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Abnormalities in osteoclastic generation or activity disrupt bone homeostasis and are highly involved in many pathologic bone-related diseases, including rheumatoid arthritis, osteopetrosis, and osteoporosis. Control of osteoclast-mediated bone resorption is crucial for treating these bone diseases. However, the mechanisms of control of osteoclastogenesis are incompletely understood. In this study, we identified that inosine 5'-monophosphate dehydrogenase type II (Impdh2) positively regulates bone resorption. By histomorphometric analysis, Impdh2 deletion in mouse myeloid lineage cells (Impdh2 LysM-/- mice) showed a high bone mass due to the reduced osteoclast number. qPCR and western blotting results demonstrated that the expression of osteoclast marker genes, including Nfatc1, Ctsk, Calcr, Acp5, Dcstamp, and Atp6v0d2, was significantly decreased in the Impdh2 LysM-/- mice. Furthermore, the Impdh inhibitor MPA treatment inhibited osteoclast differentiation and induced Impdh2-cytoophidia formation. The ability of osteoclast differentiation was recovered after MPA deprivation. Interestingly, genome-wide analysis revealed that the osteoclastic mitochondrial biogenesis and functions, such as oxidative phosphorylation, were impaired in the Impdh2 LysM-/- mice. Moreover, the deletion of Impdh2 alleviated ovariectomy-induced bone loss. In conclusion, our findings revealed a previously unrecognized function of Impdh2, suggesting that Impdh2-mediated mechanisms represent therapeutic targets for osteolytic diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Despite the fact that China amounts to one-fifth of the world's population, has a higher proportion of the elderly, and has a higher prevalence of osteoporosis and fracture, limited studies have investigated the association between dietary patterns and bone mineral density (BMD) as well as fracture risk among the elderly Chinese population. We aimed to investigate the association between different dietary patterns and BMD as well as the risk of fractures, and this association may vary between elderly women and men., Methods: Building upon the China Osteoporosis Prevalence Study, we included 17,489 subjects aged ≥40 years old randomly sampled across 44 counties/districts of 11 provinces or municipalities in China who completed a food frequency questionnaire. BMD was measured by dual x-ray absorptiometry. Vertebral fracture was defined based on lateral spine radiographs using the semi-quantitative technique of Genant., Results: A diet rich in "carnivorous", "vegetarian", "dairy, fruit, and egg" was significantly associated with higher BMD at total hip (TH), femoral neck (FN), and lumbar spine 1-4 (L1-4). Yet, a diet rich in "beverage and fried food" was associated with a lower BMD at the FN and L1-4. High quartiles of the carnivorous diet were associated with 34%-39% reduced risk of clinical fracture in the past 5 years and vertebral fracture. Stronger associations were observed among women. Sensitivity analysis among postmenopausal women presented even stronger positive associations between carnivorous and vegetarian diets and high BMD, as well as between carnivorous diet and reduced risk of fractures., Conclusions: Our study suggested that a diet rich in meat, vegetables, and dairy, fruit, and eggs might be associated with greater BMD and a lower fracture risk, while beverage and fried foods may be associated with a lower BMD at L1-4, especially among elderly women. These findings are relevant to provide recommendations on dietary nutrition regarding the elderly population at high risk of osteoporosis and fractures, especially postmenopausal women., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Zhao, Yin, Chen, Tang, Lin, Cui, Jin, Xie, Jiang, Cui, Yu, Cummings, Wang and Xia.)

Background: Osteoporosis is a systemic skeletal disease with increasing bone fragility and prone to fracture. Osteocalcin (OC), as the most abundant non collagen in bone matrix, has been extensively used in clinic as a biochemical marker of osteogenesis. Two forms of OC were stated on circulation, including carboxylated osteocalcin (cOC) and undercarboxylated osteocalcin (ucOC). OC was not only involved in bone mineralization, but also in the regulation of muscle function., Objective: This study explored the relationship between serum OC, cOC, ucOC levels and bone mineral density (BMD), bone microarchitecture, muscle mass and physical activity in Chinese postmenopausal women., Method: 216 community-dwelling postmenopausal women were randomized enrolled. All subjects completed biochemical measurements, including serum β-isomer of C-terminal telopeptides of type I collagen (β-CTX), N-terminal propeptide of type 1 procollagen (P1NP), alkaline phosphatase (ALP), OC, cOC and ucOC. They completed X-ray absorptiometry (DXA) scan to measure BMD, appendicular lean mass (ALM) and trabecular bone score (TBS). They completed high resolution peripheral quantitative CT (HR-pQCT) to assess peripheral bone microarchitectures., Results: Serum OC, cOC and ucOC were elevated in osteoporosis postmenopausal women. In bone geometry, serum ucOC was positively related with total bone area (Tt.Ar) and trabecular area(Tb.Ar). In bone volumetric density, serum OC and ucOC were negatively associated with total volume bone mineral density (Tt.vBMD) and trabecular volume bone mineral density (Tb.vBMD). In bone microarchitecture, serum OC and ucOC were negatively correlative with Tb.N and Tb.BV/TV, and were positively correlated with Tb.Sp. Serum OC and ucOC were positively associated with Tb.1/N.SD. Serum OC was negatively related with Tb.Th. Serum ucOC was positively associated with ALM. The high level of serum OC was the risk factor of osteoporosis. ALM was the protective factor for osteoporosis., Conclusion: All forms of serum OC were negatively associated with BMD. Serum OC and ucOC mainly influenced microstructure of trabecular bone in peripheral skeletons. Serum ucOC participated in modulating both bone microstructure and muscle mass., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Despite the potentially destructive effect of sympathetic activity on bone metabolism, its impact on bone microarchitecture, a key determinant of bone quality, has not been thoroughly investigated. This study aims to evaluate the impact of sympathetic activity on bone microarchitecture and bone strength in patients with pheochromocytoma and paraganglioma (PPGL)., Methods: A cross-sectional study was conducted in 38 PPGL patients (15 males and 23 females). Bone turnover markers serum procollagen type 1 N-terminal propeptide (P1NP) and β-carboxy-terminal crosslinked telopeptide of type 1 collagen (β-CTX) were measured. 24-h urinary adrenaline (24hUE) and 24-h urinary norepinephrine levels (24hUNE) were measured to indicate sympathetic activity. High-resolution peripheral quantitative computed tomography (HR-pQCT) was conducted to evaluate bone microarchitecture in PPGL patients and 76 age-, sex-matched healthy controls (30 males and 46 females). Areal bone mineral density (aBMD) was measured by dual-energy X-ray absorptiometry (DXA) simultaneously., Results: PPGL patients had a higher level of β-CTX. HR-pQCT assessment revealed that PPGL patients had notably thinner and more sparse trabecular bone (decreased trabecular number and thickness with increased trabecular separation), significantly decreased volume BMD (vBMD), and bone strength at both the radius and tibia compared with healthy controls. The deterioration of Tt.vBMD, Tb.Sp, and Tb.1/N.SD was more pronounced in postmenopausal patients compared with the premenopausal subjects. Moreover, subjects in the highest 24hUNE quartile (Q4) showed markedly lower Tb.N and higher Tb.Sp and Tb.1/N.SD at the tibia than those in the lowest quartile (Q1). Age-related bone loss was also exacerbated in PPGL patients to a certain extent., Conclusions: PPGL patients had significantly deteriorated bone microarchitecture and strength, especially in the trabecular bone, with an increased bone resorption rate. Our findings provide clinical evidence that sympathetic overstimulation may serve as a secondary cause of osteoporosis, especially in subjects with increased sympathetic activity., (© 2023. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Background: Obstructive sleep apnea (OSA) and osteoporosis are both prevalent diseases with shared pathophysiological mechanisms and risk factors. However, the association between the two diseases is seldom studied. This study aimed to identify the link between OSA and bone metabolism., Methods: Male participants aged 30-59-years who visited the sleep clinic were continuously recruited. Polysomnography was used to evaluate sleep and respiratory conditions. Blood samples were collected to detect metabolic, inflammatory and bone turnover indicators. High-resolution peripheral quantitative computer tomography was used to measure the non-dominant lateral radius and tibia., Results: Ninety subjects were recruited. The cortical area (Ct.Ar) of tibia of the severe OSA group was significantly higher than that of the mild and moderate OSA groups (P = 0.06 and P = 0.048). There were significant differences between the four groups in terms of total volumetric bone mineral density (vBMD) (F = 2.990, P = 0.035), meta trabecular vBMD (F = 3.696, P = 0.015), trabecular thickness (Tb.Th) (F = 7.060, P = 0.000) and cortical thickness (Ct.Th) (F = 4.959, P = 0.003). The mean values of the OSA groups were lower than control group. Hypopnea index and percentage of total sleep time with SpO 2  < 90% were both positively correlated with alkaline phosphatase (R = 0.213, P = 0.044; R = 0.212, P = 0.045). Sleep efficiency was correlated with multiple indicators of the radius., Conclusions: In non-elderly male populations, OSA patients tended to have lower vBMD, Tb.Th and Ct.Th than non-OSA patients. The negative effect of OSA may mainly affect the osteogenesis process, and is presumed to be related to sleep-related hypoxemia and sleep efficiency., (© 2024. The Author(s).)

