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Objective: The study analyses the performances of FRAX algorithm and quantitative ultrasound (QUS) tool in relationship to the dual-energy X-ray absorptiometry (DXA) categorization to identify patients at risk of osteoporosis during menopause and to reach new thresholds for recommending the first DXA examination., Design: Retrospective cohort study., Patients and Measurements: Two hundred eighty-two postmenopausal patients filled out a questionnaire which determined their FRAX index and performed a bone evaluation by QUS of the calcaneus to determine their stiffness index (SI). Thereafter, they underwent assessments by the gold-standard DXA bone examination., Results: Statistically significant correlations were observed between FRAX (calculated without BMD) and both QUS and DXA diagnosis. FRAX mean indices of risk corresponding to the diagnosis of osteoporosis by QUS and DXA were similar. Receiver operating characteristic (ROC) curve analysis showed that both FRAX and QUS tests were sufficiently accurate in predicting the alteration of bone mineral composition. The ROC curves of QUS allowed us to identify, in our population, SI cutoff for normal patients (SI > 90.5) and for patients having osteoporosis (SI < 78.5). We selected a cutoff screening value from FRAX ROC curve for major clinical fracture (2.94). The following diagnostic algorithm demonstrated that the use of FRAX test alone has a sensitivity of 85.3 % and a specificity of 33.8 % while the use of QUS exam alone showed a sensitivity of 81.3 % and a specificity of 45.1 %. When considering the capacity of QUS exam in combination with FRAX test, the final algorithm showed a sensitivity of 69.4 % and a specificity of 57.7 %., Conclusions: The use of QUS test with adjusted cutoffs offers a similar performance to the FRAX test alone in terms of sensitivity. The combined use of the tests reduces the sensibility but increases the specificity and adds clinical information related to the bone status of the patient.

Although a higher protein intake, particularly from vegetable sources, has been shown to be associated with higher bone mineral density (BMD) the relative impact of specific amino acids on BMD and risk of osteoporosis remains to be determined. Mechanistic research suggests that a number of specific amino acids, including five nonessential amino acids--alanine, arginine, glutamic acid, glycine, and proline--may play a role in bone health, principally through improved production of insulin and insulin-like growth factor 1 and the synthesis of collagen and muscle protein. However to date, no previous studies have examined the associations between habitual intake of amino acids and direct measures of BMD and prevalence of osteoporosis or osteopenia, and no studies have examined this relationship in discordant identical twin-pairs. In these analyses of female monozygotic twin-pairs discordant for amino acid intake (n = 135), twins with higher intakes of alanine and glycine had significantly higher BMD at the spine than their co-twins with within-pair differences in spine-BMD of 0.012 g/cm(2) (SE 0.01; p = 0.039) and 0.014 g/cm(2) (SE 0.01; p = 0.026), respectively. Furthermore, in cross-sectional multivariable analyses of 3160 females aged 18 to 79 years, a higher intake of total protein was significantly associated with higher DXA-measured BMD at the spine (quartile Q4 to quartile Q1: 0.017 g/cm(2), SE 0.01, p = 0.035) and forearm (Q4 to Q1: 0.010 g/cm(2), SE 0.003, p = 0.002). Intake of six amino acids (alanine, arginine, glutamic acid, leucine, lysine, and proline) were associated with higher BMD at the spine and forearm with the strongest association observed for leucine (Q4 to Q1: 0.024 g/cm(2), SE 0.01, p = 0.007). When intakes were stratified by protein source, vegetable or animal, prevalence of osteoporosis or osteopenia was 13% to 19% lower comparing extreme quartiles of vegetable intake for five amino acids (not glutamic acid or proline). These data provide evidence to suggest that intake of protein and several amino acids, including alanine and glycine, may be beneficial for bone health, independent of genetic background., (© 2015 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.)

Alpinia officinarum rhizome has been used as a traditional herbal remedy to treat inflammatory and internal diseases. Based on the previously observed inhibitory effect of A. officinarum rhizome in an arthritis model, we evaluated whether a water extract of A. officinarum rhizome (WEAO) would enhance in vitro osteoblast mineralization using calvarial osteoblast precursor cells or would inhibit in vitro osteoclast differentiation and bone resorption using bone marrow derived macrophages. In osteoblasts, WEAO enhanced the mRNA levels of transcription factor (runt-related transcription factor 2, smad1, smad5, and junB) and marker (bone morphogenetic protein-2, collagen type 1alpha1, and osteocalcin) genes related to osteoblast mineralization, consistent with increased alizarin red S staining intensity. WEAO markedly inhibited osteoclast differentiation by suppressing the receptor activator for nuclear factor-[Formula: see text]B ligand-induced downregulation of inhibitor of DNA binding 2 and V-maf musculoaponeurotic fibrosarcoma oncogene homolog B and the phosphorylation of c-Jun N-terminal kinase, p38, nuclear factor-[Formula: see text]B, c-Src, and Bruton's tyrosine kinase to induce nuclear factor of activated T cells cytoplasmic 1 expression. WEAO also suppressed the resorbing activity of mature osteoclasts by altering actin ring formation. Therefore, the results of this study demonstrate that WEAO stimulates osteoblast mineralization and inhibits osteoclast differentiation. Thus, WEAO may be a promising herbal candidate to treat or prevent pathological bone diseases by regulating the balance between osteoclast and osteoblast activity.

Skeletal fragility associated with underlying childhood chronic disease is a systemic disorder of poor bone growth and reduction in bone turnover which can lead to abnormal bone mass, geometry and microarchitecture. Due to the growth potential unique to children, remarkable bone recovery following a transient threat to the bone can occur if there is concurrent growth. Addressing bone health in these children should focus on improvement in growth, puberty and removing the primary insult. In conditions where there is a little scope for bone recovery and limited residual growth, bone-targeted therapy may need to be considered, even though there is currently limited evidence. The importance of early detection of signs of bone fragility, by active screening for vertebral fracture using newer imaging techniques such as dual-energy X-ray absorptiometry lateral vertebral morphometry, may now be possible. There is currently, a paucity of evidence to support prophylactic use of anti-resorptive therapy. Where poor growth and low bone turnover are seen, the use of growth-promoting therapies and anabolic bone-protective agents may be more physiological and should be evaluated in well-designed trials. Collaborative studies on long-term fracture outcome and well-designed trials of bone-protective therapies are needed and to be encouraged., (© 2016 S. Karger AG, Basel.)

