Daily walking mileage was assessed by 9 week stepmeter records and kinematic analysis of video filming. Subjects were designated as exercisers and nonexercisers. Exercisers participated in recreational exercise at least two times each week. The results demonstrated that BMD at all sites correlated with back and biceps strength (p < 0.01 to p = 0.0001). Body weight correlated with tibia and whole-body BMD (p < 0.001); age negatively correlated with Ward's triangle BMD (p < 0.01). In stepwise multiple regressions, back strength was the only independent predictor of spine and femoral neck density (R2 = 0.27). Further, back strength was the most robust predictor of BMD at the trochanter, Ward's triangle, whole body, and tibia, although biceps strength, age, body weight, and leg strength contributed significantly to BMD at these skeletal sites, accounting for 35-52% of the variance in BMD. Exercisers and nonexercisers were similar for walking (3.97 versus 3.94 miles/day), age (37.8 versus 38.5) years, and weight (80.0 versus 77.7 kg). However, BMD and muscle strength were significantly greater in exercises than in nonexercisers.(ABSTRACT TRUNCATED AT 250 WORDS).

  18. AN INVESTIGATION OF THE MINERAL IN DUCTILE AND BRITTLE CORTICAL MOUSE BONE

    PubMed Central

    Rodriguez-Florez, Naiara; Garcia-Tunon, Esther; Mukadam, Quresh; Saiz, Eduardo; Oldknow, Karla J.; Farquharson, Colin; Millán, José Luis; Boyde, Alan; Shefelbine, Sandra J.

    2015-01-01

    Bone is a strong and tough material composed of apatite mineral, organic matter and water. Changes in composition and organization of these building blocks affect bone’s mechanical integrity. Skeletal disorders often affect bone’s mineral phase, either by variations in the collagen or directly altering mineralization. The aim of the current study was to explore the differences in the mineral of brittle and ductile cortical bone at the mineral (nm) and tissue (µm) levels using two mouse phenotypes. Osteogenesis imperfecta murine (oim−/−) mice were used to model brittle bone; PHOSPHO1 mutants (Phospho1−/−) had ductile bone. They were compared to their respective wild-type controls. Femora were defatted and ground to powder to measure average mineral crystal size using X-ray diffraction (XRD), and to monitor the bulk mineral to matrix ratio via thermogravimetric analysis (TGA). XRD scans were run after TGA for phase identification, to assess the fractions of hydroxyapatite and β-tricalcium phosphate. Tibiae were embedded to measure elastic properties with nanoindentation and the extent of mineralization with backscattered electron microscopy (qbSEM). Interestingly, the mineral of brittle oim−/− and ductile Phospho1−/− bones had many similar characteristics. Both pathology models had smaller apatite crystals, lower mineral to matrix ratio, and showed more thermal conversion to β-tricalcium phosphate than their wild-types, indicating deviations from stoichiometric hydroxyapatite in the original mineral. The degree of mineralization of the bone matrix was different for each strain: oim−/− were hypermineralized, while Phospho1−/− were hypomineralized. However, alterations in the mineral were associated with reduced tissue elastic moduli in both pathologies. Results revealed that despite having extremely different whole bone mechanics, the mineral of oim−/− and Phospho1−/− has several similar trends at smaller length scales. This

  19. Optimal management of bone mineral disorders in chronic kidney disease and ESRD

    PubMed Central

    Lundquist, Andrew L.; Nigwekar, Sagar U.

    2016-01-01

    Purpose of review This review summarizes recent studies on chronic kidney disease-mineral bone disorders, with a focus on new developments in disease management. Recent findings The term chronic kidney disease-mineral bone disorder has come to describe an increasingly complex network of alterations in minerals and skeletal disorders that contribute to the significant cardiovascular morbidity and mortality seen in patients with chronic kidney disease and ESRD. Clinical studies continue to suggest associations with clinical outcomes, yet current clinical trials have failed to support causality. Variability in practice exists as current guidelines for management of bone-mineral disorders are often based on weak evidence. Recent studies implicate novel pathways for therapeutic intervention in clinical trials. Summary Mineral-bone disorders in chronic kidney disease arise from alterations in a number of molecules in an increasingly complex physiological network interconnecting bone and the cardiovascular system. Despite extensive associations with improved outcomes in a number of molecules, clinical trials have yet to prove causality and there is an absence of new therapies available to improve patient outcomes. Additional clinical trials that can incorporate the complexity of mineral bone disorders and with the ability to intervene on more than one pathway are needed to advance patient care. PMID:26785065

  20. [Bone mineral density in residents living on radioactive territories of Cheliabinsk Region].

    PubMed

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

    2010-01-01

    Operation of "Mayak" plutonium production complex resulted in radioactive contamination of the part of Chelyabinsk Region in 1950-60s. Significant gas-aerosol emissions of 1311 occurred since 1948; in 1957, a radiation accident resulted in 90Sr contamination of large territories. This paper presents comparison of bone mineral density of persons lived on territories with different levels of soil 90Sr-contamination with a control group. It was found that in 1970-1975 the bone mineral density, estimated from mineral content in bone samples, in residents of contaminated areas born in 1936-1952 was significantly lower compared with the control group. For persons born in 1880-1935 such differences were not found. It was shown that the decrease in bone mineral density was not related to 90Sr exposure of osteogenic cells in the dose range from 0.1 to 1300 mGy: the coefficient of correlation between individual 90Sr-doses and bone mineral contents was not significant. The decrease in bone mineral density of persons born in 1936-1952 could be associated with exposure of thyroid and parathyroid glands (systemic regulators of calcium turnover) by 131I from gas-aerosol emissions from "Mayak". Maximum gas-aerosol emissions occurred in 1948-1954 and coincided with growth and development of thyroid gland, characterizing by intensive accumulation of 131I, and with growth and maturation of the skeleton of persons born in these calendar years.

  1. Prolactinoma: A Massive Effect on Bone Mineral Density in a Young Patient

    PubMed Central

    2016-01-01

    This case highlights a prolactinoma in a young male, and its impact on bone health. Osteoporosis has been noted to be an issue in postmenopausal women with prolactinomas. This case shows a similar impact on bone health in a young male resulting in low bone mineral density for age based on Z-score. This case report highlights the possible mechanisms for the bone loss in the setting of prolactinoma and the need for assessing bone health in such patients. Furthermore it highlights the need for a thorough evaluation in such patients. PMID:27446618

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

    NASA Technical Reports Server (NTRS)

    Makuch, Lauren A.

    2004-01-01

    osteoblasts, including increased proliferation, osteoblastic differentiation, alkaline phosphatase activity, and production of nitric oxide, prostaglandins, and osteopontin. Several proteins have been implicated in osteoblastic mechanotransduction including Bone Morphogenetic Protein-2 (BMP-2), parathyroid hormone, 1,25-dihydroxyvitamin D3 receptor, osteopontin (OPN), osteoprotegerin (OPG), and alkaline phosphatase (AP). We will characterize relative levels of each protein in mineralizing or non-mineralizing MC3T3 osteoblastic cells that have been exposed to fluid flow compared to non-fluid flow using immunofluorescent staining and two- photon laser microscopy as well as western blotting. Because calcium-mediated pathways are important in osteoblastic signaling, we will transfect MC3T3 cells with cameleon probes for Ca2+ containing YFP and CFP. Results will be analyzed using FRET/FLIM to study differential release of intracellular Ca(2+) in response to fluid flow and conditions inducing matrix mineralization. In addition, we plan to conduct several microarray experiments to determine differential gene expression in MC3T3 cells in response to fluid flow and conditions inducing mineralization.

  3. Milk calcium taken with cheese increases bone mineral density and bone strength in growing rats.

    PubMed

    Kato, Ken; Takada, Yukihiro; Matsuyama, Hiroaki; Kawasaki, Yoshihiro; Aoe, Seiichiro; Yano, Hideo; Toba, Yasuhiro

    2002-11-01

    We investigated the calcium bioavailability of milk calcium, taken with or without cheese. Twenty-four 6-week-old male rats for a meal-feeding experiment were trained to consume an AIN-76 diet within 2 h (2 times per day) for 2 weeks. The rats were then divided into three experimental groups, each fed 2 types of experimental diets: Control group, Cheese group, and Ca-Cheese group. The rats were each alternately given 2 types of experimental diets at 2-h meal-feeding for 31 days. The breaking force and energy of the femur in the Ca-Cheese group were significantly higher than in the control group. The bone mineral density (BMD) of the lumbar spine and the femur in the Ca-Cheese group was also significantly higher than in the other two groups. These results indicate that milk calcium taken with cheese increases bone strength and BMD efficiently, results that may be useful for the prevention of osteoporosis.

  4. Assessing Bone Quality in Terms of Bone Mineral Density, Buckling Ratio and Critical Fracture Load

    PubMed Central

    Anitha, D

    2014-01-01

    Background Bone mineral density (BMD) is used as a sole parameter in the diagnosis of osteoporosis. Due to the ease of acquirement of BMD, clinical diagnosis still involves its usage although the limitations of BMD are quite well-established. Therefore, this preliminary study hoped to reduce the errors introduced by BMD alone by incorporating geometric and structural predictors simultaneously to observe if strength was implicitly dependent on the geometry and BMD. Hence, we illustrated the triadic relationship between BMD, buckling ratio (BR) and critical fracture load (Fcr). Methods The geometric predictor was the BR as it involves both the changes in the periosteum and the cortical thickness. Also, structural changes were monitored by finite element (FE) analysis-predicted Fcr. These BR and Fcr measurements were plotted with their respective femoral neck BMD values in elderly female patients (n=6) in a 3-year follow-up study, treated with ibandronate. Results In all the three-dimensional plots (baseline, mid and final year), high Fcr values were found at regions containing high BMD and low BR values. Quantitatively, this was also proven where an averaged highest Fcr across the three years had a relatively higher BMD (46%) and lower BR (19%) than that of the averaged lowest Fcr. The dependence of FE predicted strength on both the geometry and bone density was illustrated. Conclusions We conclude that use of triadic relationships for the evaluation of osteoporosis and hip fractures with the combination of strength, radiology-derived BR and bone density will lay the foundation for more accurate predictions in the future. PMID:25489572

  5. The effect of enamel matrix proteins and deproteinized bovine bone mineral on heterotopic bone formation.

    PubMed

    Donos, Nikolaos; Kostopoulos, Lambros; Tonetti, Maurizio; Karring, Thorkild; Lang, Niklaus P

    2006-08-01

    To evaluate the osteoinductive potential of deproteinized bovine bone mineral (DBBM) and an enamel matrix derivative (EMD) in the muscle of rats. Sixteen rats were used in this study. The animals were divided in three groups. Group A: a pouch was created in one of the pectoralis profundis muscles of the thorax of the rats and DBBM particles (Bio-Oss) were placed into the pouch. Healing: 60 days. Group B: a small pouch was created on both pectoralis profundis muscles at each side of the thorax midline. In one side, a mixture of EMD (Emdogain) mixed with DBBM was placed into one of the pouches, whereas in the contralateral side of the thorax the pouch was implanted with DBBM mixed with the propylene glycol alginate (PGA--carrier for enamel matrix proteins of EMD). Healing: 60 days. Group C: the same procedure as group B, but with a healing period of 120 days. Qualitative histological analysis of the results was performed. At 60 days, the histological appearance of the DBBM particles implanted alone was similar to that of the particles implanted together with EMD or PGA at both 60 and 120 days. The DBBM particles were encapsulated into a connective tissue stroma and an inflammatory infiltrate. At 120 days, the DBBM particles implanted together with EMD or PGA exhibited the presence of resorption lacunae in some cases. Intramuscular bone formation was not encountered in any group. The implantation of DBBM particles alone, combined with EMD or its carrier (PGA) failed to exhibit extraskeletal, bone-inductive properties.

  6. Strong familial association of bone mineral density between parents and offspring: KNHANES 2008-2011.

    PubMed

    Choi, H S; Park, J H; Kim, S H; Shin, S; Park, M J

    2017-03-01

    Bone mineral density (BMD) of offspring was significantly associated with their parents' BMD. Parental BMD Z-score ≤-1 was a significant predictor for BMD Z-score ≤-1 in their offspring. Peak bone mass acquisition during early adulthood is more substantially influenced by genetic factors rather than lifestyle or environmental factors.

  7. Anisotropy in the compressive mechanical properties of bovine cortical bone and the mineral and protein constituents.

    PubMed

    Novitskaya, Ekaterina; Chen, Po-Yu; Lee, Steve; Castro-Ceseña, Ana; Hirata, Gustavo; Lubarda, Vlado A; McKittrick, Joanna

    2011-08-01

    The mechanical properties of fully demineralized, fully deproteinized and untreated cortical bovine femur bone were investigated by compression testing in three anatomical directions (longitudinal, radial and transverse). The weighted sum of the stress-strain curves of the treated bones was far lower than that of the untreated bone, indicating a strong molecular and/or mechanical interaction between the collagen matrix and the mineral phase. Demineralization and deproteinization of the bone demonstrated that contiguous, stand-alone structures result, showing that bone can be considered an interpenetrating composite material. Structural features of the samples from all groups were studied by optical and scanning electron microscopy. Anisotropic mechanical properties were observed: the radial direction was found to be the strongest for untreated bone, while the longitudinal one was found to be the strongest for deproteinized and demineralized bones. A possible explanation for this phenomenon is the difference in bone microstructure in the radial and longitudinal directions.

  8. Enzymatic mineralization of hydrogels for bone tissue engineering by incorporation of alkaline phosphatase.

    PubMed

    Douglas, Timothy E L; Messersmith, Philip B; Chasan, Safak; Mikos, Antonios G; de Mulder, Eric L W; Dickson, Glenn; Schaubroeck, David; Balcaen, Lieve; Vanhaecke, Frank; Dubruel, Peter; Jansen, John A; Leeuwenburgh, Sander C G

    2012-08-01

    Alkaline phosphatase (ALP), an enzyme involved in mineralization of bone, is incorporated into three hydrogel biomaterials to induce their mineralization with calcium phosphate (CaP). These are collagen type I, a mussel-protein-inspired adhesive consisting of PEG substituted with catechol groups, cPEG, and the PEG/fumaric acid copolymer OPF. After incubation in Ca-GP solution, FTIR, EDS, SEM, XRD, SAED, ICP-OES, and von Kossa staining confirm CaP formation. The amount of mineral formed decreases in the order cPEG > collagen > OPF. The mineral:polymer ratio decreases in the order collagen > cPEG > OPF. Mineralization increases Young's modulus, most profoundly for cPEG. Such enzymatically mineralized hydrogel/CaP composites may find application as bone regeneration materials.

  9. Enzymatic mineralization of hydrogels for bone tissue engineering by incorporation of alkaline phosphatase

    PubMed Central

    Douglas, Timothy E.L.; Messersmith, Philip B.; Chasan, Safak; Mikos, Antonios G.; de Mulder, Eric L.W.; Dickson, Glenn; Schaubroeck, David; Balcaen, Lieve; Vanhaecke, Frank; Dubruel, Peter; Jansen, John A.

    2013-01-01

    Alkaline Phosphatase (ALP), an enzyme involved in mineralization of bone, was incorporated into three hydrogel biomaterials to induce their mineralization with calcium phosphate (CaP). These were collagen type I, a mussel protein-inspired adhesive consisting of PEG substituted with catechol groups, cPEG, and the PEG-fumaric acid copolymer OPF. After incubation in calcium glycerophosphate (Ca-GP) solution, FTIR, EDS, SEM, XRD, SAED, ICP-OES and von Kossa staining confirmed CaP formation. The amount of mineral formed decreased in the order cPEG > collagen > OPF. Mineral:polymer ratio decreased in the order collagen > cPEG > OPF. Mineralization increased Young’s modulus, most profoundly for cPEG. Such enzymatically mineralized hydrogel-CaP composites could find application as bone regeneration materials. PMID:22648976

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

    SciTech Connect

    Sacco-Gibson, N.; Abrams, J.; Chaudhry, S.; Hurst, D.; Peterson, D.; Bhattacharyya, M.

    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 resulted 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.

  11. Longitudinal bone mineral content and density in Rett syndrome and their contributing factors.

    PubMed

    Jefferson, Amanda; Fyfe, Sue; Downs, Jenny; Woodhead, Helen; Jacoby, Peter; Leonard, Helen

    2015-05-01

    Bone mass and density are low in females with Rett syndrome. This study used Dual energy x-ray absorptiometry to measure annual changes in z-scores for areal bone mineral density (aBMD) and bone mineral content (BMC) in the lumbar spine and total body in an Australian Rett syndrome cohort at baseline and then after three to four years. Bone mineral apparent density (BMAD) was calculated in the lumbar spine. Annual changes in lean tissue mass (LTM) and bone area (BA) were also assessed. The effects of age, genotype, mobility, menstrual status and epilepsy diagnosis on these parameters were also investigated. The baseline sample included 97 individuals who were representative of the total live Australian Rett syndrome population under 30years in 2005 (n=274). Of these 74 had a follow-up scan. Less than a quarter of females were able to walk on their own at follow-up. Bone area and LTM z-scores declined over the time between the baseline and follow-up scans. Mean height-standardised z-scores for the bone outcomes were obtained from multiple regression models. The lumbar spine showed a positive mean annual BMAD z-score change (0.08) and a marginal decrease in aBMD (-0.04). The mean z-score change per annum for those 'who could walk unaided' was more positive for LS BMAD (p=0.040). Total body BMD mean annual z-score change from baseline to follow-up was negative (-0.03). However this change was positive in those who had achieved menses prior to the study (0.03, p=0,040). Total body BMC showed the most negative change (-0.60), representing a decrease in bone mineral content over time. This normalised to a z-score change of 0.21 once adjusted for the reduced lean tissue mass mean z-score change (-0.21) and bone area mean z-score change (-0.14). Overall, the bone mineral content, bone mineral density, bone area and lean tissue mass z-scores for all outcome measures declined, with the TB BMC showing significant decreases. Weight, height and muscle mass appear to have

  12. Relationship between mechanical properties and bone mineral density of human femoral bone retrieved from patients with osteoarthritis.

    PubMed

    Haba, Yvonne; Lindner, Tobias; Fritsche, Andreas; Schiebenhöfer, Ann-Kristin; Souffrant, Robert; Kluess, Daniel; Skripitz, Ralf; Mittelmeier, Wolfram; Bader, Rainer

    2012-01-01

    The objective of this study was to analyse retrieved human femoral bone samples using three different test methods, to elucidate the relationship between bone mineral density and mechanical properties. Human femoral heads were retrieved from 22 donors undergoing primary total hip replacement due to hip osteoarthritis and stored for a maximum of 24 hours postoperatively at + 6 °C to 8 °C.Analysis revealed an average structural modulus of 232±130 N/mm(2) and ultimate compression strength of 6.1±3.3 N/mm(2) with high standard deviations. Bone mineral densities of 385±133 mg/cm(2) and 353±172 mg/cm(3) were measured using thedual energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT), respectively. Ashing resulted in a bone mineral density of 323±97 mg/cm(3). In particular, significant linear correlations were found between DXA and ashing with r = 0.89 (p < 0.01, n = 22) and between structural modulus and ashing with r = 0.76 (p < 0.01, n = 22).Thus, we demonstrated a significant relationship between mechanical properties and bone density. The correlations found can help to determine the mechanical load capacity of individual patients undergoing surgical treatments by means of noninvasive bone density measurements.

  13. State of the mineral component of rat bone tissue during hypokinesia and the recovery period

    NASA Technical Reports Server (NTRS)

    Volozhin, A. I.; Stupakov, G. P.; Pavlova, M. N.; Muradov, I. S.

    1980-01-01

    Experiments were conducted on young growing rats. Hypokinesia lasting from 20 to 200 days caused retarded gain in weight and volume of the femur and delayed development of the cortical layer of the diaphysis. In contrast, the density of the cortical layer of the femoral diaphysis increased due to elevation of the mineral saturation of the bone tissue microstructures. Incorporation of Ca into the bone tissue in hypokinesia had a tendency to reduce. Partial normalization of the bone tissue mineral component occurred during a 20 day recovery period following hypokinesia.

  14. Osteopenia of Prematurity: Does Physical Activity Improve Bone Mineralization in Preterm Infants?

    PubMed

    Stalnaker, Kelsey A; Poskey, Gail A

    2016-01-01

    Bone mineralization of preterm infants is significantly less than full-term infants at birth, placing preterm infants at risk for osteopenia of prematurity and other metabolic bone diseases. Advances in nutritional supplementation and standard nursing care alone have been unsuccessful in improving bone mineralization postnatally. Research supports a daily physical activity protocol of passive range of motion and gentle joint compression when combined with adequate nutritional supplementation reduces osteopenia of prematurity. This article provides a systematic review of the current evidence surrounding early physical activity and neonatal massage for the treatment of osteopenia and indicates the need for universal handling protocols in caring for this unique population.

  15. The association of chronic kidney disease-mineral bone disorder and cardiovascular risk.

    PubMed

    Eddington, Helen; Kalra, Philip A

    2010-05-01

    Chronic kidney disease-mineral bone disorder (CKD-MBD) is a multifaceted definition used to help describe the systemic derangement of mineral bone metabolism in renal disease. This was previously referred to, rather simplistically, as 'renal osteodystrophy' or 'renal bone disease'. In this review, we will try to show the evidence relating these factors to cardiovascular morbidity and mortality and give some evidence as to the mechanisms for this. The treatments used for this condition are also integral to the increased cardiovascular mortality seen in renal patients and a summary of these effects will also be covered.

  16. Palmitic Acid Reduces Circulating Bone Formation Markers in Obese Animals and Impairs Osteoblast Activity via C16-Ceramide Accumulation.

    PubMed

    Alsahli, Ahmad; Kiefhaber, Kathryn; Gold, Tziporah; Muluke, Munira; Jiang, Hongfeng; Cremers, Serge; Schulze-Späte, Ulrike

    2016-05-01

    Obesity and impaired lipid metabolism increase circulating and local fatty acid (FA) levels. Our previous studies showed that a high high-saturated -fat diet induced greater bone loss in mice than a high high-unsaturated-fat diet due to increased osteoclast numbers and activity. The impact of elevated FA levels on osteoblasts is not yet clear. We induced obesity in 4 week old male mice using a palmitic acid (PA)- or oleic acid (OA)-enriched high fat high-fat diet (HFD) (20 % of calories from FA), and compared them to mice on a normal (R) caloric diet (10 % of calories from FA). We collected serum to determine FA and bone metabolism marker levels. Primary osteoblasts were isolated; cultured in PA, OA, or control (C) medium; and assessed for mineralization activity, gene expression, and ceramide levels. Obese animals in the PA and OA groups had significantly lower serum levels of bone formation markers P1NP and OC compared to normal weight animals (*p < 0.001), with the lowest marker levels in animals on an PA-enriched HFD (*p < 0.001). Accordingly, elevated levels of PA significantly reduced osteoblast mineralization activity in vitro (*p < 0.05). Elevated PA intake significantly increased C16 ceramide accumulation. This accumulation was preventable through inhibition of SPT2 (serine palmitoyl transferase 2) using myriocin. Elevated levels of PA reduce osteoblast function in vitro and bone formation markers in vivo. Our findings suggest that saturated PA can compromise bone health by affecting osteoblasts, and identify a potential mechanism through which obesity promotes bone loss.

  17. Bone formation is not impaired by hibernation (disuse) in black bears Ursus americanus

    USGS Publications Warehouse

    Donahue, S.W.; Vaughan, M.R.; Demers, L.M.; Donahue, H.J.

    2003-01-01

    Disuse by bed rest, limb immobilization or space flight causes rapid bone loss by arresting bone formation and accelerating bone resorption. This net bone loss increases the risk of fracture upon remobilization. Bone loss also occurs in hibernating ground squirrels, golden hamsters, and little brown bats by arresting bone formation and accelerating bone resorption. There is some histological evidence to suggest that black bears Ursus americanus do not lose bone mass during hibernation (i.e. disuse). There is also evidence suggesting that muscle mass and strength are preserved in black bears during hibernation. The question of whether bears can prevent bone loss during hibernation has not been conclusively answered. The goal of the current study was to further assess bone metabolism in hibernating black bears. Using the same serum markers of bone remodeling used to evaluate human patients with osteoporosis, we assayed serum from five black bears, collected every 10 days over a 196-day period, for bone resorption and formation markers. Here we show that bone resorption remains elevated over the entire hibernation period compared to the pre-hibernation period, but osteoblastic bone formation is not impaired by hibernation and is rapidly accelerated during remobilization following hibernation.

  18. Mineralization and bone regeneration using a bioactive elastin-like recombinamer membrane.

    PubMed

    Tejeda-Montes, Esther; Klymov, Alexey; Nejadnik, M Reza; Alonso, Matilde; Rodriguez-Cabello, J Carlos; Walboomers, X Frank; Mata, Alvaro

    2014-09-01

    The search for alternative therapies to improve bone regeneration continues to be a major challenge for the medical community. Here we report on the enhanced mineralization, osteogenesis, and in vivo bone regeneration properties of a bioactive elastin-like recombinamer (ELR) membrane. Three bioactive ELRs exhibiting epitopes designed to promote mesenchymal stem cell adhesion (RGDS), mineralization (DDDEEKFLRRIGRFG), and both cell adhesion and mineralization were synthesized using standard recombinant protein techniques. The ELR materials were then used to fabricate membranes comprising either a smooth surface (Smooth) or channel microtopographies (Channels). Mineralization and osteoblastic differentiation of primary rat mesenchymal stem cells (rMSCs) were analyzed in both static and dynamic (uniaxial strain of 8% at 1 Hz frequency) conditions. Smooth mineralization membranes in static condition exhibited the highest quantity of calcium phosphate (Ca/P of 1.78) deposition with and without the presence of cells, the highest Young's modulus, and the highest production of alkaline phosphatase on day 10 in the presence of cells growing in non-osteogenic differentiation medium. These membranes were tested in a 5 mm-diameter critical-size rat calvarial defect model and analyzed for bone formation on day 36 after implantation. Animals treated with the mineralization membranes exhibited the highest bone volume within the defect as measured by micro-computed tomography and histology with no significant increase in inflammation. This study demonstrates the possibility of using bioactive ELR membranes for bone regeneration applications.

  19. Intensive Hemodialysis, Mineral and Bone Disorder, and Phosphate Binder Use.

    PubMed

    Copland, Michael; Komenda, Paul; Weinhandl, Eric D; McCullough, Peter A; Morfin, Jose A

    2016-11-01

    Mineral and bone disorder is a common complication of end-stage renal disease. Notably, hyperphosphatemia likely promotes calcification of the myocardium, valves, and arteries. Hyperphosphatemia is associated with higher risk for cardiovascular mortality and morbidity along a gradient beginning at 5.0mg/dL. Among contemporary hemodialysis (HD) patients, mean serum phosphorus level is 5.2mg/dL, although 25% of patients have serum phosphorus levels of 5.5 to 6.9mg/dL; and 13%, >7.0mg/dL. Treatment of hyperphosphatemia is burdensome. Dialysis patients consume a mean of 19 pills per day, half of which are phosphate binders. Medicare Part D expenditures on binders for dialysis patients approached $700 million in 2013. Phosphorus removal with thrice-weekly HD (4 hours per session) is ∼3,000mg/wk. However, clearance is unlikely to counterbalance dietary intake, which varies around a mean of 7,000mg/wk. Dietary restriction and phosphate binders are important interventions, but each has limitations. Dietary control is complicated by limited access to healthy food choices and unclear labeling. Meanwhile, adherence to phosphate binders is poor, especially in younger patients and those with high pill burden. Multiple randomized clinical trials show that intensive HD reduces serum phosphorus levels. In the Frequent Hemodialysis Network (FHN) trial, short daily and nocturnal schedules reduced serum phosphorus levels by 0.6 and 1.6mg/dL, respectively, relative to 3 sessions per week. A similar effect of nocturnal HD was observed in an earlier trial. In the daily arm of the FHN trial, intensive HD significantly lowered estimated phosphate binder dose per day, whereas in the nocturnal arm, intensive HD led to binder discontinuation in 75% of patients. However, intensive HD appears to have no meaningful effects on serum calcium and parathyroid hormone concentrations. In conclusion, intensive HD, especially nocturnal HD, lowers serum phosphorus levels and decreases the need for

  20. The Rare Bone Disease Working Group: report from the 2016 American Society for Bone and Mineral Research Annual Meeting.

    PubMed

    Drake, Matthew T; Collins, Michael T; Hsiao, Edward C

    2017-01-20

    A working group on rare bone diseases was held in Atlanta, Georgia as part of the 2016 annual meeting of the American Society for Bone and Mineral Research. The meeting was organized by Matthew Drake. Given recent advances in our understanding of fibrodysplasia ossificans progressiva (FOP), the initial portion of the program was devoted to basic, translational, and clinical aspects of FOP. The remainder of the program was divided into updates on an array of rare bone diseases as detailed below. In total, there were more than 120 scientists from academia and industry in attendance.

  1. Long-term safety of antiresorptive treatment: bone material, matrix and mineralization aspects

    PubMed Central

    Misof, Barbara M; Fratzl-Zelman, Nadja; Paschalis, Eleftherios P; Roschger, Paul; Klaushofer, Klaus

    2015-01-01

    It is well established that long-term antiresorptive use is effective in the reduction of fracture risk in high bone turnover osteoporosis. Nevertheless, during recent years, concerns emerged that longer bone turnover reduction might favor the occurrence of fatigue fractures. However, the underlying mechanisms for both beneficial and suspected adverse effects are not fully understood yet. There is some evidence that their effects on the bone material characteristics have an important role. In principle, the composition and nanostructure of bone material, for example, collagen cross-links and mineral content and crystallinity, is highly dependent on tissue age. Bone turnover determines the age distribution of the bone structural units (BSUs) present in bone, which in turn is decisive for its intrinsic material properties. It is noteworthy that the effects of bone turnover reduction on bone material were observed to be dependent on the duration of the antiresorptive therapy. During the first 2–3 years, significant decreases in the heterogeneity of material properties such as mineralization of the BSUs have been observed. In the long term (5–10 years), the mineralization pattern reverts towards normal heterogeneity and degree of mineralization, with no signs of hypermineralization in the bone matrix. Nevertheless, it has been hypothesized that the occurrence of fatigue fractures (such as atypical femoral fractures) might be linked to a reduced ability of microdamage repair under antiresorptive therapy. The present article examines results from clinical studies after antiresorptive, in particular long-term, therapy with the aforementioned potentially positive or negative effects on bone material. PMID:25709811

  2. Calcium Regulation and Bone Mineral Metabolism in Elderly Patients with Chronic Kidney Disease

    PubMed Central

    Tejwani, Vickram; Qian, Qi

    2013-01-01

    The elderly chronic kidney disease (CKD) population is growing. Both aging and CKD can disrupt calcium (Ca2+) homeostasis and cause alterations of multiple Ca2+-regulatory mechanisms, including parathyroid hormone, vitamin D, fibroblast growth factor-23/Klotho, calcium-sensing receptor and Ca2+-phosphate product. These alterations can be deleterious to bone mineral metabolism and soft tissue health, leading to metabolic bone disease and vascular calcification and aging, termed CKD-mineral and bone disorder (MBD). CKD-MBD is associated with morbid clinical outcomes, including fracture, cardiovascular events and all-cause mortality. In this paper, we comprehensively review Ca2+ regulation and bone mineral metabolism, with a special emphasis on elderly CKD patients. We also present the current treatment-guidelines and management options for CKD-MBD. PMID:23760058

  3. Biosynthesis and in vitro evaluation of macroporous mineralized bacterial nanocellulose scaffolds for bone tissue engineering.

    PubMed

    Sundberg, Johan; Götherström, Cecilia; Gatenholm, Paul

    2015-01-01

    Macroporous bacterial nanocellulose (BNC) scaffolds with calcium phosphate coated surfaces is a candidate for future bone tissue engineering applications. The mineralization of the macroporous BNC scaffolds was achieved by a biomimetic process, resulting in an environment resembling native bone tissues' mineralized extra cellular matrix both topographically and chemically. The deposited crystals were analyzed with electron spectroscopy for chemical analysis (ESCA), energy-dispersive X-ray spectroscopy (EDX) and X-ray crystallography (XRD). MSCs were cultured in osteogeneic medium for 21 days on the scaffolds. The results of this study show that macroporous BNC can be mineralized with hydroxyapatite and that MSCs retain their ability to proliferate and differentiate towards an osteoblastic phenotype within the mineralized BNC, showing the promise of this material in bone tissue engineering applications.

  4. Rapidly Assessing Changes in Bone Mineral Balance Using Natural Stable Calcium Isotopes

    NASA Technical Reports Server (NTRS)

    Morgan, J. L. L.; Gordon, G. W.; Romaniello, S. J.; Skulan, J. L.; Smith, S. M.; Anbar, A. D.

    2011-01-01

    We demonstrate that variations in the Ca isotope ratios in urine rapidly and quantitatively reflect changes in bone mineral balance. This variation occurs because bone formation depletes soft tissue of light Ca isotopes, while bone resorption releases that isotopically light Ca back into soft tissue. In a study of 12 individuals confined to bed rest, a condition known to induce bone resorption, we show that Ca isotope ratios shift in a direction consistent with net bone loss after just 7 days, long before detectible changes in bone density occur. Consistent with this interpretation, the Ca isotope variations track changes observed in N-teleopeptide, a bone resorption biomarker, while bone-specific alkaline phosphatase, a bone formation biomarker, is unchanged. Ca isotopes can in principle be used to quantify net changes in bone mass. Ca isotopes indicate an average loss of 0.62 +/- 0.16 % in bone mass over the course of this 30-day study. The Ca isotope technique should accelerate the pace of discovery of new treatments for bone disease and provide novel insights into the dynamics of bone metabolism.

  5. Fructus Ligustri Lucidi (FLL) ethanol extract increases bone mineral density and improves bone properties in growing female rats.

    PubMed

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

    2014-11-01

    Osteoporosis is a chronic disease affecting millions of people worldwide. It is generally accepted that acquisition of a high peak bone mass (PBM) early in life can reduce the risk of osteoporosis later in life. The aims of this study were to investigate the effects of Fructus Ligustri Lucidi (FLL) ethanol extract on bone mineral density and its mechanical properties in growing female rats and to explore the underlying mechanisms. The rats were given different doses of FLL extract mixed with AIN-93G formula (0.40, 0.65 and 0.90 %), and a group given AIN-93G diet treatment only was used as control. The intervention lasted for 16 weeks until the animals were about 5 months old, the time when the animals almost reach their PBM. Our results showed that FLL treatment increased bone mineral density and improved bone mechanical properties in the growing female rats in a dose-dependent manner. In addition, FLL treatment significantly decreased the serum bone-resorbing marker, CTX-I, while significantly increasing serum 25(OH)D3 and thereby increasing Ca absorption and Ca retention. Intriguingly, both in vivo and in vitro results demonstrated that FLL treatment could reduce the RANKL/OPG ratio. In conclusion, FLL ethanol extract exerted beneficial effects on peak bone mass acquisition and the improvement of bone mechanical properties by favoring Ca metabolism and decreasing the RANKL/OPG ratio.

  6. Assessment of bone mineral status in children with Marfan syndrome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder with skeletal involvement. It is caused by mutations in fibrillin1 (FBN1) gene resulting in activation of TGF-ßeta, which developmentally regulates bone mass and matrix properties. There is no consensus regarding bone minerali...

  7. Bone mineral density in elite adolescent female figure skaters

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Elite adolescent figure skaters must accommodate both the physical demands of competitive training and the accelerated rate of bone growth that is associated with adolescence. Although, these athletes apparently undergo sufficient physical activity to develop healthy bones, it is possible that other...

  8. Bone mineral density and osteoporosis after preterm birth: the role of early life factors and nutrition.

    PubMed

    Wood, Claire L; Wood, Alexander M; Harker, Caroline; Embleton, Nicholas D

    2013-01-01

    The effects of preterm birth and perinatal events on bone health in later life remain largely unknown. Bone mineral density (BMD) and osteoporosis risk may be programmed by early life factors. We summarise the existing literature relating to the effects of prematurity on adult BMD and the Developmental Origins of Health and Disease hypothesis and programming of bone growth. Metabolic bone disease of prematurity and the influence of epigenetics on bone metabolism are discussed and current evidence regarding the effects of breastfeeding and aluminium exposure on bone metabolism is summarised. This review highlights the need for further research into modifiable early life factors and their effect on long-term bone health after preterm birth.