Context: Mutations in WNT1 can cause rare inherited disorders such as osteogenesis imperfecta (OI) and early-onset osteoporosis (EOOP). Owing to its rarity, the clinical characteristics and pathogenic mechanism of WNT1 mutations remain unclear., Objective: We aimed to explore the phenotypic and genotypic spectrum and treatment responses of a large cohort of patients with WNT1-related OI/OP and the molecular mechanisms of WNT1 variants., Methods: The phenotypes and genotypes of patients and their responses to bisphosphonates or denosumab were evaluated. Western blot analysis, quantitative polymerase chain reaction, and immunofluorescence staining were used to evaluate the expression levels of WNT1, total β-catenin, and type I collagen in the tibial bone or skin from one patient., Results: We included 16 patients with 16 mutations identified in WNT1, including a novel mutation. The types of WNT1 mutations were related to skeletal phenotypes, and biallelic nonsense mutations or frameshift mutations could lead to an earlier occurrence of fragility fractures and more severe skeletal phenotypes. Some rare comorbidities were identified in this cohort, including cerebral abnormalities, hematologic diseases, and pituitary adenoma. Bisphosphonates and denosumab significantly increased the spine and proximal hip BMD of patients with WNT1 mutations and reshaped the compressed vertebrae. We report for the first time a decreased β-catenin level in the bone of patient 10 with c.677C > T and c.502G > A compared to the healthy control, which revealed the potential mechanisms of WNT1-induced skeletal phenotypes., Conclusion: Biallelic nonsense mutations or frameshift mutations of WNT1 could lead to an earlier occurrence of fragility fractures and a more severe skeletal phenotype in OI and EOOP induced by WNT1 mutations. The reduced osteogenic activity caused by WNT pathway downregulation could be a potential pathogenic mechanism of WNT1-related OI and EOOP., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Inflammation leads to systemic osteoporosis or local bone destruction, however, the underlying molecular mechanisms are still poorly understood. In this study, we report that PRL2 is a negative regulator of osteoclastogenesis and bone absorption. Mice with PRL2 deficiency exhibit a decrease in bone volume and an increase in osteoclast numbers. PRL2 negatively regulates RANKL-induced reactive oxygen species production through the activation of RAC1, thus PRL2 deficient osteoclast precursors have both increased osteoclast differentiation ability and bone resorptive capacity. During inflammation, oxidized PRL2 is a selected substrate of HSC70 and conditions of oxidative stress trigger rapid degradation of PRL2 by HSC70 mediated endosomal microautophagy and chaperone-mediated autophagy. Ablation of PRL2 in mouse models of inflammatory bone disease leads to an increase in the number of osteoclasts and exacerbation of bone damage. Moreover, reduced PRL2 protein levels in peripheral myeloid cells are highly correlated with bone destruction in a mouse arthritis model and in human rheumatoid arthritis, while the autophagy inhibitor hydroxychloroquine blocked inflammation-induced PRL2 degradation and bone destruction in vivo. Therefore, our findings identify PRL2 as a new regulator in osteoimmunity, providing a link between inflammation and osteoporosis. As such, PRL2 is a potential therapeutic target for inflammatory bone disease and inhibition of HSC70 mediated autophagic degradation of PRL2 may offer new therapeutic tools for the treatment of inflammatory bone disease., (© 2022. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.)

Famine exposure in early life has been found to have a long-term effect on metabolic diseases, but its effect on bone health was not clear. In this study, we found women, who suffered from famine exposure during their childhood or adolescence period, had significantly decreased BMD at several skeletal sites compared to the age-matched non-exposed groups. The risk of clinical fracture was also elevated in adolescence-exposed women., Purpose: To investigate the correlation between famine exposure at certain stages and bone mass in adulthood., Methods: We enrolled participants born in 1943-1962 from the China Osteoporosis Prevalence Study (COPS), which were classified into three famine exposure groups according to their birth year: fetal-famine exposure (1959-1962, n = 1693), childhood-famine exposure (1949-1958, n = 5557), and adolescence-famine exposure (1943-1948, n = 1530). We also selected age-balanced non-exposed participants as the control groups for men and women separately. Bone mineral density (BMD) and vertebral fractures (VFs) were measured by dual X-ray absorptiometry (DXA) and X-ray, respectively. The associations of famine exposure in early life with BMD were assessed via multiple linear regression. Logistic regression was performed to examine the association of famine exposure in early life with fracture risk with adjustments for covariates., Results: In women, the childhood-exposed and adolescence-exposed groups had significantly decreased BMD at several skeletal sites compared to the age-matched non-exposed groups. No significant decreased BMD was found in the fetal-exposed groups compared to the non-exposed groups in both sexes. Multiple linear regression analysis showed that famine exposure during childhood and adolescence was negatively associated with BMD at the femoral neck after adjusting for covariates in women. The risk of clinical fracture was also elevated in adolescence-exposed women., Conclusion: Famine exposure during early life especially childhood and adolescence is associated with decreased bone mass in adulthood in women but did not affect bone mass in men., (© 2023. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Introduction: Hemophilia is a rare X-linked recessive inherited bleeding disorder caused by mutations of the genes encoding coagulation factor VIII (FVIII) or IX (FIX). Patients with hemophilia (PWH) often have a high risk of osteoporosis and fractures that is usually ignored. Herein, we review the underlying mechanisms of osteoporosis and the increased risk of fractures and their treatment in patients with FVIII or FIX deficiency., Methods: The PubMed, Web of Science, Embase, and Cochrane Library databases were searched to identify original research articles, meta-analyses, and scientific reviews on the mechanisms or treatment of osteoporosis in PWH., Results: The pathogenic mechanisms of osteoporosis in PWH are multifactorial and remain unclear. The available evidence shows that FVIII and FIX deficiency may directly affect bone metabolism by interfering with the RANK/RANKL/OPG pathway. Other potential mechanisms of osteoporosis in PWH include thrombin deficiency and the unloading and immobilization of bone, which will affect osteoblast and osteoclast activity by changing the cytokine profiles. The treatment of osteoporosis in PWH includes antiresorptive, anabolic, and dual-action drugs; weight-bearing exercise; fall prevention; and prophylactic coagulation factor replacement therapy. However, clinical studies of the efficacy of anti-osteoporotic agents in osteoporosis of PWH are urgently needed., Conclusion: This review summarizes recent progress in research on the pathogenesis of osteoporosis in PWH and provides insights into potential treatment for osteoporosis in PWH., (© 2022. The Author(s).)