Resistance exercise has been proved to be effective in improving bone quality in both animal and human studies. However, the issue about whether resistance exercise can inhibit obesity-induced bone loss has not been previously investigated. In the present study, we have evaluated the effects of ladder-climbing training, one of the resistance exercises, on bone mechanical properties and microarchitecture in high-fat (HF) diet-induced obese rats. Twenty-four rats were randomly assigned to the Control, HF + sedentary (HF-S) and HF + ladder-climbing training (HF-LCT) groups. Rats in the HF-LCT group performed ladder-climbing training for 8 weeks. The results showed that ladder-climbing training significantly reduced body and fat weight, and increased muscle mass along with a trend toward enhanced muscle strength in diet-induced obese rats. MicroCT analysis demonstrated that obesity-induced bone loss and architecture deterioration were significantly mitigated by ladder-climbing training, as evidenced by increased trabecular bone mineral density, bone volume over total volume, trabecular number and thickness, and decreased trabecular separation and structure model index. However, neither HF diet nor ladder-climbing training had an impact on femoral biomechanical properties. Moreover, ladder-climbing training significantly increased serum adiponectin, decreased serum leptin, TNF-α, IL-6 levels, and downregulated myostatin (MSTN) expression in diet-induced obese rats. Taken together, ladder-climbing training prevents bone loss and microarchitecture deterioration in diet-induced obese rats through multiple mechanisms including increasing mechanical loading on bone due to improved skeletal muscle mass and strength, regulating the levels of myokines and adipokines, and suppressing the release of pro-inflammatory cytokines. It indicates that resistance exercise may be a promising therapy for treating obesity-induced bone loss.

Increasing calcium (Ca) intake is important for female athletes with a risk of weak bone caused by inadequate food intake. The aim of the present study was to examine the preventive effect of Ca supplementation on low bone strength in young female athletes with inadequate food intake, using the rats as an experimental model. Seven-week-old female Sprague-Dawley rats were divided into four groups: the sedentary and ad libitum feeding group (SED), voluntary running exercise and ad libitum feeding group (EX), voluntary running exercise and 30% food restriction group (EX-FR), and a voluntary running exercise, 30% food-restricted and high-Ca diet group (EX-FR+Ca). To Ca supplementation, we used 1.2% Ca diet as "high-Ca diet" that contains two-fold Ca of normal Ca diet. The experiment lasted for 12 weeks. As a result, the energy availability, internal organ weight, bone strength, bone mineral density, and Ca absorption in the EX-FR group were significantly lower than those in the EX group. The bone strength and Ca absorption in the EX-FR+Ca group were significantly higher than those in the EX-FR group. However, the bone strength in the EX-FR+Ca group did not reach that in the EX group. These results suggested that Ca supplementation had a positive effect on bone strength, but the effect was not sufficient to prevent lower bone strength caused by food restriction in young female athletes.

Background: Aging, chronic inflammation and/or many chronic conditions may result in loss of bone, loss of muscle and increased adiposity, manifested either overtly (overweight) or furtively as fat infiltration into bone and muscle. This combined condition has been identified as osteosarcopenic obesity. Micronutrients are required, not just to prevent deficiency diseases, but for optimal health and metabolic homeostasis. Further, micronutrients have multifunctional roles in the body. However, it is unknown if the micronutrient intake of the Western diet contributes to bone and muscle loss, increased adiposity, and ultimately osteosarcopenic obesity., Objective: The aim of this review is to examine the micronutrient intake using US National Health and Nutrition Examination Survey (NHANES) data, and explore if the insufficiencies, or excesses present contribute to the development of osteosarcopenic obesity in aging., Method: First NHANES food intake data from 2002-2012 were obtained and transposed to Microsoft Excel for analysis. A literature search of PubMed and Medline for human data using combinations and synonyms of osteoporosis, sarcopenia and obesity, and each mineral and vitamin indicated as insufficient by NHANES., Results: NHANES data suggested phosphorus, calcium, magnesium, potassium, iron, and vitamins B6/B12/C/A/D/E and K were candidates for further evaluation. 170 articles were included., Conclusion: While chronic single/multiple micronutrient insufficiency/excess is not studied in clinical trials, NHANES data suggest that they have existed for at least a decade. Examining the status and roles of those nutrients may be important to understanding the health issues associated with Western-type diets, including development of osteosarcopenic obesity.

Objective: Hormone replacement therapy has been used as an effective treatment for the prevention of bone loss in postmenopausal women. In our previous study, QiBaoMeiRan formula (QBMR) had estrogenic activity and could relieve symptoms of hot flushes and body weight increase induced by estrogen decline. However, no evidence base links QBMR to preventing bone loss. The aim of this study is to investigate the effect of QBMR on bone loss., Methods: The ovariectomized rat model was established, and ovariectomized rats were treated with QBMR at doses of 0.875, 1.75, and 3.5 g/kg per day for 8 weeks. Biochemical parameters, bone mineral density, structural morphometric traits and histological characteristics of trabecular bone were assessed., Results: QBMR treatment significantly decreased the increase in serum alkaline phosphatase, bone Gla-protein and C-telopeptide fragments of type I collagen and decreased the decline of serum calcium and phosphorus in the circulation of ovariectomized rats. QBMR completely corrected the decrease in bone mineral density in lumbar vertebrae (L4-L6) comparable to the sham group. In addition, QBMR treatment also significantly ameliorated the decrease of structural parameters of femur trabecular bone, bone volume fraction, trabecular number, trabecular thickness and bone mineral density as well as the increase in trabecular separation by micro-computerized tomography scanning. These were also confirmed by bone histological results that showed its protective action., Conclusions: Our results indicated that QBMR had a definite anti-bone loss effect and will have potential to be used for the treatment of postmenopausal osteoporosis.

Diabetic patients have increased fracture risk. The pathogenesis underlying the status of bone alterations in diabetes mellitus is not completely understood but is multifactorial. The major deficits appear to be related to a deficit in mineralized surface area, a decrement in the rate of mineral apposition, deceased osteoid surface, depressed osteoblast activity, and decreased numbers of osteoclasts due to abnormal insulin signaling pathway. Other prominent features of diabetes mellitus are an increased urinary excretion of calcium and magnesium, accumulation of advanced glycation end products, and oxidative stress leading to sweet bones (altered bone's strength, metabolism, and structure). Every diabetic patient should be assessed for risk factors for fractures and osteoporosis. The pathogenesis of the bone alterations in diabetes mellitus as well as their molecular mechanisms needs further study.