  9. Digestive efficiency mediated by serum calcium predicts bone mineral density in the common marmoset (Callithrix jacchus).

    PubMed

    Jarcho, Michael R; Power, Michael L; Layne-Colon, Donna G; Tardif, Suzette D

    2013-02-01

    Two health problems have plagued captive common marmoset (Callithrix jacchus) colonies for nearly as long as those colonies have existed: marmoset wasting syndrome and metabolic bone disease. While marmoset wasting syndrome is explicitly linked to nutrient malabsorption, we propose metabolic bone disease is also linked to nutrient malabsorption, although indirectly. If animals experience negative nutrient balance chronically, critical nutrients may be taken from mineral stores such as the skeleton, thus leaving those stores depleted. We indirectly tested this prediction through an initial investigation of digestive efficiency, as measured by apparent energy digestibility, and serum parameters known to play a part in metabolic bone mineral density of captive common marmoset monkeys. In our initial study on 12 clinically healthy animals, we found a wide range of digestive efficiencies, and subjects with lower digestive efficiency had lower serum vitamin D despite having higher food intakes. A second experiment on 23 subjects including several with suspected bone disease was undertaken to measure digestive and serum parameters, with the addition of a measure of bone mineral density by dual-energy X-ray absorptiometry (DEXA). Bone mineral density was positively associated with apparent digestibility of energy, vitamin D, and serum calcium. Further, digestive efficiency was found to predict bone mineral density when mediated by serum calcium. These data indicate that a poor ability to digest and absorb nutrients leads to calcium and vitamin D insufficiency. Vitamin D absorption may be particularly critical for indoor-housed animals, as opposed to animals in a more natural setting, because vitamin D that would otherwise be synthesized via exposure to sunlight must be absorbed from their diet. If malabsorption persists, metabolic bone disease is a possible consequence in common marmosets. These findings support our hypothesis that both wasting syndrome and metabolic bone

  10. Physical activity and lifestyle effects on bone mineral density among young adults: sociodemographic and biochemical analysis

    PubMed Central

    Alghadir, Ahmad H.; Gabr, Sami A.; Al-Eisa, Einas

    2015-01-01

    [Purpose] The purpose of this study was to assess the possible role of physical activities, calcium consumption and lifestyle factors in both bone mineral density and bone metabolism indices in 350 young adult volunteers. [Subjects and Methods] All volunteers were recruited for the assessment of lifestyle behaviors and physical activity traits using validated questioners, and bone mineral density (BMD), serum osteocalcin (s-OC), bone-specific alkaline phosphatase (BAP), and calcium were estimated using dual-energy X-ray absorptiometry analysis, and immunoassay techniques. [Results] Male participants showed a significant increase in BMD along with an increase in bone metabolism markers compared with females in all groups. However, younger subjects showed a significant increase in BMD, OC, BAP, and calcium compared with older subjects. Osteoporosis was more common in older subjects linked with abnormal body mass index and waist circumference. Bone metabolism markers correlated positively with BMD, physically activity and negatively with osteoporosis in all stages. Also, moderate to higher calcium and milk intake correlated positively with higher BMD. However, low calcium and milk intake along with higher caffeine, and carbonated beverage consumption, and heavy cigarette smoking showed a negative effect on the status of bone mineral density. Stepwise regression analysis showed that life style factors including physical activity and demographic parameters explained around 58–69.8% of the bone mineral density variation in young adults especially females. [Conclusion] body mass index, physical activity, low calcium consumption, and abnormal lifestyle have role in bone mineral density and prognosis of osteoporosis in young adults. PMID:26311965

  11. Relationship of serum GDF11 levels with bone mineral density and bone turnover markers in postmenopausal Chinese women

    PubMed Central

    Chen, Yusi; Guo, Qi; Zhang, Min; Song, Shumin; Quan, Tonggui; Zhao, Tiepeng; Li, Hongliang; Guo, Lijuan; Jiang, Tiejian; Wang, Guangwei

    2016-01-01

    Growth differentiation factor 11 (GDF11) is an important circulating factor that regulates aging. However, the role of GDF11 in bone metabolism remains unclear. The present study was undertaken to investigate the relationship between serum GDF11 level, bone mass, and bone turnover markers in postmenopausal Chinese women. Serum GDF11 level, bone turnover biochemical markers, and bone mineral density (BMD) were determined in 169 postmenopausal Chinese women (47–78 years old). GDF11 serum levels increased with aging. There were negative correlations between GDF11 and BMD at the various skeletal sites. After adjusting for age and body mass index (BMI), the correlations remained statistically significant. In the multiple linear stepwise regression analysis, age or years since menopause, BMI, GDF11, and estradiol were independent predictors of BMD. A significant negative correlation between GDF11 and bone alkaline phosphatase (BAP) was identified and remained significant after adjusting for age and BMI. No significant correlation was noted between cross-linked N-telopeptides of type I collagen (NTX) and GDF11. In conclusion, GDF11 is an independent negative predictor of BMD and correlates with a biomarker of bone formation, BAP, in postmenopausal Chinese women. GDF11 potentially exerts a negative effect on bone mass by regulating bone formation. PMID:27408764

  12. A versatile new mineralized bone stain for simultaneous assessment of tetracycline and osteoid seams.

    PubMed

    Villanueva, A R; Lundin, K D

    1989-05-01

    A versatile mineralized bone stain (MIBS) for demonstrating osteoid seams and tetracycline fluorescence simultaneously in thin or thick undecalcified sections has been developed. Bone specimens are fixed in 70% ethanol, but 10% buffered formalin is permissible. Depending upon one's preference, these specimens can be left unstained or be prestained before plastic embedding. Osteoid seams are stained green to jade green, or light to dark purple. Mineralized bone matrix is unstained or green. Osteoblast and osteoclast nuclei are light to dark purple, cytoplasm varies from slightly gray to pink. The identification of osteoid seams by this method agrees closely with identification by in vivo tetracycline uptake using the same section from the same biopsy. The method demonstrates halo volumes, an abnormal, lacunar, low density bone around viable osteocytes in purple. This phenomenon is commonly seen in vitamin D-resistant rickets, fluorosis, renal osteodystrophy, hyperparathyroidism, and is sometimes seen in fluoride treated osteoporotic patients. In osteomalacic bone, most osteoid seams are irregularly stained as indicated by the presence of unmineralized osteoid between mineralized lamellae. The method has been used effectively in staining new bone formation in hydroxyapatite implants and bone grafts. Old, unstained, plastic embedded undecalcified sections are stained as well as fresh sections after removal of the coverslip. This stain also promises to be valuable in the study of different metabolic bone diseases from the point of view of remodeling, histomorphometry, and pathology.

  13. Effect of inulin on growth performance, intestinal tract sizes, mineral retention and tibial bone mineralisation in broiler chickens.

    PubMed

    Ortiz, L T; Rodríguez, M L; Alzueta, C; Rebolé, A; Treviño, J

    2009-05-01

    1. A 5-week feeding trial with 240 one-day-old male broiler chickens was conducted to investigate the responses of performance, intestinal tract measurements, relative apparent retention of minerals (Ca, Mg, Fe, Zn and Cu), and tibial bone measurements and mineral content (ash and Ca) to dietary graded levels of inulin. Treatments consisted of a maize-soybean meal control diet without or with supplemental antibiotic (flavomycin, 40 mg/kg diet) and 4 diets containing inulin at concentrations of 5, 10, 15 and 20 g/kg. 2. Growth performance of birds and morphological measurements of intestinal tract (duodenum, jejunum, ileum and caeca) showed no response to dietary levels of inulin as compared with the control diet and the control diet with flavomycin. 3. Dietary inulin improved the relative apparent retention of Ca, Zn and Cu (up to 18.4, 35.5 and 466%, respectively), did no affect that of Mg and impaired the retention of Fe. Differences among inulin treatments and control with flavomycin were significant only for Mg content. 4. Dietary inulin increased the concentration of ash and Ca in the tibiae. This effect was not reflected in the tibial bone morphology (weight, length and width). In conclusion, the results from the current study suggest that feeding inulin to broiler chickens may have a beneficial effect on bone quality.

  14. Correlating chemical changes in subchondral bone mineral due to aging or defective type II collagen by Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Dehring, Karen A.; Roessler, Blake J.; Morris, Michael D.

    2007-02-01

    We show that early indicators of osteoarthritis are observed in Raman spectroscopy by probing femur surfaces excised from mouse models of early-onset osteoarthritis. Current clinical methods to examine arthritic joints include radiological examination of the joint, but may not be capable of detecting subtle chemical changes in the bone tissue, which may provide the earliest indications of osteoarthritis. Recent research has indicated that the subchondral bone may have a more significant role in the onset of osteoarthritis than previously realized. We will report the effect of age and defective type II collagen on Raman band area ratios used to describe bone structure and function. The carbonate-to-phosphate ratio is used to assess carbonate substitution into the bone mineral and the mineral-to-matrix ratio is used to measure bone mineralization. Mineral-to-matrix ratios indicate that subchondral bone becomes less mineralized as both the wild-type and Del1 (+/-) transgenic mice age. Moreover, the mineral-to-matrix ratios show that the subchondral bone of Del1 (+/-) transgenic mice is less mineralized than that of the wild-type mice. Carbonate-to-phosphate ratios from Del1 (+/-) transgenic mice follow the same longitudinal trend as wild-type mice. The ratio is slightly higher in the transgenic mice, indicating more carbonate content in the bone mineral. Raman characterization of bone mineralization provides an invaluable insight into the process of cartilage degeneration and the relationship with subchondral bone at the ultrastructural level.

  15. Tracking Circadian Rhythms of Bone Mineral Deposition in Murine Calvarial Organ Cultures

    PubMed Central

    McElderry, John-David P.; Zhao, Guisheng; Khmaladze, Alexander; Wilson, Christopher G.; Franceschi, Renny T.; Morris, Michael D.

    2013-01-01

    Osteoblasts, which orchestrate the deposition of small apatite crystals through the expression of nucleating proteins, have been shown to also express clock genes associated with the circadian signaling pathway. We hypothesized that protein-mediated bone mineralization may be linked to circadian oscillator mechanisms functioning in peripheral bone tissue. In this study, Per1 expression in ex vivo neonatal murine calvaria organ cultures was monitored for 6 days using a Per1-luciferase transgene as a bioluminescent indicator of clock function. Fluctuations in Per1 expression had a period of 25±4 hours (n=14) with early expression at CT09:59±03:37 (circadian time). We also established the kinetics of mineral deposition in developing bone by using non-invasive Raman microscopy to track mineral accumulation in calvarial tissue. The content and quality of newly deposited mineral was continually examined at the interparietal bone/fontanel boundary for a period of 6 days with 1 hour temporal resolution. Using this approach, mineralization over time exhibited bursts of mineral deposition followed by little or no deposition, which was recurrent with a periodicity of 26.8±9.6 hours. As many as 6 near-daily mineralization events were observed in the calvaria before deposition ceased. Earliest mineralization events occurred at CT16:51±03:45, which is 6 hours behind Per1 expression. These findings are consistent with the hypothesis that mineralization in developing bone tissue is regulated by a local circadian oscillator mechanism. PMID:23505073

  16. Can acetazolamide be used to treat diseases involving increased bone mineral density?

    PubMed Central

    González-Rodríguez, Juan David; Luis-Yanes, María Isabel; Inglés-Torres, Esther; Arango-Sancho, Pedro; Cabrera-Sevilla, José Eugenio; Duque-Fernández, María Rosario; Gil-Sánchez, Salvador; García-Nieto, Víctor Manuel

    2016-01-01

    Summary Sclerosing bone dysplasias are a series of clinically and genetically heterogeneous diseases characterized by functional failure of the osteoclasts in bone resorption, leading to an excessive amount of bone mineral density (BMD) which could have serious clinical consequences. We treated three children affected with seriously high levels of BMD with acetazolamide, with the intention of inducing metabolic acidosis, thus increasing bone resorption and reducing BMD. All our patients tolerated and followed the treatment well and the clinical response was satisfactory in all cases. PMID:27904825

  17. Dietary l-carnitine supplementation improves bone mineral density by suppressing bone turnover in aged ovariectomized rats.

    PubMed

    Hooshmand, Shirin; Balakrishnan, Anju; Clark, Richard M; Owen, Kevin Q; Koo, Sung I; Arjmandi, Bahram H

    2008-08-01

    Postmenopausal bone loss is a major public health concern. Although drug therapies are available, women are interested in alternative/adjunct therapies to slow down the bone loss associated with ovarian hormone deficiency. The purpose of this study was to determine whether dietary supplementation of l-carnitine can influence bone density and slow the rate of bone turnover in an aging ovariectomized rat model. Eighteen-month-old Fisher-344 female rats were ovariectomized and assigned to two groups: (1) a control group in which rats were fed ad libitum a carnitine-free (-CN) diet (AIN-93M) and (2) another fed the same diet but supplemented with l-carnitine (+CN). At the end of 8 weeks of feeding, animals were sacrificed and bone specimens were collected for measuring bone mineral content (BMC) and density (BMD) using dual energy X-ray absorptiometry. Femoral microarchitectural properties were assessed by microcomputed tomography. Femoral mRNA levels of selected bone matrix proteins were determined by northern blot analysis. Data showed that tibial BMD was significantly higher in the rat fed the +CN diet than those fed the -CN (control) diet. Dietary carnitine significantly decreased the mRNA level of tartrate-resistant acid phosphatase (TRAP), an indicator of bone resorption by 72.8%, and decreased the mRNA abundance of alkaline phosphatase (ALP) and collagen type-1 (COL), measures of bone formation by 63.6% and 61.2%, respectively. The findings suggest that carnitine supplementation slows bone loss and improves bone microstructural properties by decreasing bone turnover.

  18. Decreased Bone Volume and Bone Mineral Density in the Tibial Trabecular Bone Is Associated with Per2 Gene by 405 nm Laser Stimulation

    PubMed Central

    Yoo, Yeong-Min; Lee, Myung-Han; Park, Ji Hyung; Seo, Dong-Hyun; Lee, Sangyeob; Jung, Byungjo; Kim, Han Sung; Bae, Kiho

    2015-01-01

    Low-level laser therapy/treatment (LLLT) using a minimally invasive laser needle system (MILNS) might enhance bone formation and suppress bone resorption. In this study, the use of 405 nm LLLT led to decreases in bone volume and bone mineral density (BMD) of tibial trabecular bone in wild-type (WT) and Per2 knockout (KO) mice. Bone volume and bone mineral density of tibial trabecular bone was decreased by 405 nm LLLT in Per2 KO compared to WT mice at two and four weeks. To determine the reduction in tibial bone, mRNA expressions of alkaline phosphatase (ALP) and Per2 were investigated at four weeks after 405 nm laser stimulation using MILNS. ALP gene expression was significantly reduced in the LLLT-stimulated right tibial bone of WT and Per2 KO mice compared to the non-irradiated left tibia (p < 0.001). Per2 mRNA expression in WT mice was significantly reduced in the LLLT-stimulated right tibial bone compared to the non-irradiated left tibia (p < 0.001). To identify the decrease in tibial bone mediated by the Per2 gene, levels of runt-related transcription factor 2 (Runx2) and ALP mRNAs were determined in non-irradiated WT and Per2 KO mice. These results demonstrated significant downregulation of Runx2 and ALP mRNA levels in Per2 KO mice (p < 0.001). Therefore, the reduction in tibial trabecular bone resulting from 405 nm LLLT using MILNS might be associated with Per2 gene expression. PMID:26580614

  19. Comparison of nutritional intake, body composition, bone mineral density, and isokinetic strength in collegiate female dancers.

    PubMed

    Lim, Se-Na; Chai, Joo-Hee; Song, Jong Kook; Seo, Myong-Won; Kim, Hyun-Bae

    2015-12-01

    This study compared nutritional intake, body composition, bone mineral density, and isokinetic strength by dance type in collegiate female dancers. The study subjects included Korean dancers (n=12), ballet dancers (n=13), contemporary dancers (n=8), and controls (n=12). Nutritional intake was estimated using the Computer Aided Nutritional Analysis Program. Body composition and bone mineral density were measured using dual-energy X-ray absorptiometry. Isokinetic knee joint strength was measured by Cybex 770-NORM. All statistical analyses were performed by SAS 9.2. Means and standard deviations were calculated using descriptive statistics. One-way analysis of variance was applied to evaluate nutritional intake, body composition, bone mineral density, and isokinetic strength differences. Duncan multiple range test was used for post hoc testing. A level of significance was set at P<0.05. The study results indicated no significant differences in nutritional in-take among dancer types. Despite no significant differences in body composition among dancer types, contemporary and ballet dancers had lower body fat percentages than controls (P<0.05). No significant differences were seen in bone mineral density and bone mineral contents among dancer types. No significant differences were found in isokinetic strength in right or left knee flexion and extension at 60°/sec (P<0.05). There were significant differences in body composition and isokinetic strength between dancer groups and the control group. Further studies of different professional dance type and more scientific methods of dance training are needed.

  20. Comparison of nutritional intake, body composition, bone mineral density, and isokinetic strength in collegiate female dancers

    PubMed Central

    Lim, Se-Na; Chai, Joo-Hee; Song, Jong Kook; Seo, Myong-Won; Kim, Hyun-Bae

    2015-01-01

    This study compared nutritional intake, body composition, bone mineral density, and isokinetic strength by dance type in collegiate female dancers. The study subjects included Korean dancers (n=12), ballet dancers (n=13), contemporary dancers (n=8), and controls (n=12). Nutritional intake was estimated using the Computer Aided Nutritional Analysis Program. Body composition and bone mineral density were measured using dual-energy X-ray absorptiometry. Isokinetic knee joint strength was measured by Cybex 770-NORM. All statistical analyses were performed by SAS 9.2. Means and standard deviations were calculated using descriptive statistics. One-way analysis of variance was applied to evaluate nutritional intake, body composition, bone mineral density, and isokinetic strength differences. Duncan multiple range test was used for post hoc testing. A level of significance was set at P<0.05. The study results indicated no significant differences in nutritional in-take among dancer types. Despite no significant differences in body composition among dancer types, contemporary and ballet dancers had lower body fat percentages than controls (P<0.05). No significant differences were seen in bone mineral density and bone mineral contents among dancer types. No significant differences were found in isokinetic strength in right or left knee flexion and extension at 60°/sec (P<0.05). There were significant differences in body composition and isokinetic strength between dancer groups and the control group. Further studies of different professional dance type and more scientific methods of dance training are needed. PMID:26730387

  1. The Impairment of Osteogenesis in Bone Sialoprotein (BSP) Knockout Calvaria Cell Cultures Is Cell Density Dependent

    PubMed Central

    Bouet, Guenaelle; Bouleftour, Wafa; Juignet, Laura; Linossier, Marie-Thérèse; Thomas, Mireille; Vanden-Bossche, Arnaud; Aubin, Jane E.; Vico, Laurence; Marchat, David; Malaval, Luc

    2015-01-01

    Bone sialoprotein (BSP) belongs to the "small integrin-binding ligand N-linked glycoprotein" (SIBLING) family, whose members interact with bone cells and bone mineral. BSP is strongly expressed in bone and we previously showed that BSP knockout (BSP-/-) mice have a higher bone mass than wild type (BSP+/+) littermates, with lower bone remodelling. Because baseline bone formation activity is constitutively lower in BSP-/- mice, we studied the impact of the absence of BSP on in vitro osteogenesis in mouse calvaria cell (MCC) cultures. MCC BSP-/- cultures exhibit fewer fibroblast (CFU-F), preosteoblast (CFU-ALP) and osteoblast colonies (bone nodules) than wild type, indicative of a lower number of osteoprogenitors. No mineralized colonies were observed in BSP-/- cultures, along with little/no expression of either osteogenic markers or SIBLING proteins MEPE or DMP1. Osteopontin (OPN) is the only SIBLING expressed in standard density BSP-/- culture, at higher levels than in wild type in early culture times. At higher plating density, the effects of the absence of BSP were partly rescued, with resumed expression of osteoblast markers and cognate SIBLING proteins, and mineralization of the mutant cultures. OPN expression and amount are further increased in high density BSP-/- cultures, while PHEX and CatB expression are differentiatlly regulated in a manner that may favor mineralization. Altogether, we found that BSP regulates mouse calvaria osteoblast cell clonogenicity, differentiation and activity in vitro in a cell density dependent manner, consistent with the effective skeletogenesis but the low levels of bone formation observed in vivo. The BSP knockout bone microenvironment may alter the proliferation/cell fate of early osteoprogenitors. PMID:25710686

  2. Magnesium intake mediates the association between bone mineral density and lean soft tissue in elite swimmers.

    PubMed

    Matias, Catarina N; Santos, Diana A; Monteiro, Cristina P; Vasco, Ana M; Baptista, Fátima; Sardinha, Luís B; Laires, Maria J; Silva, Analiza M

    2012-01-01

    Magnesium (Mg) deficiency has been associated with bone disorders. Physical activity is also crucial for bone mineralization. Bone mass loss has been observed to be accelerated in subjects with low Mg intake. We aim to understand if Mg intake mediates the association between bone mineral density (BMD) and lean soft tissue (LST) in elite swimmers. Seventeen elite swimmers (eight males; nine females) were evaluated. Bone mineral content, BMD, LST, and fat mass were assessed using dual energy X-ray absorptiometry. Energy and nutrient intake were assessed during a seven-day period and analyzed with Food Processor SQL. Males presented lower values than the normative data for BMD. Mg, phosphorus (P) and vitamin D intake were significantly lower than the recommended daily allowance. A linear regression model demonstrated a significant association between LST and BMD. When Mg intake was included, we observed that this was a significant, independent predictor of BMD, with a significant increase of 24% in the R(2) of the initial predictive model. When adjusted for energy, vitamin D, calcium, and P intake, Mg remained a significant predictor of BMD. In conclusion, young athletes engaged in low impact sports, should pay special attention to Mg intake, given its potential role in bone mineral mass acquisition during growth.

  3. The Kidney-Vascular-Bone Axis in the Chronic Kidney Disease-Mineral Bone Disorder

    PubMed Central

    Seifert, Michael E.; Hruska, Keith A.

    2015-01-01

    The last 25 years have been characterized by dramatic improvements in short-term patient and allograft survival after kidney transplantation. Long-term patient and allograft survival remains limited by cardiovascular disease and chronic allograft injury, among other factors. Cardiovascular disease remains a significant contributor to mortality in native chronic kidney disease as well, as cardiovascular mortality in chronic kidney disease more than doubles that of the general population. The chronic kidney disease-mineral bone disorder (CKD-MBD) is a syndrome recently coined to embody the biochemical, skeletal, and cardiovascular pathophysiology that results from disrupting the complex systems biology between the kidney, skeleton, and cardiovascular system in native and transplant kidney disease. The CKD-MBD is a unique kidney disease-specific syndrome containing novel cardiovascular risk factors, with an impact reaching far beyond traditional notions of renal osteodystrophy and hyperparathyroidism. This Overview reviews current knowledge of the pathophysiology of the CKD-MBD, including emerging concepts surrounding the importance of circulating pathogenic factors released from the injured kidney that directly cause cardiovascular disease in native and transplant chronic kidney disease, with potential application to mechanisms of chronic allograft injury and vasculopathy. PMID:26356179

  4. The Kidney-Vascular-Bone Axis in the Chronic Kidney Disease-Mineral Bone Disorder.

    PubMed

    Seifert, Michael E; Hruska, Keith A

    2016-03-01

    The last 25 years have been characterized by dramatic improvements in short-term patient and allograft survival after kidney transplantation. Long-term patient and allograft survival remains limited by cardiovascular disease and chronic allograft injury, among other factors. Cardiovascular disease remains a significant contributor to mortality in native chronic kidney disease as well as cardiovascular mortality in chronic kidney disease more than doubles that of the general population. The chronic kidney disease (CKD)-mineral bone disorder (MBD) is a syndrome recently coined to embody the biochemical, skeletal, and cardiovascular pathophysiology that results from disrupting the complex systems biology between the kidney, skeleton, and cardiovascular system in native and transplant kidney disease. The CKD-MBD is a unique kidney disease-specific syndrome containing novel cardiovascular risk factors, with an impact reaching far beyond traditional notions of renal osteodystrophy and hyperparathyroidism. This overview reviews current knowledge of the pathophysiology of the CKD-MBD, including emerging concepts surrounding the importance of circulating pathogenic factors released from the injured kidney that directly cause cardiovascular disease in native and transplant chronic kidney disease, with potential application to mechanisms of chronic allograft injury and vasculopathy.

  5. Feeding soy protein isolate prevents impairment of bone acquisition by western diets as a result of insulin signaling in bone

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Excessive consumption of high fat/high cholesterol “Western” diets during postnatal life results in increased energy intake, development of obesity and systemic insulin resistance. However, how this diet impairs bone development and remodeling is not well understood, and no effective dietary interve...

  6. Investigation of the relationship between low environmental exposure to metals and bone mineral density, bone resorption and renal function.

    PubMed

    Callan, A C; Devine, A; Qi, L; Ng, J C; Hinwood, A L

    2015-07-01

    Environmental exposure to metals has been linked to adverse health outcomes. Exposure to cadmium has been associated with decreased bone density, an increased risk of osteoporotic fracture and possible renal dysfunction. Older women are a group at risk of renal and bone density impacts and exposure to metals may be an important risk factor for these health outcomes. This study was a cross sectional study of 77 women aged 50 years and above examining the relationship between metals exposure and renal and bone health. Urinary and blood metals concentrations, plasma creatinine, iron, ferritin and transferrin were measured in these subjects. Bone biomarkers assessed included the pyridinium crosslinks, pyridinoline and deoxypyridinoline measured by ELISA. Renal function was assessed using eGFR and KIM-1. Whole body, hip and lumbar spine bone mineral density was assessed using DEXA. Blood and urinary metals concentrations were generally low in the subjects, with a median urinary cadmium concentration of 0.26 μg/g creatinine (range <0.065-1.03 μg/g). Urinary cadmium was found to be a significant predictor of bone mineral density at whole body, lumber spine, total hip and femoral neck, with increasing urinary Cd concentrations associated with decreased bone density. Urinary cadmium and aluminium concentrations were positively correlated with bone resorption whilst blood zinc and mercury concentrations were negatively correlated. Urinary aluminium was positively correlated with KIM-1 concentrations, a marker of early kidney damage, however blood zinc concentrations were significantly negatively correlated with this biomarker. This study provides additional support for low cadmium exposure being of concern for the health of older women. Further investigation into the role of exposure to other metals on bone and renal health is warranted.

  7. Chemistry of bone mineral, based on the hypermineralized rostrum of the beaked whale Mesoplodon densirostris

    PubMed Central

    Li, Zhen

    2014-01-01

    Carbonate-substituted hydroxylapatite is the inorganic component in bone. The nanometer size of bone crystallites and their interweaving with subequal volumes of collagen fibrils make the chemical analysis of the bone mineral extremely difficult. The few chemical analyses that are available commonly were made on ashed bone, which, in addition to mineral, also includes chemical residues of collagen. For the present study, we chose the rostrum of the whale Mesoplodon densirostris. Its mineral content of up to 96 wt% makes it an ideal material for pursuing the chemistry of bioapatite within bone. Both bulk (X-ray fluorescence, thermogravimetry, and carbon analysis) and point analyses and element mapping (electron microprobe) were applied to this densest of bone materials. Its bioapatite has an average carbonate content of ~8 wt% and an average Ca/P atomic ratio of 1.7. The rostrum shows extremely low-concentration trace elements (Al, Si, Fe, Ti and Sr) and some minor elements (K and Cl) as in typical bone materials. Homogeneity of elemental distribution is demonstrated in typical mineral-dominated areas within the rostrum sections except around a few vascular holes and vessels. The very good correlation between electron microprobe point analyses and the XRF bulk analyses of the rostrum indicate the latter to be a useful chemical model of bone mineral. The bulk analysis shows that the bioapatite in the rostrum has an average composition of (Ca8.40Mg0.20Na0.54)[(PO4)4.87(CO3)1.13] (OH)0.87. PMID:25484370

  8. The role of Dkk1 in bone mass regulation: correlating serum Dkk1 expression with bone mineral density.

    PubMed

    Butler, Joseph S; Murray, David W; Hurson, Conor J; O'Brien, Julie; Doran, Peter P; O'Byrne, John M

    2011-03-01

    The Wnt/β-catenin pathway is a major signaling cascade in bone biology, playing a key role in regulating bone development and remodeling, with aberrations in signaling resulting in disturbances in bone mass. The objectives of our study were to correlate serum Dkk1 expression with bone mineral density (BMD) and assess the potential role of Dkk1 as a serological marker of bone mass. Serum was collected from a cohort of patients (n = 36), 18 patients with a reduced BMD and 18 control patients. Serum Dkk1 expression as quantified by ELISA was correlated with lumbar and femoral t- and z-scores. Serum Dkk1 concentration in the osteoporosis group was significantly higher than control group (941 ± 116 vs. 558 ± 47 pg/ml, p < 0.01). Serum Dkk1 expression was highly correlated with bone mass variables with inverse associations found between serum Dkk1 expression and lumbar t-score (r = -0.34, p = 0.00433), lumbar z-score (r = -0.22, p = 0.1907), femur t-score (r = -0.42, p = 0.0101), and femur z-score (r = -0.43, p = 0.0089). Our data further emphasizes the pivotal role played by Wnt/β-catenin signaling in bone mass regulation. Dkk1, a powerful antagonist of canonical Wnt signaling, may have a role to play as a serological marker for disorders of bone mass, warranting further evaluation.

  9. Value of bone scintigraphy for detection and ageing of vertebral fractures in patients with severe osteoporosis and correlation between bone scintigraphy and mineral bone density.

    PubMed

    Kucukalic-Selimovic, Elma; Begic, Amela

    2004-01-01

    Osteoporosis is the most common of the metabolic bone diseases, and is an important cause of morbidity in the elderly. Bone scintigraphy is used to detect skeletal lesions at the earliest possible time, to monitor the course of the skeletal discase and to evaluate the metabolic activity of skeletal lesions. The aim of this study was to determine, by using the bone scan age of vertebral fractures in patients with severe osteoporosis, and make correlation between bone scintigraphy and mineral bone density. Material and methods 30 female patients were studied with bone scintigraphy after BMD.BMD was measurred with DEXA Hologic QDR 4500 Elite System. Correlation between T-score and uptake of radiofarmaceutical (Tc-99mMDP) was 0.849, and it was high. Intensity of uptake of Tc-99m MDP scintigraphy is an accurate method for the detection and ageing of fractures in osteoporotic patients.

  10. Prediction of Areal Bone Mineral Density and Bone Mineral Content in Children and Adolescents Living With HIV Based on Anthropometric Variables.

    PubMed

    Lima, Luiz Rodrigo Augustemak de; Krug, Rodrigo de Rosso; Silva, Rosane Carla Rosendo da; Carvalho, Aroldo Prohmann de; González-Chica, David Alejandro; Back, Isabela de Carlos; Petroski, Edio Luiz

    2016-10-01

    Children and adolescents living with HIV have low bone mass for age. There are reliable and accurate methods for evaluation of bone mass, however, alternative methods are necessary, especially, for application in limited-resource scenarios. Anthropometry is a noninvasive and low cost method that can predict bone mass in healthy youths. The aim of the study was to develop predictive equations for bone mineral content and bone mineral density in children and adolescents living with HIV based on anthropometric variables. Forty-eight children and adolescents of both sexes (24 females) from 7 to 17 years, living in greater Florianopolis area, Santa Catarina, Brazil, who were under clinical follow-up at "Hospital Infantil Joana de Gusmão", participated in the study. Dual-energy X-ray absorptiometry was used to evaluate whole-body bone mineral content (BMC) and areal bone mineral density (aBMD). Height, body weight, bone diameters, arm circumference, and triceps skinfold were measured and the body mass index and arm muscle area were calculated. Multiple regression models were fitted to predict BMC and aBMD, using backward selection (p ≥ 0.05). Two predictive models with high R(2) values (84%-94%) were developed. Model 1 to estimate aBMD [Y = -0.1450124 + (height × 0.0033807) + (age × 0.0146381) + (body mass index × 0.0158838) + (skin color × 0.0421068)], and model 2 to estimate BMC [Y = 1095.1 + (body weight × 45.66973) + (age × 31.36516) + (arm circumference × -53.27204) + (femoral diameter × -9.594018)].The predictive models using anthropometry provided reliable estimates and can be useful to monitor aBMD and BMC in children and adolescents living with human immunodeficiency virus where limited resources are available.

  11. Techniques to assess bone ultrastructure organization: orientation and arrangement of mineralized collagen fibrils

    PubMed Central

    Georgiadis, Marios; Müller, Ralph; Schneider, Philipp

    2016-01-01

    Bone's remarkable mechanical properties are a result of its hierarchical structure. The mineralized collagen fibrils, made up of collagen fibrils and crystal platelets, are bone's building blocks at an ultrastructural level. The organization of bone's ultrastructure with respect to the orientation and arrangement of mineralized collagen fibrils has been the matter of numerous studies based on a variety of imaging techniques in the past decades. These techniques either exploit physical principles, such as polarization, diffraction or scattering to examine bone ultrastructure orientation and arrangement, or directly image the fibrils at the sub-micrometre scale. They make use of diverse probes such as visible light, X-rays and electrons at different scales, from centimetres down to nanometres. They allow imaging of bone sections or surfaces in two dimensions or investigating bone tissue truly in three dimensions, in vivo or ex vivo, and sometimes in combination with in situ mechanical experiments. The purpose of this review is to summarize and discuss this broad range of imaging techniques and the different modalities of their use, in order to discuss their advantages and limitations for the assessment of bone ultrastructure organization with respect to the orientation and arrangement of mineralized collagen fibrils. PMID:27335222

  12. Techniques to assess bone ultrastructure organization: orientation and arrangement of mineralized collagen fibrils.

    PubMed

    Georgiadis, Marios; Müller, Ralph; Schneider, Philipp

    2016-06-01

    Bone's remarkable mechanical properties are a result of its hierarchical structure. The mineralized collagen fibrils, made up of collagen fibrils and crystal platelets, are bone's building blocks at an ultrastructural level. The organization of bone's ultrastructure with respect to the orientation and arrangement of mineralized collagen fibrils has been the matter of numerous studies based on a variety of imaging techniques in the past decades. These techniques either exploit physical principles, such as polarization, diffraction or scattering to examine bone ultrastructure orientation and arrangement, or directly image the fibrils at the sub-micrometre scale. They make use of diverse probes such as visible light, X-rays and electrons at different scales, from centimetres down to nanometres. They allow imaging of bone sections or surfaces in two dimensions or investigating bone tissue truly in three dimensions, in vivo or ex vivo, and sometimes in combination with in situ mechanical experiments. The purpose of this review is to summarize and discuss this broad range of imaging techniques and the different modalities of their use, in order to discuss their advantages and limitations for the assessment of bone ultrastructure organization with respect to the orientation and arrangement of mineralized collagen fibrils.

  13. Bone

    NASA Astrophysics Data System (ADS)

    Helmberger, Thomas K.; Hoffmann, Ralf-Thorsten

    The typical clinical signs in bone tumours are pain, destruction and destabilization, immobilization, neurologic deficits, and finally functional impairment. Primary malignant bone tumours are a rare entity, accounting for about 0.2% of all malignancies. Also benign primary bone tumours are in total rare and mostly asymptomatic. The most common symptomatic benign bone tumour is osteoid osteoma with an incidence of 1:2000.

  14. Adipocyte Accumulation in the Bone Marrow during Obesity and Aging Impairs Stem Cell-Based Hematopoietic and Bone Regeneration.

    PubMed

    Ambrosi, Thomas H; Scialdone, Antonio; Graja, Antonia; Gohlke, Sabrina; Jank, Anne-Marie; Bocian, Carla; Woelk, Lena; Fan, Hua; Logan, Darren W; Schürmann, Annette; Saraiva, Luis R; Schulz, Tim J

    2017-03-13

    Aging and obesity induce ectopic adipocyte accumulation in bone marrow cavities. This process is thought to impair osteogenic and hematopoietic regeneration. Here we specify the cellular identities of the adipogenic and osteogenic lineages of the bone. While aging impairs the osteogenic lineage, high-fat diet feeding activates expansion of the adipogenic lineage, an effect that is significantly enhanced in aged animals. We further describe a mesenchymal sub-population with stem cell-like characteristics that gives rise to both lineages and, at the same time, acts as a principal component of the hematopoietic niche by promoting competitive repopulation following lethal irradiation. Conversely, bone-resident cells committed to the adipocytic lineage inhibit hematopoiesis and bone healing, potentially by producing excessive amounts of Dipeptidyl peptidase-4, a protease that is a target of diabetes therapies. These studies delineate the molecular identity of the bone-resident adipocytic lineage, and they establish its involvement in age-dependent dysfunction of bone and hematopoietic regeneration.