Postmenopausal women are at significant risk for osteoporotic fractures due to their rapid bone loss. Half of all postmenopausal women will get an osteoporosis-related fracture over their lifetime, with 25% developing a spine deformity and 15% developing a hip fracture. By 2050, more than half of all osteoporotic fractures will occur in Asia, with postmenopausal women being the most susceptible. Early management can halt or even reverse the progression of osteoporosis. Consequently, on October 31, 2020, the Taiwanese Osteoporosis Association hosted the Asia-Pacific (AP) Postmenopausal Osteoporotic Fracture Prevention (POFP) consensus meeting, which was supported by the Asian Federation of Osteoporosis Societies (AFOS) and the Asia Pacific Osteoporosis Foundation (APOF). International and domestic experts developed ten applicable statements for the prevention of osteoporotic fractures in postmenopausal women with low bone mass or osteoporosis but no fragility fractures in the AP region. The experts advocated, for example, that postmenopausal women with a high fracture risk be reimbursed for pharmaceutical therapy to prevent osteoporotic fractures. More clinical experience and data are required to modify intervention tactics., Competing Interests: Declaration of competing interest Chih-Hsing Wu received honoraria for lectures, attending meetings, and/or travel from Eli Lilly, Roche, Amgen, Merck, Servier laboratories, GE Lunar, Harvester, TCM Biotech, and Alvogen/Lotus. E Michael Lewiecki is an investigator, consultant, and speaker for Amgen, and an investigator for Radius., (Copyright © 2023 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

In this population-based, cross-sectional study, we investigated vertebral fracture (VF) prevalence among Chinese postmenopausal women. We found 14.7% of population had VFs, which increased with age. Age ≥ 65 years, hip fracture, and densitometric osteoporosis were significantly associated with VFs. The prevalence of osteoporosis was remarkably high., Purpose: To investigate VF prevalence among Chinese postmenopausal women in this population-based, randomized-sampling, cross-sectional study., Methods: The investigator obtained lists of women from communities. Randomization was performed using SAS programming based on age group in each region. Postmenopausal women aged ≥ 50 years in the urban community were included. The investigator interviewed subjects to collect self-reported data and measured BMD. Spine radiographs were adjudicated by Genant's semi-quantitative method. VFs were defined as fractures of at least one vertebra classified by Genant's score 1-3 and were analyzed using descriptive statistics., Results: A total of 31,205 women listed for randomized sampling from 10 Tier-3 hospitals at 5 regions. Of 2634 women in the full analysis set, 14.7% (388/2634, 95% CI: 13.4, 17.1) had prevalent VFs. VF prevalence increased with age (Cochran-Armitage test p < 0.0001) and was significantly higher in women aged ≥ 65. VF prevalence did not differ between North (14.4%, 95% CI: 12.5, 16.4) and South China (15.1%, 95% CI: 13.3, 17.1). In women with no prior VFs, prevalent VFs were 12.4% (95% CI: 11.2, 13.7). Age ≥ 65 years (OR: 2.57, 95% CI: 1.91, 3.48), hip fracture (OR: 2.28, 95% CI: 1.09, 4.76), and densitometric osteoporosis (OR: 2.52, 95% CI: 1.96, 3.22) were significantly associated with prevalent VFs. Prevalence of osteoporosis was 32.9% measured by BMD and 40.8% using NOF/IOF clinical diagnosis criteria., Conclusion: VFs are prevalent among Chinese postmenopausal women who were ≥ 50 years and community-dwelled. Osteoporosis prevalence is remarkable when fragile fractures were part of clinical diagnosis., (© 2022. The Author(s).)

The efficacy of generic teriparatide in improving BMD at lumbar spine in patients with osteoporosis was similar to that of alendronate. It provided a new choice for osteoporosis treatment in Chinese population., Introduction: To determine whether the efficacy of generic teriparatide is noninferior to alendronate for Chinese postmenopausal women with osteoporosis., Methods: Eligible patients were randomly assigned (2:1) in a 48-week, open-label design to receive 20 µg sc daily teriparatide or 70 mg oral weekly alendronate. Primary outcome was percentage change in BMD at the lumbar spine from baseline to 48 weeks and was assessed for non-inferiority. The same outcome was further assessed for superiority as a secondary endpoint., Results: Three hundred ninety-one and 196 participants were randomly assigned to the teriparatide or alendronate group, of whom 379 and 194 receiving at least one dose of teriparatide and alendronate treatment were eligible for the efficacy analysis. Teriparatide was non-inferior to alendronate for BMD change at lumbar spine (treatment difference: 0.7%, 95% CI: - 0.3 to 1.7%), which excluded the predefined non-inferiority margin of - 1.5%. However, teriparatide was not statistically superior to alendronate in improving BMD at lumbar spine (P = 0.169). At 48 weeks, changes in BMD at total hip were - 1.0% and 2.2% in teriparatide and alendronate group, respectively (P < 0.001). The incidence of new fracture showed no statistical difference between groups (P = 0.128). Serum P1NP and β-CTX levels significantly increased in the teriparatide group and markedly decreased in alendronate group (all P < 0.001 vs baseline). The adverse events (AEs) and serious AEs were more common in the teriparatide group than in the alendronate group, which were mainly teriparatide-related hypercalcemia, elevated alkaline phosphatase or parathyroid hormone, dizziness, and arthralgia., Conclusions: Teriparatide was not inferior to alendronate in increasing BMD at lumbar spine in Chinese postmenopausal women, and they achieved these effects through different mechanisms., (© 2022. The Author(s).)

Background: Obesity is associated with improved bone mass and microarchitecture in Caucasian individuals, but evidence in obese Asian individuals is lacking., Objective: To analyze the areal bone mineral density (aBMD) and bone microarchitecture in normal-weight, overweight, and obese postmenopausal Chinese women., Methods: A total of 243 postmenopausal women from the Chinese Vertebral Osteoporosis Study (ChiVOS) were included and were divided into three groups (OB, obese group; OW, overweight group; NW, normal weight group) by BMI level. aBMD, trabecular bone score (TBS), and appendicular lean mass (ALM) were measured by dual-energy X-ray absorptiometry (DXA). Bone microarchitecture was measured by HR-pQCT at the distal radius and tibia. X-ray was performed to confirm vertebral fractures (VFs). Multiple linear regression was used to evaluate the correlations between bone parameters and ALM after adjusting for confounding variables., Results: The prevalence of VFs and clinical fractures were similar among the groups. Participants in the OB group showed a lower level of osteocalcin with comparable levels of other bone turnover markers (BTMs). The aBMD at several skeletal sites was higher in the OB group than in the NW group after adjusting for age ( p <0.01 for all comparisons). At the radius, the OB group had a higher Ct.Ar, Tb.vBMD, Tb.BV/TV, Tb.N, Tb.Th, and Ct.Th than the NW group after adjusting for covariates ( p <0.05 for all). Differences of a similar magnitude were found at the distal tibia. There was a trend of decreasing trend in Tb.Sp, Tb.1/N/SD, and Ct.Po among groups at both sites. However, the bone microarchitecture did not differ between participants with severe obesity (BMI≥35.0kg/m 2 ) and those with 30.0≤BMI<35 kg/m 2 . Multiple linear regression revealed that the associations between ALM and most of the bone microarchitecture parameters at both sites were much stronger than the association between body weight and bone parameters., Conclusion: We have observed significant improvements in aBMD, bone geometry, and bone microarchitecture in obese postmenopausal Chinese women. Except for a lower level of osteocalcin in the OB group, no significant differences in BTMs were found among the groups. Compared with body weight, ALM may explain greater variance in the improvement of bone microarchitecture parameters., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Qi, Jiang, Liu, Chi, Jiajue, Pang, Wang, Li, Xing, Yu and Xia.)