Unlabelled: We investigated the effect of calcitonin (CT) on lumbar intervertebral disk degeneration (LIDD) in rats with ovariectomy-induced osteopenia. CT protected ovariectomized rats from LIDD by, at least in part, modifying extracellular matrix metabolism of the disks and preserving the microarchitecture and biomechanical properties of adjacent vertebrae., Introduction: The present study aimed to investigate the effect of CT on lumbar vertebral bone mineral density and intervertebral disk degeneration in ovariectomized (OVX) rats., Methods: We first subjected 50 3-month-old female rats to either OVX (n = 30) or sham (n = 20). Twelve weeks later, ten OVX and ten sham rats were necropsied. The remaining OVX rats began to receive either saline vehicle (OVX + V, n = 10), or salmon CT (OVX + CT, 16 IU/kg/2 days, n = 10). After 12 weeks of treatment, necropsy was conducted and bone mineral density was determined in L3-4 and L5-6 vertebrae. The microstructure and biomechanical properties of L3 vertebrae were detected by micro-computed tomography and compression test, respectively. L5-6 was also used to measure intervertebral disk height and observe intervertebral disk histological changes by Van Gieson staining and histological scores, as well as immunohistochemistry (IHC) analysis of matrix metalloprotease (MMP)-1, MMP-13, and collagen II expression., Results: At 12 weeks post-OVX, OVX rats had lower BV/TV and Tb.N and higher intervertebral disk histological score than sham rats. After 24 weeks, OVX + CT rats had higher BMD, BV/TV, Tb.N, and bone biomechanical strength values than OVX + V rats. Histological analysis showed OVX + CT rats had significantly lower disk degeneration scores than OVX + V rats. IHC analysis revealed CT treatment decreased expression of MMP-1 and MMP-13 and increased expression of collagen II compared with OVX + V rats., Conclusions: Our data demonstrate that CT-treated OVX rats display less intervertebral disk degeneration and favorable changes in intervertebral disk metabolism, associated with higher trabecular bone mass, better trabecular microarchitecture, and better biomechanical strength when compared to vehicle-treated OVX rats.

A considerable volume of evidence has accumulated to suggest that whole-body vibration (WBV) may have a therapeutic role to play in the prevention of osteoporotic fracture, particularly for individuals who are unable to tolerate vigorous exercise interventions. There is moderate to strong evidence that WBV will prevent falls (likely due to enhanced neuromuscular function), but also some indication that the effects of WBV do not outstrip those of targeted exercise. Animal data indicates that WBV will also improve bone mass, including preventing loss due to hormone withdrawal, disuse and glucocorticoid exposure. Human trials, however, have produced equivocal outcomes for bone. Positive trends are apparent at the hip and spine, but shortcomings in study designs have limited statistical power. The mechanism of the vibration effect on bone tissue is likely to be mechanical coupling between an oscillating cell nucleus and the cytoskeleton. More robust dose-response human data are required before therapeutic guidelines can be developed.

The low density lipoprotein receptor-related protein-5 (LRP5), a co-receptor in the Wnt signaling pathway, modulates bone mass in humans and in mice. Lrp5 knock-out mice have severely impaired responsiveness to mechanical stimulation whereas Lrp5 gain-of-function knock-in and transgenic mice have enhanced responsiveness to mechanical stimulation. Those observations highlight the importance of Lrp5 protein in bone cell mechanotransduction. It is unclear if and how high bone mass-causing (HBM) point mutations in Lrp5 alter the bone-wasting effects of mechanical disuse. To address this issue we explored the skeletal effects of mechanical disuse using two models, tail suspension and Botulinum toxin-induced muscle paralysis, in two different Lrp5 HBM knock-in mouse models. A separate experiment employing estrogen withdrawal-induced bone loss by ovariectomy was also conducted as a control. Both disuse stimuli induced significant bone loss in WT mice, but Lrp5 A214V and G171V were partially or fully protected from the bone loss that normally results from disuse. Trabecular bone parameters among HBM mice were significantly affected by disuse in both models, but these data are consistent with DEXA data showing a failure to continue growing in HBM mice, rather than a loss of pre-existing bone. Ovariectomy in Lrp5 HBM mice resulted in similar protection from catabolism as was observed for the disuse experiments. In conclusion, the Lrp5 HBM alleles offer significant protection from the resorptive effects of disuse and from estrogen withdrawal, and consequently, present a potential mechanism to mimic with pharmaceutical intervention to protect against various bone-wasting stimuli.

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

Swimming is generally considered ineffective for increasing bone mass in humans, at least compared with weight-bearing sports. However, swimming exercise has sometimes been shown to have a strong positive effect on bone mass in small animals. This study investigated the effects of swimming on bone mass, strength, and microarchitecture in ovariectomized (OVX) rats. OVX or sham operations were performed on 18-wk-old female Fisher 344 rats. Rats were randomly divided into four groups: sham sedentary (Sham-CON), sham swimming exercised (Sham-SWI), OVX sedentary (OVX-CON), and OVX swimming exercised (OVX-SWI). Rats in exercise groups performed swimming in a water bath for 60 min/day, 5 days/wk, for 12 wk. Bone mineral density (BMD) in right femurs was analyzed using dual-energy X-ray absorptiometry. Three-dimensional trabecular architecture at the distal femoral metaphysis was analyzed using microcomputed tomography (μCT). Geometrical properties of diaphyseal cortical bone were evaluated in the midfemoral region using μCT. The biomechanical properties of femurs were analyzed using three-point bending. Femoral BMD was significantly decreased following ovariectomy. This change was suppressed by swimming. Trabecular bone thickness, number, and connectivity were decreased by ovariectomy, whereas structure model index (i.e., ratio of rod-like to plate-like trabeculae) increased. These changes were also suppressed by swimming exercise. Femurs displayed greater cortical width and maximum load in SWI groups than in CON groups. Together, these results demonstrate that swimming exercise drastically alleviated both OVX-induced decreases in bone mass and mechanical strength and the deterioration of trabecular microarchitecture in rat models of osteoporosis., (Copyright © 2015 the American Physiological Society.)

Breast cancer survivors are at risk of bone loss due to hormonal treatment. We conducted a case note audit to investigate patterns of care and adherence to guidelines for initial management of risk of bone loss in 42 women receiving hormonal therapy. All those receiving aromatase inhibitors (n = 14) and 10 on tamoxifen had a bone density assessment. Eleven (26%) women had osteopenia and four (9.5%) osteoporosis. Management was variable and not always aligned with the guidelines., (© 2015 Royal Australasian College of Physicians.)

Purpose: The purpose of this paper was to review the literature concerning the treatment of chronic kidney disease-mineral bone disorder (CKD-MBD) in the elderly peritoneal dialysis (PD) patient., Results: Chronic kidney disease-mineral bone disorder is a major problem in the elderly PD patient, with its associated increased fracture risk, vascular calcification, and accelerated mortality fracture risk. Peritoneal dialysis, however, bears a lower risk than hemodialysis (HD). The approach to CKD-MBD prophylaxis and treatment in the elderly PD patient is similar to other CKD patients, with some important differences. Avoidance of hypercalcemia, hyperphosphatemia, and hyperparathyroidism is important, as in other CKD groups, and is generally easier to attain. Calcium-free phosphate binders are recommended for normocalcemic and hypercalcemic patients. Normalization of vitamin D levels to > 75 nmol/L (> 30 pg/L) and low-dose active vitamin D therapy is recommended for all patients. Hyperparathryoidism is to be avoided by using active vitamin D and cinacalcet. Particular attention should be paid to treating protein malnutrition. Fracture prophylaxis (exercise, use of walkers, dwelling modifications) are important. Hypomagnesemia is common in PD and can be treated with magnesium supplements. Vitamin K deficiency is also common and has been identified as a cause of vascular calcification. Accordingly, warfarin treatment for this age group is problematic., Conclusion: While treatment principles are similar to other dialysis patient groups, physicians should be aware of the special problems of the elderly group., (Copyright © 2015 International Society for Peritoneal Dialysis.)