  15. Clodronate stimulates bone formation as well as inhibits bone resorption and increases bone mineral density in rats fed a low-calcium diet.

    PubMed

    Horie, Daisuke; Takahashi, Mariko; Aoki, Kazuhiro; Ohya, Keiichi

    2003-03-01

    The pharmacological actions of bisphosphonates are due to the inhibitory effects on bone resorption, but little is known about the bisphosphonate action on bone formation. The purpose of this study is to elucidate the actions of bisphosphonates, clodronate, on bone formation in the experimental in vivo and in vitro rat models. The bone mineral density (BMD) was decreased in the rats fed a low-calcium diet (0.05% Ca) for 6 days compared with the rats fed a normal-calcium diet (0.5% Ca). The decrease in BMD was suppressed in the 2 mgP/day and the 4 mgP/day clodronate administrations. Bone formation rate (BFR) in rats fed a low-calcium diet was significantly increased compared with the rats fed a normal-calcium diet, and the 2 mgP clodronate administration further increased the BFR. In the cultured rat bone marrow cells, the area of mineralized nodules was significantly increased at 10(-7) and 10(-6) M clodronate, but high concentration of clodronate decreased the area. From these results, it is concluded that clodronate stimulates bone formation when the drug was given to a rat with a relatively lower dose that is sufficient to prevent bone resorption and that this effect may be due to the stimulatory effect on the differentiation process of osteoblasts.

  16. A Piece of the Puzzle: The Bone Health Index of the BoneXpert Software Reflects Cortical Bone Mineral Density in Pediatric and Adolescent Patients

    PubMed Central

    Schündeln, Michael M.; Marschke, Laura; Bauer, Jens J.; Hauffa, Pia K.; Schweiger, Bernd; Führer-Sakel, Dagmar; Lahner, Harald; Poeppel, Thorsten D.; Kiewert, Cordula; Hauffa, Berthold P.; Grasemann, Corinna

    2016-01-01

    Introduction Suspected osteopathology in chronically ill children often necessitates the assessment of bone mineral density. The most frequently used methods are dual-energy X-ray-absorption (DXA) and peripheral quantitative computed tomography (pQCT). The BoneXpert software provides an automated radiogrammatic method to assess skeletal age from digitalized X-rays of the left hand. Furthermore, the program calculates the Bone Health Index (BHI), a measure of cortical thickness and mineralization, which is obtained from indices of three metacarpal bones. In our study, we analyzed the manner in which BHI information provided by BoneXpert compares with DXA or pQCT measurements in youths. Study Design The BHI was retrospectively obtained using digitalized X-rays of the left hand and compared with the results of 203 corresponding DXA readings (Lunar Prodigy, GE Healthcare) of the lumbar vertebrae and femur as well as 117 pQCT readings (XCT 900, Stratec) of the distal radius. Results The BHI values showed a strong positive correlation with the DXA readings at each and all lumbar vertebrae (L1 –L4: r = 0.73; P < 0.0001). The age-adjusted Z-score of L1 –L4 and the height-adjusted score showed a positive correlation with the BHI-SDS (standard deviation score, r = 0.23; P < 0.002 and r = 0.27; P < 0.001, respectively). Total bone mineral density, as assessed via pQCT, also positively correlated with the BHI (r = 0.39; P < 0.0001), but the trabecular values displayed only a weak correlation. Conclusions The BHI obtained using BoneXpert can be a useful parameter in the assessment of bone health in children in most cases. This technique provides observer-independent information on cortical thickness and mineralization based on X-ray imaging of the hands. PMID:27014874

  17. Inhibition of GSK-3β rescues the impairments in bone formation and mechanical properties associated with fracture healing in osteoblast selective connexin 43 deficient mice.

    PubMed

    Loiselle, Alayna E; Lloyd, Shane A J; Paul, Emmanuel M; Lewis, Gregory S; Donahue, Henry J

    2013-01-01

    Connexin 43 (Cx43) is the most abundant gap junction protein in bone and is required for osteoblastic differentiation and bone homeostasis. During fracture healing, Cx43 is abundantly expressed in osteoblasts and osteocytes, while Cx43 deficiency impairs bone formation and healing. In the present study we selectively deleted Cx43 in the osteoblastic lineage from immature osteoblasts through osteocytes and tested the hypothesis that Cx43 deficiency results in delayed osteoblastic differentiation and impaired restoration of biomechanical properties due to attenuated β-catenin expression relative to wild type littermates. Here we show that Cx43 deficiency results in alterations in the mineralization and remodeling phases of healing. In Cx43 deficient fractures the mineralization phase is marked by delayed expression of osteogenic genes. Additionally, the decrease in the RankL/Opg ratio, osteoclast number and osteoclast size suggest decreased osteoclast bone resorption and remodeling. These changes in healing result in functional deficits as shown by a decrease in ultimate torque at failure. Consistent with these impairments in healing, β-catenin expression is attenuated in Cx43 deficient fractures at 14 and 21 days, while Sclerostin (Sost) expression, a negative regulator of bone formation is increased in Cx43cKO fractures at 21 days, as is GSK-3β, a key component of the β-catenin proteasomal degradation complex. Furthermore, we show that alterations in healing in Cx43 deficient fractures can be rescued by inhibiting GSK-3β activity using Lithium Chloride (LiCl). Treatment of Cx43 deficient mice with LiCl restores both normal bone formation and mechanical properties relative to LiCl treated WT fractures. This study suggests that Cx43 is a potential therapeutic target to enhance fracture healing and identifies a previously unknown role for Cx43 in regulating β-catenin expression and thus bone formation during fracture repair.

  18. Aging impairs peritoneal but not bone marrow-derived macrophage phagocytosis.

    PubMed

    Linehan, Eimear; Dombrowski, Yvonne; Snoddy, Rachel; Fallon, Padraic G; Kissenpfennig, Adrien; Fitzgerald, Denise C

    2014-08-01

    Aging results in deterioration of the immune system, which is associated with increased susceptibility to infection and impaired wound healing in the elderly. Phagocytosis is an essential process in both wound healing and immune defence. As such, age-related impairments in phagocytosis impact on the health of the elderly population. Phagocytic efficiency in peritoneal macrophages, bone marrow-derived macrophages and bone marrow monocytes from young and old mice was investigated. Aging significantly impaired phagocytosis by peritoneal macrophages, both in vitro and in vivo. However, bone marrow-derived macrophages and bone marrow monocytes did not exhibit age-related impairments in phagocytosis, suggesting no intrinsic defect in these cells. We sought to investigate underlying mechanisms in age-related impairments in phagocytosis by peritoneal macrophages. We hypothesized that microenvironmental factors in the peritoneum of old mice impaired macrophage phagocytosis. Indeed, macrophages from young mice injected into the peritoneum of old mice exhibited impaired phagocytosis. Proportions of peritoneal immune cells were characterized, and striking increases in numbers of T cells, B1 and B2 cells were observed in the peritoneum of old mice compared with young mice. In addition, B cell-derived IL-10 was increased in resting and LPS-activated peritoneal cell cultures from old mice. These data demonstrate that aging impairs phagocytosis by tissue-resident peritoneal macrophages, but not by bone marrow-derived macrophages/monocytes, and suggest that age-related defects in macrophage phagocytosis may be due to extrinsic factors in the tissue microenvironment. As such, defects may be reversible and macrophages could be targeted therapeutically in order to boost immune function in the elderly.

  19. Comparison of radiograph-based texture analysis and bone mineral density with three-dimensional microarchitecture of trabecular bone

    SciTech Connect

    Ranjanomennahary, P.; Ghalila, S. Sevestre; Malouche, D; Marchadier, A.; Rachidi, M.; Benhamou, Cl.; Chappard, C.

    2011-01-15

    Purpose: Hip fracture is a serious health problem and textural methods are being developed to assess bone quality. The authors aimed to perform textural analysis at femur on high-resolution digital radiographs compared to three-dimensional (3D) microarchitecture comparatively to bone mineral density. Methods: Sixteen cadaveric femurs were imaged with an x-ray device using a C-MOS sensor. One 17 mm square region of interest (ROI) was selected in the femoral head (FH) and one in the great trochanter (GT). Two-dimensional (2D) textural features from the co-occurrence matrices were extracted. Site-matched measurements of bone mineral density were performed. Inside each ROI, a 16 mm diameter core was extracted. Apparent density (D{sub app}) and bone volume proportion (BV/TV{sub Arch}) were measured from a defatted bone core using Archimedes' principle. Microcomputed tomography images of the entire length of the core were obtained (Skyscan 1072) at 19.8 {mu}m of resolution and usual 3D morphometric parameters were computed on the binary volume after calibration from BV/TV{sub Arch}. Then, bone surface/bone volume, trabecular thickness, trabecular separation, and trabecular number were obtained by direct methods without model assumption and the structure model index was calculated. Results: In univariate analysis, the correlation coefficients between 2D textural features and 3D morphological parameters reached 0.83 at the FH and 0.79 at the GT. In multivariate canonical correlation analysis, coefficients of the first component reached 0.95 at the FH and 0.88 at the GT. Conclusions: Digital radiographs, widely available and economically viable, are an alternative method for evaluating bone microarchitectural structure.

  20. Effects of lactation on bone mineral content in healthy postpartum women

    SciTech Connect

    Hayslip, C.C.; Klein, T.A.; Wray, H.L.; Duncan, W.E.

    1989-04-01

    Bone mineral contents were estimated by dual photon absorptiometry of the lumbar spine (L2-L4) and single photon absorptiometry of the mid- and distal radius in 19 healthy women on their second postpartum day and at 6 months postpartum. All bone mineral measurements were performed by one technician, and the single and dual photon absorptiometry results were read by one observer. Daily oral calcium intakes were estimated from dietary histories obtained by a dietitian. Twelve women who breast-fed exclusively throughout the first 6 months postpartum were compared with seven formula-feeding women who did not breast-feed or who breast-fed for less than 3 months postpartum. No differences were found in age, parity, height, weight, or daily calcium intake between the breast- and formula-feeding women. Breast-feeding women had a significant decrease (averaging 6.5%) in bone mineral of the lumbar spine at 6 months postpartum as compared with 2 days postpartum (1.14 +/- 0.03 versus 1.22 +/- 0.03 g/cm2, mean +/- SEM; P less than .001), whereas no significant change occurred in the formula-feeding women at 6 months (1.24 +/- 0.03 versus 1.26 +/- 0.04 g/cm2). At 6 months postpartum, the breast-feeding women had a significantly lower mean bone mineral content of the lumbar spine than did formula-feeding women (P less than .05). No significant changes were noted in bone mineral content of the mid- or distal radius in either group of women during the period of evaluation. We conclude that during the first 6 months postpartum, breast-feeding is associated with bone mineral loss from the lumbar spine, but not from the mid- or distal radius.

  1. Bone resorption and mineral excretion in rats during spaceflight

    NASA Technical Reports Server (NTRS)

    Cann, C. E.; Adachi, R. R.

    1983-01-01

    Bone resorption was measured directly in flight and synchronous control rats during COSMOS 1129. Continuous tracer administration techniques were used, with replacement of dietary calcium with isotopically enriched Ca-40 and measurement by neutron activation analysis of the Ca-48 released by the skeleton. There is no large change in bone resorption in rats at the end of 20 days of spaceflight as has been found for bone formation. Based on the time course of changes, the measured 20-25 percent decrease in resorption is probably secondary to a decrease in total body calcium turnover. The excretion of sodium, potassium, and zinc all increase during flight, sodium and potassium to a level four to five times control values.

  2. Mathematical modeling of the effects of CK2.3 on mineralization in osteoporotic bone

    PubMed Central

    Lisberg, A; Ellis, R; Nicholson, K; Moku, P; Swarup, A; Dhurjati, P

    2017-01-01

    Osteoporosis is caused by decreased bone mineral density (BMD) and new treatments for this disease are desperately needed. Bone morphogenetic protein 2 (BMP2) is crucial for bone formation. The mimetic peptide CK2.3 acts downstream of BMP2 and increases BMD when injected systemically into the tail vein of mice. However, the most effective dosage needed to induce BMD in humans is unknown. We developed a mathematical model for CK2.3‐dependent bone mineralization. We used a physiologically based pharmacokinetic (PBPK) model to derive the CK2.3 concentration needed to increase BMD. Based on our results, the ideal dose of CK2.3 for a healthy individual to achieve the maximum increase of mineralization was about 409 µM injected in 500 µL volume, while dosage for osteoporosis patients was about 990 µM. This model showed that CK2.3 could increase the average area of bone mineralization in patients and in healthy adults. PMID:28181418

  3. Probabilistic Failure Analysis of Bone Using a Finite Element Model of Mineral-Collagen Composites

    PubMed Central

    Dong, X. Neil; Guda, Teja; Millwater, Harry R.; Wang, Xiaodu

    2009-01-01

    Microdamage accumulation is a major pathway for energy dissipation during the post-yield deformation of bone. In this study, a two-dimensional probabilistic finite element model of a mineral-collagen composite was developed to investigate the influence of the tissue and ultrastructural properties of bone on the evolution of microdamage from an initial defect in tension. The probabilistic failure analyses indicated that the microdamage progression would be along the plane of the initial defect when the debonding at mineral-collagen interfaces was either absent or limited in the vicinity of the defect. In this case, the formation of a linear microcrack would be facilitated. However, the microdamage progression would be scattered away from the initial defect plane if interfacial debonding takes place at a large scale. This would suggest the possible formation of diffuse damage. In addition to interfacial debonding, the sensitivity analyses indicated that the microdamage progression was also dependent on the other material and ultrastructural properties of bone. The intensity of stress concentration accompanied with microdamage progression was more sensitive to the elastic modulus of the mineral phase and the nonlinearity of the collagen phase, whereas the scattering of failure location was largely dependent on the mineral to collagen ratio and the nonlinearity of the collagen phase. The findings of this study may help understanding the post-yield behavior of bone at the ultrastructural level and shed light on the underlying mechanism of bone fractures. PMID:19058806

  4. The role of bone in CKD-mediated mineral and vascular disease.

    PubMed

    Khouzam, Nadine M; Wesseling-Perry, Katherine; Salusky, Isidro B

    2015-09-01

    Cardiovascular disease is the leading cause of death in pediatric patients with chronic kidney disease (CKD), and vascular calcifications start early in the course of CKD. Based on the growing body of evidence that alterations of bone and mineral metabolism and the therapies designed to treat the skeletal consequences of CKD are linked to cardiovascular calcifications, the Kidney Disease, Improving Global Outcomes (KDIGO) working group redefined renal osteodystrophy as a systemic disorder of mineral and bone metabolism due to CKD, and this newly defined disorder is now known as "chronic kidney disease-mineral bone disorder (CKD-MBD)". Elevated fibroblast growth factor 23 (FGF23), a bone-derived protein, is the first biochemical abnormality to be associated with CKD-MBD, and high FGF23 levels correlate with increased cardiovascular morbidity and mortality, suggesting that bone is central to both initiating and perpetuating the abnormal mineral metabolism and vascular disease in CKD. The current standard therapies for CKD-MBD affect FGF23 levels differently; non-calcium-based binders with or without concurrent use of dietary phosphate restriction reduce FGF23 levels, while calcium-based binders seem to either increase or have no effect on FGF23 levels. Active vitamin D sterols increase FGF23 levels, whereas therapy with calcimimetics decreases FGF23 levels. Thus, the appropriate therapy that will minimize the rise in FGF23 and prevent cardiovascular morbidity remains to be defined.

  5. Mineralization of human bone tissue under hypokinesia and physical exercise with calcium supplements

    NASA Astrophysics Data System (ADS)

    Zorbas, Yan G.; Verentsov, Grigori E.; Abratov, Nikolai I.

    It has been suggested that physical exercise and calcium supplements may be used to prevent demineralization of bone tissue under hypokinesia (diminished muscular activity). Thus, the aim of this study was to determine mineral content of bones of 12 physically healthy men aged 19-24 years under 90 days of hypokinesia and intensive physical exercise (PE) with calcium lactate (C) supplements. They were divided into experimental and control groups with 6 men in each. The experimental group of men were subjected to hypokinesia (HK) and intensive PE and took 650 mg C 6 times per day; the control group was placed under pure HK, i.e. without the use of any preventive measures. The mineral content of different bone tissues was measured with a densitometric X-ray method in milligrams of calcium per 1 mm 3 before and after exposure to HK. The level of bone density of the examined bone tissues decreased by 7-9% and 5-7% for the control and experimental groups of men, respectively. A statistical analysis revealed that the reduction of bone mineralization was significant with P < 0.01 in both groups of men. A comparison between bone density changes in the control and experimental groups of men failed to demonstrate significant differences. It was concluded that the level of mineralization of bone tissues decreased under hypokinesia and physical exercise with calcium supplements. Experimental studies of hypokinetic physiology are generally based on the assumption that diminished muscular activity (progressive reduction of number of steps per day) is detrimental to animal and human organisms, since the entire animal kingdom had been formed in an environment of high motor activity which left its imprint on the evolution, structure, function and behaviour of animals and men. The impossibility of the body tissues to retain optimum amounts of fluid and electrolytes is the dominant hypokinetic effect.

  6. Automated measurement of bone-mineral-density (BMD) values of vertebral bones based on X-ray torso CT images.

    PubMed

    Zhou, X; Hayashi, T; Chen, H; Hara, T; Yokoyama, R; Kanematsu, M; Hoshi, H; Fujita, H

    2009-01-01

    Bone is one of the most important anatomical structures in humans and osteoporosis is one of the major public health concerns in the world. Osteoporosis is a main target disease of bone, which can be detected by medical image techniques. The purpose of this study is to develop a fully automated computer scheme to measure bone-mineral-density (BMD) values for vertebral trabecular bones. This scheme will aid osteoporosis diagnosis performed using computer tomography (CT) images. This scheme includes the following processing steps: segmentation of the bone region, recognition of the skeletal structures and measurement of the BMD value in vertebral trabecular bone of each vertebral body. The proposed scheme was applied to 20 X-ray torso CT cases to measure the BMD values for vertebral trabecular bones. The experimental results show that the mean and standard deviation of the difference between the BMD values measured by using the proposed method and those measured using a manual segmentation method were 6.93 mg/cm(3) and 6.82 mg/cm(3) respectively. The accuracy of the proposed scheme satisfied the requirement for a computer-aided system used in osteoporosis diagnosis.

  7. Automated, foot-bone registration using subdivision-embedded atlases for spatial mapping of bone mineral density.

    PubMed

    Liu, Lu; Commean, Paul K; Hildebolt, Charles; Sinacore, Dave; Prior, Fred; Carson, James P; Kakadiaris, Ioannis; Ju, Tao

    2013-06-01

    We present an atlas-based registration method for bones segmented from quantitative computed tomography (QCT) scans, with the goal of mapping their interior bone mineral densities (BMDs) volumetrically. We introduce a new type of deformable atlas, called subdivision-embedded atlas, which consists of a control grid represented as a tetrahedral subdivision mesh and a template bone surface embedded within the grid. Compared to a typical lattice-based deformation grid, the subdivision control grid possesses a relatively small degree of freedom tailored to the shape of the bone, which allows efficient fitting onto subjects. Compared with previous subdivision atlases, the novelty of our atlas lies in the addition of the embedded template surface, which further increases the accuracy of the fitting. Using this new atlas representation, we developed an efficient and fully automated pipeline for registering atlases of 12 tarsal and metatarsal bones to a segmented QCT scan of a human foot. Our evaluation shows that the mapping of BMD enabled by the registration is consistent for bones in repeated scans, and the regional BMD automatically computed from the mapping is not significantly different from expert annotations. The results suggest that our improved subdivision-based registration method is a reliable, efficient way to replace manual labor for measuring regional BMD in foot bones in QCT scans.

  8. Impaired Function of Bone Marrow Stromal Cells in Systemic Mastocytosis

    PubMed Central

    Nemeth, K.; Wilson, T.M.; Ren, J.J.; Sabatino, M.; Stroncek, D.F.; Krepuska, M.; Bai, Y.; Robey, P.G.; Metcalfe, D.D.; Mezey, E.

    2015-01-01

    Patients with systemic mastocytosis (SM) have a wide variety of problems, including skeletal abnormalities. The disease results from a mutation of the stem cell receptor (c-kit) in mast cells and we wondered if the function of bone marrow stromal cells (BMSCs; also known as MSCs or mesenchymal stem cells) might be affected by the invasion of bone marrow by mutant mast cells. As expected, BMSCs from SM patients do not have a mutation in c-kit, but they proliferate poorly. In addition, while osteogenic differentiation of the BMSCs seems to be deficient, their adipogenic potential appears to be increased. Since the hematopoietic supportive abilities of BMSCs are also important, we also studied the engraftment in NSG mice of human CD34+ hematopoietic progenitors, after being co-cultured with BMSCs of healthy volunteers vs. BMSCs derived from patients with SM. BMSCs derived from the bone marrow of patients with SM could not support hematopoiesis to the extent that healthy BMSCs do. Finally, we performed an expression analysis and found significant differences between healthy and SM derived BMSCs in the expression of genes with a variety of functions, including the WNT signaling, ossification, and bone remodeling. We suggest that some of the symptoms associated with SM might be driven by epigenetic changes in BMSCs caused by dysfunctional mast cells in the bone marrow of the patients. PMID:26001169

  9. Are the High Hip Fracture Rates Among Norwegian Women Explained by Impaired Bone Material Properties?

    PubMed

    Duarte Sosa, Daysi; Vilaplana, Laila; Güerri, Roberto; Nogués, Xavier; Wang-Fagerland, Morten; Diez-Perez, Adolfo; F Eriksen, Erik

    2015-10-01

    Hip fracture rates in Norway rank among the highest in the world, more than double that of Spanish women. Previous studies were unable to demonstrate significant differences between the two populations with respect to bone mass or calcium metabolism. In order to test whether the difference in fracture propensity between both populations could be explained by differences in bone material quality we assessed bone material strength using microindentation in 42 Norwegian and 46 Spanish women with normal BMD values, without clinical or morphometric vertebral fractures, no clinical or laboratory signs of secondary osteoporosis, and without use of drugs with known influence on bone metabolism. Bone material properties were assessed by microindentation of the thick cortex of the mid tibia following local anesthesia of the area using the Osteoprobe device (Active Life Scientific, Santa Barbara, CA, USA). Indentation distance was standardized against a calibration phantom of methylmethacrylate and results, as percentage of this reference value, expressed as bone material strength index units (BMSi). We found that the bone material properties reflected in the BMSi value of Norwegian women was significantly inferior when compared to Spanish women (77 ± 7.1 versus 80.7 ± 7.8, p < 0.001). Total hip BMD was significantly higher in Norwegian women (1.218 g/cm(2) versus 0.938 g/cm(2) , p < 0.001) but regression analysis revealed that indentation values did not vary with BMD r(2)  = 0.03 or age r(2)  = 0.04. In conclusion Norwegian women show impaired bone material properties, higher bone mass, and were taller than Spanish women. The increased height will increase the impact on bone after falls, and impaired bone material properties may further enhance the risk fracture after such falls. These ethnic differences in bone material properties may partly explain the higher propensity for fracture in Norwegian women.

  10. [In vitro culture of human autologous osteoblast cells on natural bone mineral].

    PubMed

    Behrens, P; Wolf, E; Bruns, J

    2000-02-01

    Different methods are available for the treatment of osseous defects. In recent years the use of autologous bone was established as the golden standard. However, significant disadvantages are limited availability of the bone graft and its harvest implies additional morbidity for the patient. Alternatives to the use of autologous bone, as allogeneic bone from bone banks or biomaterials like hydroxyapatite are therefore of special interest. However, the currently available methods have severe disadvantages; allogenic bone carries a high risk of transmitting infectious diseases, most biomaterials show an unsatisfying osseous integration as well as prolonged healing with disability for the patient. Therefore, the aim has to be the development of a biomaterial that is as close as possible to human bone. In this in vitro study the natural bone mineral Bio-Oss/Orthos was used as a matrix for human osteoblast-like cells isolated from bone marrow of healthy patients. Even after three months the cell showed typical osteblast-like behaviour. Histologic evaluation demonstrated the ability of Bio-Oss/Orthos to guide cell growth within its matrix structure and therefore mimics in vivo situation of the healthy bone. The results show that culturing human osteoblast-like cells under standardised conditions is possible and that the combination of human osteoblast-like cell with an appropriate matrix may have the potential for a new treatment option of osseous defects.

  11. Associations of lean and fat mass measures with whole body bone mineral content and bone mineral density in female adolescent weightlifters and swimmers.

    PubMed

    Koşar, Şükran Nazan

    2016-01-01

    Body composition and sport participation have been associated with bone mass. The purpose of this study was to determine the associations of lean and fat mass measures with whole body bone mineral content (BMC) and bone mineral density (BMD) in female adolescent weightlifters, swimmers and non-athletic counterparts. This study included a total of 25 female adolescents (mean age: 15.3±1.1 years). Body composition and bone mass were measured by dual-energy X-ray absorptiometry. In most of the studied variables weight lifters had higher values compared to swimmers and non-athletes (p < 0.05). No significant difference was observed between swimmers and non-athletes (p > 0.05). Lean and fat mass measures were positively associated with BMC and BMD for the total participants (p < 0.05) while the associations differed when the study groups were analysed separately. In conclusion, both lean and fat mass measures were strongly related to BMC and BMD in female adolescents while these associations differed in swimmers, weightlifters and non-athletes.

  12. Effects of chronic lead exposure on bone mineral properties in femurs of growing rats.

    PubMed

    Álvarez-Lloret, Pedro; Lee, Ching Ming; Conti, María Inés; Terrizzi, Antonela Romina; González-López, Santiago; Martínez, María Pilar

    2017-02-15

    Lead exposure has been associated with several defective skeletal growth processes and bone mineral alterations. The aim of the present study is to make a more detailed description of the toxic effects of lead intoxication on bone intrinsic material properties as mineral composition, morphology and microstructural characteristics. For this purpose, Wistar rats were exposed (n=12) to 1000ppm lead acetate in drinking water for 90days while control group (n=8) were treated with sodium acetate. Femurs were examined using inductively coupled plasma optical emission spectrometry (ICP-OES), Attenuated Total Reflection Fourier transform infrared spectroscopy (ATR-FTIR), X-ray diffraction (XRD), and micro-Computed Tomography (μCT). Results showed that femur from the lead-exposed rats had higher carbonate content in bone mineral and (Ca(2+)+Mg(2+)+ Na(+))/P ratio values, although no variations were observed in crystal maturity and crystallite size. From morphological analyses, lead exposure rats showed a decreased in trabecular bone surface and distribution while trabecular thickness and cortical area increased. These overall effects indicate a similar mechanism of bone maturation normally associated to age-related processes. These responses are correlated with the adverse actions induced by lead on the processes regulating bone turnover mechanism. This information may explain the osteoporosis diseases associated to lead intoxication as well as the risk of fracture observed in populations exposed to this toxicant.

  13. Effect of strontium ranelate on bone mineral: Analysis of nanoscale compositional changes.

    PubMed

    Rossi, André L; Moldovan, Simona; Querido, William; Rossi, Alexandre; Werckmann, Jacques; Ersen, Ovidiu; Farina, Marcos

    2014-01-01

    Strontium ranelate has been used to prevent bone loss and stimulate bone regeneration. Although strontium may integrate into the bone crystal lattice, the chemical and structural modifications of the bone when strontium interacts with the mineral phase are not completely understood. The objective of this study was to evaluate apatite from the mandibles of rats treated with strontium ranelate in the drinking water and compare its characteristics with those from untreated rats and synthetic apatites with and without strontium. Electron energy loss near edge structures from phosphorus, carbon, calcium and strontium were obtained by electron energy loss spectroscopy in a transmission electron microscope. The strontium signal was detected in the biological and synthetic samples containing strontium. The relative quantification of carbon by analyzing the CK edge at an energy loss of ΔE = 284 eV showed an increase in the number of carbonate groups in the bone mineral of treated rats. A synthetic strontium-containing sample used as control did not exhibit a carbon signal. This study showed physicochemical modifications in the bone mineral at the nanoscale caused by the systemic administration of strontium ranelate.

  14. MEPE-Derived ASARM Peptide Inhibits Odontogenic Differentiation of Dental Pulp Stem Cells and Impairs Mineralization in Tooth Models of X-Linked Hypophosphatemia

    PubMed Central

    Khaddam, Mayssam; Naji, Jiar; Coyac, Benjamin R.; Baroukh, Brigitte; Letourneur, Franck; Lesieur, Julie; Decup, Franck; Le Denmat, Dominique; Nicoletti, Antonino; Poliard, Anne; Rowe, Peter S.; Huet, Eric; Vital, Sibylle Opsahl; Linglart, Agnès; McKee, Marc D.; Chaussain, Catherine

    2013-01-01

    Mutations in PHEX (phosphate-regulating gene with homologies to endopeptidases on the X-chromosome) cause X-linked familial hypophosphatemic rickets (XLH), a disorder having severe bone and tooth dentin mineralization defects. The absence of functional PHEX leads to abnormal accumulation of ASARM (acidic serine- and aspartate-rich motif) peptide − a substrate for PHEX and a strong inhibitor of mineralization − derived from MEPE (matrix extracellular phosphoglycoprotein) and other matrix proteins. MEPE-derived ASARM peptide accumulates in tooth dentin of XLH patients where it may impair dentinogenesis. Here, we investigated the effects of ASARM peptides in vitro and in vivo on odontoblast differentiation and matrix mineralization. Dental pulp stem cells from human exfoliated deciduous teeth (SHEDs) were seeded into a 3D collagen scaffold, and induced towards odontogenic differentiation. Cultures were treated with synthetic ASARM peptides (phosphorylated and nonphosphorylated) derived from the human MEPE sequence. Phosphorylated ASARM peptide inhibited SHED differentiation in vitro, with no mineralized nodule formation, decreased odontoblast marker expression, and upregulated MEPE expression. Phosphorylated ASARM peptide implanted in a rat molar pulp injury model impaired reparative dentin formation and mineralization, with increased MEPE immunohistochemical staining. In conclusion, using complementary models to study tooth dentin defects observed in XLH, we demonstrate that the MEPE-derived ASARM peptide inhibits both odontogenic differentiation and matrix mineralization, while increasing MEPE expression. These results contribute to a partial mechanistic explanation of XLH pathogenesis: direct inhibition of mineralization by ASARM peptide leads to the mineralization defects in XLH teeth. This process appears to be positively reinforced by the increased MEPE expression induced by ASARM. The MEPE-ASARM system can therefore be considered as a potential therapeutic

  15. [Bone diseases caused by impaired glucose and lipid metabolism].

    PubMed

    Kanazawa, Ippei; Sugimoto, Toshitsugu

    2013-11-01

    The number of patients with lifestyle-related diseases is rapidly increasing in Japan. Metabolic syndrome caused by abdominal fat accumulation induces diabetes mellitus, dyslipidemia, and hypertension, resulting in an increase in cardiovascular diseases. On the other hand, recent studies have shown that the lifestyle-related diseases are risk factors of osteoporotic fractures. Although it remains still unclear how metabolic disorders affect bone tissue, oxidative stress and/or glycation stress might directly have negative impacts on bone tissue and increase the risk of fractures. In this review, we describe the association of diabetes mellitus and dyslipidemia with the fracture risk through oxidative stress and glycation stress.

  16. The Soy Isoflavones to Reduce Bone Loss (SIRBL) Study: Three Year Effects on pQCT Bone Mineral Density and Strength Measures in Postmenopausal Women

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Soy isoflavones exert inconsistent bone density preserving effects, but the bone strength preserving effects in humans are unknown. Our double-blind randomized controlled trial examined 2 soy isoflavone doses (80 or 120 mg/d) vs placebo tablets on volumetric bone mineral density (vBMD) and strength ...

  17. The recent prevalence of Osteoporosis and low bone mass in the United States based on bone mineral density at the Femoral Neck or Lumbar Spine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The goal of our study was to estimate the prevalence of osteoporosis and low bone mass based on bone mineral density (BMD) at the femoral neck and the lumbar spine in adults 50 years and older in the United States (US). We applied prevalence estimates of osteoporosis or low bone mass at the femoral ...

  18. Vitamin C supplementation does not modify bone mineral content or mineral absorption in growing pigs.

    PubMed

    Pointillart, A; Denis, I; Colin, C; Lacroix, H

    1997-08-01

    We have demonstrated that alkaline phosphatase activity and collagen synthesis are dose-dependently stimulated by ascorbic acid in differentiated pig osteoblasts. In this study we further examined the relationship between ascorbic acid and bone metabolism by feeding young pigs large amounts of ascorbic acid. Three groups of seven 47-d-old pigs were given no ascorbic acid supplement (control), 500 (500 AA) or 1000 (1000 AA) mg ascorbic acid/kg diet for 4 mo. Calcium and P absorption and retention were evaluated by a 14-d balance trial immediately before killing in control and 1000 AA groups only (n = 6). Bones were collected at death and the bone ash and bending moment (three-point bending test) determined. Various plasma and urine indices of bone metabolism, especially those reflecting collagen degradation (hydroxyproline, deoxypyridinoline) and synthesis (carboxyterminal propeptide of type I collagen) were monitored. The plasma ascorbic acid concentrations increased with time and paralleled the dietary concentrations (P < 0.01). The Ca and P balances and the bone ash and bending moments in the ascorbic acid-supplemented pigs did not differ from those of the controls. Plasma osteocalcin was elevated (P < 0.05), whereas the other bone formation markers, alkaline phosphatase and carboxy terminal propeptide of type I collagen, were not affected by ascorbic acid. The plasma concentrations of Ca, P and 1,25-dihydroxycholecalciferol did not differ among the three groups. The unaffected urinary excretion of deoxypyridinoline and hydroxyproline in the ascorbic acid-supplemented pigs indicates that ascorbic acid does not alter bone resorption. Thus, high intakes of ascorbic acid have no positive influence on bone metabolism and bone characteristics in pigs. The in vivo long-term effects do not correlate with the short-term in vitro effects previously reported.

  19. Using Natural Stable Calcium Isotopes to Rapidly Assess Changes in Bone Mineral Balance Using a Bed Rest Model to Induce Bone Loss

    NASA Technical Reports Server (NTRS)

    Morgan, J. L. L.; Skulan, J. L.; Gordon, G. E.; Smith, Scott M.; Romaniello, S. J.; Anbar, A. D.

    2012-01-01

    Metabolic bone diseases like osteoporosis result from the disruption of normal bone mineral balance (BMB) resulting in bone loss. During spaceflight astronauts lose substantial bone. Bed rest provides an analog to simulate some of the effects of spaceflight; including bone and calcium loss and provides the opportunity to evaluate new methods to monitor BMB in healthy individuals undergoing environmentally induced-bone loss. Previous research showed that natural variations in the Ca isotope ratio occur because bone formation depletes soft tissue of light Ca isotopes while bone resorption releases that isotopically light Ca back into soft tissue (Skulan et al, 2007). Using a bed rest model, we demonstrate that the Ca isotope ratio of urine shifts in a direction consistent with bone loss after just 7 days of bed rest, long before detectable changes in bone mineral density (BMD) occur. The Ca isotope variations tracks changes observed in urinary N-teleopeptide, a bone resorption biomarker. Bone specific alkaline phosphatase, a bone formation biomarker, is unchanged. The established relationship between Ca isotopes and BMB can be used to quantitatively translate the changes in the Ca isotope ratio to changes in BMD using a simple mathematical model. This model predicts that subjects lost 0.25 0.07% ( SD) of their bone mass from day 7 to day 30 of bed rest. Given the rapid signal observed using Ca isotope measurements and the potential to quantitatively assess bone loss; this technique is well suited to study the short-term dynamics of bone metabolism.

  20. [Secondary anticoagulant prophylaxis with low molecular heparins or oral anticoagulants and bone mineral density].