Background: Subjects with type 2 diabetes mellitus (T2DM) are susceptible to osteoporosis. This study was conducted to evaluate the association between glycemic variability evaluated by continuous glucose monitoring (CGM) and osteoporosis in type 2 diabetic patient., Methods: A total of 362 type 2 diabetic subjects who underwent bone mineral density (BMD) measurement and were monitored by a CGM system from Jan 2019 to May 2020 were enrolled in this cross-sectional study. Glycemic variability was calculated with the Easy GV software, including 24-hour mean blood glucose (24-h MBG), the standard deviation of 24-h MBG (SDBG), coefficient of variation (CV), mean amplitude of glycemic excursions (MAGE), and time in range between 3.9 and 10.0 mmol/L (TIR). Other potential influence factors for osteoporosis were also examined., Results: Based on the T-scores of BMD measurement, there were 190 patients with normal bone mass, 132 patients with osteopenia and 40 patients with osteoporosis. T2DM patients with osteoporosis showed a higher 24-h MBG, SDBG, CV, and MAGE, but a lower TIR (all p < 0.05). Multivariate logistic regression analysis revealed that age, female gender, body mass index (BMI), low-density lipoprotein cholesterol (LDL-C), serum uric acid (SUA) and MAGE independently contribute to osteoporosis, and corresponding odds ratio [95% confidence interval (CI)] was 1.129 (1.072-1.190), 4.215 (1.613-11.012), 0.801 (0.712-0.901), 2.743 (1.385-5.431), 0.993 (0.988-0.999), and 1.380 (1.026-1.857), respectively. Further receiver operating characteristic analysis with Youden index indicated that the area under the curve and its 95% CI were 0.673 and 0.604-0.742, with the optimal cut-off value of MAGE predicting osteoporosis being 4.31 mmol/L., Conclusion: In addition to conventional influence factors including age, female gender, BMI, LDL-C and SUA, increased glycemic variability assessed by MAGE is associated with osteoporosis in type 2 diabetic patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, Wang, Shen, Cai, Zhou, Wang, Xia, Ding, Yan, Li, Wu and Ma.)

Eldecalcitol (ELD) is a new oral analog of the active form of vitamin D with anti-resorptive properties. We conducted a meta-analysis to investigate the efficacy and safety of ELD in osteoporosis. Compared with alfacalcidol, ELD significantly lowered vertebral facture risk, increased bone mineral density, but also had a higher risk of hypercalciuria., Purpose: This study aimed to investigate the efficacy and safety of eldecalcitol (ELD) in osteoporosis by examining fracture rates, bone mineral density (BMD), bone turnover markers, and adverse events as outcomes., Methods: PubMed, EMBASE, and Cochrane Library were searched up to July 20, 2020, to identify eligible randomized controlled trials. The odds ratio (OR) or weighted mean difference (WMD) with 95% confidence interval was calculated by the random-effects model., Results: ELD significantly increased lumbar BMD (WMD: 2.80; 95% CI: 1.60, 4.00; P < 0.001, 2 studies involved), total hip BMD (WMD: 2.11; 95% CI: 0.68, 3.55; P = 0.004, 2 studies involved), and femoral neck BMD (WMD: 1.78; 95% CI: 0.76, 2.79; P = 0.001, 1 study involved) compared with alfacalcidol. Moreover, ELD caused a significantly lower rate of vertebral fracture (OR: 0.52; 95% CI: 0.29-0.95; P = 0.034, 2 studies involved) than alfacalcidol, but did not lower the rate of non-vertebral facture (OR: 0.44; 95% CI: 0.06-3.05; P = 0.405, 2 studies involved) compared with alfacalcidol. ELD significantly reduced the percentage change in bone-specific alkaline phosphatase (WMD: - 15.40; 95% CI: - 20.30, - 10.60; P < 0.001, 1 study involved) and serum type I collagen C-telopeptide (WMD: - 38.50; 95% CI: - 50.00, - 27.10; P < 0.001, 1 study involved) as compared with alfacalcidol. ELD was also associated with higher risk of hypercalciuria compared with alfacalcidol (OR: 1.64; 95% CI: 1.22, 2.20; P = 0.001, 2 studies involved)., Conclusions: This systematic review indicated that ELD was superior than alfacalcidol for improving vertebral fracture risk and BMD. Further large-scale trials should be conducted to verify the long-term effects and safety of ELD in osteoporosis., Prospero Registration Number: CRD42020147518., (© 2022. The Author(s).)

Objective: To understand the prevalence of osteoporosis and related factors in postmenopausal women aged ≥40 years in China and provide scientific evidence for osteoporosis prevention and control. Methods: Data of this study were from the 2018 China Osteoporosis Epidemiological Survey, covering 44 counties (districts) in 11 provinces in China. Related variables were collected by questionnaire survey and physical measurement, and the BMD of lumbar spine and proximal femur was measured by dual-energy X-ray absorption method. The prevalence of osteoporosis and its 95% CI in postmenopausal women aged ≥40 years were estimated with complex sampling weights. Results: A total of 5 728 postmenopausal women aged ≥40 years were included in the analysis and the prevalence of osteoporosis was 32.5% (95% CI : 30.3%-34.7%). The prevalence of osteoporosis in postmenopausal women aged 40-49 years, 50-59 years, 60-69 years, 70-79 years, and ≥80 years were 16.0% (95% CI :4.5%-27.5%), 18.4% (95% CI :15.9%-20.8%), 37.5% (95% CI :34.5%-40.4%), 52.9% (95% CI : 47.5%-58.3%), and 68.0% (95% CI :55.9%-80.1%) respectively. The prevalence of osteoporosis was higher ( P <0.001) in those with education level of primary school or below (47.2%, 95% CI : 43.0%-51.3%) and in those with individual annual income less than 10 000 Yuan, (40.3%, 95% CI : 36.9%-43.7%). The prevalence of osteoporosis was 35.1% in rural areas (95% CI : 32.0%-38.1%), which was higher than that in urban areas ( P <0.001). The prevalence of osteoporosis in low weight, normal weight, overweight and obese groups were 69.9% (95% CI : 59.0%-80.8%), 42.2% (95% CI : 38.7%-45.7%), 24.2% (95% CI : 21.3%-27.1%) and 14.6% (95% CI : 11.1%-18.0%), respectively. The prevalence of osteoporosis in those with menstrual maintenance years ≤30 years and in those with menopause years ≥11 years were 46.1% (95% CI :40.8%-51.3%) and 48.2% (95% CI :45.0%-51.3%), respectively. Multivariate logistic analysis showed that age ≥60 years, education level of primary school or below, annual household income per capita less than 10 000 Yuan, low body weight, menstrual maintenance years ≤30 years, menopause years ≥11 years were risk factors of osteoporosis in postmenopausal women in China. Conclusions: The prevalence of osteoporosis was high in postmenopausal women aged ≥40 years in China, and there were differences in osteoporosis prevalence among different socioeconomic groups. Effective interventions should be taken for the prevention and control of osteoporosis in key groups in the future.