Physical activity and risedronate sodium have effects on metabolic bone diseases, maintaining the integrity of bone tissue. Our objective was to evaluate the effects of swimming associated with risedronate as a prophylactic means in osteopenic bone of ovariectomized rats. A total of 24 animals of the Wistar strain were used and separated into four groups containing six animals: Ovariectomy (OVX), ovariectomy and swimming (OVXS), ovariectomy and risedronate (OVXM), ovariectomy, risedronate and swimming (OVXMS). The effectiveness of the treatments were evaluated using the tibia by means of biomechanical, radiographic, histomorphometric analyzes. Statistical analysis was performed by the non-parametric Kruskal-Wallis test (p<0.05). The OVXM and OVXMS groups showed higher values ​​compared to OVX in maximum strength and rigidity. Microscopic analysis showed increased trabecular bone in the OVXM group in relation to the others, and in the OVXMS compared to OVXS. Proximal densitometry in the OVXM and OVXMS groups showed higher values than the OVX and OVXS groups. There were no significant differences in overall densitometry. In conclusion, when comparing the prophylactic means, risedronate was able to preserve bone mass significantly, unlike exercise where an improvement of bone tissue was observed, although not significant, and when swimming and risedronate are combined the result was even better., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Relatively little is known about the relations between dietary patterns and bone health in adolescence, which is a period of substantial bone mass accrual., Objectives: We derived dietary patterns that were hypothesized to be related to bone health on the basis of their protein, calcium, and potassium contents and investigated their prospective associations with bone mineral density (BMD), bone area, and bone mineral content (BMC) in a cohort of young adults., Design: The study included 1024 young adults born to mothers who were participating in the Western Australian Pregnancy Cohort (Raine) Study. Dietary information was obtained from food-frequency questionnaires at 14 and 17 y of age. Dietary patterns were characterized according to protein, calcium, and potassium intakes with the use of reduced-rank regression. BMD, bone area, and BMC were estimated with the use of a total body dual-energy X-ray absorptiometry scan at 20 y of age., Results: We identified 2 major dietary patterns. The first pattern was positively correlated with intakes of protein, calcium, and potassium and had high factor loadings for low-fat dairy products, whole grains, and vegetables. The second pattern was positively correlated with protein intake but negatively correlated with intakes of calcium and potassium and had high factor loadings for meat, poultry, fish, and eggs. After adjustment for anthropometric, sociodemographic, and lifestyle factors, a higher z score for the first pattern at 14 y of age was positively associated with BMD and BMC at 20 y of age [differences: 8.6 mg/cm(2) (95% CI: 3.0, 14.1 mg/cm(2)) and 21.9 g (95% CI: 6.5, 37.3 g), respectively, per SD increase in z score]. The z score for this same pattern at 17 y of age was not associated with bone outcomes at 20 y of age. The second pattern at 14 or 17 y of age was not associated with BMD, BMC, or bone area., Conclusions: A dietary pattern characterized by high intakes of protein, calcium, and potassium in midadolescence was associated with higher BMD and BMC at 20 y of age. Our results indicate that high consumption of low-fat dairy products, whole grains, and vegetables in adolescence are associated with beneficial effects on bone development., (© 2015 American Society for Nutrition.)

Metabolic bone diseases such as osteopenia and osteoporosis increase the risk of bone fracture that negatively affects quality of life of individuals. Patients with inflammatory bowel disease(IBD), including ulcerative colitis(UC)and Crohn's disease(CD), have been shown to be at increased risk of decreased bone mineral density, however frequency of metabolic bone disease in IBD and identified risk factors are varied among reports.

Background: Cholestatic liver diseases exhibit higher levels of serum γ-glutamyl transpeptidase (GGT) and incidence of secondary osteoporosis. GGT has been identified as a novel bone-resorbing factor that stimulates osteoclast formation. The aim of this study was to elucidate the interaction of elevated GGT levels and cholestatic liver disease-induced bone loss., Methods: Wistar rats were divided into three groups: sham-operated control (SO) rats, bile duct ligation (BDL) rats, and anti-GGT antibody-treated BDL rats (AGT). Serum GGT level was measured. Bone mineral density (BMD) was analyzed by dual-energy X-ray absorptiometry. Bone morphometric parameters and microarchitectural properties were determined by micro-computed tomography and histomorphometry of the distal metaphysis of femurs. Alterations of bone metabolism-related factors were evaluated by cytokine array. Effects of GGT on osteoblasts or stromal cells were evaluated by RT-PCR, enzyme activity, and mineralization ability., Results: Serum levels of GGT were significantly elevated in the BDL-group. In the BDL group, BMD, bone mass percentage, and osteoblast number were significantly decreased, whereas osteoclast number was significantly increased. These alterations were markedly attenuated in the AGT group. The mRNA levels of vascular endothelial growth factor-A, LPS-induced CXC chemokine, monocyte chemoattractant protein-1, tumor necrosis factor-α interleukin-1β and receptor activator of nuclear factor-kappa B ligand were upregulated, and those of interferon-γ and osteoprotegerin were downregulated in the GGT-treated stromal cells. Furthermore, GGT inhibited mineral nodule formation and expression of alkaline phosphatase and bone sialo-protein in osteoblastic cells., Conclusion: Our results indicate that elevated GGT level is involved in hepatic osteodystrophy through secretion of bone resorbing factor from GGT-stimulated osteoblasts/bone marrow stromal cells. In addition, GGT also possesses suppressive effects on bone formation. Managing elevated GGT levels by anti-GGT antibody may become a novel therapeutic agent for hepatic osteodystrophy in chronic liver diseases.

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.

Although β-cryptoxanthin, a xanthophyll carotenoid, has been shown to exert an anabolic effect on bone calcification, little attention has been paid thus far to the precise mechanism of bone remodeling. Daily oral administration of β-cryptoxanthin significantly inhibited osteoclastic activation as well as reduction of bone volume in ovariectomized mice. In vitro studies revealed that β-cryptoxanthin inhibited differentiation and maturation of osteoclasts by repression of the nuclear factor-κB-dependent transcriptional pathway. Our results suggest that supplementation with β-cryptoxanthin would be beneficial for prophylaxis and for therapy of metabolic bone diseases associated with abnormal osteoclast activation., (Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