    PubMed

    Wawrzyńska, L; Przedlacki, J; Hajduk, B; Tomkowski, W; Fijałkowska, A; Ostrowski, K; Torbicki, A

    2000-11-01

    A broad spectrum of indications for low molecular weight heparin (LMWH) requires an assessment of side effects especially during prolonged administration. There are common risk factors for venous thromboembolism (VTE) and osteoporosis; heparin is "the drug of choice" for VTE treatment. The aim of our study was to assess the effect of treatment and prophylaxis with LMWH (enoxaparine sodium) and oral anticoagulant (acenocoumarol) for bone structure. Material consists of in- and outpatients. 49 densitometries were performed in 31 patients (in 15 cases double examination). We observed a decrease of bone mineral density in comparison to the initial examination in most cases: mean change of bone mass for examined areas was 3.05%.

  1. Muscle and Bone Impairment in Children With Marfan Syndrome: Correlation With Age and FBN1 Genotype.

    PubMed

    Haine, Elsa; Salles, Jean-Pierre; Khau Van Kien, Philippe; Conte-Auriol, Françoise; Gennero, Isabelle; Plancke, Aurélie; Julia, Sophie; Dulac, Yves; Tauber, Maithé; Edouard, Thomas

    2015-08-01

    Marfan syndrome (MFS) is a rare connective tissue disorder caused by mutation in the gene encoding the extracellular matrix protein fibrillin-1 (FBN1), leading to transforming growth factor-beta (TGF-β) signaling dysregulation. Although decreased axial and peripheral bone mineral density (BMD) has been reported in adults with MFS, data about the evolution of bone mass during childhood and adolescence are limited. The aim of the present study was to evaluate bone and muscle characteristics in children, adolescents, and young adults with MFS. The study population included 48 children and young adults (22 girls) with MFS with a median age of 11.9 years (range 5.3 to 25.2 years). The axial skeleton was analyzed at the lumbar spine using dual-energy X-ray absorptiometry (DXA), whereas the appendicular skeleton (hand) was evaluated using the BoneXpert system (with the calculation of the Bone Health Index). Muscle mass was measured by DXA. Compared with healthy age-matched controls, bone mass at the axial and appendicular levels and muscle mass were decreased in children with MFS and worsened from childhood to adulthood. Vitamin D deficiency (<50 nmol/L) was found in about a quarter of patients. Serum vitamin D levels were negatively correlated with age and positively correlated with lumbar spine areal and volumetric BMD. Lean body mass (LBM) Z-scores were positively associated with total body bone mineral content (TB-BMC) Z-scores, and LBM was an independent predictor of TB-BMC values, suggesting that muscle hypoplasia could explain at least in part the bone loss in MFS. Patients with a FBN1 premature termination codon mutation had a more severe musculoskeletal phenotype than patients with an inframe mutation, suggesting the involvement of TGF-β signaling dysregulation in the pathophysiologic mechanisms. In light of these results, we recommend that measurement of bone mineral status should be part of the longitudinal clinical investigation of MFS children.

  2. Chronic Psychosocial Stress Impairs Bone Homeostasis: A Study in the Social Isolation Reared Rat

    PubMed Central

    Schiavone, Stefania; Morgese, Maria G.; Mhillaj, Emanuela; Bove, Maria; De Giorgi, Angelo; Cantatore, Francesco P.; Camerino, Claudia; Tucci, Paolo; Maffulli, Nicola; Cuomo, Vincenzo; Trabace, Luigia

    2016-01-01

    Chronic psychosocial stress is a key player in the onset and aggravation of mental diseases, including psychosis. Although a strong association between this psychiatric condition and other medical co-morbidities has been recently demonstrated, few data on the link between psychosis and bone homeostasis are actually available. The aim of this study was to investigate whether chronic psychosocial stress induced by 4 or 7 weeks of social isolation in drug-naïve male Wistar rats could alter bone homeostasis in terms of bone thickness, mineral density and content, as well as markers of bone formation and resorption (sclerostin, cathepsin K, and CTX-I). We found that bone mineral density was increased in rats exposed to 7 weeks of social isolation, while no differences were detected in bone mineral content and area. Moreover, 7 weeks of social isolation lead to increase of femur thickness with respect to controls, suggesting the development of a hyperostosis condition. Isolated rats showed no changes in sclerostin levels, a marker of bone formation, compared to grouped animals. Conversely, bone resorption markers were significantly altered after 7 weeks of social isolation in terms of decrease in cathepsin K and increase of CTX-I. No alterations were found after 4 weeks of isolation rearing. Our observations suggest that chronic psychosocial stress might affect bone homeostasis, more likely independently from drug treatment. Thus, the social isolation model might help to identify possible new therapeutic targets to treat the burden of chronic psychosocial stress and to attempt alternative therapy choices. PMID:27375486

  3. The diabetic paradox: Bone mineral density and fracture in type 2 diabetes.

    PubMed

    Botella Martínez, Sonsoles; Varo Cenarruzabeitia, Nerea; Escalada San Martin, Javier; Calleja Canelas, Amparo

    2016-11-01

    Type 2 diabetes mellitus prevalence and morbidity are increasing. Osteoporotic fractures are among the 'non-classical' complications of diabetes and been overlooked for a long time, maybe because of their complex diagnostic and therapeutic approach. The usual tools for preventing fragility fractures (such as the fracture risk assessment tool and bone densitometry) underestimate risk of fractures in type2 diabetic patients. New techniques, such as trabecular bone score or bone turnover markers, could be useful, but greater scientific evidence is required to recommend their use in clinical practice. The special characteristics of their pathophysiology result in decreased bone remodeling with normal or even increased bone mineral density, but with low quality. These changes lead to the occurrence of osteoporotic fractures without evidence of densitometric changes, which could be called 'the diabetic paradox'.

  4. Mussel-inspired transformation of CaCO3 to bone minerals.

    PubMed

    Kim, Sungjin; Park, Chan Beum

    2010-09-01

    We report a mussel-inspired route to create carbonated bone hydroxyapatite from CaCO(3) vaterite microspheres. When catechol-containing dopamine, a biomimetic small molecule of mussel adhesive proteins, was incorporated during the mineralization of CaCO(3), the oxidative polymerization of dopamine stabilized the formation of spherical vaterite, the most unstable phase among CaCO(3) crystalline structures. Thus-formed vaterite microspheres were readily transformed to carbonated hydroxyapatite crystals when incubated in a simulated body fluid at human body temperature. We found that dopamine not only stabilized the vaterite phase but also influenced the level of conversion to carbonated hydroxyapatites. Considering that carbonated hydroxyapatites are highly bioresorbable, similar to natural bone and dentin, the synthesis of a mussel-inspired hybrid material showing good in vitro bone bioactivity should present a new prospect for future applications in the treatment of bone defects and bone degenerative diseases.

  5. Risk Factors for Low Bone Mineral Density in Individuals Residing in a Facility for the People with Intellectual Disability

    ERIC Educational Resources Information Center

    Jaffe, J. S.; Timell, A. M.; Elolia, R.; Thatcher, S. S.

    2005-01-01

    Background: Individuals with intellectual disability (ID) are known to have a high prevalence of both low bone mineral density (BMD) and fractures with significant attendant morbidity. Effective strategies aimed at reducing fractures will be facilitated by the identification of predisposing risk factors. Methods: Bone mineral density was measured…

  6. Bone mineral density and body composition in a myelomeningocele children population: effects of walking ability and sport activity.

    PubMed

    Ausili, E; Focarelli, B; Tabacco, F; Fortunelli, G; Caradonna, P; Massimi, L; Sigismondi, M; Salvaggio, E; Rendeli, C

    2008-01-01

    Myelomeningocele causes serious locomotor disability, osteoporosis and pathologic fractures. The aim of this study was to investigate the relationship between body composition, bone mineral density, walking ability and sport activity in myelomeningocele children. 60 patients aged between 5 and 14 yrs with myelomeningocele (22 ambulatory and 38 non-ambulatory), were studied. Fat mass and fat-free-mass were calculated by anthropometry. The bone mineral density at lumbar and femoral neck were evaluated. Bone mineral density at the lumbar and femoral neck was lower than in the normal population. In the non-ambulaty group, bone mineral density was approximately 1 SD lower than in the ambulatory one (p < 0.01). Fat mass was greater than expected but without significantly differences between walking group (mean 26%) and wheel-chair users (25%). Patients practised sport activity had a better bone mineral density and body fat compared with other patients with the same disability. Patients with myelomeningocele have decreased bone mineral density and are at higher risk of pathologic bone fractures. All subjects showed an excess of fat as percentage of body weight and are shorter than normal children. The measurement of bone mineral density may help to identify those patients at greatest risk of suffering of multiple fractures. Walk ability and sport activity, associated with the development of muscle mass, are important factors in promoting bone and body growth, to reduce the risk of obesity and of pathological fractures.

  7. Relating Crack-tip Deformation to Mineralization and Fracture Resistance in Human Femur Cortical Bone

    PubMed Central

    Chan, Kwai S.; Chan, Candace K.; Nicolella, Daniel P.

    2009-01-01

    The risk of bone fracture increases with age because of a variety of factors that include, among others, decreasing bone quantity and quality. Despite recent advances, the roles of bone microstructure and trace mineralization in the fracture process are not well understood. In this study, we utilize a combination of in-situ fracture toughness testing, digital strain mapping, and x-ray photoelectron spectroscopy techniques to characterize the near-tip strain field, fracture toughness, and chemical elements on the fracture surface of bone specimens from donors of two ages (48-year-old and 78-year-old females). We show that age-related embrittlement of bone fracture is associated with higher near-tip strains by lamellar shear and crack defection at lamellar interfaces in the young bone and their absence in the old bone. The different near-tip deformation behaviors may be associated with the presence of Si and Zn in the young bone but more Ca and P and the lack of Si and Zn in the old bone. PMID:19497396

  8. A pilot study on the impact of body composition on bone and mineral metabolism in Parkinson's disease.

    PubMed

    Fernández, María C; Parisi, Muriel S; Díaz, Sergio P; Mastaglia, Silvina R; Deferrari, Juan M; Seijo, Mariana; Bagur, Alicia; Micheli, Federico; Oliveri, Beatriz

    2007-08-01

    The impact of body composition on bone and mineral metabolism in Parkinson's disease (PD) was evaluated. Body fat mass, lean mass, bone mineral content, and bone mineral density (BMD) were measured by DXA in 22 PD patients and 104 controls. Female patients exhibited reduced body mass index, fat mass, and BMD compared to controls (p<0.05). Significant positive correlation was found between 25 OHD levels and BMC. Diminished bone mass in women with PD was found to be associated with alterations in body composition and low 25 OHD levels.

  9. Modulation of vitamin d status and dietary calcium affects bone mineral density and mineral metabolism in göttingen minipigs.

    PubMed

    Scholz-Ahrens, Katharina E; Glüer, Claus-Christian; Bronner, Felix; Delling, Günter; Açil, Yahya; Hahne, Hans-Jürgen; Hassenpflug, Joachim; Timm, Wolfram; Schrezenmeir, Jürgen

    2013-01-01

    Calcium and vitamin D deficiency impairs bone health and may cause rickets in children and osteomalacia in adults. Large animal models are useful to study experimental osteopathies and associated metabolic changes. We intended to modulate vitamin D status and induce nutritional osteomalacia in minipigs. The control group (n = 9) was fed a semisynthetic reference diet with 6 g calcium and 6,500 IU vitamin D3/kg and the experimental group (n = 10) the same diet but with only 2 g calcium/kg and without vitamin D. After 15 months, the deficient animals were in negative calcium balance, having lost bone mineral density significantly (means ± SEM) with -51.2 ± 14.7 mg/cm(3) in contrast to controls (-2.3 ± 11.8 mg/cm(3)), whose calcium balance remained positive. Their osteoid surface was significantly higher, typical of osteomalacia. Their plasma 25(OH)D dropped significantly from 60.1 ± 11.4 nmol/L to 15.3 ± 3.4 nmol/L within 10 months, whereas that of the control group on the reference diet rose. Urinary phosphorus excretion and plasma 1,25-dihydroxyvitamin D concentrations were significantly higher and final plasma calcium significantly lower than in controls. We conclude that the minipig is a promising large animal model to induce nutritional osteomalacia and to study the time course of hypovitaminosis D and associated functional effects.

  10. Evaluation of the effect of cola drinks on bone mineral density and associated factors.

    PubMed

    Ogur, Recai; Uysal, Bulent; Ogur, Torel; Yaman, Halil; Oztas, Emin; Ozdemir, Aysegul; Hasde, Metin

    2007-05-01

    The aim of the study was to determine bone mineral density changes caused by consumption of cola drinks and the associated factors. Thirty Sprague-Dawley rats were divided into four groups. Groups 1 and 2, consisting of 10 male and 10 female rats, respectively, were provided with as much food, water and cola drinks as they wanted. Groups 3 and 4, consisting of five rats each, received only rat chow and water. The bone mineral density of the rats was measured using dual energy X-ray absorptiometry at the end of 30 days. The blood values and weights of the animals were also determined. The oesophagus and kidneys were removed for histopathological examination. The weight gain was higher in the groups consuming cola drinks than the control group rats (P < 0.05). Water consumption decreased 5.9 times while total fluid consumption increased 1.6-1.9 times in the group consuming cola drinks. No significant change was detected in the blood calcium levels. There was a significant decrease in the bone mineral density of test groups when compared to the control groups (P < 0.05). While we did not detect any pathological oesophageal changes in the rats consuming cola drinks, examination of the kidneys revealed general glomerular congestion and intertubular bleeding. We suggest that the decrease in bone mineral density might be related to the renal damage caused by cola drinks in addition to other related factors.

  11. Bone mineral density evaluation of patients with type 2 diabetes mellitus.

    PubMed

    Adil, Camli; Aydın, Teoman; Taşpınar, Özgür; Kızıltan, Huriye; Eriş, Ali Hikmet; Hocaoglu, Ilknur Turk; Poşul, Sevde; Kepekci, Muge; Denizli, Ebru; Güler, Mustafa

    2015-01-01

    [Purpose] Diabetes mellitus is a metabolic disorder resulting from a defect in insulin secretion, insulin action, or both. A consequence of this is chronic hyperglycemia with disturbances in carbohydrate, fat and protein metabolism. We investigated whether there is any difference among DM patients and a control group in terms of lumbar and femur BMD (bone mineral density), and standard deviation scores (Z score and T score). [Subjects and Methods] This randomized, prospective, controlled, single-blind study was conducted in the Physical Medicine and Rehabilitation Department Faculty of Medicine, Bezm-i Alem Vakıf University. Patients with type 2 diabetes mellitus were included in the patient groups. Healthy individuals were included in the control group. [Results] A total of 126 patients completed the study (63 in the study group, 63 in the control group). There was no significant difference in the results of the laboratory examinations of the cases. The bone mineral densities of the cases were found to be significantly low in terms of the lumbar (L1-4) T scores in the type 2 diabetes group. [Conclusion] Although osteoporosis is one of the potential complications of type 1 diabetes, its effect on bone mineral density in type 2 DM is controversial. In different studies, the bone mineral density values have increased, decreased or remained normal. With the exception of the lumbar (L1-4) T score, similar results were obtained in this study.

  12. Mechanism by Sambucus nigra Extract Improves Bone Mineral Density in Experimental Diabetes

    PubMed Central

    Badescu, Laurentiu; Badulescu, Oana; Badescu, Magda; Ciocoiu, Manuela

    2012-01-01

    The effects of polyphenols extracted from Sambucus nigra fruit were studied in streptozotocin- (STZ-) induced hyperglycemic rats to evaluate its possible antioxidant, anti-inflammatory, antiglycosylation activity, and antiosteoporosis effects in diabetes. DEXA bone mineral density tests were performed in order to determine bone mineral density (BMD), bone mineral content (BMC), and fat (%Fat) in control and diabetic animals, before and after polyphenol delivery. As compared to the normoglycemic group, the rats treated with STZ (60 mg/kg body weight) revealed a significant malondialdehyde (MDA) increase, as an index of the lipid peroxidation level, by 69%, while the total antioxidant activity (TAS) dropped by 36%, with a consistently significant decrease (P < 0.05) in the activity of superoxide dismutase (SOD) and glutathione peroxidase (GPX). Also, the treatment of rats with STZ revealed a significant increase of IL-6, glycosylated haemoglobin (HbA1c), and osteopenia detected by DEXA bone mineral density tests. The recorded results highlight a significant improvement (P < 0.001) in the antioxidative capacity of the serum in diabetic rats treated with natural polyphenols, bringing back to normal the concentration of reduced glutathione (GSH), as well as an important decrease in the serum concentration of MDA, with improved osteoporosis status. Knowing the effects of polyphenols could lead to the use of the polyphenolic extract of Sambucus nigra as a dietary supplement in diabetic osteoporosis. PMID:23024697

  13. Strong Association Between Tibial Plateau Bone Mineral Density and Cartilage Damage

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Tibial bone mineral density (BMD) is associated with radiographic features of osteoarthritis (OA), but no study has looked at its relationship with a direct measure of cartilage damage. We hypothesize that a relative increase in medial and lateral tibial BMD will be associated with cartilage damage...

  14. Uric acid and bone mineral density in postmenopausal osteoporotic women: the link lies within the fat.

    PubMed

    Pirro, M; Mannarino, M R; Bianconi, V; De Vuono, S; Sahebkar, A; Bagaglia, F; Franceschini, L; Scarponi, A M; Mannarino, E; Merriman, T

    2017-03-01

    The association between serum uric acid (SUA) levels and bone mineral density (BMD) is controversial. Fat accumulation is linked to SUA and BMD, thus possibly explaining the mixed results. We found that adiposity drives part of the association between SUA and BMD in women with postmenopausal osteoporosis.

  15. Mechanical and mineral properties of osteogenesis imperfecta human bones at the tissue level.

    PubMed

    Imbert, Laurianne; Aurégan, Jean-Charles; Pernelle, Kélig; Hoc, Thierry

    2014-08-01

    Osteogenesis imperfecta (OI) is a genetic disorder characterized by an increase in bone fragility on the macroscopic scale, but few data are available to describe the mechanisms involved on the tissue scale and the possible correlations between these scales. To better understand the effects of OI on the properties of human bone, we studied the mechanical and chemical properties of eight bone samples from children suffering from OI and compared them to the properties of three controls. High-resolution computed tomography, nanoindentation and Raman microspectroscopy were used to assess those properties. A higher tissue mineral density was found for OI bone (1.131 gHA/cm3 vs. 1.032 gHA/cm3, p=0.032), along with a lower Young's modulus (17.6 GPa vs. 20.5 GPa, p=0.024). Obviously, the mutation-induced collagen defects alter the collagen matrix, thereby affecting the mineralization. Raman spectroscopy showed that the mineral-to-matrix ratio was higher in the OI samples, while the crystallinity was lower, suggesting that the mineral crystals were smaller but more abundant in the case of OI. This change in crystal size, distribution and composition contributes to the observed decrease in mechanical strength.

  16. Effects of Physical Training and Calcium Intake on Bone Mineral Density of Students with Mental Retardation

    ERIC Educational Resources Information Center

    Hemayattalab, Rasool

    2010-01-01

    The purpose of this study was to investigate the effects of physical training and calcium intake on bone mineral density (BMD) of students with mental retardation. Forty mentally retarded boys (age 7-10 years old) were randomly assigned to four groups (no differences in age, BMD, calcium intake and physical activity): training groups with or…

  17. Adolescence: How do we increase intestinal calcium absorption to allow for bone mineral mass accumulation?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An increase in calcium absorptive efficiency (fractional absorption of dietary calcium) during adolescence is associated with a rapid increase in total body bone mineral mass (BMM) accumulation. This increase occurs across a range of calcium intakes. It appears to be principally mediated by hormonal...

  18. Association between sleep duration, insomnia symptoms and bone mineral density in older Puerto Rican adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: To examine the association between sleep patterns (sleep duration and insomnia symptoms) and total and regional bone mineral density (BMD) among older Boston Puerto Rican adults. Materials/Methods: We conducted a cross-sectional study including 750 Puerto Rican adults, aged 47–79 y livi...

  19. Exercise Effects on Fitness and Bone Mineral Density in Early Postmenopausal Women: 1-Year EFOPS Results.

    ERIC Educational Resources Information Center

    Kemmler, Wolfgang; Engelke, Klaus; Lauber, Dirk; Weineck, Juergen; Hensen, Johannes; Kalender, Willi A.

    2002-01-01

    Investigated the effect of intense exercise training on physical fitness, coronary heart disease, bone mineral density (BMD), and parameters related to quality of life in early postmenopausal women with osteopenia. Data on woman in control and exercise training groups indicated that the intense exercise training program was effective in improving…

  20. Electromagnetic field versus circuit weight training on bone mineral density in elderly women

    PubMed Central

    Elsisi, Hany Farid Eid Morsy; Mousa, Gihan Samir Mohamed; ELdesoky, Mohamed Taher Mahmoud

    2015-01-01

    Background and purpose Osteoporosis is a common skeletal disorder with costly complications and a global health problem and one of the leading causes of morbidity and mortality worldwide. Magnetic field therapy and physical activity have been proven as beneficial interventions for prevention and treatment of osteoporosis. The purpose of this study was to compare the response of bone mineral content and bone mineral density (BMD) in elderly women to either low-frequency low-intensity pulsed magnetic field (LFLIPMF) or circuit weight training (CWT) on short-run basis (after 12 weeks). Patients and methods Thirty elderly women, aged 60–70 years, were randomly assigned into two groups (magnetic field and CWT) (n=15 each group). The session was performed three times per week for magnetic field and CWT groups, for 12 weeks. BMD and bone mineral content of lumbar spine (L2–L4) and femoral neck, trochanter, and Ward’s triangle were evaluated before and after 12 weeks of treatment. Results Both magnetic field and CWT for 12 weeks in elderly women seem to yield beneficial and statistically significant increasing effect on BMD and bone mineral content (P<0.05). But magnetic field seems to have more beneficially and statistically significant effect than does CWT. Conclusion It is possible to conclude that LFLIPMF and CWT programs are effective modalities in increasing BMD but LFLIPMF is more effective in elderly women. PMID:25834412

  1. Associations of APOE gene polymorphisms with bone mineral density and fracture risk: a meta-analysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Apolipoprotein E (APOE) has been studied for its potential role in osteoporosis risk. It is hypothesized that genetic variation at common APOE loci, known as E2, E3, and E4, may modulate bone mineral density (BMD) through its effects on lipoproteins and vitamin K transport. To determine the associa...

  2. Bone Mineral Density in Adults With Down Syndrome, Intellectual Disability, and Nondisabled Adults

    ERIC Educational Resources Information Center

    Geijer, Justin R.; Stanish, Heidi I.; Draheim, Christopher C.; Dengel, Donald R.

    2014-01-01

    Individuals with intellectual disability (ID) or Down syndrome (DS) may be at greater risk of osteoporosis. The purpose of this study was to compare bone mineral density (BMD) of DS, ID, and non-intellectually disabled (NID) populations. In each group, 33 participants between the ages of 28 and 60 years were compared. BMD was measured with…

  3. Does nutrition affect bone porosity and mineral tissue distribution in deer antlers? The relationship between histology, mechanical properties and mineral composition.

    PubMed

    Landete-Castillejos, T; Currey, J D; Ceacero, F; García, A J; Gallego, L; Gomez, S

    2012-01-01

    It is well known that porosity has an inverse relationship with the mechanical properties of bones. We examined cortical and trabecular porosity of antlers, and mineral composition, thickness and mechanical properties in the cortical wall. Samples belonged to two deer populations: a captive population of an experimental farm having a high quality diet, and a free-ranging population feeding on plants of lower nutritive quality. As shown for minerals and mechanical properties in previous studies by our group, cortical and trabecular porosity increased from the base distally. Cortical porosity was always caused by the presence of incomplete primary osteons. Porosity increased along the length of the antler much more in deer with lower quality diet. Despite cortical porosity being inversely related to mechanical properties and positively with K, Zn and other minerals indicating physiological effort, it was these minerals and not porosity that statistically better explained variability in mechanical properties. Histochemistry showed that the reason for this is that Zn is located around incomplete osteons and also in complete osteons that were still mineralizing, whereas K is located in non-osteonal bone, which constitutes a greater proportion of bone where osteons are incompletely mineralized. This suggests that, K, Zn and other minerals indicate reduction in mechanical performance even with little porosity. If a similar process occurred in internal bones, K, Zn and other minerals in the bone may be an early indicator of decrease in mechanical properties and future osteoporosis. In conclusion, porosity is related to diet and physiological effort in deer.

  4. Impaired bone homeostasis in amyotrophic lateral sclerosis mice with muscle atrophy.

    PubMed

    Zhu, Ke; Yi, Jianxun; Xiao, Yajuan; Lai, Yumei; Song, Pingping; Zheng, Wei; Jiao, Hongli; Fan, Jie; Wu, Chuanyue; Chen, Di; Zhou, Jingsong; Xiao, Guozhi

    2015-03-27

    There is an intimate relationship between muscle and bone throughout life. However, how alterations in muscle functions in disease impact bone homeostasis is poorly understood. Amyotrophic lateral sclerosis (ALS) is a neuromuscular disease characterized by progressive muscle atrophy. In this study we analyzed the effects of ALS on bone using the well established G93A transgenic mouse model, which harbors an ALS-causing mutation in the gene encoding superoxide dismutase 1. We found that 4-month-old G93A mice with severe muscle atrophy had dramatically reduced trabecular and cortical bone mass compared with their sex-matched wild type (WT) control littermates. Mechanically, we found that multiple osteoblast properties, such as the formation of osteoprogenitors, activation of Akt and Erk1/2 pathways, and osteoblast differentiation capacity, were severely impaired in primary cultures and bones from G93A relative to WT mice; this could contribute to reduced bone formation in the mutant mice. Conversely, osteoclast formation and bone resorption were strikingly enhanced in primary bone marrow cultures and bones of G93A mice compared with WT mice. Furthermore, sclerostin and RANKL expression in osteocytes embedded in the bone matrix were greatly up-regulated, and β-catenin was down-regulated in osteoblasts from G93A mice when compared with those of WT mice. Interestingly, calvarial bone that does not load and long bones from 2-month-old G93A mice without muscle atrophy displayed no detectable changes in parameters for osteoblast and osteoclast functions. Thus, for the first time to our knowledge, we have demonstrated that ALS causes abnormal bone remodeling and defined the underlying molecular and cellular mechanisms.

  5. Tanshinol Rescues the Impaired Bone Formation Elicited by Glucocorticoid Involved in KLF15 Pathway

    PubMed Central

    Yang, Yajun; Su, Yanjie; Wang, Dongtao; Chen, Yahui; Liu, Yuyu; Luo, Shiying; Wu, Tie

    2016-01-01

    Decreased bone formation is responsible for the pathogenesis of glucocorticoid- (GC-) induced osteoporosis (GIO), while the mechanism remains to be elucidated. The aim was to investigate how natural antioxidant tanshinol attenuates oxidative stress and rescues impaired bone formation elicited by GC in Sprague-Dawley rats and in C2C12 cells and/or MC3T3-E1 cells. The results showed that tanshinol prevented bone loss and decreased biomechanical characteristics and suppressed reduction of biomarkers related to osteogenesis in GIO rats. Further study revealed that tanshinol reversed decrease of transcription activity of Osterix-luc and rescued impairment of osteoblastic differentiation and bone formation involved in induction of KLF15 mRNA. Meanwhile, tanshinol diminished inhibition of protein expression of β-catenin and Tcf4 and transcription activity of Tcf4-luc induced by GC, especially under conditions of KLF siRNA in vitro. Additionally, tanshinol attenuated increase of reactive oxygen species (ROS) generation, phosphorylation of p66Shc expression, TUNEL-positive cells, and caspase-3 activity elicited by KLF15 under conditions of GC. Taken together, the present findings suggest that tanshinol attenuated the decrease of bone formation and bone mass and bone quality elicited by GC involved in KLF15/Wnt signaling transduction and counteracted GC-evoked oxidative stress and subsequent cell apoptosis involved in KLF15/p66Shc pathway cascade. PMID:27051474

  6. Discriminative ability of total body bone-mineral measured by dual photon absorptiometry.

    PubMed

    Gotfredsen, A; Pødenphant, J; Nilas, L; Christiansen, C

    1989-04-01

    We investigated the discriminative ability of total body bone-mineral expressed as the total body bone-density (TBBD) measured by dual photon absorptiometry (DPA) in 79 healthy premenopausal women, 27 healthy postmenopausal women, and 120 female osteoporotic fracture patients presenting with either Colles' fracture, vertebral fracture or femoral neck-fracture. TBBD was compared to the bone-mineral density of the lumbar spine (BMDspine) also measured by DPA, and to the bone-mineral content of the forearms (BMCforearm) measured by single photon absorptiometry (SPA). TBBD, BMDspine and BMCforearm showed that all the fracture patient groups had significantly reduced bone-mass. Using receiver operating characteristic (ROC) analysis, we found that TBBD had a tendency towards better discriminative ability than BMDspine or BMCforearm with regard to the discrimination between healthy premenopausal women and the three types of osteoporotic fractures (not significant in spinal fracture patients). BMCforearm had an intermediate position, whereas BMDspine had the smallest discriminative ability. TBBD also discriminated better between healthy postmenopausal women and hip-fracture patients than BMDspine or BMCforearm, whereas there was no significant difference between the three methods regarding the discrimination between the healthy postmenopausal women and the Colles' and spinal fracture patients. We conclude that the TBBD measurement by DPA has a discriminative potential which is better than the local spine or forearm measurements.

  7. Bone mineral response to ammonium sulphate offered as a lick supplement in beef calves.

    PubMed

    Motsei, L E; Beighle, D E

    2006-03-01

    Sixteen Bonsmara calves (4 males, 12 females) between 10 and 18 months of age were blocked according to age and sex and randomly assigned to 2 groups. They were offered licks containing bone meal and salt (50:50 ratio) (control) and bone meal and ammonium sulphate (NH4SO4) at 1.25, 2.5, 5, 10, 15, and 18% (treatment) to evaluate the effects of dietary anions on bone phosphate (P) concentration. Bone P concentration was significantly (P < 0.05) higher in the NH4SO4 group compared with the control group, indicating that NH4SO4 was able to increase the P content of bone at each of the 6 concentrations used in the lick relative to the control animals, thereby improving the P status of the animals. Ammonium sulphate at 15% and 18 % in the lick also significantly (P < 0.05) increased bone P compared with the lower concentrations of NH4SO4. Bone calcium (Ca) fluctuated as a result of the acidogenic lick. There was absorption of Ca when P was being resorbed and resorption of Ca when P was being absorbed into and out of bone. Bone Ca:P ratio ranged from 3.2 to 6.4 among the control group and 1.6 to 4.3 among the treatment group. Animals receiving the acidogenic lick had a higher percentage ash compared to the control group for most of the experimental period. Bone magnesium (Mg) fluctuated in response to the acidogenic lick, and it was difficult to show a relationship between bone Mg and Ca or P. The overall mean cortical bone thickness was significantly (P < 0.05) greater in treatment (1.60 mm) compared with control (1.43 mm) calves and this was also true at sampling periods 2, 4, 5 and 6. Bone thickness followed bone P and not bone Ca. Results from this research indicate that the addition of ammonium sulphate to a lick had a beneficial effect in improving the P status by increasing bone P and improving the mineral status of bone by increasing the thickness of cortical bone and percentage ash.

  8. ADAR1 ablation decreases bone mass by impairing osteoblast function in mice.

    PubMed

    Yu, Shibing; Sharma, Rohit; Nie, Daibang; Jiao, Hongli; Im, Hee-Jeong; Lai, Yumei; Zhao, Zhongfang; Zhu, Ke; Fan, Jie; Chen, Di; Wang, Qingde; Xiao, Guozhi

    2013-01-15

    Bone mass is controlled through a delicate balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption. We show here that RNA editing enzyme adenosine deaminase acting on RNA 1 (ADAR1) is critical for proper control of bone mass. Postnatal conditional knockout of Adar1 (the gene encoding ADAR1) resulted in a severe osteopenic phenotype. Ablation of the Adar1 gene significantly suppressed osteoblast differentiation without affecting osteoclast differentiation in bone. In vitro deletion of the Adar1 gene decreased expression of osteoblast-specific osteocalcin and bone sialoprotein genes, alkaline phosphatase activity, and mineralization, suggesting a direct intrinsic role of ADAR1 in osteoblasts. ADAR1 regulates osteoblast differentiation by, at least in part, modulation of osterix expression, which is essential for bone formation. Further, ablation of the Adar1 gene decreased the proliferation and survival of bone marrow stromal cells and inhibited the differentiation of mesenchymal stem cells towards osteoblast lineage. Finally, shRNA knockdown of the Adar1 gene in MC-4 pre-osteoblasts reduced cyclin D1 and cyclin A1 expression and cell growth. Our results identify ADAR1 as a new key regulator of bone mass and suggest that ADAR1 functions in this process mainly through modulation of the intrinsic properties of osteoblasts (i.e., proliferation, survival and differentiation).

  9. The roles of the skeleton and phosphorus in the CKD mineral bone disorder.

    PubMed

    Hruska, Keith A; Mathew, Suresh

    2011-03-01

    The CKD mineral bone disorder is a new term coined to describe the multiorgan system failure that is a major component of the excess cardiovascular mortality and morbidity complicating decreased kidney function. This syndrome embodies new discoveries of organ-to-organ communication including the skeletal hormone fibroblast growth factor-23 (FGF-23), which signals the status of skeletal mineral deposition to the kidney. The CKD mineral bone disorder begins with mild decreases in kidney function (stage 2 CKD) affecting the skeleton, as marked by increased FGF-23 secretion. At this stage, the stimulation of cardiovascular risk has begun and the increases in FGF-23 levels are strongly predictive of cardiovascular events. Later in CKD, hyperphosphatemia ensues when FGF-23 and hyperparathyroidism are no longer sufficient to maintain phosphate excretion. Hyperphosphatemia has been shown to be a direct stimulus to several cell types including vascular smooth muscle cells migrating to the neointima of atherosclerotic plaques. Phosphorus stimulates FGF-23 secretion by osteocytes and expression of the osteoblastic transcriptome, thereby increasing extracellular matrix mineralization in atherosclerotic plaques, hypertrophic cartilage, and skeletal osteoblast surfaces. In CKD, the skeleton positively contributes to hyperphosphatemia through excess bone resorption and inhibition of matrix mineralization. Thus, through the action of phosphorus, FGF-23, and other newly discovered skeletal hormones, such as osteocalcin, the skeleton plays an important role in the occurrence of cardiovascular morbidity in CKD.

  10. Osteoblast extracellular Ca2+ -sensing receptor regulates bone development, mineralization, and turnover.

    PubMed

    Dvorak-Ewell, Melita M; Chen, Tsui-Hua; Liang, Nathan; Garvey, Caitlin; Liu, Betty; Tu, Chialing; Chang, Wenhan; Bikle, Daniel D; Shoback, Dolores M

    2011-12-01

    The extracellular Ca(2+) -sensing receptor (CaR), a G protein-coupled receptor responsible for maintenance of calcium homeostasis, is implicated in regulation of skeletal metabolism. To discern the role of the osteoblast CaR in regulation of bone development and remodeling, we generated mice in which the CaR is excised in a broad population of osteoblasts expressing the 3.6-kb a(1) (I) collagen promoter. Conditional knockouts had abnormal skeletal histology at birth and developed progressively reduced mineralization secondary to retarded osteoblast differentiation, evident by significantly reduced numbers of osteoblasts and decreased expression of collagen I, osteocalcin, and sclerostin mRNAs. Elevated expression of ankylosis protein, ectonucleotide pyrophosphatase/phosphodiesterase 1, and osteopontin mRNAs in the conditional knockout indicate altered regulation of genes important in mineralization. Knockout of the osteoblast CaR also resulted in increased expression of the receptor activator of NF-κB ligand (RANKL), the major stimulator of osteoclast differentiation and function, consistent with elevated osteoclast numbers in vivo. Osteoblasts from the conditional knockouts exhibited delayed differentiation, reduced mineralizing capacity, altered expression of regulators of mineralization, and increased ability to promote osteoclastogenesis in coculture experiments. We conclude that CaR signaling in a broad population of osteoblasts is essential for bone development and remodeling and plays an important role in the regulation of differentiation and expression of regulators of bone resorption and mineralization.

  11. Minodronic acid (ONO-5920/YM529) prevents decrease in bone mineral density and bone strength, and improves bone microarchitecture in ovariectomized cynomolgus monkeys.