Purpose: The increased social and economic burdens make osteoporosis in men an emerging public health issue. However, the quality of life among men with osteoporosis is still unclear. This systematic review and meta-analysis aimed to evaluate the health-related quality of life (HRQoL) among men with osteoporosis or osteoporotic fracture., Methods: PubMed, EMBASE, and the Cochrane Library database were systematically searched from inception to May 2021. Studies were included if they used validated questionnaires to measure HRQoL among osteoporotic men. A meta-analysis was performed using a random-effects model or fixed-effects model to calculate the standard mean difference (SMD) or mean difference (MD) with 95% confidential interval (95% CI)., Results: 14 studies involving 6338 male participants were chosen for systematic review, of which 10 were included in the meta-analysis. Men with osteoporosis had poorer global HRQoL and multiple dimensions of HRQoL than men without osteoporosis. Hip fracture, vertebral fractures, or wrist fractures dramatically impaired HRQoL of men, and physical function was declined even before hip fracture (SMD = -0.60, 95% CI, -0.82 to -0.39). Femoral and lumbar BMD was positively correlated with HRQoL, and a number of fragility fractures and time since fracture had negative effects on HRQoL. Effective anti-osteoporotic drugs could improve HRQoL of men., Conclusion: The health-related life quality of men was significantly impaired by osteoporosis and fracture of the hip, vertebral, or wrist. We should pay more attention to the diagnosis and treatment of male osteoporosis to improve the life quality of men., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Bone mineral density (BMD) measurement using dual-energy X-ray absorptiometry (DXA) is considered a diagnostic parameter for osteoporosis by the World Health Organization (WHO). DXA densitometers have different scanning modes for BMD measurements, although the specific scanning modes vary based upon the manufacturer. For DXA machines manufactured by Hologic, which are used globally, a range of scanning modes exist, including but not limited to (in order of decreasing spatial resolution) Array, Fast Array, and Express Array. Only a handful of prior studies have compared the reproducibility of BMD measurements across scan modes. The present study aimed to add to this body of literature by investigating the differences in BMD measured between 3 scanning modes in Hologic DXA machines at 19 different health centers. As part of cross-calibration activities for two multi-center studies in China measuring BMD, the European spine phantom (ESP, 1.000 g/cm 2 ) was scanned on 19 different Hologic DXA machines. To measure differences in BMD between the 3 scan modes most commonly found on the Hologic models available (i.e., Array, Fast Array, Express Array), the ESP measurement was performed 10 times for each scan mode on each Hologic DXA machine. One-sample t test was used to compare the average difference between the measured ESP results of the 3 scanning modes at each hospital and reference ESP values. Single factor analysis of variance was performed to compare the average differences between the pairs of scanning modes using the reference ESP. Statistically significant differences between the measured ESP results with reference ESP values were found with each scanning mode at 19 hospitals (all p values <0.05). Consistent with this finding, differences in average BMD between the Array mode and Fast Array mode were invariably the smallest compared to differences seen between the other two pairs of scan modes. Significant differences were observed between average ESP BMD for the Array and Express Array scan modes (0.971 ± 0.013 vs 0.935 ± 0.027, p < 0.001), and between Fast Array and Express Array scan modes (0.972 ± 0.012 vs 0.935 ± 0.027, p < 0.001). However, no significant difference in average ESP BMD was observed between the Array and Fast Array scan modes (0.971 ± 0.013 vs 0.972 ± 0.012, p = 0.997). The selection of ideal scanning mode requires a balance of scanning time, radiation exposure, and measurement accuracy. In this ex vivo study, the Fast Array scanning mode appeared to be a reasonable choice compared with Array and Express Array for BMD measurements by Hologic DXA. Future in vivo studies can help guide the clinical application of these findings., (Copyright © 2021 The International Society for Clinical Densitometry. All rights reserved.)

Annual osteoporotic fractures is projected to increase by 135% from 6.9 M (2020) to 16.2 M (2040), increasing the economic burden by 121% from $29.9B (2020) to $65.9B (2040)., Introduction: Globally, aging populations drive significant increases in osteoporosis prevalence. In China, the number of women aged ≥ 65 years is expected to more than double from 2020 (91.5 M) to 2040 (183.6 M). Using a microsimulation model, impact of increased diagnosis and treatment of postmenopausal women (PMW) with osteoporosis on anticipated reduction in fractures and associated costs in China from 2020 to 2040 was projected., Methods: A microsimulation model was developed to project annual incidence and costs of osteoporotic fractures among PMW in China from 2020 to 2040. Fracture risk was estimated using the simplified Fracture Risk Assessment Tool (FRAX). Fractures estimates were based on annualized FRAX risk and impact of treatment. Published literature informed inputs for direct and indirect fracture costs, DXA screening costs, and treatment costs and efficacy. China's current screening and treatment rates were compared against 50% increases to (i) case finding (screening rate and subsequent treatment rate) and (ii) treatment rate among those at highest fracture risk., Results: From 2020 to 2040, 241.7 M osteoporotic fractures are projected to cost $997B. Increased treatment scenario prevented 24.6 M fractures and saved $56B. Increased case finding scenario prevented 26 M fractures and saved $61.7B., Conclusion: Osteoporosis underdiagnosis and undertreatment among the aging Chinese population will considerably burden patients, caregivers, and society. Policy changes to increase screening and treatment rates may result in significant cost savings and clinical benefits., (© 2021. International Osteoporosis Foundation and National Osteoporosis Foundation.)

Importance: The aging of the population is associated with an increasing burden of fractures worldwide. However, the epidemiological features of fractures in mainland China are not well known., Objective: To assess the prevalence of and factors associated with osteoporosis, clinical fractures, and vertebral fractures in an adult population 40 years or older in mainland China., Design, Setting. And Participants: This cross-sectional study, the China Osteoporosis Prevalence Study, was conducted from December 2017 to August 2018. A random sample of individuals aged 20 years or older who represented urban and rural areas of China were enrolled, with a 99% participation rate., Main Outcomes and Measures: Weighted prevalence of osteoporosis, clinical fracture, and vertebral fracture by age, sex, and urban vs rural residence as determined by x-ray absorptiometry, questionnaire, and radiography., Results: A total of 20 416 participants were included in this study; 20 164 (98.8%; 11 443 women [56.7%]; mean [SD] age, 53 [13] years) had a qualified x-ray absorptiometry image and completed the questionnaire, and 8423 of 8800 (95.7%) had a qualified spine radiograph. The prevalence of osteoporosis among those aged 40 years or older was 5.0% (95% CI, 4.2%-5.8%) among men and 20.6% (95% CI, 19.3%-22.0%) among women. The prevalence of vertebral fracture was 10.5% (95% CI, 9.0%-12.0%) among men and 9.7% (95% CI, 8.2%-11.1%) among women. The prevalence of clinical fracture in the past 5 years was 4.1% (95% CI, 3.3%-4.9%) among men and 4.2% (95% CI, 3.6%-4.7%) among women. Among men and women, 0.3% (95% CI, 0.0%-0.7%) and 1.4% (95% CI, 0.8%-2.0%), respectively, with osteoporosis diagnosed on the basis of bone mineral density or with fracture were receiving antiosteoporosis treatment to prevent fracture., Conclusions and Relevance: In this cross-sectional study of an adult population in mainland China, the prevalence of osteoporosis and vertebral fracture were high and the prevalence of vertebral fracture and clinical fracture was similarly high in men and women. These findings suggest that current guidelines for screening and treatment of fractures among patients in China should focus equally on men and women and should emphasize the prevention of vertebral fractures.

Osteoporosis is a major health issue. By 2050, a greater than 2-fold increase in patients number with hip fractures will occur in Asia representing 50% of all hip fractures worldwide. For the Asia-Pacific (AP) region, more efforts on controlling osteoporosis and the subsequent fractures are crucial. Bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA) is commonly used to diagnose osteoporosis and monitor osteoporosis treatment. However, the inconvenience, cost, limited availability of DXA and the delay in detection of BMD changes after treatment initiation support an important role for bone turnover markers (BTMs), as short-term tools to monitor therapy. With regards to low adherence rates of medical treatment of osteoporosis, the experts reached consensus on the use of BTMs for both raising awareness and short-term monitoring of osteoporosis treatment in the AP region. The experts endorse the use of BTMs, especially serum C-terminal telopeptide of type 1 collagen (CTX) and serum procollagen type 1 N propeptide (P1NP), as short-term monitoring tools to help clinicians assess the responses to osteoporosis therapies and appropriately adjust treatment regimens earlier than BMD. Either the absolute values or the degree of change from baseline in BTMs can be used to monitor the potential efficacy of osteoporosis therapies. The use of BTMs can be incorporated in osteoporosis care programs, such as fracture liaison service (FLS), to improve patient adherence and treatment outcomes. Encouraging sufficient reimbursement from health care systems may facilitate widespread use of BTMs in clinical practice in the AP region., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Eldecalcitol increased bone mineral density (BMD) and prevented vertebral fractures in vitamin D-sufficient osteoporotic subjects. However, the effect of eldecalcitol on BMD under vitamin D insufficiency is unknown. We examined the effect of eldecalcitol on BMD compared with alfacalcidol in osteoporotic patients without vitamin D or calcium supplementation. This is a randomized, double-blind, active comparator trial. 265 Chinese osteoporotic patients were randomly assigned to receive 0.75 μg eldecalcitol or 1.0 μg alfacalcidol for 12 months without vitamin D or calcium supplementation. Baseline calcium intakes were less than 550 mg/day and mean serum 25-hydroxyvitamin D [25(OH)D] was below 43 nmol/L in both groups. Baseline BMD tended to be lower in patients with lower calcium intake and serum 25(OH)D. Lumbar BMD increased by 2.05% higher in eldecalcitol than alfacalcidol group at 12 months. Total hip and femoral neck BMD also increased by 1.33 and 1.78%, respectively, in the eldecalcitol than the alfacalcidol group. The effect of eldecalcitol on BMD was not affected by serum 25(OH)D or calcium intake. The incidence of adverse events was not different between the two groups. Incidence of hypercalcemia in the edecalcitol group was not affected by serum 25(OH)D. In conclusion, baseline BMD tended to be lower in patients with low calcium intake and serum 25(OH)D. Eldecalcitol increased lumbar and hip BMD more than alfacalcidol regardless of serum 25(OH)D or calcium intake without vitamin D or calcium supplementation. These results suggest that eldecalcitol is effective in increasing the BMD of osteoporotic patients regardless of vitamin D status or calcium intake.Clinical Trial Registration number JAPIC CTI 152904.