PTH is an osteoanabolic for treating osteoporosis but its potency wanes. Disabling the transcription factor nuclear matrix protein 4 (Nmp4) in healthy, ovary-intact mice enhances bone response to PTH and bone morphogenetic protein 2 and protects from unloading-induced osteopenia. These Nmp4(-/-) mice exhibit expanded bone marrow populations of osteoprogenitors and supporting CD8(+) T cells. To determine whether the Nmp4(-/-) phenotype persists in an osteoporosis model we compared PTH response in ovariectomized (ovx) wild-type (WT) and Nmp4(-/-) mice. To identify potential Nmp4 target genes, we performed bioinformatic/pathway profiling on Nmp4 chromatin immunoprecipitation sequencing (ChIP-seq) data. Mice (12 w) were ovx or sham operated 4 weeks before the initiation of PTH therapy. Skeletal phenotype analysis included microcomputed tomography, histomorphometry, serum profiles, fluorescence-activated cell sorting and the growth/mineralization of cultured WT and Nmp4(-/-) bone marrow mesenchymal stem progenitor cells (MSPCs). ChIP-seq data were derived using MC3T3-E1 preosteoblasts, murine embryonic stem cells, and 2 blood cell lines. Ovx Nmp4(-/-) mice exhibited an improved response to PTH coupled with elevated numbers of osteoprogenitors and CD8(+) T cells, but were not protected from ovx-induced bone loss. Cultured Nmp4(-/-) MSPCs displayed enhanced proliferation and accelerated mineralization. ChIP-seq/gene ontology analyses identified target genes likely under Nmp4 control as enriched for negative regulators of biosynthetic processes. Interrogation of mRNA transcripts in nondifferentiating and osteogenic differentiating WT and Nmp4(-/-) MSPCs was performed on 90 Nmp4 target genes and differentiation markers. These data suggest that Nmp4 suppresses bone anabolism, in part, by regulating IGF-binding protein expression. Changes in Nmp4 status may lead to improvements in osteoprogenitor response to therapeutic cues.

Loss-of-function mutations in genes involved in the vitamin D/vitamin D receptor system have clearly evidenced its critical role for mineral and skeletal homeostasis. Adequate levels of 1,25-dihydroxyvitamin D [1,25(OH)2D], the active form of vitamin D are therefore required and depend on sufficient sunlight exposure or dietary intake. Intestinal calcium absorption is a primary target of 1,25(OH)2D action and this pathway indirectly promotes calcium incorporation in bone. Severe vitamin D deficiency may thus decrease bone quality and leads to osteomalacia, whereas less severe deficiency increases the risk of osteoporosis and bone fractures. On the other hand, high vitamin D levels together with low dietary calcium intake will increase bone resorption and decrease bone mineralization in order to maintain normal serum calcium levels. Appropriate dietary calcium intake and sufficient serum vitamin D levels are thus important for skeletal health. Dosing of calcium and vitamin D supplements is still debated and requires further investigation., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Vitamin D deficiency is common and may contribute to osteopenia, osteoporosis and falls risk in the elderly. Screening for vitamin D deficiency is important in high-risk patients, especially for patients who suffered minimal trauma fractures. Vitamin D deficiency should be treated according to the severity of the deficiency. In high-risk adults, follow-up serum 25-hydroxyvitamin D concentration should be measured 3-4 months after initiating maintenance therapy to confirm that the target level has been achieved. All patients should maintain a calcium intake of at least 1,000 mg for women aged ≤ 50 years and men ≤ 70 years, and 1,300 mg for women > 50 years and men > 70 years.

After acute spinal cord injury (SCI), rapid depletion of the sublesional skeleton occurs, particularly at the distal femur and proximal tibia. Subsequently, fragility fractures of the knee may occur. We determined the efficacy of zoledronic acid to prevent sublesional bone mineral density (BMD) loss at 6 and 12 months after acute SCI. Thirteen subjects with acute motor-complete SCI were prospectively studied: 6 patients received zoledronic acid (5 mg) and 7 subjects did not receive the drug (controls). Zoledronic acid was administered intravenously within 16 weeks of acute injury. Areal BMD was performed by dual energy X-ray absorptiometry at baseline, 6, and 12 months after administration of drug. The treatment group demonstrated sparing of BMD at the total hip at month 6 (p < 0.0006) and at month 12 (p < 0.01). In contrast to the findings at the hip, the treatment group had a greater loss of BMD compared to the control group at the distal femur and proximal tibia at month 6 (-7.9% ± 3.4 vs.-2.7% ± 5.0, respectively, p = 0.054; and -10.5% ± 6.4 vs. -4.8% ± 6.8, respectively, p = NS) and at month 12 (-18.5% ± 3.9 vs. -8.4% ± 7.2, respectively, p = 0.01; and -20.4% ± 8.8 vs.-7.9% ± 12.3, respectively, p = 0.06). A single dose of zoledronic acid administered soon after acute SCI reduced the %BMD loss at the hip, but appeared to have no effect to prevent %BMD loss at the knee, the site where fracture risk is greatest in persons with SCI.

Type 2 diabetes is associated with increased fracture risk and delayed fracture healing; the underlying mechanism, however, remains poorly understood. We systematically investigated skeletal pathology in leptin receptor-deficient diabetic mice on a C57BLKS background (db). Compared with wild type (wt), db mice displayed reduced peak bone mass and age-related trabecular and cortical bone loss. Poor skeletal outcome in db mice contributed high-glucose- and nonesterified fatty acid-induced osteoblast apoptosis that was associated with peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) downregulation and upregulation of skeletal muscle atrogenes in osteoblasts. Osteoblast depletion of the atrogene muscle ring finger protein-1 (MuRF1) protected against gluco- and lipotoxicity-induced apoptosis. Osteoblast-specific PGC-1α upregulation by 6-C-β-d-glucopyranosyl-(2S,3S)-(+)-5,7,3',4'-tetrahydroxydihydroflavonol (GTDF), an adiponectin receptor 1 (AdipoR1) agonist, as well as metformin in db mice that lacked AdipoR1 expression in muscle but not bone restored osteopenia to wt levels without improving diabetes. Both GTDF and metformin protected against gluco- and lipotoxicity-induced osteoblast apoptosis, and depletion of PGC-1α abolished this protection. Although AdipoR1 but not AdipoR2 depletion abolished protection by GTDF, metformin action was not blocked by AdipoR depletion. We conclude that PGC-1α upregulation in osteoblasts could reverse type 2 diabetes-associated deterioration in skeletal health., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

The continuous advances in intensive care have led to increased survival of premature infants. As a consequence, the problem of less imminent, slowly progressing disorders such as osteopenia of prematurity has been emerging. Osteopenia of prematurity (OOP) also called metabolic bone disease of prematurity (MBD) or rickets of prematurity is characterized by a reduction in bone mineral content usually manifest between 6th to 12th weeks of corrected gestational age. It occurs in up to 55% of infants born with weight <1000gm and 23% of infants weighing <1500gm. Clinical features of osteopenia of prematurity are mostly non-specific often appears as a late symptoms. Several biochemical markers have frequently been used as screening tools and diagnostic markers, but timing of measurements and the levels at which treatment should be initiated vary widely. Dual energy X-ray absorptiometry (DEXA) and Quantitative ultrasnogram are important diagnostic tool. Standard X-ray, a widely accepted but cannot detect osteopenia unless 20% loss of bone mineralization. The treatment of osteopenia includes provision of adequate mineral supplementation. Monitoring of serum and urinary markers are mandatory. The focus on prevention has largely centered on providing adequate intake of phosphorus and calcium but more research is needed. Till date there are neither enough data regarding clinical risk factors, valid biochemical markers which can detect premature babies at risk of osteopenia nor supplementation as well as appropriate timely management protocol is practicing in Bangladesh.