    PubMed

    Mori, Hiroshi; Tanaka, Makoto; Kayasuga, Ryoji; Masuda, Taisei; Ochi, Yasuo; Yamada, Hiroyuki; Kishikawa, Katsuya; Ito, Masako; Nakamura, Toshitaka

    2008-11-01

    This study examined the effect of the highly potent nitrogen-containing bisphosphonate, minodronic acid (ONO-5920/YM529), on bone mineral density (BMD), bone turnover, bone microarchitecture and bone strength in ovariectomized (OVX) cynomolgus monkeys. Skeletally mature female cynomolgus monkeys, aged 9-17 years, were ovariectomized or sham-operated. Minodronic acid was administered orally once a day in doses of 0, 0.015, and 0.15 mg/kg from the day after surgery for 17 months. Bone resorption markers (urinary N-terminal cross-linking telopeptide of type I collagen and deoxypyridinoline), bone formation markers (serum osteocalcin and bone alkaline phosphatase) and lumbar vertebral BMD were measured at baseline and at 4, 8, 12 and 16 months after surgery. Treatment with minodronic acid dose-dependently inhibited OVX-induced increase in bone turnover markers and decrease in lumbar vertebral BMD, and minodronic acid at 0.15 mg/kg completely prevented these changes. At 17 months after surgery, minodronic acid also suppressed bone resorption (Oc.S/BS and N.Oc/BS) and bone formation (OS/BS, MS/BS, MAR, BFR/BS, and BFR/BV) in the lumbar vertebral bodies and tibia. In the mechanical tests, ultimate load on lumbar vertebral bodies and femoral neck of the OVX-control animals were significantly reduced compared to the sham animals. Minodronic acid prevented these reductions in bone strength at 0.15 mg/kg. There was significant correlation between BMD and bone strength, suggesting that the increase in bone strength was associated with the increase in BMD produced by minodronic acid. In micro-CT analysis of the lumbar vertebral bodies, minodronic acid improved trabecular architecture, converting rod structures into plate structures, and preventing the increase in trabecular disconnectivity at 0.15 mg/kg. In conclusion, similar to patients with postmenopausal osteoporosis, reduction in bone strength of lumbar vertebral bodies and femoral neck was clearly demonstrated in OVX

  12. Effects of variations in dietary calcium and phosphorus supply on plasma and bone osteocalcin concentrations and bone mineralization in growing pigs.

    PubMed

    Nicodemo, M L; Scott, D; Buchan, W; Duncan, A; Robins, S P

    1998-09-01

    Growing pigs were fed diets supplying 45% (low), 70% (intermediate) and 100% (high) recommended dietary allowances of calcium (the Ca:P ratio was kept constant), but otherwise adequate in nutrients. The effects of varying calcium and phosphorus intakes on bone and plasma osteocalcin were monitored. Mineral content of the diet did not affect feed conversion and live weight gain. Plasma phosphorus concentrations decreased significantly in pigs fed a low mineral diet compared with those fed the high mineral diet, but there were no changes in plasma calcium and osteocalcin concentrations. Bones from the low mineral group had marked reductions in dry matter, calcium and phosphorus contents, as well as increased collagen, pyridinoline and deoxypyridinoline concentrations: osteocalcin concentrations in bone were unaffected by treatment. The results showed no direct link between osteocalcin and the degree of bone mineralization.

  13. 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.

  14. Increased fracture risk and low bone mineral density in patients with loeys-dietz syndrome.

    PubMed

    Tan, Eric W; Offoha, Roosevelt U; Oswald, Gretchen L; Skolasky, Richard L; Dewan, Ashvin K; Zhen, Gehua; Shapiro, Jay R; Dietz, Harry C; Cao, Xu; Sponseller, Paul D

    2013-08-01

    Loeys-Dietz syndrome is a recently recognized connective tissue disorder with widespread systemic involvement. Little is known about its skeletal phenotype. Our goal was to investigate the risk of fracture and incidence of low bone mineral density in patients with Loeys-Dietz syndrome. We performed a cross-sectional, descriptive, survey-based study with subsequent chart review from July 2011 to April 2012. Fifty-seven patients (26 men, 31 women) with Loeys-Dietz syndrome confirmed by genetic testing completed the survey (average age, 25.3 years; range, 0.9-79.6 years). There were a total of 51 fractures (33 patients): 35 fractures in the upper extremities, 14 in the lower extremities, and two in the spine. Fourteen patients (24.6%) reported two or more fractures. There was a 50% risk of fracture by age 14 years. The incidence of any fracture in this cohort was 3.86 per 100 person-years. Seventeen patients had dual-energy X-ray absorptiometry scans available for review, 11 (64.7%) of whom had at least one fracture. Thirteen included lumbar spine absorptiometry reports; eight (61.5%) indicated low or very low bone mineral density. In the left hip, ten of 14 participants (71.4%) had low or very low bone mineral density. In the left femoral neck, nine of 13 participants (69.2%) had low or very low bone mineral density. The lowest Z- and T-scores were not associated with an increased number of fractures. Patients with Loeys-Dietz syndrome have a high risk of fracture and a high incidence of low bone mineral density.

  15. VEGF serum concentrations in patients with long bone fractures: a comparison between impaired and normal fracture healing.

    PubMed

    Sarahrudi, Kambiz; Thomas, Anita; Braunsteiner, Tomas; Wolf, Harald; Vécsei, Vilmos; Aharinejad, Seyedhossein

    2009-10-01

    Vascular endothelial growth factor (VEGF) plays an important role in the bone repair process as a potent mediator of angiogenesis and it influences directly osteoblast differentiation. Inhibiting VEGF suppresses angiogenesis and callus mineralization in animals. However, no data exist so far on systemic expression of VEGF with regard to delayed or failed fracture healing in humans. One hundred fourteen patients with long bone fractures were included in the study. Serum samples were collected over a period of 6 months following a standardized time schedule. VEGF serum concentrations were measured. Patients were assigned to one of two groups according to their course of fracture healing. The first group contained 103 patients with physiological fracture healing. Eleven patients with delayed or nonunions formed the second group of the study. In addition, 33 healthy volunteers served as controls. An increase of VEGF serum concentration within the first 2 weeks after fracture in both groups with a following decrease within 6 months after trauma was observed. Serum VEGF concentrations in patients with impaired fracture healing were higher compared to the patients with physiological healing during the entire observation period. However, statistically significant differences were not observed at any time point between both groups. VEGF concentrations in both groups were significantly higher than those in controls. The present results show significantly elevated serum concentrations of VEGF in patients after fracture of long bones especially at the initial healing phase, indicating the importance of VEGF in the process of fracture healing in humans.

  16. Natural calcium isotonic composition of urine as a marker of bone mineral balance

    USGS Publications Warehouse

    Skulan, J.; Bullen, T.; Anbar, A.D.; Puzas, J.E.; Shackelford, L.; LeBlanc, A.; Smith, S.M.

    2007-01-01

    Background: We investigated whether changes in the natural isotopic composition of calcium in human urine track changes in net bone mineral balance, as predicted by a model of calcium isotopic behavior in vertebrates. If so, isotopic analysis of natural urine or blood calcium could be used to monitor short-term changes in bone mineral balance that cannot be detected with other techniques. Methods: Calcium isotopic compositions are expressed as ??44Ca, or the difference in parts per thousand between the 44Ca/40Ca of a sample and the 44Ca/ 40Ca of a standard reference material. ??44Ca was measured in urine samples from 10 persons who participated in a study of the effectiveness of countermeasures to bone loss in spaceflight, in which 17 weeks of bed rest was used to induce bone loss. Study participants were assigned to 1 of 3 treatment groups: controls received no treatment, one treatment group received alendronate, and another group performed resistive exercise. Measurements were made on urine samples collected before, at 2 or 3 points during, and after bed rest. Results: Urine ??44Ca values during bed rest were lower in controls than in individuals treated with alendronate (P <0.05, ANOVA) or exercise (P <0.05), and lower than the control group baseline (P <0.05, Mest). Results were consistent with the model and with biochemical and bone mineral density data. Conclusion: Results confirm the predicted relationship between bone mineral balance and calcium isotopes, suggesting that calcium isotopic analysis of urine might be refined into a clinical and research tool. ?? 2007 American Association for Clinical Chemistry.

  17. Moderate alcohol consumption and increased bone mineral density: potential ethanol and non-ethanol mechanisms.

    PubMed

    Jugdaohsingh, R; O'Connell, M A; Sripanyakorn, S; Powell, J J

    2006-08-01

    Mounting epidemiological evidence indicates an association between the moderate ingestion of alcoholic beverages and higher bone mineral density (v. abstainers). More limited findings provide some evidence for translation of this association into reduced fracture risk, but further studies are required. Here, these data are reviewed and caveats in their assimilation, comparison and interpretation as well as in the use and application of bone health indices are discussed. Whilst it is concluded that evidence is now strong for the moderate alcohol-bone health association, at least in relation to bone mineral density, mechanisms are less clear. Both ethanol and non-ethanol components have been implicated as factors that positively affect bone health in the light of moderate consumption of alcoholic beverages, and four particular areas are discussed. First, recent findings suggest that moderate ethanol consumption acutely inhibits bone resorption, in a non-parathyroid hormone- and non-calcitonin-dependent fashion, which can only partly be attributed to an energy effect. Second, critical review of the literature does not support a role for moderate ethanol consumption affecting oestrogen status and leading to a knock-on effect on bone. Third, Si is present at high levels in certain alcoholic beverages, especially beer, and may have a measurable role in promoting bone formation. Fourth, a large body of work indicates that phytochemicals (e.g. polyphenols) from alcoholic beverages could influence bone health, but human data are lacking. With further work it is hoped to be able to model epidemiological observations and provide a clear pathway between the magnitude of association and the relative contribution of these mechanisms for the major classes of alcoholic beverage.

  18. Sarcopenia in premenopausal and postmenopausal women with osteopenia, osteoporosis and normal bone mineral density.

    PubMed

    Walsh, Marianne C; Hunter, Gary R; Livingstone, Margaret Barbara

    2006-01-01

    Sarcopenia, the decline of muscle mass with age, causes impaired gait, disability and falls. It may therefore increase the risk of fracture for osteoporotic women. The aims of this study were to determine the prevalence of sarcopenia in osteopenic and osteoporotic women, and to determine if hormone replacement therapy (HRT), diet, or physical activity (PA) has a role in the prevention of sarcopenia. One hundred and thirty-one premenopausal and 82 postmenopausal (54 taking HRT) healthy women (17-77 years) volunteered for the study. Body composition was measured by dual X-ray absorptiometry (DXA). Sarcopenia was defined as a relative skeletal muscle index (RSMI) (appendicular skeletal muscle mass divided by height) below 5.45 kg/m2. Osteopenia was defined by a densitometric t-score for bone mineral density (BMD) (g/cm2) below -1.0 and osteoporosis by a t-score below -2.5. Nutrient intake was assessed using 3-day food records and physical activity (PA) was measured using the Baecke Physical Activity Questionnaire. Pearson chi-squared, independent t-tests, simple correlation and multiple regression were used to analyze the data. In premenopausal osteopenic women the prevalence of sarcopenia was 12.5%. In postmenopausal women it was 25% for those with osteopenia, and 50% for those with osteoporosis. PA was independently related to RSMI (beta=0.222, p=0.0001), but diet and HRT were not. After adjusting for PA, RSMI was not significantly related to BMD. These data suggest that the relationship between RSMI, BMD and risk of osteoporosis may largely be mediated through participation in PA. Sarcopenia screening simultaneous to BMD examinations by DXA, may be of value in identifying osteoporotic women with sarcopenia, a group that may be most in need of exercise interventions to increase muscle and BMD.

  19. The application of backscattered ultrasound and photoacoustic signals for assessment of bone collagen and mineral contents

    PubMed Central

    Lashkari, Bahman; Yang, Lifeng

    2015-01-01

    Background This study examines the backscattered ultrasound (US) and back-propagating photoacoustic (PA) signals from trabecular bones, and their variations with reduction in bone minerals and collagen content. While the collagen status is directly related to the strength of the bone, diagnosis of its condition using US remains a challenge. Methods For both PA and US methods, coded-excitation signals and matched filtering were utilized to provide high sensitivity of the detected signal. The optical source was a 805-nm CW laser and signals were detected employing a 2.2-MHz ultrasonic transducer. Bone decalcification and decollagenization were induced with mild ethylenediaminetetraacetic acid (EDTA) and sodium hypochlorite solutions, respectively. Results The PA and US signals were measured on cattle bones, and apparent integrated backscatter/back-propagating (AIB) parameters were compared before and after demineralization and decollagenization. Conclusions The results show that both PA and US are sensitive to mineral changes. In addition, PA is also sensitive to changes in the collagen content of the bone, but US is not significantly sensitive to these changes. PMID:25694953

  20. Single-walled carbon nanotubes functionalized with sodium hyaluronate enhance bone mineralization

    PubMed Central

    Sá, M.A.; Ribeiro, H.J.; Valverde, T.M.; Sousa, B.R.; Martins-Júnior, P.A.; Mendes, R.M.; Ladeira, L.O.; Resende, R.R.; Kitten, G.T.; Ferreira, A.J.

    2015-01-01

    The aim of this study was to evaluate the effects of sodium hyaluronate (HY), single-walled carbon nanotubes (SWCNTs) and HY-functionalized SWCNTs (HY-SWCNTs) on the behavior of primary osteoblasts, as well as to investigate the deposition of inorganic crystals on titanium surfaces coated with these biocomposites. Primary osteoblasts were obtained from the calvarial bones of male newborn Wistar rats (5 rats for each cell extraction). We assessed cell viability using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay and by double-staining with propidium iodide and Hoechst. We also assessed the formation of mineralized bone nodules by von Kossa staining, the mRNA expression of bone repair proteins, and the deposition of inorganic crystals on titanium surfaces coated with HY, SWCNTs, or HY-SWCNTs. The results showed that treatment with these biocomposites did not alter the viability of primary osteoblasts. Furthermore, deposition of mineralized bone nodules was significantly increased by cells treated with HY and HY-SWCNTs. This can be partly explained by an increase in the mRNA expression of type I and III collagen, osteocalcin, and bone morphogenetic proteins 2 and 4. Additionally, the titanium surface treated with HY-SWCNTs showed a significant increase in the deposition of inorganic crystals. Thus, our data indicate that HY, SWCNTs, and HY-SWCNTs are potentially useful for the development of new strategies for bone tissue engineering. PMID:26648087

  1. Control of in vivo mineral bone cement degradation.

    PubMed

    Kanter, Britta; Geffers, Martha; Ignatius, Anita; Gbureck, Uwe

    2014-07-01

    The current study aimed to prevent the formation of hydroxyapatite reprecipitates in brushite-forming biocements by minimizing the availability of free Ca(2+) ions in the cement matrix. This was achieved by both maximizing the degree of cement setting to avoid unreacted, calcium-rich cement raw materials which can deliver Ca(2+) directly to the cement matrix after dissolution, and by a reduction in porosity to reduce Ca(2+) diffusion into the set cement matrix. In addition, a biocement based on the formation of the magnesium phosphate mineral struvite (MgNH4PO4·6H2O) was tested, which should prevent the formation of low-solubility hydroxyapatite reprecipitates due to the high magnesium content. Different porosity levels were fabricated by altering the powder-to-liquid ratio at which the cements were mixed and the materials were implanted into mechanically unloaded femoral defects in sheep for up to 10 months. While the higher-porosity brushite cement quantitatively transformed into crystalline octacalcium phosphate after 10 months, slowing down cement resorption, a lower-porosity brushite cement modification was found to be chemically stable with the absence of reprecipitate formation and minor cement resorption from the implant surface. In contrast, struvite-forming cements were much more degradable due to the absence of mineral reprecipitates and a nearly quantitative cement degradation was found after 10 months of implantation.

  2. Minerals and vitamins in bone health: the potential value of dietary enhancement.

    PubMed

    Bonjour, Jean-Philippe; Guéguen, Léon; Palacios, Cristina; Shearer, Martin J; Weaver, Connie M

    2009-06-01

    Nutrition is important to bone health, and a number of minerals and vitamins have been identified as playing a potential role in the prevention of bone diseases, particularly osteoporosis. Despite this, there is currently no consensus on maximum levels to allow in food or as dietary supplements. The benefits of supplementation of populations at risk of osteoporosis with Ca and vitamin D are well established. Prolonged supplementation of Ca and vitamin D in elderly has been shown to prevent bone loss, and in some intervention studies to prevent fragility fractures. Although P is essential to bone health, the average intake is considered to be more than sufficient and supplementation could raise intake to adverse levels. The role of vitamin K in bone health is less well defined, though it may enhance the actions of Ca and vitamin D. Sr administered in pharmacological doses as the ranelate salt was shown to prevent fragility fractures in postmenopausal osteoporosis. However, there is no hard evidence that supplementation with Sr salts would be beneficial in the general population. Mg is a nutrient implicated in bone quality, but the benefit of supplementation via foodstuffs remains to be established. A consensus on dietary supplementation for bone health should balance the risks, for example, exposure of vulnerable populations to values close to maximal tolerated doses, against evidence for benefits from randomised clinical trials, such as those for Ca and vitamin D. Feedback from community studies should direct further investigations and help formulate a consensus on dietary supplementation for bone health.

  3. ToF-SIMS analysis of osteoblast-like cells and their mineralized extracellular matrix on strontium enriched bone cements.

    PubMed

    Kokesch-Himmelreich, Julia; Schumacher, Matthias; Rohnke, Marcus; Gelinsky, Michael; Janek, Jürgen

    2013-12-01

    Commonly used implants for therapeutic approaches of non-systemically impaired bone do not sufficiently support the healing process of osteoporotic bone. Since strontium (II) has been proven as an effective anti-osteoporotic drug new types of strontium enriched calcium phosphate bone cements were developed. As osteoporosis is characterized by an imbalance of osteoblast and osteoclast activity the influence of this newly generated strontium enriched biomaterials on the cellular behavior of osteoblast-like cells was investigated by time of flight secondary ion mass spectrometry (ToF-SIMS). ToF-SIMS is used to analyze whether strontium is incorporated in the mineralized extracellular matrix (mECM) and whether there is strontium uptake by osteogenically differentiated human mesenchymal stem cells (hMSCs). Therefore hMSCs were cultured in osteogenic differentiation medium for 21 days on two different strontium enriched bone cements (S100 and A10) and for reference also on the pure calcium phosphate cement (CPC) and on a silicon wafer. The distribution of strontium in the osteoblast-like cells and within their mineralized extracellular matrix was analyzed. A higher intensity of the strontium signal could be detected in the region of the mECM, synthesized by cells cultivated on the Sr- substituted bone cement (S100) in comparison to the reference groups. The osteoblast-like cells used the released strontium from the biomaterial to synthesize their mECM. Apart from that a uniform strontium distribution was measured within all investigated cells. However, different amounts of strontium were found in cells cultured on different biomaterials and substrates. Compared to the negative controls the strontium content in the cells on the strontium enriched biomaterials was much higher. A higher concentration of strontium inside the cells means that more strontium can take part in signaling pathways. As strontium is known for its beneficial effects on osteoblasts by promoting

  4. Comparative investigation of bone mineral density using CT and DEXA in a canine femoral model.

    PubMed

    Lucas, Karin; Behrens, Bernd-Arno; Nolte, Ingo; Galindo-Zamora, Vladimir; Betancur, Stefanie; Almohallami, Amer; Bouguecha, Anas; Mostafa, Ayman; Lerch, Matthias; Stukenborg-Colsman, Christina; Wefstaedt, Patrick

    2017-04-07

    Bone density measurements using computed tomography (CT) instead of dual-energy X-ray absorptiometry (DEXA) are currently of great interest in human and veterinary medical research as it would be beneficial to use CT scans obtained for other indications also for determining bone density. For Hounsfield units (HU) measured with CT in specific regions of interests (ROIs) in one or several slice/s a corrrelation with bone mineral density (BMD) measured by DEXA in humans and dogs of between 0.44 and 0.77 is reported in the literature. In the present study instead certain volumes of interest (VOIs) obtained by CT scan and the corresponding HU to the respective VOIs were compared with the bone mineral density of the corresponding areas measured by DEXA. The aim of the study was to investigate whether this procedure gives more accurate information about bone density of the bones as 3-dimensional objects of the respective patient. Correlation between measured HU in the respective VOI and BMD measured with DEXA in the corresponding ROI showed a very good correlation of 0.93. Linear regression with R(2) = 0.85 (p = 0.0262) was calculated. Except for VOI5, similar distribution of values and significant differences (p < 0.0001-0.0087) between ROIs/VOIs were detected. Determining HU for assessing bone mineral density in a certain volume provides more accurate results than those previously reported from 2-dimensional (2D) CT measurements. This article is protected by copyright. All rights reserved.

  5. Decreased osteoclastogenesis and high bone mass in mice with impaired insulin clearance due to liver-specific inactivation to CEACAM1.

    PubMed

    Huang, S; Kaw, M; Harris, M T; Ebraheim, N; McInerney, M F; Najjar, S M; Lecka-Czernik, B

    2010-04-01

    Type 2 diabetes is associated with normal-to-higher bone mineral density (BMD) and increased rate of fracture. Hyperinsulinemia and hyperglycemia may affect bone mass and quality in the diabetic skeleton. In order to dissect the effect of hyperinsulinemia from the hyperglycemic impact on bone homeostasis, we have analyzed L-SACC1 mice, a murine model of impaired insulin clearance in liver causing hyperinsulinemia and insulin resistance without fasting hyperglycemia. Adult L-SACC1 mice exhibit significantly higher trabecular and cortical bone mass, attenuated bone formation as measured by dynamic histomorphometry, and reduced number of osteoclasts. Serum levels of bone formation (BALP) and bone resorption markers (TRAP5b and CTX) are decreased by approximately 50%. The L-SACC1 mutation in the liver affects myeloid cell lineage allocation in the bone marrow: the (CD3(-)CD11b(-)CD45R(-)) population of osteoclast progenitors is decreased by 40% and the number of (CD3(-)CD11b(-)CD45R(+)) B-cell progenitors is increased by 60%. L-SACC1 osteoclasts express lower levels of c-fos and RANK and their differentiation is impaired. In vitro analysis corroborated a negative effect of insulin on osteoclast recruitment, maturation and the expression levels of c-fos and RANK transcripts. Although bone formation is decreased in L-SACC1 mice, the differentiation potential and expression of the osteoblast-specific gene markers in L-SACC1-derived mesenchymal stem cells (MSC) remain unchanged as compared to the WT. Interestingly, however, MSC from L-SACC1 mice exhibit increased PPARgamma2 and decreased IGF-1 transcript levels. These data suggest that high bone mass in L-SACC1 animals results, at least in part, from a negative regulatory effect of insulin on bone resorption and formation, which leads to decreased bone turnover. Because low bone turnover contributes to decreased bone quality and an increased incidence of fractures, studies on L-SACC1 mice may advance our understanding of

  6. Angiopoietin-1 peptide QHREDGS promotes osteoblast differentiation, bone matrix deposition and mineralization on biomedical materials.

    PubMed

    Feric, Nicole; Cheng, Calvin C H; Goh, M Cynthia; Dudnyk, Vyacheslav; Di Tizio, Val; Radisic, Milica

    2014-10-01

    Bone loss occurs as a consequence of a variety of diseases as well as from traumatic injuries, and often requires therapeutic intervention. Strategies for repairing and replacing damaged and/or lost bone tissue include the use of biomaterials and medical implant devices with and without osteoinductive coatings. The soluble growth factor angiopoietin-1 (Ang-1) has been found to promote cell adhesion and survival in a range of cell types including cardiac myocytes, endothelial cells and fibroblasts through an integrin-dependent mechanism. Furthermore, the short sequence QHREDGS has been identified as the integrin-binding sequence of Ang-1 and as a synthetic peptide has been found to possess similar integrin-dependent effects as Ang-1 in the aforementioned cell types. Integrins have been implicated in osteoblast differentiation and bone mineralization, processes critical to bone regeneration. By binding integrins on the osteoblast surface, QHREDGS could promote cell survival and adhesion, as well as conceivably osteoblast differentiation and bone mineralization. Here we immobilized QHREDGS onto polyacrylate (PA)-coated titanium (Ti) plates and polyethylene glycol (PEG) hydrogels. The osteoblast differentiation marker, alkaline phosphatase, peaked in activity 4-12 days earlier on the QHREDGS-immobilized PA-coated Ti plates than on the unimmobilized, DGQESHR (scrambled)- and RGDS-immobilized surfaces. Significantly more bone matrix was deposited on the QHREDGS-immobilized Ti surface than on the other surfaces as determined by atomic force microscopy. The QHREDGS-immobilized hydrogels also had a significantly higher mineral-to-matrix (M/M) ratio determined by Fourier transform infrared spectroscopy. Alizarin Red S and von Kossa staining and quantification, and environmental scanning electron microscopy showed that while both the QHREDGS- and RGDS-immobilized surfaces had extensive mineralization relative to the unimmobilized and DGQESHR-immobilized surfaces, the

  7. Mineralization induction effects of osteopontin, bone sialoprotein, and dentin phosphoprotein on a biomimetic collagen substrate.

    PubMed

    Zurick, Kevin M; Qin, Chunlin; Bernards, Matthew T

    2013-06-01

    Native bone tissue is composed of a matrix of collagen, noncollagenous proteins, and calcium phosphate minerals, which are primarily hydroxyapatite. The SIBLING (small integrin-binding ligand, N-linked glycoprotein) family of proteins is the primary noncollagenous protein group found in mineralized tissues. In this work, the mineralization induction capabilities of three of the SIBLING members, bone sialoprotein (BSP), osteopontin (OPN), and the calcium-binding subdomain of dentin sialophosphoprotein, dentin phosphoprotein (DPP), are directly compared on a biomimetic collagen substrate. A self-assembled, loosely aligned collagen fibril substrate was prepared, and then (125) I-radiolabeled adsorption isotherms were developed for BSP, OPN, and DPP. The results showed that BSP exhibited the highest binding capacity for collagen at lower concentrations, followed by DPP and OPN. However, at the highest concentrations, all three proteins had similar adsorption levels. The adsorption isotherms were then used to identify conditions that resulted in identical amounts of adsorbed protein. These substrates were prepared and placed in simulated body fluid for 5, 10, and 24 h at 37°C. The resulting mineral morphology was assessed by atomic force microscopy, and the composition was determined using photochemical assays. Mineralization was seen in the presence of all the proteins. However, DPP was seen to be the only protein that formed individual mineral nodules similar to those seen in developing bone. This suggests that DPP plays a significant role in the biomineralization process and that the incorporation of DPP into tissue engineering constructs may facilitate the induction of biomimetic mineral formation.

  8. GLUCOCORTICOID EFFECTS ON CHANGES IN BONE MINERAL DENSITY AND CORTICAL STRUCTURE IN CHILDHOOD NEPHROTIC SYNDROME

    PubMed Central

    Tsampalieros, Anne; Gupta, Pooja; Denburg, Michelle R; Shults, Justine; Zemel, Babette S; Mostoufi-Moab, Sogol; Wetzsteon, Rachel J; Herskovitz, Rita M; Whitehead, Krista M; Leonard, Mary B.

    2012-01-01

    The impact of glucocorticoids (GC) on skeletal development has not been established. The objective of this study was to examine changes in volumetric BMD (vBMD) and cortical structure over one year in childhood nephrotic syndrome (NS) and to identify associations with concurrent GC exposure and growth. Fifty-six NS participants, ages 5–21 years, were enrolled a median of 4.3 (0.5, 8.1) years after diagnosis. Tibia peripheral quantitative CT (pQCT) scans were obtained at enrollment and 6 and 12 months later. Sex, race and age-specific Z-scores were generated for trabecular vBMD (TrabBMD-Z), cortical vBMD (CortBMD-Z), and cortical area (CortArea-Z) based on > 650 reference participants. CortArea-Z was further adjusted for tibia length-for-age Z-score. Quasi-least squares regression was used to identify determinants of changes in pQCT Z-scores. At enrollment, mean TrabBMD-Z (−0.54 ±1.32) was significantly lower (p=0.0001) and CortBMD-Z (0.73 ± 1.16, p<0.0001) and CortArea-Z (0.27 ± 0.91, p=0.03) significantly greater in NS, vs. reference participants, as previously described. Forty-eight (86%) participants were treated with GC over the study interval (median dose 0.29 mg/kg/day). On average, TrabBMD-Z and CortBMD-Z did not change significantly over the study interval; however, CortArea-Z decreased (p=0.003). Greater GC dose (p<0.001), lesser increases in tibia length (p<0.001) and lesser increases in CortArea-Z (p=0.003) were independently associated with greater increases in CortBMD-Z. Greater increases in tibia length were associated with greater declines in CortArea-Z (p < 0.01); this association was absent in reference participants (interaction p<0.02). In conclusion, GC therapy was associated with increases in CortBMD-Z, potentially related to suppressed bone formation and greater secondary mineralization. Conversely, greater growth and expansion of CortArea-Z (i.e. new bone formation) were associated with declines in CortBMD-Z. Greater linear growth was

  9. Loss of insulin receptor in osteoprogenitor cells impairs structural strength of bone.

    PubMed

    Thrailkill, Kathryn; Bunn, R Clay; Lumpkin, Charles; Wahl, Elizabeth; Cockrell, Gael; Morris, Lindsey; Kahn, C Ronald; Fowlkes, John; Nyman, Jeffry S

    2014-01-01

    Type 1 diabetes mellitus (T1D) is associated with decreased bone mineral density, a deficit in bone structure, and subsequently an increased risk of fragility fracture. These clinical observations, paralleled by animal models of T1D, suggest that the insulinopenia of T1D has a deleterious effect on bone. To further examine the action of insulin signaling on bone development, we generated mice with an osteoprogenitor-selective (osterix-Cre) ablation of the insulin receptor (IR), designated OIRKO. OIRKO mice exhibited an 80% decrease in IR in osteoblasts. Prenatal elimination of IR did not affect fetal survival or gross morphology. However, loss of IR in mouse osteoblasts resulted in a postnatal growth-constricted phenotype. By 10-12 weeks of age, femurs of OIRKO mice were more slender, with a thinner diaphyseal cortex and, consequently, a decrease in whole bone strength when subjected to bending. In male mice alone, decreased metaphyseal trabecular bone, with thinner and more rodlike trabeculae, was also observed. OIRKO mice did not, however, exhibit abnormal glucose tolerance. The skeletal phenotype of the OIRKO mouse appeared more severe than that of previously reported bone-specific IR knockdown models, and confirms that insulin receptor expression in osteoblasts is critically important for proper bone development and maintenance of structural integrity.

  10. Time Related Changes of Mineral and Collagen and Their Roles in Cortical Bone Mechanics of Ovariectomized Rabbits

    PubMed Central

    Xu, Chao; Wu, Zi-Xiang; Zhang, Yang; Feng, Ya-Fei; Yan, Ya-Bo; Lei, Wei

    2015-01-01

    As cortical bone has a hierarchical structure, the macroscopic bone strength may be affected by the alterations of mineral crystal and collagen, which are main components of cortical bone. Limited studies focused on the time related alterations of these two components in osteoporosis, and their contributions to bone mechanics at tissue level and whole-bone level. Therefore, the purpose of this study was to elucidate the time related changes of mineral and collagen in cortical bone of ovariectomized (OVX) rabbits, and to relate these changes to cortical bone nanomechanics and macromechanics. 40 Rabbits (7-month-old) were randomly allocated into two groups (OVX and sham). OVX group received bilateral ovariectomy operation. Sham group received sham-OVX operation. Cortical bone quality of five rabbits in each group were assessed by DXA, μCT, nanoindentation, Fourier transform infrared (FTIR) spectroscopy and biomechanical tests (3-point bending of femoral midshaft) at pre-OVX, 4, 6, and 8 weeks after OVX. As time increased from pre-OVX to 8 weeks, the mineral to matrix ratio decreased with time, while both collagen crosslink ratio and crystallinity increased with time in OVX group. Elastic modulus and hardness measured by nanoindentation, whole-bone strength measured by biomechanical tests all decreased in OVX group with time. Bone material properties measured by FTIR correlated well with nano or whole-bone level mechanics. However, bone mineral density (BMD), structure, tissue-level and whole-bone mechanical properties did not change with age in sham group. Our study demonstrated that OVX could affect the tissue-level mechanics and bone strength of cortical bone. And this influence was attributed to the time related alterations of mineral and collagen properties, which may help us to design earlier interventions and more effective treatment strategies on osteoporosis. PMID:26046792

  11. Multiple Myeloma Impairs Bone Marrow Localization of Effector Natural Killer Cells by Altering the Chemokine Microenvironment.

    PubMed

    Ponzetta, Andrea; Benigni, Giorgia; Antonangeli, Fabrizio; Sciumè, Giuseppe; Sanseviero, Emilio; Zingoni, Alessandra; Ricciardi, Maria Rosaria; Petrucci, Maria Teresa; Santoni, Angela; Bernardini, Giovanni

    2015-11-15

    Natural killer (NK) cells are key innate immune effectors against multiple myeloma, their activity declining in multiple myeloma patients with disease progression. To identify the mechanisms underlying NK cell functional impairment, we characterized the distribution of functionally distinct NK cell subsets in the bone marrow of multiple myeloma-bearing mice. Herein we report that the number of KLRG1(-) NK cells endowed with potent effector function rapidly and selectively decreases in bone marrow during multiple myeloma growth, this correlating with decreased bone marrow NK cell degranulation in vivo. Altered NK cell subset distribution was dependent on skewed chemokine/chemokine receptor axes in the multiple myeloma microenvironment, with rapid downmodulation of the chemokine receptor CXCR3 on NK cells, increased CXCL9 and CXCL10, and decreased CXCL12 expression in bone marrow. Similar alterations in chemokine receptor/chemokine axes were observed in patients with multiple myeloma. Adoptive transfer experiments demonstrated that KLRG1(-) NK cell migration to the bone marrow was more efficient in healthy than multiple myeloma-bearing mice. Furthermore, bone marrow localization of transferred CXCR3-deficient NK cells with respect to wild type was enhanced in healthy and multiple myeloma-bearing mice, suggesting that CXCR3 restrains bone marrow NK cell trafficking. Our results indicate that multiple myeloma-promoted CXCR3 ligand upregulation together with CXCL12 downmodulation act as exit signals driving effector NK cells outside the bone marrow, thus weakening the antitumor immune response at the primary site of tumor growth.

  12. Plasminogen Activator Inhibitor-1 Is Involved in Impaired Bone Repair Associated with Diabetes in Female Mice

    PubMed Central

    Mao, Li; Kawao, Naoyuki; Tamura, Yukinori; Okumoto, Katsumi; Okada, Kiyotaka; Yano, Masato; Matsuo, Osamu; Kaji, Hiroshi

    2014-01-01

    Previous studies suggest that fracture healing is impaired in diabetes; however, the underlying mechanism remains unclear. Here, we investigated the roles of plasminogen activator inhibitor-1 (PAI-1) in the impaired bone repair process by using streptozotocin (STZ)-induced diabetic female wild-type (PAI-1+/+) and PAI-1-deficient (PAI-1−/−) mice. Bone repair and the number of alkaline phosphatase (ALP)-positive cells at the site of a femoral bone damage were comparable in PAI-1+/+ and PAI-1−/− mice without STZ treatment. Although the bone repair process was delayed by STZ treatment in PAI-1+/+ mice, this delayed bone repair was blunted in PAI-1−/− mice. The reduction in the number of ALP-positive cells at the site of bone damage induced by STZ treatment was attenuated in PAI-1−/− mice compared to PAI-1+/+ mice. On the other hand, PAI-1 deficiency increased the levels of ALP and type I collagen mRNA in female mice with or without STZ treatment, and the levels of Osterix and osteocalcin mRNA, suppressed by diabetic state in PAI-1+/+ mice, were partially protected in PAI-1−/− mice. PAI-1 deficiency did not affect formation of the cartilage matrix and the levels of types II and X collagen and aggrecan mRNA suppressed by STZ treatment, although PAI-1 deficiency increased the expression of chondrogenic markers in mice without STZ treatment. The present study indicates that PAI-1 is involved in the impaired bone repair process induced by the diabetic state in part through a decrease in the number of ALP-positive cells. PMID:24651693

  13. Plasminogen activator inhibitor-1 is involved in impaired bone repair associated with diabetes in female mice.

    PubMed

    Mao, Li; Kawao, Naoyuki; Tamura, Yukinori; Okumoto, Katsumi; Okada, Kiyotaka; Yano, Masato; Matsuo, Osamu; Kaji, Hiroshi

    2014-01-01

    Previous studies suggest that fracture healing is impaired in diabetes; however, the underlying mechanism remains unclear. Here, we investigated the roles of plasminogen activator inhibitor-1 (PAI-1) in the impaired bone repair process by using streptozotocin (STZ)-induced diabetic female wild-type (PAI-1+/+) and PAI-1-deficient (PAI-1-/-) mice. Bone repair and the number of alkaline phosphatase (ALP)-positive cells at the site of a femoral bone damage were comparable in PAI-1+/+ and PAI-1-/- mice without STZ treatment. Although the bone repair process was delayed by STZ treatment in PAI-1+/+ mice, this delayed bone repair was blunted in PAI-1-/- mice. The reduction in the number of ALP-positive cells at the site of bone damage induced by STZ treatment was attenuated in PAI-1-/- mice compared to PAI-1+/+ mice. On the other hand, PAI-1 deficiency increased the levels of ALP and type I collagen mRNA in female mice with or without STZ treatment, and the levels of Osterix and osteocalcin mRNA, suppressed by diabetic state in PAI-1+/+ mice, were partially protected in PAI-1-/- mice. PAI-1 deficiency did not affect formation of the cartilage matrix and the levels of types II and X collagen and aggrecan mRNA suppressed by STZ treatment, although PAI-1 deficiency increased the expression of chondrogenic markers in mice without STZ treatment. The present study indicates that PAI-1 is involved in the impaired bone repair process induced by the diabetic state in part through a decrease in the number of ALP-positive cells.