Background: Osteoporosis has been one of the most common but largely under-diagnosed clinical problems among elderly population. The disease burden is even greater in China because of limited medical resources and large population size. This article is aimed to provide an overview of disease burden, secular trend, and management gap of osteoporosis and related fractures in China., Methods: Based on the related studies published in English and Chinese from 1990 to 2017, we investigated the prevalence/incidence of osteoporosis and osteoporotic fracture in Chinese mainland, Hong Kong, and Taiwan, characterizing the secular trend and disease burden in different regions. Strict inclusion criteria were applied to control the study quality. We further examined the diagnosis and treatment gap of osteoporosis management observed in clinical practice in China and summarized the efforts made by Chinese government and scholars to combat this situation., Results: Twenty-seven studies concerning osteoporosis prevalence in China (including Chinese mainland, Hong Kong, and Taiwan) met the inclusion criteria and were included in the final analysis. Another 15 studies about hip fracture incidence and 13 studies about vertebral fracture prevalence/incidence were also included. The epidemiological data varied greatly across studies due to different design and population included. A higher prevalence was indicated in female population, older age groups, and residents in northern China compared to their counterparts. Though attenuated increased rates or slight decline patterns have been observed in Hong Kong and Taiwan, osteoporotic fracture incidence still showed steady increase in Chinese mainland. The diagnosis and treatment of osteoporosis as well as post-fracture management were still insufficient in China., Conclusion: Due to its silent nature, osteoporosis and its related fractures remain largely under-diagnosed and under-managed in China. It also highlights the scarcity of high-quality studies specifically focus on longtime documentation of disease burden change and male population, especially in mainland area.

Substantial evidence exists that diabetes mellitus is associated with an increased risk of osteoporotic fractures. Low bone strength as well as bone extrinsic factors are probably contributing to the increased bone fragility in diabetes. Bone density and quality are important determinants of bone strength. Although bone mineral density (BMD) and the fracture risk assessment tool (FRAX) are very useful clinical tools in assessing bone strength, they may underestimate the fracture risk in diabetes mellitus. Through advances in new technologies such as trabecular bone score (TBS) and peripheral quantitative computed tomography (pQCT), we can better assess the bone quality and fracture risk of patients with diabetes mellitus. Invasive assessments such as microindentation and histomorphometry have been great complement to the existing bone analysis techniques. Bone turnover markers have been found to be altered in diabetes mellitus patients and may be associated with fractures. This review will give a brief summary of the current development and clinical uses of these assessments.

Background: Breast cancer survivors are at high risk for fracture due to cancer treatment-induced bone loss, however, data is scarce regarding the scope of this problem from an epidemiologic and health services perspective among Chinese women with breast cancer., Methods: We designed a cross-sectional study comparing prevalence of vertebral fractures among age- and BMI-matched women from two cohorts. Women in the Breast Cancer Survivors cohort were enrolled from a large cancer hospital in Beijing. Eligibility criteria included age 50-70 years, initiation of treatment for breast cancer at least 5 years prior to enrollment, and no history of metabolic bone disease or bone metastases. Data collected included sociodemographic characteristics; fracture-related risk factors, screening and preventive measures; breast cancer history; and thoracolumbar x-ray. The matched comparator group was selected from participants enrolled in the Peking Vertebral Fracture Study, an independent cohort of healthy community-dwelling postmenopausal women from Beijing., Results: Two hundred breast cancer survivors were enrolled (mean age 57.5 ± 4.9 years), and compared with 200 matched healthy women. Twenty-two (11%) vertebral fractures were identified among breast cancer survivors compared with 7 (3.5%) vertebral fractures in the comparison group, yielding an adjusted odds ratio for vertebral fracture of 4.16 (95%CI 1.69-10.21, p < 0.01). The majority had early stage (85.3%) and estrogen and/or progesterone receptor positive (84.6%) breast cancer. Approximately half of breast cancer survivors reported taking calcium supplements, 6.1% reported taking vitamin D supplements, and only 27% reported having a bone density scan since being diagnosed with breast cancer., Conclusions: Despite a four-fold increased odds of prevalent vertebral fracture among Chinese breast cancer survivors in our study, rates of screening for osteoporosis and fracture risk were low reflecting a lack of standardization of care regarding cancer-treatment induced bone loss.

We identified a novel large fragment deletion from intron 9 to 3'UTR in PLS3 (E10-E16del) in one Chinese boy with X-linked early-onset osteoporosis and vertebral fractures, which expanded the pathogenic spectrum of X-linked early-onset osteoporosis. Treatment with zoledronic acid was beneficial for increasing BMD and reshaping the vertebral bodies of this patient., Introduction: X-linked early-onset osteoporosis is a rare disease, which is characterized by low bone mineral density (BMD), vertebral compression fractures (VCFs), and/or long bone fractures. We aimed to detect the phenotype and the underlying pathogenic mutation of X-linked early-onset osteoporosis in a boy from a nonconsanguineous Chinese family., Methods: We investigated the pathogenic mutation of the patient with X-linked early-onset osteoporosis by targeted next-generation sequencing and confirmed it by Sanger sequencing. We also observed the effects of zoledronic acid on fracture frequency and BMD of the patient., Results: Low BMD and multiple VCFs were the main phenotypes of X-linked early-onset osteoporosis. We identified a total of 12,229 bp deletion in PLS3, involving intron 9 to the 3'UTR (E10-E16 del). This large fragment deletion might be mediated by Alu repeats and microhomology of 26 bp at each breakpoint junction. Zoledronic acid treatment could significantly increase the Z-score of BMD and reshape the compressed vertebral bodies., Conclusion: We identified a large fragment deletion mutation in PLS3 for the first time and elucidated the possible mechanism of the deletion, which led to X-linked early-onset osteoporosis and multiple vertebral fractures. Our findings would enrich the etiology spectrum of this rare disease.

Osteoporotic femur fractures are the most common fragility fracture and account for approximately one million injuries per year. Local intervention by intra-marrow injection is potentially a good choice for preventing osteoporotic bone loss when the osteoporotic femoral fracture was treated. Previously, it was shown that trace element co-doped calcium phosphate (teCaP) implants could stimulate osteoporotic bone marrow mesenchymal stem cell activity in vitro and bone regeneration in femoral bone defects in osteoporotic animal models. They hypothesized that local intra-marrow injection of teCaP particles could improve bone function because the teCaP can sustain release of biologically essential inorganic minerals and improve bone remodeling in osteoporosis. The teCaP and CaP particles were synthesized in simulated body fluid with and without adding silicon, zinc and strontium ions. Female rats (8 months) were ovariectomized (OVX) or sham-operated, and then intervened in the femoral marrow space at 12 months old. Groups include: (1) saline water; (2) CaP particles; and (3) teCaP particles. After 2-3 months of intervention, the sham groups showed higher bone mineral density (MBD) in the femur, and teCaP group increased the BMD in the OVX groups. The compressive strength of the OVX-teCaP group was significantly higher than that in the OVX-CaP group. Significant differences between OVX-teCaP and OVX-CaP groups were found for bone mineral microarchitecture, bone mineral density, and trace mineral content, but not for feces composition. These results confirm the teCaP particles could suppress osteoporotic bone loss by local intramarrow injection. Therefore, this biomaterial could be used as a next-generation combination treatment for osteoporotic trauma and osteoporosis itself. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1422-1432, 2017., (© 2017 Wiley Periodicals, Inc.)