Introduction: Bone metabolic disease is an important issue in newborns with very low birth weight. The 80 percent of the transport of calcium (Ca) and phosphor (P) from mother to fetus takes place in the third trimester of pregnancy. This transport process is impaired with the preterm delivery of the newborn. On the other side, breast milk and formula are not competent resources to supply sufficient amounts of Ca and P to meet the requirements of the preterm newborn, thereby a greater reduction in the storage of these minerals. The current study has been done with the purpose of comparing the effects of two feeding methods on the indices of metabolic bone disease in newborns with very low birth weights (VLBW)., Materials & Methods: The study design was cohort and the study was done on a total of 58 newborns with very low birth weights in Kashan Shahid Beheshti Hospital. The newborns were divided into two groups with 29 placed in the group of alternate feeding on preterm formula (preNan) and the other 29 placed in the group of breast milk and preterm formula (preNan). Eventually, the indices of bone metabolic disease were measured in both groups and were statistically analyzed., Results: The difference between the mean serum levels of Ca in different weeks and also between the two groups were significant (p=0.001). However, the changes in mean serum level of P in the two groups were not significant (P=0.151). The comparison of serum levels of alkaline phosphatase between the two groups indicated that their difference was significant and that they had been influenced by the feeding method (P=0.001). The serum level of bicarbonate, when compared between the two groups, was found to make a significant difference (P=0.001). The difference between the two feeding methods in precipitating rickets and osteopenia was not significant., Conclusion: According to the findings of current study, feeding on preterm formula (preNan) is associated with better and more desirable results, though the occurrence of rickets in the two groups had no significant difference.

Mineral and bone disorder is common in individuals with kidney transplant as a sequelae of chronic kidney disease. Rapid bone density loss that occurs during the first year after transplant along with pre-existing bone disorder, places these patients at risk of bone fractures at three times higher than the general population. This article examines the efficacy of current evidence-based clinical interventions in reducing the incidence of bone fractures among recipients of kidney transplant.

Type-2 diabetes mellitus (T2DM) induces bone frailty. Protein and polyunsaturated fatty acids (PUFA) contained in fish can be effective in enhancing bone quality, but the bone developing effect of fish protein containing less PUFA has not been evaluated in young animals with T2DM. We prepared a bonito fish (BF) and defatted BF (DBF) and hypothesized that protein contained in BF and DBF would be effective for mitigating the effects of T2DM-induced bone frailty. We mainly evaluated the effect of dietary BF and DBF on bone and apparent calcium absorption in young Goto-Kakizaki (GK) rats with T2DM. GK rats were divided into 3 groups based on diets (casein, BF, and DBF) and fed with each diet for 6 wk. Wistar rats were fed with the casein diet as a non-T2DM control. Bone mass, bone strength, apparent calcium absorption, and serum biochemical parameters were determined. The dry weight and strength of the femurs were lower in the GK rats than in the Wistar rats fed with the casein diet. Dietary intake of the BF and DBF diets enhanced the maximum load and dry weight of the femurs and suppressed the serum alkaline phosphatase activity although the apparent calcium absorption was lower in the GK rats fed with the BF and DBF diets than in those fed with the casein diet. These parameters were not different between the rats fed with the BF and DBF diets. Our data suggest that protein contained in the BF and DBF diets improved T2DM-induced bone frailty., (© 2015 Institute of Food Technologists®)

It was investigated, in a female rat model of low and moderate lifetime human exposure to cadmium (Cd), whether polyphenols from Aronia melanocarpa berries (chokeberry; AMP) may offer protection from this heavy metal-induced disorders in bone metabolism. For this purpose, numerous indices of bone formation (osteocalcin, alkaline phosphatase, osteoprotegerin) and resorption (carboxy-terminal cross-linking telopeptides of type I collagen, soluble receptor activator of nuclear factor-κB ligand) in the serum and/or distal femur epiphysis (trabecular bone region), as well as bone mineral status (volumetric bone mineral density of the femur and content of mineral components, including calcium, in the bone tissue at the distal femur epiphysis) were evaluated in female Wistar rats that received a 0.1% aqueous extract of AMP, as the only drinking fluid (prepared from lyophilized extract by Adamed Consumer Healthcare), and/or Cd in diet (1 and 5mg/kg) for 3, 10, 17, and 24 months. Examination of the phytochemical profile of the aronia extract revealed high content of polyphenols (612.40 ± 3.33 mg/g), including anthocyanins, proanthocyanidins, phenolic acids, and flavonoids. Among detected compounds anthocyanins were identified as dominating. The exposure to Cd, dose- and duration-dependently, enhanced resorption and inhibited formation of the bone tissue resulting in its decreased mineralization. The administration of AMP under the exposure to 1 and 5 mgCd/kg diet provided important protection from this heavy metal-induced disturbances in the bone turnover and changes in the bone mineral status, and the beneficial impact of polyphenols resulted from their independent action and interaction with Cd. These findings suggest that consumption of Aronia melanocarpa polyphenols may play a role in prevention against female skeleton damage due to chronic exposure to Cd and that chokeberry represents the good natural plant candidate for further investigations of its prophylactic use under environmental exposure to this heavy metal., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

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

Semaphorins have been recently targeted as new molecules directly implicated in the cell-cell communication that occurs between osteoclasts and osteoblasts. Overexpression of certain semaphorins, such as semaphorin4D (sema4D), is found in an osteoporotic phenotype and plays a key role in osteoclast activity by suppressing osteoblast maturation, thus significantly altering the bone modeling cycle. In the present study, we fabricate a site-specific bone-targeting drug-delivery system from polymeric nanoparticles with the incorporation of siRNA interference molecule for sema4D and demonstrate their cellular uptake and intracellular trafficking within osteoclasts, thus preventing the suppression of osteoblast activity. We then demonstrate in an osteoporotic animal model induced by ovariectomy that weekly intravenous injections led to a significantly greater number of active osteoblasts at the bone surface, resulting in higher bone volume in compromised animals. The findings from the present study demonstrate a novel and promising site-specific therapeutic option for the treatment of osteoporosis via interference of the sema4D-plexin cell communication pathway between osteoclasts and osteoblasts., (© 2014 American Society for Bone and Mineral Research.)