  14. Dietary modifications alone do not improve bone mineral density in children with idiopathic hypercalciuria.

    PubMed

    Schwaderer, A L; Srivastava, T; Schueller, L; Cronin, R; Mahan, J D; Hains, D

    2011-11-01

    Prior cross-sectional studies have demonstrated an association between hypercalciuria and low bone mineral density (BMD) in children and adults. However, the natural history of BMD in children with hypercalciuria and its response to therapy has not been evaluated. The objective of this retrospective study was to determine the change over time in lumbar (L1 - L4) BMD Z-score measured on sequential DXA scans in 19 children with hypercalciuria treated with dietary recommendations without (n = 12, Group A) and with citrate (n = 7, Group B). The mean lumbar bone density Z-score/year decreased in Group A (-0.11 ±/0.41) indicating that children with hypercalciuria lose L1 - L4 BMD over time. In contrast, the L1 - L4 BMD Zscore/ year increased in Group B (0.19 ± 0.38) suggesting that pharmacologic therapy may reverse this trend. Similarly 75% of patients in Group A, but only 29% patients in Group B had a decrease in L1 - L4 BMD. There was a definite, although not significant, trend towards improved mean bone mineral density Z-score per year and a lower percentage of patients with a decreased Z-score in hypercalciuric children treated with potassium citrate. Our findings suggest the possibility that dietary recommendations alone is not adequate as the bone mineral density of children with hypercalciuria will decrease over time, potentially increasing the risk for osteoporosis as an adult.

  15. Cadmium and lead in blood in relation to low bone mineral density and tubular proteinuria.

    PubMed Central

    Alfvén, Tobias; Järup, Lars; Elinder, Carl-Gustaf

    2002-01-01

    Long-term exposure to cadmium may cause kidney and bone damage. Urinary cadmium is commonly used as the dose estimate for the body burden of cadmium. However, elevated levels of cadmium in the urine may reflect not only high levels of cadmium dose but also renal dysfunction. In this study we used blood cadmium as the dose estimate. In addition, we analyzed blood lead. We examined 479 men and 542 women, ages 16-81 years, who were environmentally or occupationally exposed to cadmium and lead. We used urinary protein alpha 1-microglobulin as a marker for tubular proteinuria and measured forearm bone mineral density using dual-energy X-ray absorptiometry. The relationship between blood cadmium and tubular proteinuria was strong, even when we excluded occupationally exposed participants. The subgroup with the highest blood cadmium levels had a 4-fold risk of tubular proteinuria compared to the subgroup with the lowest blood cadmium levels. In the older age group (age > 60), the risk of low bone mineral density (z-score < -1) for the subgroup with the highest blood cadmium levels was almost 3-fold compared to the group with lowest blood cadmium levels. We found no similar associations for lead. The observed effects may be caused by higher cadmium exposure in the past. This study strengthens previous evidence that cadmium exposure may affect both bone mineral density and kidney function. PMID:12117647

  16. Effects of aluminum and nicotinic acid on bone minerals and growth in chicks

    SciTech Connect

    Johnson, N.E.; Dunn, M.A.; Ross, E.; Zierold, C. )

    1991-03-15

    One-day old Brown Leghorn-Cross male chicks were divided into three groups of ten chicks for each of the following experimental treatments: control; .05% Al and AlCl{sub 3}; 1.5% nicotinic acid (nic); .05% Al + 1.5% nic (Alnic). A standard corn-soybean meal chick starter diet served as the basal diet. Feed consumption and growth rates were recorded during the 14-day study. Chicks were sacrificed at the end of the study. Tibias were taken, weighed, ashed and dissolved in dilute acid. The acid digests were analyzed for mineral content (P, Ca, Mg, Fe, Zn) using induction-coupled-plasma emission spectroscopy. There were no significant differences between treatments based on mineral content per gram of bone. Bone weights of the Alnic group were decreased by 33% as compared to the control and all other groups; control being 6.49 {plus minus} 1.28g and Alnic being 4.37 {plus minus} 1.32. Body weight was decreased by 21% in the Alnic group. Although Al or nic had no effect on mineral content of bone, the combination of Al and nic caused a decrease in bone weight of the chicks. The combination was more toxic than administrative of either Al or nic alone. This finding may be relevant to the use of nicotinic acid as a supplement when Al containing substances are ingested at the same time.

  17. Antagonizing the αv β3 integrin inhibits angiogenesis and impairs woven but not lamellar bone formation induced by mechanical loading.

    PubMed

    Tomlinson, Ryan E; Schmieder, Anne H; Quirk, James D; Lanza, Gregory M; Silva, Matthew J

    2014-09-01

    Angiogenesis and osteogenesis are critically linked, although the role of angiogenesis is not well understood in osteogenic mechanical loading. In this study, either damaging or non-damaging cyclic axial compression was used to generate woven bone formation (WBF) or lamellar bone formation (LBF), respectively, at the mid-diaphysis of the adult rat forelimb. αv β3 integrin-targeted nanoparticles or vehicle was injected intravenously after mechanical loading. β3 integrin subunit expression on vasculature was maximal 7 days after damaging mechanical loading, but was still robustly expressed 14 days after loading. Accordingly, targeted nanoparticle delivery in WBF-loaded limbs was increased compared with non-loaded limbs. Vascularity was dramatically increased after WBF loading (+700% on day 14) and modestly increased after LBF loading (+50% on day 14). This increase in vascularity was inhibited by nanoparticle treatment in both WBF- and LBF-loaded limbs at days 7 and 14 after loading. Decreased vascularity led to diminished woven, but not lamellar, bone formation. Decreased woven bone formation resulted in impaired structural properties of the skeletal repair, particularly in post-yield behavior. These results demonstrate that αv β3 integrin-mediated angiogenesis is critical for recovering fracture resistance after bone injury but is not required for bone modeling after modest mechanical strain. © 2014 American Society for Bone and Mineral Research.

  18. Asymmetric (99m)Tc-MDP uptake in mineralized tendons might mimic bone lesions: heterotopic tendon mineralization on a (99m)Tc-MDP bone scan and a (18)F-FDG PET/CT scan.

    PubMed

    Chen, Yu-Ren; Hsieh, Te-Chun; Yen, Kuo-Yang; Shen, Yeh-You; Kao, Chia-Hung

    2014-05-01

    A 55-year-old man was a hepatocellular carcinoma patient, diagnosed by sonography and a biopsy. Because of his musculoskeletal tenderness, a bone scan was performed to exclude skeletal metastasis. A subsequent F-FDG PET/CT scan revealed that the unilateral abnormal uptake seen on the bone scan was actually a mineralized tendon. A mineralized tendon is easily detectable using Tc-MDP; therefore, it is imperative to differentiate between bone lesions and mineralized tendons. In addition, few studies have reported F-FDG uptake in a calcified tendon.

  19. Expanding the Description of Spaceflight Effects beyond Bone Mineral Density [BMD]: Trabecular Bone Score [TBS] in ISS Astronauts

    NASA Technical Reports Server (NTRS)

    Sibonga, J. D.; Spector, E. R.; King, L. J.; Evans, H. J.; Smith, S. A.

    2014-01-01

    Dual-energy x-ray absorptiometry [DXA] is the widely-applied bone densitometry method used to diagnose osteoporosis in a terrestrial population known to be at risk for age-related bone loss. This medical test, which measures areal bone mineral density [aBMD] of clinically-relevant skeletal sites (e.g., hip and spine), helps the clinician to identify which persons, among postmenopausal women and men older than 50 years, are at high risk for low trauma or fragility fractures and might require an intervention. The most recognized osteoporotic fragility fracture is the vertebral compression fracture which can lead to kyphosis or hunched backs typically seen in the elderly. DXA measurement of BMD however is recognized to be insufficient as a sole index for assessing fracture risk. DXA's limitation may be related to its inability to monitor changes in structural parameters, such as trabecular vs. cortical bone volumes, bone geometry or trabecular microarchitecture. Hence, in order to understand risks to human health and performance due to space exposure, NASA needs to expand its measurements of bone to include other contributors to skeletal integrity. To this aim, the Bone and Mineral Lab conducted a pilot study for a novel measurement of bone microarchitecture that can be obtained by retrospective analysis of DXA scans. Trabecular Bone Score (TBS) assesses changes to trabecular microarchitecture by measuring the grey color "texture" information extracted from DXA images of the lumbar spine. An analysis of TBS in 51 ISS astronauts was conducted to assess if TBS could detect 1) an effect of spaceflight and 2) a response to countermeasures independent of DXA BMD. In addition, changes in trunk body lean tissue mass and in trunk body fat tissue mass were also evaluated to explore an association between body composition, as impacted by ARED exercise, and bone microarchitecture. The pilot analysis of 51 astronaut scans of the lumbar spine suggests that, following an ISS

  20. Bone Collagen: New Clues to its Mineralization Mechanism From Recessive Osteogenesis Imperfecta

    PubMed Central

    Eyre, David R.; Ann Weis, Mary

    2013-01-01

    Until 2006 the only mutations known to cause osteogenesis imperfecta (OI) were in the two genes coding for type I collagen chains. These dominant mutations affecting the expression or primary sequence of collagen α1(I) and α2(I) chains account for over 90% of OI cases. Since then a growing list of mutant genes causing the 5–10% of recessive cases has rapidly emerged. They include CRTAP, LEPRE1 and PPIB, which encode three proteins forming the prolyl 3-hydroxylase complex; PLOD2 and FKBP10, which encode respectively lysyl hydroxylase 2 and a foldase required for its activity in forming mature cross-links in bone collagen; SERPIN H1, which encodes the collagen chaperone HSP47; SERPIN F1, which encodes pigment epithelium-derived factor required for osteoid mineralization; and BMP1, which encodes the type I procollagen C-propeptidase. All cause fragile bone in infancy, which can include over-mineralization or under-mineralization defects as well as abnormal collagen post-translational modifications. Consistently both dominant and recessive variants lead to abnormal cross-linking chemistry in bone collagen. These recent discoveries strengthen the potential for a common pathogenic mechanism of misassembled collagen fibrils. Of the new genes identified, eight encode proteins required for collagen post-translational modification, chaperoning of newly synthesized collagen chains into native molecules or transport through the endoplasmic reticulum and Golgi for polymerization, cross-linking and mineralization. In reviewing these findings, we conclude that a common theme is emerging in the pathogenesis of brittle bone disease of mishandled collagen assembly with important insights on post-translational features of bone collagen that have evolved to optimize it as a biomineral template. PMID:23508630

  1. Degradability of injectable calcium sulfate/mineralized collagen-based bone repair material and its effect on bone tissue regeneration.

    PubMed

    Chen, Zonggang; Kang, Lingzhi; Meng, Qing-Yuan; Liu, Huanye; Wang, Zhaoliang; Guo, Zhongwu; Cui, Fu-Zhai

    2014-12-01

    The nHAC/CSH composite is an injectable bone repair material with controllable injectability and self-setting properties prepared by introducing calcium sulfate hemihydrate (CSH) into mineralized collagen (nHAC). When mixed with water, the nHAC/CSH composites can be transformed into mineralized collagen/calcium sulfate dihydrate (nHAC/CSD) composites. The nHAC/CSD composites have good biocompatibility and osteogenic capability. Considering that the degradation behavior of bone repair material is another important factor for its clinical applications, the degradability of nHAC/CSD composites was studied. The results showed that the degradation ratio of the nHAC/CSD composites with lower nHAC content increased with the L/S ratio increase of injectable materials, but the variety of L/S ratio had no significant effect on the degradation ratio of the nHAC/CSD composites with higher nHAC content. Increasing nHAC content in the composites could slow down the degradation of nHAC/CSD composite. Setting accelerator had no significant effect on the degradability of nHAC/CSD composites. In vivo histological analysis suggests that the degradation rate of materials can match the growth rate of new mandibular bone tissues in the implanted site of rabbit. The regulable degradability of materials resulting from the special prescriptions of injectable nHAC/CSH composites will further improve the workability of nHAC/CSD composites.

  2. Strain-guided mineralization in the bone-PDL-cementum complex of a rat periodontium

    PubMed Central

    Grandfield, Kathryn; Herber, Ralf Peter; Chen, Ling; Djomehri, Sabra; Tam, Caleb; Lee, Ji-Hyun; Brown, Evan; Woolwine, Wood R.; Curtis, Don; Ryder, Mark; Schuck, Jim; Webb, Samuel; Landis, William; Ho, Sunita

    2015-01-01

    Objective The objective of this study was to investigate the effect of mechanical strain by mapping physicochemical properties at periodontal ligament (PDL)-bone and PDL-cementum attachment sites and within the tissues per se. Design Accentuated mechanical strain was induced by applying a unidirectional force of 0.06N for 14 days on molars in a rat model. The associated changes in functional space between tooth and bone, mineral formation and resorbing events at the PDL-bone and PDL-cementum attachment sites were identified by using micro-X-ray computed tomography (micro-XCT), atomic force microscopy (AFM), dynamic histomorphometry, Raman microspectroscopy, AFM-based nanoindentation technique, and were correlated with histochemical stains specific to low and high molecular weight GAGs, including biglycan, and osteoclast distribution through tartrate-resistant acid phosphatase (TRAP) staining. Results Unique chemical and mechanical qualities including heterogenous bony fingers with hygroscopic Sharpey’s fibers contributing to a higher organic (amide III - 1240 cm−1) to inorganic (phosphate - 960 cm−1) ratio, with lower average elastic modulus of 8 GPa versus 12 GPa in unadapted regions were identified. Furthermore, an increased presence of elemental Zn in cement lines and mineralizing fronts of PDL-bone was observed. Adapted regions containing bony fingers exhibited woven bone-like architecture and these regions rich in biglycan (BGN) and bone sialoprotein (BSP) also contained high-molecular weight polysaccharides predominantly at the site of polarized bone growth. Conclusions From a fundamental science perspective the shift in local properties due to strain amplification at the soft-hard tissue attachment sites is governed by semiautonomous cellular events at the PDL-bone and PDL-cementum sites. Over time, these strain-mediated events can alter the physicochemical properties of tissues per se, and consequently the overall biomechanics of the bone

  3. Effects of Trypsinization and Mineralization on Intrasynovial Tendon Allograft Healing to Bone

    PubMed Central

    Qu, Jin; van Alphen, Nick A.; Thoreson, Andrew R.; Chen, Qingshan; An, Kai-Nan; Amadio, Peter C.; Schmid, Thomas M.; Zhao, Chunfeng

    2014-01-01

    The purpose of the current study was to develop a novel technology to enhance tendon-to-bone interface healing by trypsinizing and mineralizing (TM) an intrasynovial tendon allograft in a rabbit bone tunnel model. Eight rabbit flexor digitorum profundus (FDP) tendons were used to optimize the trypsinization process. An additional 24 FDP tendons were stratified into control and TM groups; in each group, 4 tendons were used for in vitro evaluation of TM and 8 were transplanted into proximal tibial bone tunnels in rabbits. The samples were evaluated histologically and with mechanical testing at postoperative week 8. Maximum failure strength and linear stiffness were not significantly different between the control and TM tendons. A thin fibrous band of scar tissue formed at the graft-to-bone interface in the control group. However, only the TM group showed obvious new bone formation inside the tendon graft and a visible fibrocartilage layer at the bone tunnel entrance. This study is the first to explore effects of TM on the intrasynovial allograft healing to a bone tunnel. TM showed beneficial effects on chondrogenesis, osteogenesis, and integration of the intrasynovial tendon graft, but mechanical strength was the same as the control tendons in this short-term in vivo study. PMID:25611186

  4. Effects of trypsinization and mineralization on intrasynovial tendon allograft healing to bone.

    PubMed

    Qu, Jin; van Alphen, Nick A; Thoreson, Andrew R; Chen, Qingshan; An, Kai-Nan; Amadio, Peter C; Schmid, Thomas M; Zhao, Chunfeng

    2015-04-01

    The purpose of the current study was to develop a novel technology to enhance tendon-to-bone interface healing by trypsinizing and mineralizing (TM) an intrasynovial tendon allograft in a rabbit bone tunnel model. Eight rabbit flexor digitorum profundus (FDP) tendons were used to optimize the trypsinization process. An additional 24 FDP tendons were stratified into control and TM groups; in each group, 4 tendons were used for in vitro evaluation of TM and 8 were transplanted into proximal tibial bone tunnels in rabbits. The samples were evaluated histologically and with mechanical testing at postoperative week 8. Maximum failure strength and linear stiffness were not significantly different between the control and TM tendons. A thin fibrous band of scar tissue formed at the graft-to-bone interface in the control group. However, only the TM group showed obvious new bone formation inside the tendon graft and a visible fibrocartilage layer at the bone tunnel entrance. This study is the first to explore effects of TM on the intrasynovial allograft healing to a bone tunnel. TM showed beneficial effects on chondrogenesis, osteogenesis, and integration of the intrasynovial tendon graft, but mechanical strength was the same as the control tendons in this short-term in vivo study.

  5. Maternal beef and postweaning herring diets increase bone mineral density and strength in mouse offspring.

    PubMed

    Hussain, Aysha; Olausson, Hanna; Nilsson, Staffan; Nookaew, Intawat; Khoomrung, Sakda; Andersson, Louise; Koskela, Antti; Tuukkanen, Juha; Ohlsson, Claes; Holmäng, Agneta

    2013-12-01

    The maternal diet during gestation and lactation affects the long-term health of the offspring. We sought to determine whether maternal and postweaning crossover isocaloric diets based on fish or meat affect the geometry, mineral density, and biomechanical properties of bone in mouse offspring in adulthood. During gestation and lactation, C57BL/6 dams were fed a herring- or beef-based diet. After weaning, half of the pups in each group were fed the same diet as their dams, and half were fed the other diet. Areal bone mineral density (aBMD) and bone mineral content (BMC) of the whole body and lumbar spine were measured in the offspring by dual X-ray absorptiometry at 9 and 21 weeks of age. At 22-26 weeks, tibia bone geometry (length, cortical volumetric (v) BMD, BMC, area and thickness) was analyzed by peripheral quantitative computed tomography, and the biomechanical properties of the tibia were analyzed by the three-point bending test. Plasma insulin-like growth factor-1 was analyzed at 12 weeks. In comparison to the maternal herring diet, the maternal beef diet increased aBMD and BMC in the whole body and lumbar spine of adult offspring, as well as cortical vBMD, BMC, bone area, and thickness at the mid-diaphyseal region of the tibia and the biomechanical properties of tibia strength. In contrast, a postweaning beef diet decreased aBMD in the lumbar spine and BMC in the whole body and lumbar spine compared with a postweaning herring diet, which instead increased plasma insulin-like growth factor-1 levels. The change from a maternal beef diet before weaning to a herring diet after weaning decreased body weight and increased the cortical area, vBMD, BMC, thickness, and strength of the tibia. These significant crossover effects indicate that a preweaning maternal beef diet and a postweaning herring diet are optimal for increasing BMC and bone strength in offspring in adulthood.

  6. Bone Mineralization in Rhythmic Gymnasts Entering Puberty: Associations with Jumping Performance and Body Composition Variables

    PubMed Central

    Võsoberg, Kristel; Tillmann, Vallo; Tamm, Anna-Liisa; Maasalu, Katre; Jürimäe, Jaak

    2017-01-01

    This study examined bone mineral density (BMD) accrual in prepubertal rhythmic gymnasts entering puberty and their age-matched untrained control girls, and associations with baseline jumping performance and body composition over the 3-year period. Whole body (WB) and femoral neck (FN) BMD, WB fat mass (FM) and fat free mass (FFM), countermovement jump (CMJ) and rebound jumps for 15 s (RJ15s) were assessed in 25 rhythmic gymnasts and 25 untrained controls at baseline and after 3-year period. The changes over this period were calculated (Δ scores). Pubertal maturation over the 3-year period was slower in rhythmic gymnasts compared to untrained controls, while no difference in bone age development was seen. WB BMD increased similarly in both groups, while the increase in FN BMD was higher in rhythmic gymnasts compared with untrained controls. In rhythmic gymnasts, baseline FFM was the most significant predictor of ΔWB BMD explaining 19.2% of the variability, while baseline RJ15s was the most significant predictor of ΔFN BMD explaining 18.5% of the variability. In untrained controls, baseline FM explained 51.8 and 18.9% of the variability in ΔWB BMD and ΔFN BMD, respectively. In conclusion, mechanical loading of high-intensity athletic activity had beneficial effect on BMD accrual in rhythmic gymnasts and may have counterbalanced such negative factors on bone development as slower pubertal maturation and lower body FM. Baseline FFM and repeated jumps test performance were related to BMD accrual in rhythmic gymnasts, while baseline FM was related to BMD accrual in untrained controls. Key points Sudy examined bone mineralization in prepubertal rhythmic gymnasts entering puberty and their age-matched untrained control girls, and associations with baseline jumping performance and body composition. Jumping performance and fat free mass values predicted bone mineral accrual in rhythmic gymnasts. Fat mass predicted bone mineral accrual in untrained control girls

  7. Evaluation of bone mineral density among type 2 diabetes mellitus patients in South Karnataka

    PubMed Central

    Asokan, Athulya G.; Jaganathan, Jayakumar; Philip, Rajeev; Soman, Rino Roopak; Sebastian, Shibu Thomas; Pullishery, Fawaz

    2017-01-01

    Background: Diabetes is one of the world's biggest health problems and the disease affects almost all organ systems. The relationship between type 2 diabetes mellitus (T2DM) and bone mineral density (BMD) has been controversial. Early identification of reduction in bone mass in a diabetic patient may be helpful in preventing the bone loss and future fracture risks. Objective: The aim is to study the effect of T2DM on BMD among patients in South Karnataka. Materials and Methods: A cross-sectional study was conducted on 150 patients between 40 and 70 years of age which included 75 diabetic and 75 nondiabetic subjects. BMD was measured using qualitative ultrasound and the data were compared among age-matched subjects of both the groups. Statistical analysis was performed using unpaired Student's t-test and test of equality of proportions. Results: No significant difference was observed in bone density of both the groups. On further analyzing the data, incidence of osteoporosis was higher among diabetic subjects, whereas incidence of osteopenia was higher among nondiabetic subjects. Conclusion: Although significant difference in bone mineral density was not observed in both the groups, the incidence of osteoporosis was higher among type 2 diabetics. Hence, all type 2 diabetics should be evaluated for the risk of osteoporosis and should be offered appropriate preventive measures. PMID:28250682

  8. Availability of calcium from skim milk, calcium sulfate and calcium carbonate for bone mineralization in pigs.

    PubMed

    Pointillart, A; Coxam, V; Sève, B; Colin, C; Lacroix, C H; Guéguen, L

    2000-01-01

    Dairy products provide abundant, accessible calcium for humans, while some calcium sulfate-rich mineral waters could provide appreciable amounts of calcium. But there is little evidence that this calcium is as available as milk calcium for making bone. The availability of calcium was studied by monitoring bone parameters in 2-month-old pigs fed restricted amounts of calcium (70% RDA) for 2.5 months. The 3 main (> or = 50% Ca intake) Ca sources were either CaCO3 or CaSO4 or skim milk powder (29% of the diet). The bones of the pigs fed the "milk" diet had higher (P < 0.01) ash contents, breaking strength and density (DEXA) than those of the two others groups, in which the bone values were similar. Thus, the calcium provided by a diet containing milk appears to ensure better bone mineralization than do calcium salts included in a non-milk diet. The calcium restriction may have enhanced some milk properties to stimulate calcium absorption in these young, rapidly growing pigs.

  9. Low dose pioglitazone does not affect bone formation and resorption markers or bone mineral density in streptozocin-induced diabetic rats.

    PubMed

    Tsirella, E; Mavrakanas, T; Rager, O; Tsartsalis, S; Kallaras, K; Kokkas, B; Mironidou-Tzouveleki, M

    2012-04-01

    Our study aims to investigate the effect of a low-dose pioglitazone regimen on bone mineral density and bone formation-resorption markers in control and diabetic rats. Wistar rats were divided into 4 groups: non-diabetic controls, control rats receiving pioglitazone (3 mg/kg), streptozocin-treated diabetic rats (50 mg/kg), diabetic rats treated with pioglitazone (3 mg/kg). The duration of the experiment was 8 weeks. Diabetes in our rats was associated with weight loss, increased urinary calcium excretion and reduced plasma osteocalcin levels. Diabetes mellitus did not affect bone mineral density. Pioglitazone administration had no impact on bone formation and resorption markers levels and did not modify bone mineral density in the four studied groups. Pioglitazone at the 3 mg/kg dose was not associated with significant skeletal complications in our experimental model.

  10. Impaired secretion of parathyroid hormone, but not refractoriness of osteoblast, is a major mechanism of low bone turnover in hemodialyzed patients with diabetes mellitus.

    PubMed

    Inaba, Masaaki; Nagasue, Kyoko; Okuno, Senji; Ueda, Misako; Kumeda, Yasuro; Imanishi, Yasuo; Shoji, Tetsuo; Ishimura, Eiji; Ohta, Tomohiro; Nakatani, Tatsuya; Kim, Masao; Nishizawa, Yoshiki

    2002-06-01

    Diabetic bone disease is characterized by low bone turnover resulting from either impaired secretion of parathyroid hormone (PTH) or refractoriness of osteoblasts to PTH. The present study was performed to elucidate which factor contributes more to the reduction in bone turnover by comparison between 64 hemodialyzed patients with diabetes mellitus and 106 hemodialyzed patients without diabetes mellitus. Only men were enrolled to avoid the influence of the menstrual cycle on bone metabolism. Serum intact PTH (iPTH) levels were significantly lower in hemodialyzed patients with diabetes than those without diabetes, although no significant difference existed in age, duration of hemodialysis therapy, or serum calcium or phosphate levels. Of the biochemical markers measured, serum intact osteocalcin (iOC) and deoxypyridinoline levels were significantly lower in patients with diabetes, although serum bone-specific alkaline phosphatase (BAP) and pyridinoline levels did not differ significantly between the two groups of patients. When patients were restricted to those with serum iPTH levels greater than 180 pg/mL, this parameter correlated significantly in a positive manner with both serum iOC and BAP levels and negatively with bone mineral density at distal radius 1/3. Regression slopes between iPTH levels and these parameters were not significantly different between the two groups of patients, indicating the absence of refractoriness of bone to PTH in patients with diabetes. In conclusion, our findings suggest that impaired PTH secretion, but not refractoriness of osteoblasts to PTH, may be responsible for the low bone turnover in hemodialyzed patients with diabetes.

  11. Local Variation in Femoral Neck Cortical Bone: In Vitro Measured Bone Mineral Density, Geometry and Mechanical Properties.

    PubMed

    Coutts, Louise V; Jenkins, Thomas; Oreffo, Richard O C; Dunlop, Doug G; Cooper, Cyrus; Harvey, Nicholas C; Thurner, Philipp J

    2015-12-17

    Age- and disease (osteoporotic fractured and osteoarthritic tissue)-related changes in the distribution of cortical bone were examined, using a multimodality approach, including measurement of local density, geometry and mechanical properties, where changes in these properties can give rise to instability and increasing probability of fracture. In contrast to the majority of previously reported research, this study also focuses on the characteristic non-circular femoral neck cross-sectional geometry and variation in bone mineral density (BMD) around the femoral neck. Twenty-two osteoarthritic and 7 osteoporotic femoral neck slices, collected from elective and trauma-related arthroplasty, and 16 cadaveric donor tissue controls were tested mechanically using Reference Point Indentation (BioDent™, Active Life Technologies®, Santa Barbara, CA) and then scanned with in vitro-based radiography intended to replicate the dual-energy X-ray absorptiometry technique. All parameters were measured regionally around the circumference of the femoral neck, allowing examination of spatial variability within the cortical bone. Fractured tissue was less resistant to indentation in the thinner superolateral segment compared to other segments and other groups. BMD around the fractured femoral necks appeared more consistent than that of nonfractured tissue, where BMD was reduced in the superolateral segment for the other groups. Cortical bone was thin in the superolateral segment for all groups except for the osteoarthritic group, and was thicker in the inferomedial segment for both osteoarthritic and fractured groups, resulting in the largest variation in buckling ratio (ratio of cortical bone diameter to cortical bone thickness) around the femoral neck for the fractured group. With age, healthy controls appeared to have lower inferomedial cortical thickness, whereas no significant differences in Reference Point Indentation measurements and density were observed. The study has

  12. The effect of weight bearing on bone mineral density and bone growth in children with cerebral palsy

    PubMed Central

    Han, Eun Young; Choi, Jung Hwa; Kim, Sun-Hyun; Im, Sang Hee

    2017-01-01

    Abstract Background: The present study aims to explore the effect of weight bearing exercise on bone mineral density (BMD) and bone growth in children with cerebral palsy (CP). Methods: Twelve children with CP of functional level of gross motor functional classification scale (GMFCS) V and 6 healthy children (control group) were included in the study. Participants underwent a dual-energy X-ray absorptiometry scan to measure the BMD of the femur and full-length anteroposterior radiography to measure the bone length of the femur and tibia at baseline and after 6 months. Patients were randomly divided into 2 groups: group A with programmed standing exercises and assisted standing for more than 2 hours a day, more than 5 days a week; and group B with conventional physiotherapy with a standing program for 20 minutes a day, 2 to 3 days a week. Results: A 6-month follow-up showed significantly increased BMD on the femur neck in the control group. Although the changes in BMD were not significant in both groups, group A demonstrated an increased trend of BMD, whereas group B showed a decreased trend. Bone length was significantly increased in all 3 groups at the 6-month follow-up. Although this increase was not significant, the change in bone length was greatest in the control group. The smallest changes were observed in group B. Conclusions: Weight bearing exercise may play an important role in increasing or maintaining BMD in children with CP and is also expected to promote bone growth. Programmed standing may be used as an effective treatment method to increase BMD in children with CP. However, further studies with a larger cohort and longer follow-up period are required to reveal further information on the benefit of weight bearing exercise and to develop a detailed program. PMID:28272197

  13. Update on pediatric bone health.

    PubMed

    Henwood, Maria J; Binkovitz, Larry

    2009-01-01

    Osteoporosis has long been considered a health problem unique to older adults. Children and adolescents with chronic illness, primary bone disease, or poor nutrition, however, are also predisposed to impaired skeletal health. The present review discusses normal skeletal development, risk factors for low bone mineral density, and prevention and treatment strategies that can help optimize bone health in the pediatric population.

  14. [Bone mineral density disminution post Roux-Y bypass surgery].

    PubMed

    Papapietro, Karin; Massardo, Teresa; Riffo, Andrea; Díaz, Emma; Araya, A Verónica; Adjemian, Daniela; Montesinos, Gustavo; Castro, Gabriel

    2013-01-01

    Introducción: La cirugía bariátrica tiene complicaciones metabólicas importantes como la pérdida de masa ósea. Objetivo: Evaluar la densidad mineral ósea (DMO) posterior a by-pass gástrico en Y de Roux (BPYR) en pacientes con indicación de suplemento estándar de calcio y vitamina D. Método: En pacientes con BPYR por obesidad mórbida, 76 mujeres y 22 hombres de diversa edad, con instrucción nutricional, suplemento de calcio y vitamina D, se midió la DMO en columna lumbar y caderas con densitómetro radiológico de doble haz 2 a 3 años post-cirugía. Veinte mujeres fueron seguidas con DMO hasta 54 meses en promedio. Según criterios de Organización Mundial de la Salud (OMS), se comparó con población control joven y de su edad según sexo, evaluando osteopenia y osteoporosis. Resultados: Hubo correlación negativa de DMO con edad; positiva de DMO con índice de masa corporal y con exceso de peso preoperatorio. En mujeres menores de 45 años, se observó disminución de DMO en 26,8%, sin casos de osteoporosis y en 65,7% en las mayores de 45 años (p = 0,0011), correspondiendo a 45,7% de osteopenia y 20% de osteoporosis, predominantemente en columna lumbar. El subgrupo de mujeres con mayor seguimiento, presentó disminución progresiva de DMO, especialmente en cadera izquierda. En hombres se observó 36% de osteopenia y 14% de osteoporosis. Conclusión: Pacientes de ambos sexos y diversa edad, despues de un BPYR, presentaron osteopenia y osteoporosis, a pesar de suplemento precoz de calcio y vitamina D. Consideramos importante medir DMO seriada, individualizando terapias y controlando factores de riesgo.

  15. Osteoblast-Specific Loss of IGF1R Signaling Results in Impaired Endochondral Bone Formation During Fracture Healing.

    PubMed

    Wang, Tao; Wang, Yongmei; Menendez, Alicia; Fong, Chak; Babey, Muriel; Tahimic, Candice G T; Cheng, Zhiqiang; Li, Alfred; Chang, Wenhan; Bikle, Daniel D

    2015-09-01

    Insulin-like growth factors (IGFs) are important local regulators during fracture healing. Although IGF1 deficiency is known to increase the risk of delayed union or non-union fractures in the elderly population, the underlying mechanisms that contribute to this defect remains unclear. In this study, IGF1 signaling during fracture healing was investigated in an osteoblast-specific IGF1 receptor (IGF1R) conditional knockout (KO) mouse model. A closed tibial fracture was induced in IGF1R(flox/flox) /2.3-kb α1(1)-collagen-Cre (KO) and IGF1R(flox/flox) (control) mice aged 12 weeks. Fracture callus samples and nonfractured tibial diaphysis were collected and analyzed by μCT, histology, immunohistochemistry, histomorphometry, and gene expression analysis at 10, 15, 21, and 28 days after fracture. A smaller size callus, lower bone volume accompanied by a defect in mineralization, bone microarchitectural abnormalities, and a higher cartilage volume were observed in the callus of these KO mice. The levels of osteoblast differentiation markers (osteocalcin, alkaline phosphatase, collagen 1α1) were significantly reduced, but the early osteoblast transcription factor runx2, as well as chondrocyte differentiation markers (collagen 2α1 and collagen 10α1) were significantly increased in the KO callus. Moreover, increased numbers of osteoclasts and impaired angiogenesis were observed during the first 15 days of fracture repair, but decreased numbers of osteoclasts were found in the later stages of fracture repair in the KO mice. Although baseline nonfractured tibias of KO mice had decreased trabecular and cortical bone compared to control mice, subsequent studies with mice expressing the 2.3-kb α1(1)-collagen-Cre ERT2 construct and given tamoxifen at the time of fracture and so starting with comparable bone levels showed similar impairment in fracture repair at least initially. Our data indicate that not only is the IGF1R in osteoblasts involved in osteoblast differentiation

  16. [Relation between body mass index and bone mineral density in a sample population of Mexican women].

    PubMed

    Murillo-Uribe, A; Aranda-Gallegos, J E; Río de la Loza-Cava, M F; Ortíz-Luna, G; Mendoza-Torres, L J; Santos-González, J

    1998-07-01

    The purpose of this trial is to demonstrate that a women with high body mass index (BMI > or = 28) has greater bone mineral density (BMD) from that with lower BMI. We studied 922 healthy women who met the inclusion criteria. They were classified into four groups according to their BMI (> or = 28 and < 28) and age (> or = 35 and < 35 years). Bone mineral measurement was performed by dual-energy X-ray absorptiometry (DEXA) in the hip and at the lumbar region. BMD in overweight women older than 35 years was significantly higher in comparison with that of women with lower BMI, both in the hip and the lumbar spine. In overweight women younger than 35 years, we found greater BMD in the hip reaching statistical significance, but not at the lumbar spine. We conclude that obesity is associated with greater BMD (4% at the lumbar spine; 11% at the hip) probably due to both greater physical stress and higher estrogen levels.