Aim: We measured the levels of bone turnover markers (BTMs) in patients with early diabetic nephropathy from type 2 diabetes mellitus (T2DM), and investigated the associations of BTMs with adipokines, serum fibroblast growth factor-21 (FGF21) and osteonectin., Methods: We included 159 males and 300 females with T2DM in this cross-sectional study. Clinical characteristics, BTMs and adipokines levels were measured., Results: One-hundred and ninety-two (41.8%) patients presented with albuminuria. Patients with albuminuria had significantly higher levels of serum osteonectin (P<0.0001) and FGF21 (P=0.0125) than those with normoalbuminuria. Serum levels of P1NP were slightly lower among patients with albuminuria (P=0.031), but the difference disappeared after adjusting for FBG, PBG, and HbA1c. Serum FGF21 levels were independently and negatively related to eGFR (overall β=-0.161, P=0.001; albuminuria group β=-0.240, P=0.001) but not related to uACR. While Osteonectin was independently and positively related to uACR (overall β=0.209, P=0.001; albuminuria group β=0.170, P=0.021). The levels of serum FGF21 were independently inversely related with P1NP (overall β=-0.192, P<0.0001; albuminuria group β=-0.195, P=0.031)., Conclusions: Our results suggest that persistent hyperglycemia may inhibit bone formation. Both osteonectin and FGF21 were associated with early nephropathy in T2DM patients, albeit with different patterns., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Bone loss is common in clinical practice, such as health assessment of postmenopausal women, treatment of tumor metastasis, side-effects of glucocorticoids, and skeletal manifestations of inflammatory diseases. The imbalance of remodeling between bone resorption and bone formation, the pathophysiological basis of bone loss, increases bone fragility. The treatment of bone loss is mainly carried out from the treatment of osteoporosis. There are various pharmacological therapies for bone loss, which will be introduced in 3 aspects, including antiresorptive agents, anabolic agents and new medications. Each kind of medication has its advantages, shortcomings and side-effects. Antiresorptive agents are widely applied in the treatment of bone loss, but can lead to overall decrease of bone turnover rate. Anabolic agents, mainly PTH, are usually combined with other anti-resorptive drugs, and PTHrP might be a promising pure anabolic agent for osteoporosis. In recent years, some novel therapies have been raised and tested in clinical trials which can be promising choices available for osteoporosis treatment. Future drug targets will mainly come from RANK-RANKL-OPG system and Wnt/β-catenin signaling pathway., and the pre-existing drugs could be explored in new patterns., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Our objective was to identify suitable reference genes in serum miRNA for normalization and screen potential new biomarkers for osteoporosis diagnosis by a systematic study. Two types of osteoporosis models were used like as mechanical unloading and estrogen deficiency. Through a large-scale screening using microarray, qPCR validation and statistical algorithms, we first identified miR-25-3p as a suitable reference gene for both type of osteoporosis, which also showed stability during the differentiation processes of osteoblast and osteoclast. Then 15 serum miRNAs with differential expression in OVX rats were identified by microarray and qPCR validation. We further detected these 15 miRNAs in postmenopausal women and bedrest rhesus monkeys and evaluated their diagnostic value by ROC analysis. Among these miRNAs, miR-30b-5p was significantly down-regulated in postmenopausal women with osteopenia or osteoporosis; miR-103-3p, miR-142-3p, miR-328-3p were only significantly decreased in osteoporosis. They all showed positive correlations with BMD. Except miR328-3p, the other three miRNAs were also declined in the rhesus monkeys after long-duration bedrest. Their AUC values (all >0.75) proved the diagnostic potential. Our results provided a reliable normalization reference gene and verified a group of circulating miRNAs as non-invasive biomarkers in the detection of postmenopausal- and mechanical unloading- osteoporosis.

Osteoporosis, a skeletal disorder characterized by a reduction in bone strength, is becoming a major public health problem in the People's Republic of China, with a rapid increase observed among the population. Chinese guidelines particularly recommend use of active vitamin D in managing osteoporosis. 1,25-(OH)2D3 (calcitriol) is an active vitamin D metabolite. It plays a role in many biological processes, especially in bone metabolism and muscle function, and is mediated by vitamin D receptors. Osteoporosis in elderly men and women is characterized by uncoupled bone remodeling, which is induced by sex hormone deficiencies, somatopause, vitamin D deficiency, reduced synthesis of D hormone, and lack of receptors or receptor affinity for D hormone in target organs. Reviewed here are six randomized controlled trials on calcitriol monotherapy and five on calcitriol therapy combined with other antiosteoporotic agents. Evidence from these trials shows that calcitriol monotherapy can improve bone mineral density in elderly osteoporotic Chinese patients but may be insufficient for long-term treatment. Calcitriol can also decrease bone turnover markers and bring about significant improvements in muscle strength. Further, calcitriol in combination with other therapeutic bone agents was shown to be well tolerated and capable of additional bone-preserving effects compared with use of calcitriol alone in areas including bone mineral density, bone turnover markers, bone pain improvement, and fracture incidence. Hypercalcemia and hypercalciuria, the most common side effects of calcitriol therapy, were not documented in the trials reviewed, and might have been the result of the low dosages used. One study showed that treatment with calcitriol can improve quality of life in patients with osteoporosis, although not to the same extent as bisphosphonates.

Unlabelled: Individuals with HIV are at increased risk for osteoporosis and fracture. Using the Health Beliefs Model, we identified key relationships between knowledge, self-efficacy and health beliefs pertaining to physical activity and dietary calcium intake, two key modifiable preventive measures for osteoporosis., Purpose: Individuals with HIV are at increased risk for osteoporosis and fracture. Few studies have systematically explored concerns related to osteoporosis prevention among this group. Applying the Health Beliefs Model (HBM), we examined associations between osteoporosis-related preventive health behaviors (i.e., physical exercise and dietary intake) and knowledge, self-efficacy and health beliefs in a large cohort of Chinese individuals with HIV., Methods: We conducted a cross-sectional study with participants from an ongoing multi-center trial. Volunteers completed a questionnaire consisting of the International Physical Activity Questionnaire (IPAQ), a calcium and vitamin D intake assessment, the Osteoporosis Knowledge Test, Osteoporosis Self-Efficacy Scale, Osteoporosis Health Beliefs Scale, and relevant sociodemographic and clinical risk factors., Results: A total of 263 of 297 eligible participants enrolled in this study. Mean age of participants was 38.4 ± 9.8 years, average BMI was 21.6 ± 2.6 kg/m(2), and 76 % were men. About 30 % of the sample reported low physical activity. Consumption of foods from each calcium and vitamin D-rich category averaged between multiple times per month to weekly. Knowledge regarding osteoporosis was universally low and self-efficacy correlated directly with engagement in preventive behaviors. Women and individuals with lower education perceived greater barriers to adopting preventive behaviors. Multivariate logistic regression adjusted for age, sex and BMI showed that calcium and vitamin D intake was directly correlated with knowledge and self-efficacy, whereas physical activity correlated with manual labor occupation, perceived barriers to exercise and health motivation., Conclusions: Behavioral frameworks such as the HBM may provide important insight into promoting adoption and maintenance of osteoporosis-related preventive behaviors among individuals with HIV.