Phosphorus retention plays a pivotal role in the onset of mineral and bone disorders (MBD) in chronic kidney disease (CKD). Phosphorus retention commonly occurs as a result of net intestinal absorption exceeding renal excretion or dialysis removal. The dietary phosphorus load is crucial since the early stages of CKD, throughout the whole course of the disease, up to dialysis-dependent end-stage renal disease.Agreement exits regarding the need for dietary phosphate control, but it is quite challenging in the real-life setting. Effective strategies to control dietary phosphorus intake include restricting phosphorus-rich foods, preferring phosphorus sourced from plant origin, boiling as the preferred cooking procedure and avoiding foods with phosphorus-containing additives. Nutritional education is crucial in this regard.Based on the existing literature, we developed the "phosphorus pyramid", namely a novel, visual, user-friendly tool for the nutritional education of patients and health-care professionals. The pyramid consists of six levels in which foods are arranged on the basis of their phosphorus content, phosphorus to protein ratio and phosphorus bioavailability. Each has a colored edge (from green to red) that corresponds to recommended intake frequency, ranging from "unrestricted" to "avoid as much as possible".The aim of the phosphorus pyramid is to support dietary counseling in order to reduce the phosphorus load, a crucial aspect of integrated CKD-MBD management.

We evaluated the effectiveness of ergonomic workload reduction of switching rats from a high repetition high force (HRHF) lever pulling task to a reduced force and reach rate task for preventing task-induced osteopenic changes in distal forelimb bones. Distal radius and ulna trabecular structure was examined in young adult rats performing one of three handle-pulling tasks for 12 wk: (1) HRHF, (2) low repetition low force (LRLF); or (3) HRHF for 4 wk and than LRLF thereafter (HRHF-to-LRLF). Results were compared to age-matched controls rats. Distal forelimb bones of 12-wk HRHF rats showed increased trabecular resorption and decreased volume, as control rats. HRHF-to-LRLF rats had similar trabecular bone quality as control rats; and decreased bone resorption (decreased trabecular bone volume and serum CTX1), increased bone formation (increased mineral apposition, bone formation rate, and serum osteocalcin), and decreased osteoclasts and inflammatory cytokines, than HRHF rats. Thus, an ergonomic intervention of HRHF-to-LRLF prevented loss of trabecular bone volume occurring with prolonged performance of a repetitive upper extremity task. These findings support the idea of reduced workload as an effective approach to management of work-related musculoskeletal disorders, and begin to define reach rate and load level boundaries for such interventions.

Objectives: Osteoporosis is a skeletal disorder characterized by impaired bone turnover and compromised bone strength, thereby predisposing to increased risk of fracture. Preclinical research has shown that compounds produced by the olive tree (Olea europaea), may protect from bone loss, by increasing osteoblast activity at the expense of adipocyte formation. The aim of this exploratory study was to obtain a first insight on the effect of intake of an olive extract on bone turnover in postmenopausal women with decreased bone mass (osteopenia)., Design and Setting: For that, a double blind, placebo-controlled study was performed in which participants were randomly allocated to either treatment or placebo groups., Participants: 64 osteopenic patients, with a mean bone mineral density (BMD) T-score between -1.5 and -2.5 in the lumbar spine (L2-L4) were included in the study., Intervention and Measurements: PARTICIPANTS received for 12 months daily either 250 mg/day of olive extract and 1000 mg Ca (treatment) or 1000 mg Ca alone (placebo). Primary endpoints consisted of evaluation of bone turnover markers. Secondary endpoints included BMD measurements and blood lipid profiles., Results: After 12 months, the levels of the pro-osteoblastic marker osteocalcin were found to significantly increase in the treatment group as compared to placebo. Simultaneously, BMD decreased in the placebo group, while remaining stable in the treatment group. In addition, improved lipid profiles were observed, with significant decrease in total- and LDL-cholesterol in the treatment group., Conclusion: This exploratory study supports preclinical observations and warrants further research by showing that a specific olive polyphenol extract (Bonolive®) affects serum osteocalcin levels and may stabilize lumbar spine BMD. Moreover, the improved blood lipid profiles suggest additional health benefits associated to the intake of the olive polyphenol extract.

Conservation breeding programmes are a tool used to prevent amphibian extinctions. The husbandry requirements of amphibians are complex. Ongoing research is needed to ensure optimal management of those captive-bred animals destined, in particular, for reintroduction. The UV-B and vitamin D3 requirements of amphibians are largely unknown. Metabolic bone disease has been reported in a number of species. These include the Critically Endangered mountain chicken frog (Leptodactylus fallax) reared in captivity on diets supplemented with a high-calcium multivitamin and mineral supplement containing vitamin D3 but without UV-B provision. Captive-bred L. fallax being reared for reintroduction to Montserrat were provided with UV-B radiation from metamorphosis and were fed on insects supplemented with vitamins and minerals. Overlapping heat, light and UV-B gradients were provided, mimicking what we believe best represents the natural situation and thereby facilitated self-regulation of UV-B exposure. A subset of 10 frogs was periodically radiographed to assess skeletal health. Radiographic bone density and anatomical integrity appeared unremarkable when compared with a wild caught L. fallax. In addition to other routine health-screening, we recommend that radiography be performed to a structured schedule on a subset of all captive-bred and reared amphibians to assess skeletal health and to gauge the appropriateness of captive husbandry. We demonstrate here that, through the appropriate provision of a combination of both UV-B radiation and dietary supplementation, L. fallax can be bred and reared in captivity with healthy skeletal development., (© 2014 Wiley Periodicals, Inc.)