  17. Cardiorenal Syndrome and the Role of the Bone-Mineral Axis and Anemia

    PubMed Central

    Charytan, David M.; Fishbane, Steven; Malyszko, Jolanta; McCullough, Peter A.; Goldsmith, David

    2015-01-01

    The association between chronic kidney disease (CKD) and cardiovascular disease (CVD) is well established, and there is mounting evidence of inter-organ crosstalk that may accelerate pathological processes and the progression of organ dysfunction in both systems. This process, termed cardiorenal syndrome (CRS) by the Acute Dialysis Quality Initiative, is considered a major health problem: patients with CKD and CVD are at much higher risk of mortality than patients with either condition alone. To date, the majority of CRS research has focused on neurohormonal mechanisms and hemodynamic alterations. However, mounting evidence suggests that abnormalities in the normal pathophysiology of the bone-mineral axis, iron, and erythropoietin play a role in accelerating CKD and CVD. The goal of this manuscript is to review the role and interrelated effects of the bone-mineral axis and anemia in the pathogenesis of chronic CRS. PMID:25727384

  18. Electrical and dielectric properties of bovine trabecular bone--relationships with mechanical properties and mineral density.

    PubMed

    Sierpowska, J; Töyräs, J; Hakulinen, M A; Saarakkala, S; Jurvelin, J S; Lappalainen, R

    2003-03-21

    Interrelationships of trabecular bone electrical and dielectric properties with mechanical characteristics and density are poorly known. While electrical stimulation is used for healing fractures, better understanding of these relations has clinical importance. Furthermore, earlier studies have suggested that bone electrical and dielectric properties depend on the bone density and could, therefore, be used to predict bone strength. To clarify these issues, volumetric bone mineral density (BMDvol), electrical and dielectric as well as mechanical properties were determined from 40 cylindrical plugs of bovine trabecular bone. Phase angle, relative permittivity, loss factor and conductivity of wet bovine trabecular bone were correlated with Young's modulus, yield stress, ultimate strength, resilience and BMDvol. The reproducibility of in vitro electrical and dielectric measurements was excellent (standardized coefficient of variation less than 1%, for all parameters), especially at frequencies higher than 1 kHz. Correlations of electrical and dielectric parameters with the bone mechanical properties or density were frequency-dependent. The relative permittivity showed the strongest linear correlations with mechanical parameters (r > 0.547, p < 0.01, n = 40, at 50 kHz) and with BMDvol (r = 0.866, p < 0.01, n = 40, at 50 kHz). In general, linear correlations between relative permittivity and mechanical properties or BMDvol were highest at frequencies over 6 kHz. In addition, a significant site-dependent variation of electrical and dielectric characteristics, mechanical properties and BMDvol was revealed in bovine femur (p < 0.05, Kruskall-Wallis H-test). Based on the present results, we conclude that the measurement of electrical and dielectric properties provides quantitative information that is related to bone quantity and quality.

  19. Functional integration of skeletal traits: an intraskeletal assessment of bone size, mineralization, and volume covariance.

    PubMed

    Schlecht, Stephen H; Jepsen, Karl J

    2013-09-01

    Understanding the functional integration of skeletal traits and how they naturally vary within and across populations will benefit assessments of functional adaptation directed towards interpreting bone stiffness in contemporary and past humans. Moreover, investigating how these traits intraskeletally vary will guide us closer towards predicting fragility from a single skeletal site. Using an osteological collection of 115 young adult male and female African-Americans, we assessed the functional relationship between bone robustness (i.e. total area/length), cortical tissue mineral density (Ct.TMD), and cortical area (Ct.Ar) for the upper and lower limbs. All long bones demonstrated significant trait covariance (p < 0.005) independent of body size, with slender bones having 25-50% less Ct.Ar and 5-8% higher Ct.TMD compared to robust bones. Robustness statistically explained 10.2-28% of Ct.TMD and 26.6-64.6% of Ct.Ar within male and female skeletal elements. This covariance is systemic throughout the skeleton, with either the slender or robust phenotype consistently represented within all long bones for each individual. These findings suggest that each person attains a unique trait set by adulthood that is both predictable by robustness and partially independent of environmental influences. The variation in these functionally integrated traits allows for the maximization of tissue stiffness and minimization of mass so that regardless of which phenotype is present, a given bone is reasonably stiff and strong, and sufficiently adapted to perform routine, habitual loading activities. Covariation intrinsic to functional adaptation suggests that whole bone stiffness depends upon particular sets of traits acquired during growth, presumably through differing levels of cellular activity, resulting in differing tissue morphology and composition. The outcomes of this intraskeletal examination of robustness and its correlates may have significant value in our progression

  20. Correlation between serum leptin and bone mineral density in hemodialysis patients

    PubMed Central

    Ghorban-Sabbagh, Mahin; Nazemian, Fatemeh; Naghibi, Massih; Shakeri, Mohammad-Taghi; Ahmadi-Simab, Saeedeh; Javidi-Dasht-Bayaz, Reza

    2016-01-01

    Introduction: For diagnosing of specific types of bone lesions in hemodialysis (HD) patients, it is necessary to conduct a bone biopsy as the gold standard method. However, it is an invasive procedure. While different markers have been suggested as alternative methods, none of them has been selected. The frequency of hip fractures is 80 fold in HD patients who have two-fold mortality as compared with general population. Objectives: Recently, serum leptin has been suggested as a bone density marker. This study tries to confirm this proposal. Patients and Methods: In this study about 104 HD patients (53.8% male and 46.2% female) were enrolled. The average age was 38.28±7.89 years. Serum leptin, bone alkaline phosphatase, intact parathyroid hormone (iPTH), 25(OH)D, calcium, phosphorus and bone mineral density (BMD) (at the femoral neck and lumbar spine, as measured by dual-energy x-ray absorptiometry [DXA]) were assessed. Results: Analysis by polynomial regression revealed no correlation between BMD Z-score at two points and serum leptin level. According to the thresholds of 25 ng/mL and 18-24 ng/mL in some studies, we detected 25 ng/mL as the threshold in our patients. Under this threshold, the leptin effect on bone mass was negative, and above the threshold of 25 ng/mL, we found leptin had positive effect on bone mass. Conclusion: In this investigation, we found, leptin has a bimodal effect on bone mass. Cortical bones assessment may be a better option for assessment. PMID:27689105

  1. The levels of bone turnover markers 25(OH)D and PTH and their relationship with bone mineral density in postmenopausal women in a suburban district in China.

    PubMed

    Gao, C; Qiao, J; Li, S S; Yu, W J; He, J W; Fu, W Z; Zhang, Z L

    2017-01-01

    This study evaluated the levels of bone turnover markers (BTMs) and investigated relationships between them and bone mineral density (BMD) in postmenopausal women in China suburban district. The prevalence of osteoporosis was 25.03 % at lumbar spine and 6.23 % at femoral neck, and BTMs were negatively correlated with BMDs.

  2. Evidence of associations between feto-maternal vitamin D status, cord parathyroid hormone and bone-specific alkaline phosphatase, and newborn whole body bone mineral content

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In spite of a high prevalence of vitamin D inadequacy in pregnant women and neonates, relationships among vitamin D status [25(OH)D], parathyroid hormone (PTH), bone specific alkaline phosphatase (BALP), and whole body bone mineral content (WBBMC) in the newborn are poorly characterized. The purpose...

  3. Assessment of bone mineral density in the jaws and its relationship to radiomorphometric indices

    PubMed Central

    Gulsahi, A; Paksoy, CS; Ozden, S; Kucuk, NO; Cebeci, ARI; Genc, Y

    2010-01-01

    Objectives The aim of this study was to evaluate maxillary, mandibular and femoral neck bone mineral density using dual energy X-ray absorptiometry (DXA) and to determine any correlation between the bone mineral density of the jaws and panoramic radiomorphometric indices. Methods 49 edentulous patients (18 males and 31 females) aged between 41 and 78 years (mean age 60.2 ± 11.04) were examined by panoramic radiography. Bone mineral density (BMD) of the jaws and femoral neck was measured with a DXA; bone mineral density was calculated at the anterior, premolar and molar regions of the maxilla and mandible. Results The mean maxillary molar BMD (0.45 g cm−2) was significantly greater than the maxillary anterior and premolar BMD (0.31 g cm−2, P < 0.05). Furthermore, the mean mandibular anterior and premolar BMD (1.39 g cm−2 and 1.28 g cm−2, respectively) was significantly greater than the mean mandibular molar BMD (1.09 g cm−2, P < 0.01). Although BMD in the maxillary anterior and premolar regions were correlated, BMD in all the mandibular regions were highly correlated. Maxillary and mandibular BMD were not correlated with femoral BMD. In addition, mandibular cortical index (MCI) classification, mental index (MI) or panoramic mandibular index (PMI) values were not significantly correlated with the maxillary and mandibular BMDs (P > 0.05). Conclusions The BMD in this study was highest in the mandibular anterior region and lowest in the maxillary anterior and premolar regions. The BMD of the jaws was not correlated with either femoral BMD or panoramic radiomorphometric indices. PMID:20587652

  4. Evidence of association of vitamin D receptor Apa I gene polymorphism with bone mineral density in postmenopausal women with osteoporosis.

    PubMed

    Dundar, Umit; Solak, Mustafa; Kavuncu, Vural; Ozdemir, Mujgan; Cakir, Tuncay; Yildiz, Handan; Evcik, Deniz

    2009-10-01

    The vitamin D receptor (VDR) was the first candidate gene to be studied in relation to osteoporosis, and most attention has focused on polymorphisms situated near the 3' flank of VDR. The aim of this study was to investigate the association about VDR gene Apa I polymorphism with bone mineral density (BMD) in postmenopausal women with osteoporosis. We studied a total of 136 postmenopausal women with a mean age of 56.36 +/- 10.29 years. Among them, a total of 75 had osteoporosis, 37 had osteopenia, and 24 had normal BMD. Venous blood samples were obtained for evaluation of bone metabolism and genotyping. The VDR Apa I genotype was determined by polymerase chain reaction-restriction fragment length polymorphism. BMDs at the lumbar spine and hip were measured by dual-energy X-ray absorptiometry. Postmenopausal women with aa genotype had significantly lower BMD values (grams per centimeter square) at lumbar spines compared to persons with AA genotype. Also, postmenopausal women with AA genotype had significantly higher serum Ca level than the subjects with aa genotype. In conclusion, our result may indicate that VDR Apa I gene polymorphism may be responsible for a important part of the heritable component of lumbar spine BMD in postmenopausal women, possibly related to impaired calcium absorption from the bowel.

  5. Genetic determinism of bone and mineral metabolism in meat-type chickens: A QTL mapping study.

    PubMed

    Mignon-Grasteau, Sandrine; Chantry-Darmon, Céline; Boscher, Marie-Yvonne; Sellier, Nadine; Chabault-Dhuit, Marie; Le Bihan-Duval, Elisabeth; Narcy, Agnès

    2016-12-01

    Skeletal integrity in meat-type chickens is affected by many factors including rapid growth rate, nutrition and genetics. To investigate the genetic basis of bone and mineral metabolism, a QTL detection study was conducted in an intercross between two lines of meat-type chickens divergently selected for their high (D +) or low (D -) digestive efficiency. Tibia size (length, diameter, volume) and ash content were determined at 3 weeks of age as well as phosphorus (P) retention and plasma concentration. Heritability of these traits and their genetic correlations with digestive efficiency were estimated. A QTL mapping study was performed using 3379 SNP markers. Tibia size, weight, ash content and breaking strength were highly heritable (0.42 to 0.61). Relative tibia diameter and volume as well as P retention were strongly and positively genetically correlated with digestive efficiency (0.57 to 0.80). A total of 35 QTL were identified (9 for tibia weight, 13 for tibia size, 5 for bone strength, 5 for bone mineralization, 2 for plasma P concentration and 1 for P retention). Six QTL were genome-wide significant, and 3 QTL for tibia relative volume, weight and ash weight on chromosome 6 were fixed, the positive allele coming from the D-line. For two QTL for ash content on chromosome 18 and relative tibia length on chromosome 26, the confidence intervals were small enough to identify potential candidate genes. These findings support the evidence of multiple genetic loci controlling bone and mineral metabolism. The identification of candidate genes may provide new perspectives in the understanding of bone regulation, even beyond avian species.

  6. Rye Affects Bacterial Translocation, Intestinal Viscosity, Microbiota Composition and Bone Mineralization in Turkey Poults

    PubMed Central

    Tellez, Guillermo; Latorre, Juan D.; Kuttappan, Vivek A.; Hargis, Billy M.; Hernandez-Velasco, Xochitl

    2015-01-01

    Previously, we have reported that rye significantly increased both viscosity and Clostridium perfringens proliferation when compared with corn in an in vitro digestive model. Two independent trials were conducted to evaluate the effect of rye as a source of energy on bacterial translocation, intestinal viscosity, gut microbiota composition, and bone mineralization, when compared with corn in turkey poults. In each experiment, day-of-hatch, turkey poults were randomly assigned to either a corn or a rye diet (n = 0 /group). At 10 d of age, in both experiments, 12 birds/group were given an oral gavage dose of fluorescein isothiocyanate dextran (FITC-d). After 2.5 h of oral gavage, blood and liver samples were collected to evaluate the passage of FITC-d and bacterial translocation (BT) respectively. Duodenum, ileum and cecum gut sections were collected to evaluate intestinal viscosity and to enumerate gut microbiota. Tibias were collected for observation of bone parameters. Broilers fed with a rye diet showed increased (p<0.05) intestinal viscosity, BT, and serum FITC-d. Bacterial enumeration revealed that turkey poults fed with rye had increased the number of total lactic acid bacteria (LAB) in all three sections of the gastrointestinal tract evaluated when compared to turkey poults fed with corn. Turkey poults fed with rye also had significantly higher coliforms in duodenum and ileum but not in the ceca, whereas the total number of anaerobes increased only in duodenum. A significant reduction in bone strength and bone mineralization was observed in turkey poults fed with rye when compared with corn fed turkey poults. In conclusion, rye evoked mucosal damage in turkey poults that increased intestinal viscosity, increased leakage through the intestinal tract, and altered the microbiota composition and bone mineralization. Studies to evaluate dietary inclusion of selected Direct-Fed Microbial (DFM) candidates that produce exogenous enzymes in rye fed turkey poults are

  7. Dietary patterns and bone mineral status in young adults: the Northern Ireland Young Hearts Project.

    PubMed

    Whittle, Claire R; Woodside, Jayne V; Cardwell, Chris R; McCourt, Hannah J; Young, Ian S; Murray, Liam J; Boreham, Colin A; Gallagher, Alison M; Neville, Charlotte E; McKinley, Michelle C

    2012-10-28

    Studies of individual nutrients or foods have revealed much about dietary influences on bone. Multiple food or nutrient approaches, such as dietary pattern analysis, could offer further insight but research is limited and largely confined to older adults. We examined the relationship between dietary patterns, obtained by a posteriori and a priori methods, and bone mineral status (BMS; collective term for bone mineral content (BMC) and bone mineral density (BMD)) in young adults (20-25 years; n 489). Diet was assessed by 7 d diet history and BMD and BMC were determined at the lumbar spine and femoral neck (FN). A posteriori dietary patterns were derived using principal component analysis (PCA) and three a priori dietary quality scores were applied (dietary diversity score (DDS), nutritional risk score and Mediterranean diet score). For the PCA-derived dietary patterns, women in the top compared to the bottom fifth of the 'Nuts and Meat' pattern had greater FN BMD by 0·074 g/cm(2) (P = 0·049) and FN BMC by 0·40 g (P = 0·034) after adjustment for confounders. Similarly, men in the top compared to the bottom fifth of the 'Refined' pattern had lower FN BMC by 0·41 g (P = 0·049). For the a priori DDS, women in the top compared to the bottom third had lower FN BMD by 0·05 g/cm(2) after adjustments (P = 0·052), but no other relationships with BMS were identified. In conclusion, adherence to a 'Nuts and Meat' dietary pattern may be associated with greater BMS in young women and a 'Refined' dietary pattern may be detrimental for bone health in young men.

  8. Rye affects bacterial translocation, intestinal viscosity, microbiota composition and bone mineralization in Turkey poults.

    PubMed

    Tellez, Guillermo; Latorre, Juan D; Kuttappan, Vivek A; Hargis, Billy M; Hernandez-Velasco, Xochitl

    2015-01-01

    Previously, we have reported that rye significantly increased both viscosity and Clostridium perfringens proliferation when compared with corn in an in vitro digestive model. Two independent trials were conducted to evaluate the effect of rye as a source of energy on bacterial translocation, intestinal viscosity, gut microbiota composition, and bone mineralization, when compared with corn in turkey poults. In each experiment, day-of-hatch, turkey poults were randomly assigned to either a corn or a rye diet (n = 0 /group). At 10 d of age, in both experiments, 12 birds/group were given an oral gavage dose of fluorescein isothiocyanate dextran (FITC-d). After 2.5 h of oral gavage, blood and liver samples were collected to evaluate the passage of FITC-d and bacterial translocation (BT) respectively. Duodenum, ileum and cecum gut sections were collected to evaluate intestinal viscosity and to enumerate gut microbiota. Tibias were collected for observation of bone parameters. Broilers fed with a rye diet showed increased (p<0.05) intestinal viscosity, BT, and serum FITC-d. Bacterial enumeration revealed that turkey poults fed with rye had increased the number of total lactic acid bacteria (LAB) in all three sections of the gastrointestinal tract evaluated when compared to turkey poults fed with corn. Turkey poults fed with rye also had significantly higher coliforms in duodenum and ileum but not in the ceca, whereas the total number of anaerobes increased only in duodenum. A significant reduction in bone strength and bone mineralization was observed in turkey poults fed with rye when compared with corn fed turkey poults. In conclusion, rye evoked mucosal damage in turkey poults that increased intestinal viscosity, increased leakage through the intestinal tract, and altered the microbiota composition and bone mineralization. Studies to evaluate dietary inclusion of selected Direct-Fed Microbial (DFM) candidates that produce exogenous enzymes in rye fed turkey poults are

  9. Chemical processing does not always impair heterogeneous ice nucleation of mineral dust particles

    NASA Astrophysics Data System (ADS)

    Sullivan, R. C.; Demott, P. J.; Prenni, A. J.; Minambres, L.; Kreidenweis, S. M.; Moehler, O.

    2010-12-01

    Mineral dust particles are the most abundant heterogeneous ice nuclei in the atmosphere. They also frequently become mixed with secondary material during atmospheric transport. The effect that such atmospheric processing has on the ice nucleation properties of dust particles remains under investigation. We have studied changes in the ice nucleation ability of various mineral dust sources after exposure to nitric acid in an aerosol flow tube, and after heterogeneous nucleation of α-pinene secondary organic aerosol (SOA) in the AIDA cloud expansion chamber. Both chemical treatments altered and homogenized the dust particles’ heterogeneous ice nucleation properties below water-saturation, but had no apparent impact on the immersion-freezing fraction well above water saturation. The fraction of particles capable of nucleating ice at fixed mixed-phase cloud temperatures between -35 and -15 °C was determined using a continuous flow diffusion chamber (CFDC) as the relative humidity with respect to water (RHw) was scanned from 75% to 110% RHw. Exposure to both nitric acid and SOA impaired essentially all ice nucleation in the deposition-regime below water saturation, while causing the onset of condensation-freezing to occur in a step-wise manner over a small range of RHw just below water saturation. We interpret this as the result of an increase in particle hygroscopicity following chemical treatment. This allows the mineral particles to absorb enough water to overcome solute freezing point depression effects and nucleate ice via condensation-freezing at a slightly smaller and narrower range of RHw than the less hygroscopic untreated dust can. Immersion-freezing above water saturation was not affected by either treatment. This is in stark contrast to earlier experiments where dust was exposed to sulfuric acid from a heated vapor source; ice nucleation was notably impaired in both the deposition and immersion-freezing regimes following sulfuric acid treatment.

  10. Association of bone mineral density with polymorphism of the human calcium-sensing receptor locus.

    PubMed

    Tsukamoto, K; Orimo, H; Hosoi, T; Miyao, M; Ota, N; Nakajima, T; Yoshida, H; Watanabe, S; Suzuki, T; Emi, M

    2000-03-01

    A strong correlation between bone mass and genetic factors has been shown in twins and family studies. Some of the genes involved would regulate bone metabolism, bone formation, and resorption, all processes that determine bone mass. One candidate genes, calcium-sensing receptor (CASR) in the parathyroid gland, regulates calcium homeostasis by sensing decreases in extracellular calcium level and effecting an increase in secretion of parathyroid hormone (PTH) and calcium (Ca) reabsorption in the kidney. We have investigated a possible association between the CA-repeat polymorphism at the human CASR gene locus and the bone mineral density (BMD) of radial bone in 472 postmenopausal Japanese women. Genotypes were classified into nine groups according to the number of CA repeats present, from 20 to 12. BMD was expressed as the adjusted BMD, which was the body mass index (BMI), and age-adjusted average BMD. The 247 women who had an A3 allele (228 bp, containing 18 repeats of CA) had significantly lower adjusted BMD (mean +/- SD: 0.303 +/- 0.059 versus 0.316 +/- 0.063 g/cm(2); P = 0.0308) than the participants (n = 201) who did not carry an allele of that size. This result suggests that genetic variation at the CASR gene locus is associated with some determinants for BMD in postmenopausal women.

  11. Experimental investigation of bone mineral density in Thoroughbreds using quantitative computed tomography

    PubMed Central

    YAMADA, Kazutaka; SATO, Fumio; HIGUCHI, Tohru; NISHIHARA, Kaori; KAYANO, Mitsunori; SASAKI, Naoki; NAMBO, Yasuo

    2015-01-01

    ABSTRACT Bone mineral density (BMD) is one of the indications of the strength and health. BMD measured by quantitative computed tomography (QCT) was compared with that measured by dual energy X-ray absorptiometry (DXA) and radiographic bone aluminum equivalence (RBAE). Limbs were removed from horses that had been euthanized for reasons not associated with this study. Sixteen limbs (left and right metacarpals and metatarsals) from 4 horses were used to compare BMD as measured by QCT with those measured by DXA and RBAE. There was a strong correlation between BMD values measured by QCT and those measured by DXA (R2=0.85); correlation was also observed between values obtained by QCT and those obtained by RBAE (R2=0.61). To investigate changes in BMD with age, 37 right metacarpal bones, including 7 from horses euthanized because of fracture were examined by QCT. The BMD value of samples from horses dramatically increased until 2 years of age and then plateaued, a pattern similar to the growth curve. The BMD values of bone samples from horses euthanized because of fracture were within the population range, and samples of morbid fracture were not included. The relationship between BMD and age provides a reference for further quantitative studies of bone development and remodeling. Quantitative measurement of BMD using QCT may have great potential for the evaluation of bone biology for breeding and rearing management. PMID:26435681

  12. Binding kinetics of a fluorescently labeled bisphosphonate as a tool for dynamic monitoring of bone mineral deposition in vivo.

    PubMed

    Tower, Robert J; Campbell, Graeme M; Müller, Marc; Will, Olga; Glüer, Claus C; Tiwari, Sanjay

    2014-09-01

    Bone mineral deposition during the modeling of new bone and remodeling of old bone can be perturbed by several pathological conditions, including osteoporosis and skeletal metastases. A site-specific marker depicting the dynamics of bone mineral deposition would provide insight into skeletal disease location and severity, and prove useful in evaluating the efficacy of pharmacological interventions. Fluorescent labels may combine advantages of both radioisotope imaging and detailed microscopic analyses. The purpose of this study was to determine if the fluorescent bisphosphonate OsteoSense could detect localized changes in bone mineral deposition in established mouse models of accelerated bone loss (ovariectomy) (OVX) and anabolic bone gain resulting from parathyroid hormone (PTH) treatment. We hypothesized that the early rate of binding, as well as the total amount of bisphosphonate, which binds over long periods of time, could be useful in evaluating changes in bone metabolism. Evaluation of the kinetic uptake of bisphosphonates revealed a significant reduction in both the rate constant and plateau binding after OVX, whereas treatment with PTH resulted in a 36-fold increase in the bisphosphonate binding rate constant compared with untreated OVX controls. Localization of bisphosphonate binding revealed initial binding at sites of ossification adjacent to the growth plate and, to a lesser extent, along more distal trabecular and cortical elements. Micro-computed tomography (CT) was used to confirm that initial bisphosphonate binding is localized to sites of low tissue mineral density, associated with new bone mineral deposition. Our results suggest monitoring binding kinetics based on fluorescently labeled bisphosphonates represents a highly sensitive, site-specific method for monitoring changes in bone mineral deposition with the potential for translation into human applications in osteoporosis and bone metastatic processes and their treatment.

  13. Bones of contention: bone mineral density recovery in celiac disease--a systematic review.

    PubMed

    Grace-Farfaglia, Patricia

    2015-05-07

    Metabolic bone disease is a frequent co-morbidity in newly diagnosed adults with celiac disease (CD), an autoimmune disorder triggered by the ingestion of dietary gluten. This systematic review of studies looked at the efficacy of the gluten-free diet, physical activity, nutrient supplementation, and bisphosphonates for low bone density treatment. Case control and cohort designs were identified from PubMed and other academic databases (from 1996 to 2015) that observed newly diagnosed adults with CD for at least one year after diet treatment using the dual-energy x-ray absorptiometry (DXA) scan. Only 20 out of 207 studies met the inclusion criteria. Methodological quality was assessed using the Strengthening of the Reporting of Observational Studies in Epidemiology (STROBE) statement checklist. Gluten-free diet adherence resulted in partial recovery of bone density by one year in all studies, and full recovery by the fifth year. No treatment differences were observed between the gluten-free diet alone and diet plus bisphosphonates in one study. For malnourished patients, supplementation with vitamin D and calcium resulted in significant improvement. Evidence for the impact of physical activity on bone density was limited. Therapeutic strategies aimed at modifying lifestyle factors throughout the lifespan should be studied.

  14. Bones of Contention: Bone Mineral Density Recovery in Celiac Disease—A Systematic Review

    PubMed Central

    Grace-Farfaglia, Patricia

    2015-01-01

    Metabolic bone disease is a frequent co-morbidity in newly diagnosed adults with celiac disease (CD), an autoimmune disorder triggered by the ingestion of dietary gluten. This systematic review of studies looked at the efficacy of the gluten-free diet, physical activity, nutrient supplementation, and bisphosphonates for low bone density treatment. Case control and cohort designs were identified from PubMed and other academic databases (from 1996 to 2015) that observed newly diagnosed adults with CD for at least one year after diet treatment using the dual-energy x-ray absorptiometry (DXA) scan. Only 20 out of 207 studies met the inclusion criteria. Methodological quality was assessed using the Strengthening of the Reporting of Observational Studies in Epidemiology (STROBE) statement checklist. Gluten-free diet adherence resulted in partial recovery of bone density by one year in all studies, and full recovery by the fifth year. No treatment differences were observed between the gluten-free diet alone and diet plus bisphosphonates in one study. For malnourished patients, supplementation with vitamin D and calcium resulted in significant improvement. Evidence for the impact of physical activity on bone density was limited. Therapeutic strategies aimed at modifying lifestyle factors throughout the lifespan should be studied. PMID:25961322

  15. Body composition and bone mineral density of collegiate American football players

    PubMed Central

    Turnagöl, Hüseyin Hüsrev

    2016-01-01

    Abstract The aim of this study was to compare whole and segmental body composition and bone mineral density of collegiate American football players by playing positions. Forty collegiate American football players voluntarily participated in this study. Participants were categorized by playing positions into one of five categories i.e., defensive linemen, offensive linemen, defensive secondary players, offensive secondary players and receivers. Whole body composition and bone mineral density were measured by dual x-ray absorptiometry. Offensive and defensive linemen had higher body mass, a body mass index, lean mass and a fat mass index compared to the remaining three positions and a higher lean mass index compared to offensive secondary players and receivers. Offensive linemen had a higher body fat percentage and lower values of upper to lower lean mass than offensive and defensive secondary players and receivers, and higher total mass to the lean mass ratio and fat mass to the lean mass ratio compared to the other players. Offensive linemen had a higher fat mass index and fat mass to the lean mass ratio than defensive linemen. However, in all other measures they were similar. Offensive and defensive secondary players and receivers were similar with respect to the measured variables. Bone mineral density of the players was within the normal range and no difference in lean mass was observed between the legs. In conclusion, findings of this study showed that the total and segmental body composition profile of collegiate American football players reflected the demands of particular playing positions. PMID:28149373

  16. t10c12-CLA maintains higher bone mineral density during aging by modulating osteoclastogenesis and bone marrow adiposity.

    PubMed

    Rahman, Md M; Halade, Ganesh V; Williams, Paul J; Fernandes, Gabriel

    2011-09-01

    Conjugated linoleic acid (CLA) has been shown to positively influence calcium and bone metabolism. Earlier, we showed that CLA (equal mixture of c9t11-CLA and t10c12-CLA) could protect age-associated bone loss by modulating inflammatory markers and osteoclastogenesis. Since, c9t11-CLA and t10c12-CLA isomers differentially regulate functional parameters and gene expression in different cell types, we examined the efficacy of individual CLA isomers against age-associated bone loss using 12 months old C57BL/6 female mice fed for 6 months with 10% corn oil (CO), 9.5% CO + 0.5% c9t11-CLA, 9.5% CO + 0.5% t10c12-CLA or 9.5% CO + 0.25% c9t11-CLA + 0.25% t10c12-CLA. Mice fed a t10c12-CLA diet maintained a significantly higher bone mineral density (BMD) in femoral, tibial and lumbar regions than those fed CO and c9t11-CLA diets as measured by dual-energy-X-ray absorptiometry (DXA). The increased BMD was accompanied by a decreased production of osteoclastogenic factors, that is, RANKL, TRAP5b, TNF-alpha and IL-6 in serum. Moreover, a significant reduction of high fat diet-induced bone marrow adiposity was observed in t10c12-CLA fed mice as compared to that of CO and c9t11-CLA fed mice, as measured by Oil-Red-O staining of bone marrow sections. In addition, a significant reduction of osteoclast differentiation and bone resorbing pit formation was observed in t10c12-CLA treated RAW 264.7 cell culture stimulated with RANKL as compared to that of c9t11-CLA and linoleic acid treated cultures. In conclusion, these findings suggest that t10c12-CLA is the most potent CLA isomer and it exerts its anti-osteoporotic effect by modulating osteoclastogenesis and bone marrow adiposity.

  17. Gpr177, a novel locus for bone mineral density and osteoporosis, regulates osteogenesis and chondrogenesis in skeletal development.

    PubMed

    Maruyama, Takamitsu; Jiang, Ming; Hsu, Wei

    2013-05-01

    Human genetic analysis has recently identified Gpr177 as a susceptibility locus for bone mineral density and osteoporosis. Determining the unknown function of this gene is therefore extremely important to furthering our knowledge base of skeletal development and disease. The protein encoded by Gpr177 exhibits an ability to modulate the trafficking of Wnt, similar to the Drosophila Wls/Evi/Srt. Because it plays a critical role in Wnt regulation, Gpr177 might be required for several key steps of skeletogenesis. To overcome the early lethality associated with the inactivation of Gpr177 in mice, conditional gene deletion is used to assess its functionality. Here we report the generation of four different mouse models with Gpr177 deficiency in various skeletogenic cell types. The loss of Gpr177 severely impairs development of the craniofacial and body skeletons, demonstrating its requirement for intramembranous and endochondral ossifications, respectively. Defects in the expansion of skeletal precursors and their differentiation into osteoblasts and chondrocytes suggest that Wnt production and signaling mediated by Gpr177 cannot be substituted. Because the Gpr177 ablation impairs Wnt secretion, we therefore identify the sources of Wnt proteins essential for osteogenesis and chondrogenesis. The intercross of Wnt signaling between distinct cell types is carefully orchestrated and necessary for skeletogenesis. Our findings lead to a proposed mechanism by which Gpr177 controls skeletal development through modulation of autocrine and paracrine Wnt signals in a lineage-specific fashion.

  18. Inverse correlation between fibrinogen and bone mineral density in women: Preliminary findings.

    PubMed

    Chen, Jui-Tung; Kotani, Kazuhiko

    2016-01-01

    Hemostatic factors may be involved in bone health. The present preliminary study investigated the association between plasma fibrinogen and bone mineral density (BMD) in perimenopausal women. A significant inverse correlation between fibrinogen and BMD was observed (correlation coefficient = -0.42, p < 0.01). This correlation appeared to be more clearly observed in the subgroup with a high level of high-sensitivity C-reactive protein than in that with a low level of high-sensitivity C-reactive protein, and in the subgroup with a high level of diacron reactive oxygen metabolites (an oxidative stress marker) than in that with a low level of diacron reactive oxygen metabolites. Thus, fibrinogen may be a possible marker of BMD in this population. More studies on the associations among hemostasis, inflammation, oxidative stress, and bone metabolism are warranted in the clinical setting.

  19. Alterations of bone and mineral metabolism in diabetes mellitus. Part I. An overview.

    PubMed

    Hough, F S

    1987-07-18

    A critical review of the literature leads to the conclusion that alterations of bone and mineral metabolism occur both in diabetic patients and in animals with experimentally induced insulin deficiency syndromes. The coexistence of juvenile insulin-dependent diabetes mellitus (type 1) and radiological evidence of decreased bone mass (osteopenia) appears to be firmly established. Available data support the view that these patients have an increased propensity to skeletal fracture. Adult-onset, non-insulin-dependent diabetic populations, more heterogeneous as regards the type of diabetes, the therapy and the presence of complications or coexistent disease, are characterised by subpopulations with either a decreased, a normal or an increased bone mass. The pathogenesis of diabetic osteopenia is multifactorial. Data obtained from studies employing appropriate animal models of chronic insulin deficiency indicate that various metabolic and hormonal abnormalities may be involved.

  20. Dual-Energy X-Ray Absorptiometry: Beyond Bone Mineral Density Determination

    PubMed Central

    2016-01-01

    Significant improvements in dual-energy X-ray absorptiometry (DXA) concerning quality, image resolution and image acquisition time have allowed the development of various functions. DXA can evaluate bone quality by indirect analysis of micro- and macro-architecture of the bone, which and improve the prediction of fracture risk. DXA can also detect existing fractures, such as vertebral fractures or atypical femur fractures, without additional radiologic imaging and radiation exposure. Moreover, it can assess the metabolic status by the measurement of body composition parameters like muscle mass and visceral fat. Although more studies are required to validate and clinically use these parameters, it is clear that DXA is not just for bone mineral densitometry. PMID:26996419

  1. Known VDR polymorphisms are not associated with bone mineral density measures in pediatric Cushing disease.

    PubMed

    Lodish, Maya B; Mastroyannis, Spyridon A; Sinaii, Ninet; Boikos, Sosipatros A; Stratakis, Constantine A

    2012-01-01

    Decreased bone mineral density (BMD) has been documented in adults with Cushing disease (CD), and allelic variants of the vitamin D receptor (VDR) gene have been associated with osteopenia. Genetic factors play an important role in bone accrual and its response to various diseases; among them, the most studied are the allelic variants of the VDR gene. There is debate as to whether described variants in the VDR gene have an effect on BMD. In the current study, we sought to analyze whether BMD differences in patients with CD were associated with the Taq1 and Apal VDR allelotypes. The data showed lack of association between BMD and these widely studied VDR polymorphisms, suggesting that the effect of endogenous hypercortisolism on bone in the context of CD does not depend on VDR genotypes.