Introduction: Secondary hyperparathyroidism is highly prevalent in kidney transplant recipients, and commonly results in hypercalcaemia; an association to osteopenia and bone fractures has also been observed. Paricalcitol has proved effective to control secondary hyperparathyroidism in chronic kidney disease in both dialysed and non-dialysed patients, with a low hypercalcaemia incidence. Currently available experience on paricalcitol use in kidney transplant recipients is scarce. Our main aim was to show the effect of paricalcitol on mineral bone metabolism in kidney transplant recipients with secondary hyperparathyroidism., Material and Methods: A retrospective multicentre study in kidney transplant recipients aged>18 years with a 12-month or longer post-transplantation course, stable renal function, having received paricalcitol for more than 12 months, with available clinical follow-up for a 24-month period., Results: A total of 69 patients with a 120 ± 92-month post-transplantation course were included. Baseline creatinine was 2.2 ± 0.9 mg/dl y GFR-MDRD was 36 ± 20 ml/min/1.73 m(2). Paricalcitol doses were gradually increased during the study: baseline 3.8 ± 1.9 μg/week, 12 months 5.2 ± 2.4 μg/week; 24 months 6.0 ± 2.9 μg/week (P<.001). Serum PTH levels showed a significant fast decline: baseline 288 ± 152 pg/ml; 6 months 226 ± 184 pg/ml; 12 months 207 ± 120; 24 months 193 ± 119 pg/ml (P<.001). Reduction from baseline PTH was ≥30% in 42.4% of patients at 12 months y in 65.2% of patients at 24 months. Alkaline phosphatase showed a significant decrease in first 6 months followed by a plateau: baseline 92 ± 50 IU/l; 6 months 85 ± 36 IU/l, 12 months 81 ± 39 IU/l (P<.001). Overall, no changes were observed in serum calcium and phosphorus, and in urine calcium excretion. PTH decline was larger in patients with higher baseline levels. Patients with lower baseline calcium levels showed significantly increased levels (mean increase was 0.5-0.6 mg/dl) but still within normal range, whereas patients with baseline calcium>10mg/dl showed gradually decreasing levels. Fifteen (21.7%) patients had received prior calcitriol therapy. When shifted to paricalcitol, such patients required paricalcitol doses significantly larger than those not having received calcitriol. Paricalcitol was used concomitantly to cinacalcet in 11 patients with significant PTH reductions being achieved; clinical course was similar to other patients and paricalcitol doses were also similar., Conclusions: Paricalcitol is an effective therapy for secondary hyperparathyroidism in kidney transplant recipients. Overall, no significant changes were observed in calcium and phosphorus levels or urinary excretion. Patients having previously received calcitriol required higher paricalcitol doses. When used in patients receiving cinacalcet, paricalcitol results in a significant PTH fall, with paricalcitol doses being similar to those used in patients not receiving cinacalcet., (Copyright © 2015 The Authors. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Bones represent the most common metastatic sites in prostate cancer (PCa) patients, and in addition with androgen deprivation therapy, they represent the causative reasons of bone mineral density loss and the onset of skeletal-related events., Areas Covered: An extensive search of PubMed/Medline was performed to identify randomized, Phase II/III controlled trials reporting results regarding the prevention of skeletal morbidity in patients with PCa., Expert Opinion: Preventing bone health is an imperative issue for preserving quality of life and elongate survival and, thus, a concerted effort should be made to monitor skeletal changes and to apply treatment for preventing bone loss. Although several agents have received approval for routine use, it is of paramount importance to identify the appropriate patients who would mostly be benefited by the use of these agents with attention to documenting the toxicity and economic implications. Additionally, it remains to be justified the frequency of administration in order to balance the efficacy and the potential complications.

Objective: There is a high prevalence of low bone mineral density (BMD) among patients with inflammatory bowel disease (IBD) although there is a lack of clinical data on the impact of IBD specific medications and recommended vitamin D (VD) and calcium (Ca) supplements on it., Design: The cohort consisted of 150 IBD patients. The average change in BMD at the lumbar spine per year (∆BMDL/year) was calculated and the impact of clinical characteristics, medications and VD and Ca supplements was analysed., Results: The prevalence of osteopenia was 69/150 (46%) and osteoporosis was identified in 15/150 (10%) patients at baseline. The presence of osteoporosis was associated with the disease duration OR=1.07 per year of disease duration (95% CI=1.01-1.14), p=0.03. The average ∆BMDL/year was 0.010 g/cm(2)/year. Among patients with no IS the ∆BMDL/year was -0.001±0.010 g/cm(2)/year, with AZA -0.001±0.013 g/cm(2)/year, with anti-TNFα 0.003±0.006 g/cm(2)/year and with COMBO 0.027±0.004 g/cm(2)/year; p<0.05 COMBO vs any other subgroup. ∆BMDL/year among patients treated with CS was -0.031±0.012 g/cm(2)/year versus CS free patients 0.013±0.004 g/cm(2)/year; p<0.001. There was no effect of VD/Ca supplementation on BMDL., Conclusions: The prevalence of low BMD was 55%. Duration of disease was the only independent predictor of low BMD. The BMDL was reduced by high cumulative dose of CS and improved by combined anti-TNFα/AZA therapy. The supplementation with recommended doses of VD and Ca had no effect on BMDL., (Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

To date, intravenous drip infusion of zoledronic acid (ZA) has mainly been used for the treatment and prevention of skeletal-related events (SRE) in patients with multiple myeloma (MM). Recently, denosumab, a fully humanized monoclonal antibody against receptor activator of nuclear factor-κB ligand (RANKL), has also become available for the same purpose, but little is known about the impact of switching from ZA to denosumab. Herein, we present a retrospective study on bone metabolic markers in 10 MM patients initially treated with ZA and then switched to denosumab. Consequently, the levels of bone resorption markers, tartrate-resistant acid phosphatase 5b (TRACP-5b) and serum type-I collagen crosslinked N-telopeptide (sNTX), significantly decreased after denosumab treatment, while the levels of bone formation markers, osteocalcin (OC) and bone-specific alkaline phosphatase (BAP), showed no apparent changes. No patient developed severe hypocalcemia with denosumab treatment. In one patient not given chemotherapy, the M-protein level increased after switching from ZA to denosumab and plateaued when ZA was restarted. Based on this finding, we anticipate that switching from ZA to denosumab would exert a stronger suppressive effect on osteoclasts, but the anti-myeloma activity of ZA must be taken into consideration.

Amphibian biology is intricate, and there are many inter-related factors that need to be understood before establishing successful Conservation Breeding Programs (CBPs). Nutritional needs of amphibians are highly integrated with disease and their husbandry needs, and the diversity of developmental stages, natural habitats, and feeding strategies result in many different recommendations for proper care and feeding. This review identifies several areas where there is substantial room for improvement in maintaining healthy ex situ amphibian populations specifically in the areas of obtaining and utilizing natural history data for both amphibians and their dietary items, achieving more appropriate environmental parameters, understanding stress and hormone production, and promoting better physical and population health. Using a scientific or research framework to answer questions about disease, nutrition, husbandry, genetics, and endocrinology of ex situ amphibians will improve specialists' understanding of the needs of these species. In general, there is a lack of baseline data and comparative information for most basic aspects of amphibian biology as well as standardized laboratory approaches. Instituting a formalized research approach in multiple scientific disciplines will be beneficial not only to the management of current ex situ populations, but also in moving forward with future conservation and reintroduction projects. This overview of gaps in knowledge concerning ex situ amphibian care should serve as a foundation for much needed future research in these areas., (© 2014 Wiley Periodicals, Inc.)

Purpose of Review: It has been widely known for some time that bone loss can be seen in certain subpopulations of children undergoing urinary diversion and/or enterocystoplasty. This review will hopefully look at the recent evidence in the field and help understand the multifactorial cause of bone loss in this group of individuals, as well as look at evidence for this phenomenon in growth retardation in certain groups of these individuals., Recent Findings: Most of the recent publications indicate that in normal individuals, decreased bone mineralization does not appear to affect final growth or adult height. It would appear that over time, demineralization allows compensation of the acidosis. However, it should be noted that it does lead to an increase in both osteoclastic and osteoblastic activity., Summary: It is very likely that enterocystoplasty in childhood can lead to significant metabolic acidosis and that compensation with bone buffering does take place. It would appear that the bone demineralization secondary to increased osteoblastic and osteoclastic activity is the price paid for metabolic compensation and continued normal and near normal linear growth.