  2. Effects of estrogen deficiency and low bone mineral density on healthy knee cartilage in rabbits.

    PubMed

    Castañeda, Santos; Largo, Raquel; Calvo, Emilio; Bellido, Miriam; Gómez-Vaquero, Carmen; Herrero-Beaumont, Gabriel

    2010-06-01

    The purpose of this study was to compare the effects of estrogen deficiency and bone mass loss on normal knee cartilage in mature rabbits. Bilateral ovariectomy (OVX) was performed in 13 rabbits, 6 of which also received systemic glucocorticoid for 4 weeks. Seven additional healthy rabbits were used as controls. Bone mineral density (BMD) was measured by dual X-ray absorptiometry in lumbar spine, knee, and subchondral bone of the knee at baseline and 22 weeks after OVX. After sacrifice, the knees were dissected, macroscopy was assessed, and histological cartilage abnormalities were evaluated according to the Mankin score. Correlations of Mankin with BMD at different regions were also performed. When compared to baseline, differences in BMD were only found in spine and knee of the animals receiving glucocorticoids. All the animals subjected to OVX had a significantly higher Mankin score than controls. Mankin was upper in OVX animals receiving glucocorticoids, but differences were not significant. The Mankin score was inversely related with BMD in lumbar spine (r = -0.67; p < 0.01). Although low bone mineral density contributes to the minor osteoarthritic alterations observed in our model, estrogen deficiency itself seems to act directly to induce the main pathogenic effects in healthy cartilage of the rabbit.

  3. Study of bone mineral metabolism. [during body immobilization, bed rest, and space flight

    NASA Technical Reports Server (NTRS)

    Palmer, H. E.

    1975-01-01

    The use of Sr-85 as an indicator of the skeletal location and relative amount of bone demineralization which occurs during immobilization of the body or body parts, bed-rest or space flight was studied. The bone mineral replacement which occurs after immobilization was measured rather than the bone loss which occurs during immobilization. In a study with two adult beagle dogs, the Sr-85 uptake in a leg which had been immobilized for two months was 400 percent higher than the uptake in the legs in regular use. This increased uptake probably resulted from only a few percent loss in bone mineral and indicates that losses less than one percent can be easily detected and located. The sensitivity, simplicity, and low radiation dose associated with the use of this method indicates that it should receive consideration for use on humans in bed-rest and space flight studies. Methods for measuring changes in total body nitrogen and in assisting the Johnson Space Center in calibrating a whole body counter for total body potassium measurements were also investigated.

  4. Effect of Denosumab on Bone Mineral Density and Markers of Bone Turnover among Postmenopausal Women with Osteoporosis

    PubMed Central

    Salerni, H.; González, D.; Bagur, A.; Oliveri, B.; Farías, V.; Maffei, L.; Mansur, J. L.; Larroudé, M. S.; Pavlove, M. M.; Karlsbrum, S.

    2016-01-01

    The aim of this study was to evaluate the effect of denosumab (Dmab) on bone mineral density (BMD) and bone turnover markers after 1 year of treatment. Additionally, the effect of Dmab in bisphosphonate-naïve patients (BP-naïve) compared to patients previously treated with bisphosphonates (BP-prior) was analyzed. This retrospective study included 425 postmenopausal women treated with Dmab for 1 year in clinical practice conditions in specialized centers from Argentina. Participants were also divided according to previous bisphosphonate treatment into BP-naïve and BP-prior. A control group of patients treated with BP not switched to Dmab matched by sex, age, and body mass index was used. Data are expressed as mean ± SEM. After 1 year of treatment with Dmab the bone formation markers total alkaline phosphatase and osteocalcin were significantly decreased (23.36% and 43.97%, resp.), as was the bone resorption marker s-CTX (69.61%). Significant increases in BMD were observed at the lumbar spine, femoral neck, and total hip without differences between BP-naïve and BP-prior. A better BMD response was found in BP-prior group compared with BP treated patients not switched to Dmab. Conclusion. Dmab treatment increased BMD and decreased bone turnover markers in the whole group, with similar response in BP-naïve and BP-prior patients. A better BMD response in BP-prior patients versus BP treated patients not switched to Dmab was observed. PMID:27579211

  5. Evaluation of Bone Mineral Density and Bone Biomarkers in Patients With Type 2 Diabetes Treated With Canagliflozin

    PubMed Central

    Watts, Nelson B.; Usiskin, Keith; Polidori, David; Fung, Albert; Sullivan, Daniel; Rosenthal, Norm

    2016-01-01

    Context: Canagliflozin is a sodium glucose cotransporter 2 inhibitor developed to treat type 2 diabetes mellitus (T2DM). Objective: Our objective is to describe the effects of canagliflozin on bone mineral density (BMD) and bone biomarkers in patients with T2DM. Design: This was a randomized study, consisting of a 26-week, double-blind, placebo-controlled period and a 78-week, double-blind, placebo-controlled extension. Setting: This study was undertaken in 90 centers in 17 countries. Patients: Patients were aged 55–80 years (N = 716) and whose T2DM was inadequately controlled on a stable antihyperglycemic regimen. Interventions: Canagliflozin 100 or 300 mg or placebo were administered once daily. Outcome and Measures: BMD was assessed using dual-energy x-ray absorptiometry at weeks 26, 52, and 104. Bone strength was assessed using quantitative computed tomography and finite element analysis at week 52. Serum collagen type 1 β-carboxy-telopeptide, osteocalcin, and estradiol were assessed at weeks 26 and 52. Results: Canagliflozin doses of 100 and 300 mg were associated with a decrease in total hip BMD over 104 weeks, (placebo-subtracted changes: −0.9% and −1.2%, respectively), but not at other sites measured (femoral neck, lumbar spine, or distal forearm). No meaningful changes in bone strength were observed. At week 52, canagliflozin was associated with an increase in collagen type 1 β-carboxy-telopeptide that was significantly correlated with a reduction in body weight, an increase in osteocalcin, and, in women, a decrease in estradiol. Conclusions: In older patients with T2DM, canagliflozin showed small but significant reductions in total hip BMD and increases in bone formation and resorption biomarkers, due at least in part to weight loss. PMID:26580234

  6. Effect of Denosumab on Bone Mineral Density and Markers of Bone Turnover among Postmenopausal Women with Osteoporosis.

    PubMed

    Sánchez, A; Brun, L R; Salerni, H; Costanzo, P R; González, D; Bagur, A; Oliveri, B; Zanchetta, M B; Farías, V; Maffei, L; Premrou, V; Mansur, J L; Larroudé, M S; Sarli, M A; Rey, P; Ulla, M R; Pavlove, M M; Karlsbrum, S; Brance, M L

    2016-01-01

    The aim of this study was to evaluate the effect of denosumab (Dmab) on bone mineral density (BMD) and bone turnover markers after 1 year of treatment. Additionally, the effect of Dmab in bisphosphonate-naïve patients (BP-naïve) compared to patients previously treated with bisphosphonates (BP-prior) was analyzed. This retrospective study included 425 postmenopausal women treated with Dmab for 1 year in clinical practice conditions in specialized centers from Argentina. Participants were also divided according to previous bisphosphonate treatment into BP-naïve and BP-prior. A control group of patients treated with BP not switched to Dmab matched by sex, age, and body mass index was used. Data are expressed as mean ± SEM. After 1 year of treatment with Dmab the bone formation markers total alkaline phosphatase and osteocalcin were significantly decreased (23.36% and 43.97%, resp.), as was the bone resorption marker s-CTX (69.61%). Significant increases in BMD were observed at the lumbar spine, femoral neck, and total hip without differences between BP-naïve and BP-prior. A better BMD response was found in BP-prior group compared with BP treated patients not switched to Dmab. Conclusion. Dmab treatment increased BMD and decreased bone turnover markers in the whole group, with similar response in BP-naïve and BP-prior patients. A better BMD response in BP-prior patients versus BP treated patients not switched to Dmab was observed.

  7. 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.

  8. [MINERAL BONE DENSITY AND BODY COMPOSITION IN PARTICIPANTS IN EXPERIMENT MARS-500].

    PubMed

    Novikov, V E; Oganov, V S; Kabitskaya, O E; Murashko, L M; Naidina, V P; Chernikhova, E A

    2016-01-01

    Investigations of the bone system and body composition in Mars-500 test-subjects (prior to and on completion of the experiment) involved dual-energy X-ray absorptiometry (DXA) using the HOLOGIC Delphy densitometer and the protocol performed to examine cosmonauts. Bone density of lumber vertebrae and femoral proximal epiphysis, and body composition were measured. Reliable changes in vertebral density found in 3 test-subjects displayed different trends from +2.6 to -2.4%. At the same time, the experiment decreased significantly mineral density of the femoral proximal epiphysis, including the neck, in all test-subjects. Four test-subjects had cranial mineralization increased by 5-9%, same as in some cosmonauts after space flight. All tests-subjects incurred adipose loss from 2 to 7 kg; one test-subject lost 20 kg, i.e. his adipose mass became three times less. Changes in lean mass (1-3 kg) typically were negative; as for changes in lean mass of extremities, they could be linked with adherence to one or another type of physical activity. Therefore, extended exposure to confinement may affect mineralization of some parts of the skeleton. Unlike real space missions and long-term bedrest studies conducted at the Institute of Biomedical Problems in the past, Mars-500 did not cause clinically significant mineral losses (osteoporosis, osteopenia), probably because of the absence of effects of microgravity.

  9. In ovo feeding with minerals and vitamin D3 improves bone properties in hatchlings and mature broilers.

    PubMed

    Yair, R; Shahar, R; Uni, Z

    2015-11-01

    The objective of this study was to examine the effect of in ovo feeding (IOF) with inorganic minerals or organic minerals and vitamin D3 on bone properties and mineral consumption. Eggs were incubated and divided into 4 groups: IOF with organic minerals, phosphate, and vitamin D3 (IOF-OMD); IOF with inorganic minerals and phosphate (IOF-IM); sham; and non-treated controls (NTC). IOF was performed on embryonic day (E) 17; tibiae and yolk samples were taken on E19 and E21. Post-hatch, only chicks from the IOF-OMD, sham, and NTC were raised, and tibiae were taken on d 10 and 38. Yolk mineral content was examined by inductively coupled plasma spectroscopy. Tibiae were tested for their whole-bone mechanical properties, and mid-diaphysis bone sections were indented in a micro-indenter to determine bone material stiffness (Young's modulus). Micro-computed tomography (μCT) was used to examine cortical and trabecular bone structure. Ash content analysis was used to examine bone mineralization. A latency-to-lie (LTL) test was used to measure standing ability of the d 38 broilers. The results showed that embryos from both IOF-OMD and IOF-IM treatments had elevated Cu, Mn, and Zn amounts in the yolk on E19 and E21 and consumed more of these minerals (between E19 and E21) in comparison to the sham and NTC. On E21, these hatchlings had higher whole-bone stiffness in comparison to the NTC. On d 38, the IOF-OMD had higher ash content, elevated whole-bone stiffness, and elevated Young's modulus (in males) in comparison to the sham and NTC; however, no differences in standing ability were found. Very few structural differences were seen during the whole experiment. This study demonstrates that mineral supplementation by in ovo feeding is sufficient to induce higher mineral consumption from the yolk, regardless of its chemical form or the presence of vitamin D3. Additionally, IOF with organic minerals and vitamin D3 can increase bone ash content, as well as stiffness of the whole

  10. Concise review: diabetes, the bone marrow niche, and impaired vascular regeneration.

    PubMed

    Fadini, Gian Paolo; Ferraro, Francesca; Quaini, Federico; Asahara, Takayuki; Madeddu, Paolo

    2014-08-01

    Diabetes mellitus is a global health problem that results in multiorgan complications leading to high morbidity and mortality. Until recently, the effects of diabetes and hyperglycemia on the bone marrow microenvironment-a site where multiple organ systems converge and communicate-have been underappreciated. However, several new studies in mice, rats, and humans reveal that diabetes leads to multiple bone marrow microenvironmental defects, such as small vessel disease (microangiopathy), nerve terminal pauperization (neuropathy), and impaired stem cell mobilization (mobilopathy). The discovery that diabetes involves bone marrow-derived progenitors implicated in maintaining cardiovascular homeostasis has been proposed as a bridging mechanism between micro- and macroangiopathy in distant organs. Herein, we review the physiological and molecular bone marrow abnormalities associated with diabetes and discuss how bone marrow dysfunction represents a potential root for the development of the multiorgan failure characteristic of advanced diabetes. The notion of diabetes as a bone marrow and stem cell disease opens new avenues for therapeutic interventions ultimately aimed at improving the outcome of diabetic patients.

  11. Does cancellous screw insertion torque depend on bone mineral density and/or microarchitecture?

    PubMed

    Ab-Lazid, Rosidah; Perilli, Egon; Ryan, Melissa K; Costi, John J; Reynolds, Karen J

    2014-01-22

    During insertion of a cancellous bone screw, the torque level reaches a plateau, at the engagement of all the screw threads prior to the screw head contact. This plateau torque (T(Plateau)) was found to be a good predictor of the insertion failure torque (stripping) and also exhibited strong positive correlations with areal bone mineral density (aBMD) in ovine bone. However, correlations between T(Plateau) and aBMD, as well as correlations between T(Plateau) and bone microarchitecture, have never been explored in human bone. The aim of this study was to determine whether T(Plateau), a predictor of insertion failure torque, depends on aBMD and/or bone microarchitecture in human femoral heads. Fifty-two excised human femoral heads were obtained. The aBMD and microarchitecture of each specimen were evaluated using dual X-ray Absorptiometry and micro-computed tomography. A cancellous screw was inserted into specimens using an automated micro-mechanical test device, and T(Plateau) was calculated from the insertion profile. T(Plateau) exhibited the strongest correlation with the structure model index (SMI, R=-0.82, p<0.001), followed by bone volume fraction (BV/TV, R=0.80, p<0.01) and aBMD (R=0.76, p<0.01). Stepwise forward regression analysis showed an increase for the prediction of T(Plateau) when aBMD was combined with microarchitectural parameters, i.e., aBMD combined with SMI (R(2) increased from 0.58 to 0.72) and aBMD combined with BV/TV and BS/TV (R(2) increased from 0.58 to 0.74). In conclusion, T(Plateau), a strong predictor for insertion failure torque, is significantly dependent on bone microarchitecture (particularly SMI and BV/TV) and aBMD.

  12. Age-related decrements in bone mineral density in women over 65

    NASA Technical Reports Server (NTRS)

    Steiger, P.; Cummings, S. R.; Black, D. M.; Spencer, N. E.; Genant, H. K.

    1992-01-01

    Age-related changes in bone density contribute to the risk of fractures. To describe the relationship between age and bone mass in elderly women, we studied a large cohort of women over age 65 years who were recruited from population-based lists in four cities in the United States. Bone density in g/cm2 was measured by single-photon absorptiometry (SPA) and dual x-ray absorptiometry (DXA) at the distal and proximal radius, the calcaneus, the lumbar spine, and the proximal femur. Centralized data collection was used to control data quality and consistency. We found a strong inverse relationship between bone density and age for most sites. Decrements in bone density between women aged 65-69 years and women 85 years and older exceeded 16% in all regions except the spine, where the difference between the two age groups was 6%. Ward's triangle and the calcaneus exhibited the largest decrements, with 26 and 21%, respectively. The estimates of annual changes in bone mineral density by linear regression at sites other than the spine ranged from -0.82% at the femoral neck and trochanter to -1.30% at Ward's triangle. Correlations between the different regions ranged from r = 0.51 between the proximal radius and Ward's triangle to r = 0.66 between the distal radius and calcaneus. We conclude that the inverse relationship between age and bone mass measured by absorptiometry techniques in white women continues into the ninth decade of life. The relationship is strongest for bone density of Ward's triangle and the calcaneus and weakest for the spine.

  13. Bone mineral density response to long-term bisphosphonate therapy in fibrous dysplasia.

    PubMed

    Parisi, M S; Oliveri, M B; Mautalen, C A

    2001-01-01

    Fibrous dysplasia of bone is a rare disease related to a genetic mutation in which bone formation at osseous sites is altered. In the last few years, bisphosphonates have become one of the choice drugs to treat this disease. A 26-yr-old woman presented after 6 wk of spontaneous right leg pain owing to a fissure fracture of the right femoral neck. She reported precocious puberty at the age of 2, with diagnosis of McCune-Albright syndrome. Radioisotope bone scanning, radiographic, biochemical, and densitometric studies were performed. Treatment with bisphosphonates was started because bone turnover biochemical markers were abnormal. Oral olpadronate followed by iv pamidronate substantially decreased bone resorption. Bone mineral density (BMD) of total skeleton and subareas was assessed by dual X-ray absorptiometry (DXA) throughout the 5 yr of treatment. At the end of this period, BMD of the total skeleton had increased 6.2%. However, BMD of the areas most affected by fibrous dysplasia, the legs and pelvis, had increased 12.7 and 11%, respectively. Region of interest analysis of individual bones of the legs performed with the total skeleton scan revealed that BMD of the areas most affected by fibrous dysplasia was lower than that of the less affected contralateral bones. During the first 3 yr, treatment with bisphosphonates substantially increased BMD of the right femur and tibia (22 and 28%, respectively). After that, values seemed to stabilize. DXA evaluation of the total skeleton and its subareas was useful to evaluate the efficacy of bisphosphonate treatment. Moreover, the plateau observed in BMD values after 3 yr of treatment suggests that treatment could have been discontinued when the densitometric values stabilized.

  14. A primary phosphorus‐deficient skeletal phenotype in juvenile Atlantic salmon Salmo salar: the uncoupling of bone formation and mineralization

    PubMed Central

    Owen, M. A. G.; Fontanillas, R.; Soenens, M.; McGurk, C.; Obach, A.

    2015-01-01

    To understand the effect of low dietary phosphorus (P) intake on the vertebral column of Atlantic salmon Salmo salar, a primary P deficiency was induced in post‐smolts. The dietary P provision was reduced by 50% for a period of 10 weeks under controlled conditions. The animal's skeleton was subsequently analysed by radiology, histological examination, histochemical detection of minerals in bones and scales and chemical mineral analysis. This is the first account of how a primary P deficiency affects the skeleton in S. salar at the cellular and at the micro‐anatomical level. Animals that received the P‐deficient diet displayed known signs of P deficiency including reduced growth and soft, pliable opercula. Bone and scale mineral content decreased by c. 50%. On radiographs, vertebral bodies appear small, undersized and with enlarged intervertebral spaces. Contrary to the X‐ray‐based diagnosis, the histological examination revealed that vertebral bodies had a regular size and regular internal bone structures; intervertebral spaces were not enlarged. Bone matrix formation was continuous and uninterrupted, albeit without traces of mineralization. Likewise, scale growth continues with regular annuli formation, but new scale matrix remains without minerals. The 10 week long experiment generated a homogeneous osteomalacia of vertebral bodies without apparent induction of skeletal malformations. The experiment shows that bone formation and bone mineralization are, to a large degree, independent processes in the fish examined. Therefore, a deficit in mineralization must not be the only cause of the alterations of the vertebral bone structure observed in farmed S. salar. It is discussed how the observed uncoupling of bone formation and mineralization helps to better diagnose, understand and prevent P deficiency‐related malformations in farmed S. salar. PMID:26707938

  15. A primary phosphorus-deficient skeletal phenotype in juvenile Atlantic salmon Salmo salar: the uncoupling of bone formation and mineralization.

    PubMed

    Witten, P E; Owen, M A G; Fontanillas, R; Soenens, M; McGurk, C; Obach, A

    2016-02-01

    To understand the effect of low dietary phosphorus (P) intake on the vertebral column of Atlantic salmon Salmo salar, a primary P deficiency was induced in post-smolts. The dietary P provision was reduced by 50% for a period of 10 weeks under controlled conditions. The animal's skeleton was subsequently analysed by radiology, histological examination, histochemical detection of minerals in bones and scales and chemical mineral analysis. This is the first account of how a primary P deficiency affects the skeleton in S. salar at the cellular and at the micro-anatomical level. Animals that received the P-deficient diet displayed known signs of P deficiency including reduced growth and soft, pliable opercula. Bone and scale mineral content decreased by c. 50%. On radiographs, vertebral bodies appear small, undersized and with enlarged intervertebral spaces. Contrary to the X-ray-based diagnosis, the histological examination revealed that vertebral bodies had a regular size and regular internal bone structures; intervertebral spaces were not enlarged. Bone matrix formation was continuous and uninterrupted, albeit without traces of mineralization. Likewise, scale growth continues with regular annuli formation, but new scale matrix remains without minerals. The 10 week long experiment generated a homogeneous osteomalacia of vertebral bodies without apparent induction of skeletal malformations. The experiment shows that bone formation and bone mineralization are, to a large degree, independent processes in the fish examined. Therefore, a deficit in mineralization must not be the only cause of the alterations of the vertebral bone structure observed in farmed S. salar. It is discussed how the observed uncoupling of bone formation and mineralization helps to better diagnose, understand and prevent P deficiency-related malformations in farmed S. salar.

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

    PubMed Central

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

    2016-01-01

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

  17. Reduced hip bone mineral density is related to physical fitness and leg lean mass in ambulatory individuals with chronic stroke

    PubMed Central

    Pang, Marco YC; Eng, Janice J; McKay, Heather A; Dawson, Andrew S

    2011-01-01

    Following a stroke, reduced level of physical activity and functional use of the paretic leg may lead to bone loss and muscle atrophy. These factors and the high incidence of falls may contribute to hip fractures in the stroke population. This study was the first to examine total proximal femur bone mineral content (BMC) and bone mineral density (BMD) and their relationship to stroke-specific impairments in ambulatory individuals with chronic stroke (onset >1 year). We utilized dual-energy X-ray absorptiometry (DXA) to acquire proximal femur and total body scans on 58 (23 women) community-dwelling individuals with chronic stroke. We report total proximal femur BMC (g) and BMD (g/cm2) derived from the proximal femur scans, and lean mass (g) and fat mass (g) for each leg derived from the total body scans. Each subject was evaluated for ambulatory capacity (Six Minute Walk Test), knee extension strength (hand-held dynamometry), physical fitness [Maximal oxygen uptake (VO2max)], and spasticity (Modified Ashworth Scale). Results showed that the paretic leg had significantly lower proximal femur BMD, lean mass, and percent lean mass but higher fat mass than the non-paretic leg for both men and women. Proximal femur BMD of the paretic leg was significantly related to ambulatory capacity (r=0.33, p=0.011), muscle strength (r=0.39, p=0.002), physical fitness (r=0.57, p<0.001) but not related to spasticity (r=−0.23, p=0.080). Multiple regression analysis showed that lean mass in the paretic leg was a major predictor (R2=0.371, p<0.001) of the paretic proximal femur BMD. VO2max was a significant predictor of both paretic proximal femur BMD (R2=0.325, p<0.001) and lean mass in the paretic leg (R2=0.700, p<0.001). Further study is required to determine whether increasing physical fitness and lean mass is important to improve hip bone health in chronic stroke. PMID:15902416

  18. Reduced hip bone mineral density is related to physical fitness and leg lean mass in ambulatory individuals with chronic stroke.

    PubMed

    Pang, Marco Y C; Eng, Janice J; McKay, Heather A; Dawson, Andrew S

    2005-12-01

    Following a stroke, the reduced level of physical activity and functional use of the paretic leg may lead to bone loss and muscle atrophy. These factors and the high incidence of falls may contribute to hip fractures in the stroke population. This study was the first to examine total proximal femur bone mineral content (BMC) and bone mineral density (BMD) and their relationship to stroke-specific impairments in ambulatory individuals with chronic stroke (onset >1 year). We utilized dual-energy X-ray absorptiometry (DXA) to acquire proximal femur and total body scans on 58 (23 women) community-dwelling individuals with chronic stroke. We reported total proximal femur BMC (g) and BMD (g/cm2) derived from the proximal femur scans, and lean mass (g) and fat mass (g) for each leg derived from the total body scans. Each subject was evaluated for ambulatory capacity (Six-Minute Walk Test), knee extension strength (hand-held dynamometry), physical fitness [maximal oxygen uptake (VO2max)] and spasticity (Modified Ashworth Scale). Results showed that the paretic leg had significantly lower proximal femur BMD, lean mass and percent lean mass, but higher fat mass than the non-paretic leg for both men and women. Proximal femur BMD of the paretic leg was significantly related to ambulatory capacity (r=0.33, P=0.011), muscle strength (r=0.39, P=0.002), physical fitness (r=0.57, P<0.001), but not related to spasticity (r=-0.23, P=0.080). Multiple regression analysis showed that lean mass in the paretic leg was a major predictor (r2=0.371, P<0.001) of the paretic proximal femur BMD. VO2max was a significant predictor of both paretic proximal femur BMD (r2=0.325, P<0.001) and lean mass in the paretic leg (r2=0.700, P<0.001). Further study is required to determine whether increasing physical fitness and lean mass are important to improve hip bone health in chronic stroke.

  19. Activin A suppresses osteoblast mineralization capacity by altering extracellular matrix (ECM) composition and impairing matrix vesicle (MV) production.

    PubMed

    Alves, Rodrigo D A M; Eijken, Marco; Bezstarosti, Karel; Demmers, Jeroen A A; van Leeuwen, Johannes P T M

    2013-10-01

    During bone formation, osteoblasts deposit an extracellular matrix (ECM) that is mineralized via a process involving production and secretion of highly specialized matrix vesicles (MVs). Activin A, a transforming growth factor-β (TGF-β) superfamily member, was previously shown to have inhibitory effects in human bone formation models through unclear mechanisms. We investigated these mechanisms elicited by activin A during in vitro osteogenic differentiation of human mesenchymal stem cells (hMSC). Activin A inhibition of ECM mineralization coincided with a strong decline in alkaline phosphatase (ALP(1)) activity in extracellular compartments, ECM and matrix vesicles. SILAC-based quantitative proteomics disclosed intricate protein composition alterations in the activin A ECM, including changed expression of collagen XII, osteonectin and several cytoskeleton-binding proteins. Moreover, in activin A osteoblasts matrix vesicle production was deficient containing very low expression of annexin proteins. ECM enhanced human mesenchymal stem cell osteogenic development and mineralization. This osteogenic enhancement was significantly decreased when human mesenchymal stem cells were cultured on ECM produced under activin A treatment. These findings demonstrate that activin A targets the ECM maturation phase of osteoblast differentiation resulting ultimately in the inhibition of mineralization. ECM proteins modulated by activin A are not only determinant for bone mineralization but also possess osteoinductive properties that are relevant for bone tissue regeneration.

  20. Impaired bone health and asymptomatic vertebral compressions in fracture-prone children: a case-control study.

    PubMed

    Mäyränpää, Mervi K; Viljakainen, Heli T; Toiviainen-Salo, Sanna; Kallio, Pentti E; Mäkitie, Outi

    2012-06-01

    Frequent fractures in children may be a sign of impaired bone health, but it remains unestablished when and how fracture-prone children should be assessed. This prospective study elucidated skeletal characteristics and predisposing factors in children with recurrent fractures. Findings were used to establish guidelines for screening. During a 12-month period we recorded fracture history for all children (n = 1412) treated for an acute fracture at a large university hospital. All apparently healthy children over 4 years of age, who had sustained: (1) at least one vertebral fracture; (2) two long-bone fractures before age 10 years; or (3) three long-bone fractures before age 16 years, were recruited. They underwent dual-energy X-ray absorptiometry (DXA), laboratory tests, and spinal radiography. Information regarding family history and lifestyle factors were collected. Findings were compared with healthy controls. Sixty-six fracture-prone children (44 males, mean age 10.7 years; 5% of all children with fractures) were identified. Altogether, they had sustained 183 long-bone fractures (median 3, range 0–7); 11 children had sustained vertebral fracture(s). Patients had significantly lower bone mineral density (BMD) at lumbar spine (p < 0.001), hip (p = 0.007), and whole body (p < 0.001) than the controls; only 5 children (8%) had a BMD Z-score < −2.0. Asymptomatic vertebral compressions were prevalent, especially in those under 10 years of age. Hypercalciuria (11%) and hyperphosphaturia (22%) were significantly more prevalent than in controls. Serum concentration of 25-hydroxyvitamin D (S-25OHD) was below 50 nmol/L in 55%; low levels were associated with low BMD and vertebral compressions. The fracture-prone children had lower calcium intake, less physical activity, and more often had siblings with fractures than the controls. The findings suggest that a thorough pediatric evaluation, including DXA and spinal radiography, is often indicated

  1. The relationships between two different drinking water fluoride levels, dental fluorosis and bone mineral density of children.

    PubMed

    Grobler, S R; Louw, A J; Chikte, U M E; Rossouw, R J; van W Kotze, T J

    2009-04-03

    This field study included the whole population of children aged 10-15 years (77 from a 0.19 mg/L F area; 89 from a 3.00 mg/L F area), with similar nutritional, dietary habits and similar ethnic and socioeconomic status. The fluoride concentration in the drinking water, the bone mineral content, the bone density and the degree of dental fluorosis were determined. The left radius was measured for bone width, bone mineral content, and bone mineral density. The mean fluorosis score was 1.3 in the low fluoride area and 3,6 in the high fluoride area. More than half the children in the low fluoride area had no fluorosis (scores 0 and 1) while only 5% in the high fluoride area had none. Severe fluorosis (30%) was only observed in the high fluoride area. The Wilcoxon Rank Sum Test indicated that fluorosis levels differed significantly (p < 0.05) between the two areas. No relationships were found between dental fluorosis and bone width or between fluorosis and bone mineral density in the two areas (Spearment Rank correlations). A significant increase in bone width was found with age but no differences amongst and boys and girls. A significant positive correlation was found in the high fluoride area between bone mineral density over age. In the 12-13 and 13-14 year age groups in the high fluoride area, girls had higher bone mineral densities. However, a significant negative correlation (p<0.02) was found for the low fluoride area (0.19 mg/L F) over age.

  2. Embryonic stem cell therapy improves bone quality in a model of impaired fracture healing in the mouse; tracked temporally using in vivo micro-CT.

    PubMed

    Taiani, J T; Buie, H R; Campbell, G M; Manske, S L; Krawetz, R J; Rancourt, D E; Boyd, S K; Matyas, J R

    2014-07-01

    In the current study, we used an estrogen-deficient mouse model of osteoporosis to test the efficacy of a cell-generated bone tissue construct for bone augmentation of an impaired healing fracture. A reduction in new bone formation at the defect site was observed in ovariectomized fractures compared to the control group using repeated measures in vivo micro-computed tomography (μCT) imaging over 4 weeks. A significant increase in the bone mineral density (BMD), trabecular bone volume ratio, and trabecular number, thickness and connectivity were associated with fracture repair in the control group, whereas the fractured bones of the ovariectomized mice exhibited a loss in all of these parameters (p<0.001). In a separate group, ovariectomized fractures were treated with murine embryonic stem (ES) cell-derived osteoblasts loaded in a three-dimensional collagen I gel and recovery of the bone at the defect site was observed. A significant increase in the trabecular bone volume ratio (p<0.001) and trabecular number (p<0.01) was observed by 4 weeks in the fractures treated with cell-loaded collagen matrix compared to those treated with collagen I alone. The stem cell-derived osteoblasts were identified at the fracture site at 4 weeks post-implantation through in situ hybridization histochemistry. Although this cell tracking method was effective, the formation of an ectopic cellular nodule adjacent to the knee joints of two mice suggested that alternative in vivo cell tracking methods should be employed in order to definitively assess migration of the implanted cells. To our knowledge, this study is the first of its kind to examine the efficacy of stem cell therapy for fracture repair in an osteoporosis-related fracture model in vivo. The findings presented provide novel insight into the use of stem cell therapies for bone injuries.

  3. Conditional expression of constitutively active estrogen receptor {alpha} in chondrocytes impairs longitudinal bone growth in mice

    SciTech Connect

    Ikeda, Kazuhiro; Tsukui, Tohru; Imazawa, Yukiko; Horie-Inoue, Kuniko; Inoue, Satoshi

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer Conditional transgenic mice expressing constitutively active estrogen receptor {alpha} (caER{alpha}) in chondrocytes were developed. Black-Right-Pointing-Pointer Expression of caER{alpha} in chondrocytes impaired longitudinal bone growth in mice. Black-Right-Pointing-Pointer caER{alpha} affects chondrocyte proliferation and differentiation. Black-Right-Pointing-Pointer This mouse model is useful for understanding the physiological role of ER{alpha}in vivo. -- Abstract: Estrogen plays important roles in the regulation of chondrocyte proliferation and differentiation, which are essential steps for longitudinal bone growth; however, the mechanisms of estrogen action on chondrocytes have not been fully elucidated. In the present study, we generated conditional transgenic mice, designated as caER{alpha}{sup ColII}, expressing constitutively active mutant estrogen receptor (ER) {alpha} in chondrocytes, using the chondrocyte-specific type II collagen promoter-driven Cre transgenic mice. caER{alpha}{sup ColII} mice showed retardation in longitudinal growth, with short bone lengths. BrdU labeling showed reduced proliferation of hypertrophic chondrocytes in the proliferating layer of the growth plate of tibia in caER{alpha}{sup ColII} mice. In situ hybridization analysis of type X collagen revealed that the maturation of hypertrophic chondrocytes was impaired in caER{alpha}{sup ColII} mice. These results suggest that ER{alpha} is a critical regulator of chondrocyte proliferation and maturation during skeletal development, mediating longitudinal bone growth in vivo.

  4. Ibandronate dose response is associated with increases in bone mineral density and reductions in clinical fractures: results of a meta-analysis.

    PubMed

    Sebba, Anthony I; Emkey, Ronald D; Kohles, Joseph D; Sambrook, Philip N

    2009-03-01

    This meta-analysis pooled data from the four phase III clinical trials of ibandronate to assess the relationship between ibandronate dose, changes in bone mineral density, and rates of both clinical and non-vertebral fractures. Individual patient data from the intent-to-treat population of the BONE, IV fracture prevention, MOBILE, and DIVA studies were included for analysis. The relationship between ibandronate dose and bone mineral density at both the lumbar spine and at the total hip was assessed qualitatively. The relationship between lumbar spine bone mineral density and clinical fracture rate, and the relationship between total hip bone mineral density and non-vertebral fracture rate, were assessed both qualitatively and using mathematical models. A total of 8710 patients were included in this analysis. Both lumbar spine and total hip bone mineral density were observed to increase with increasing ibandronate dose. The incidence of all clinical fractures was observed to decrease as lumbar spine bone mineral density increased. A statistically significant inverse linear relationship was observed between percent change in lumbar spine bone mineral density and the rate of clinical fractures (P=0.005). A non-significant curvilinear relationship was observed between percent change in total hip bone mineral density and non-vertebral fracture rate. Increased ibandronate exposure is associated with increasing gains in the lumbar spine bone mineral density and decreasing clinical fracture rates. A non-linear relationship may exist between increases in the total hip bone mineral density and non-vertebral fracture rate.

  5. Assessment of bone mineral density and bone metabolism in young male adults recently diagnosed with systemic lupus erythematosus in China.

    PubMed

    Guo, Qinyue; Fan, Ping; Luo, Jing; Wu, Shufang; Sun, Hongzhi; He, Lan; Zhou, Bo

    2017-03-01

    Objective Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease. However, the exact mechanism underlying SLE-related osteopenia and osteoporosis in patients newly diagnosed with SLE remains unknown. Methods 60 male subjects with SLE aged 20-30 years were enrolled. Serum osteocalcin was examined as a marker of bone formation and type I collagen degradation products (β-crosslaps) as markers of bone resorption. Lumbar spine (L1-L4) and total hip bone mineral density (BMD) were determined by dual energy X-ray absorption (DXA). Results Among the 60 subjects with SLE at the time of diagnosis, the cohort showed a significant reduction of osteocalcin (12.62 ± 2.16 ng/mL), and serum β-crosslaps level (992.6 ± 162.6 pg/mL) was markedly elevated. Univariate correlation analyses revealed negative correlations between osteocalcin and SLEDAI, dsDNA antibody and β-crosslaps. A positive correlation was also observed between osteocalcin and C3, C4, 25-OH vitamin D, BMD L1-L4 and BMD total hip (see Table 3). Osteocalcin and β-crosslaps were strongly associated with SLE disease activity by multiple stepwise logistic regression analysis. Conclusion Osteocalcin was negatively associated with SLE disease activity, and β-crosslaps was positively associated with SLE disease activity, suggesting SLE disease activity itself directly contributed to the development of SLE-associated osteopenia and osteoporosis.

  6. Haploinsufficiency of endogenous parathyroid hormone-related peptide impairs bone fracture healing.

    PubMed

    Wang, Yin-He; Qiu, Yong; Han, Xiao-Dong; Xiong, Jin; Chen, Yi-Xin; Shi, Hong-Fei; Karaplis, Andrew

    2013-11-01

    Previous studies have demonstrated that endogenous parathyroid hormone-related peptide (PTHrP) plays a central role in the physiological regulation of bone formation. However, it is unclear whether endogenous PTHrP plays an important function in enhancing bone fracture healing. To determine whether endogenous PTHrP haploinsufficiency impaired