Objective: Compared with 17beta-estradiol, to evaluate the effects of estradiol valerate on osteopenia in ovariectomized rats., Methods: Forty two six months old female Wistar rats were randomly divided into 5 groups performed ovariectomy (OVX) or sham-operation. (1) 6 weeks after OVX (Ovxb, n = 8): sacrificed at 6 weeks after OVX; (2) Sham ovariectomized (n = 8); (3) 14 weeks after OVX (Ovxe, n = 8); (4) 17beta-estradoil treated group (O + E, n = 9, with 17beta-estradiol 20 microg x kg(-1) x d(-1) Sc.); (5) Estradoil valerate treated group (O + EV, n = 9, with estradiol valerate 800 microg x kg(-1) x d(-1) po). Treatment started 6 weeks after OVX and lasted for 8 weeks. Histomorphometry analysis of tibia, peripheral quantitative computed tomography (pQCT) scanning of femur, bone biomechanical test in femur were performed., Results: OVX induced osteopenia and increase of bone turnover. Compared with Ovxe, O + E and O + EV caused an evident reduction of urinary deoxypyridinoline/creatinine, a bone resorption marker, by 54.6% and 77.4% respectively (all P < 0.01). Both O + E and O + EV lowered the high level of eroded surface, mineral surface and bone formation rate induced by OVX. An increase of 122.3% and 119.7% in trabecular bone volume respectively in O + E and O + EV group, compared with Ovxe group. Microarchitecture of trabeculea also improved in those two groups. The trabeculae bone mineral density determined by pQCT were significantly increased in O + E and O + EV compared with Ovxe group (99.5% and 128.4% P < 0.01). Similarly, significant increases were found in cancellouse maximal load and canceallous stiffness of distal femur in O + E, but not O + EV. There was no significant difference in these changes between the group O + E and O + EV., Conclusion: Oral estradiol valerate performed effects similar to those of 17beta-estradiol Sc. in inhibiting bone turnover, protecting bone loss and increasing bone mineral density of trabecular bone.

Objective: To study the pharmaceutical effects of 1 alpha(OH)D3 on trabecular and cortical bone in ovariectomized (OVX) rats., Methods: 41 female Wistar rats of six months old were randomly divided into 5 groups: (1) Baseline control; (2) Sham control; (3) 6 weeks after OVX (OVXb); (4) 14 weeks after OVX (OVXe); (5) OVX + 0.1 microgram/(kg.d) 1 alpha(OH)D3 (O + VD), treatment started 6 weeks after OVX and lasted 8 weeks. Histomorphometry analysis of tibia, peripheral quantitative computed tomography (pQCT) scanning of femur, bone biomechanical test and serum and urinary biochemical parameters were determined., Results: The levels of bone turnover indexes increased in OVX rats, OVX also resulted in reducing of trabecular, bone mass and biomechanical properties. The ratio of urinary deoxypyridinoline crosslink/creatinine was decreased by 67.0% in O + VD group compared with OVXe group 67.0% [(43.50 +/- 11.20) nmol.L-1/mmol.L-1 vs(131.80 +/- 14.90) nmol.L-1/mmol.L-1, P < 0.01]. Percent trabecular area (Cn-BV/TV) was increased by 89.8% in O + VD group compared with OVXe group (11.03 +/- 0.73 vs 5.81 +/- 1.29, P < 0.05). Trabecular bone mineral content and density were increased by 77.3% and 91.3% compared with OVXe respectively (P < 0.05). Although cancellous maximal load and stiffness increased in O + VD group, but no statistical significance. 1 alpha(OH)D3 also enhanced polar moment of inertia (PMI) and maximal load of cortical bone in femur compared with OVXe (23.70 +/- 1.63 vs 18.23 +/- 1.41, P < 0.01 and 171.69 +/- 9.92 vs 147.58 +/- 11.29, P < 0.05 respectively)., Conclusion: 1 alpha(OH)D3 inhibited the higher bone turnover induced by OVX, increased trabecular bone in proximal tibia and bone mass in distal femur. 1 alpha(OH)D3 also improved the mechanical properties of cortical bone in femur.

Objective: To investigate the effects of alfacalcidol on osteoporosis in rats induced by ovariectomy (OVX)., Methods: Fifty-three virgin female Wistar rats of six months old were divided into 6 groups: (1) rats in baseline group (base) were sacrificed what 6 months before OVX, and those in the other 5 groups were either bilaterally OVX or sham-operated (sham) as follows: (2) Sham; (3) OVX baseline (OVXb); (4) OVX end (OVXe); (5) OVX + 17beta-estradiol 20 microgram/kg.(-1) SC. (O + E); and (6) OVX + alfacalcidol 0.1 microgram/kg.(-1) oral (O + VD). Rats in OVXb group were sacrificed 6 weeks after OVX and the others were sacrificed 14 weeks after surgery. Alfacalcidol (TEVA, Israel) was fed orally at 6 weeks after OVX and lasted for 8 weeks. Urine and serum samples were collected before sacrifice to determine the bone turnover markers. The right tibia was processed undecalcified for histomorphometric analysis, and the right femur was prepared for pQCT scanning and bone biomechanical measurement with indentation test., Results: Treatment of OVX rats with alfacalcidol (O + VD) increased tibial cancellous bone volume in histomorphometric analysis (12.0% +/- 1.1% vs 5.8% +/- 1.3%, P < 0.01). pQCT scanning showed that trabecular BMC and BMD were sharply elevated in O + VD group compared with OVXe group, increased 109.2% and 133.1% respectively (P < 0.01). In consistency with these changes in mechanical competency of cancellous bone in distal femur, maximal load was enhanced in O + VD group compared with OVXe group (21.3% +/- 4.0% N vs 7.9% +/- 1.9% N, P < 0.05). All these changes in O + VD group were similar to those in 17beta-estradiol treatment group (O + E). Serum calcium concentration increased in O + VD group. Histomorphometric and biochemical indices of bone resorption reduced in O + VD group., Conclusion: Alfacalcidol effectively prevent bone loss in OVX rats and restore partly the trabecula, with evidenced increasing density, contents as well as maximal loads of cancellous bone, and reduce bone resorption.

To evaluate the effect of estrogen on its ability to restore the bone mass and bone quality in ovariectomized rats by examining the changes of bone morphology and histomorphometry, 3-month-old rats were divided randomly into 4 groups: normal control, ovariectomized (OVX), sham-operated (Sham-O) and OVX plus estrogen (OVX + E2). Treatment initiated from the day 8 weeks after operation and continued for 12 weeks. Bone morphology and histomorphometry were examined afterwards. Results showed that comparing to control group, the trabecular bone in OVX appeared thinner and reduced in the amount. The connectivity between trabecula was decreased and the structure disordered. The free-end of trabecula was increased. The cavity of bone marrow enlarged. After treatment with estrogen, above changes improved remarkably by different degree, although did not reach the normal face. The bone histomorphometry results demonstrated that estrogen treatment increased bone mass and the amount of trabecula by 129% and 132% respectively (P < 0.05). The activity of bone resorption decreased significantly and the rate of bone formation increased to 203%. These results suggest that treatment of ovariectomized rats with estrogen can not only increase bone mass, also improve the bone structure and enhance the property of bone mechanics.

Summary: We found that the fragility hip and vertebral fractures caused excess mortality rates in this Chinese female population, which was unexpectedly lower than those in western countries and other Asian countries. This was the first nationwide survey relating to post-fracture outcomes conducted among Chinese population in Mainland China. Introduction: This study aimed to investigate the mortality, self-care ability, diagnosis, and medication treatment of osteoporosis following fragility hip and vertebral fractures through a nationwide survey among female patients aged over 50 in Mainland China. Methods: This was a multicenter, retrospective cohort study based on medical chart review and patient questionnaire. Female patients aged 50 or older admitted for low-trauma hip or vertebral fractures and discharged from Jan 1, 2008 to Dec 31, 2012 were followed. Results: Total of 1151 subjects of hip fracture and 842 subjects of vertebral fracture were included. The mean age was 73.4 ± 10.0, and the median of duration from index fracture to interview was 2.6 years. The overall 1-year, 2-year, 3-year, 4-year, and 5-year cumulative mortality rates were 3.5, 7.0, 11.2, 13.1, and 16.9 %, respectively. The first year mortality rates in hip (3.8 %, 95% CI 3.3-4.4 %) and vertebral fracture (3.1 %, 95% CI 2.5-3.7 %) were significantly higher than that in the general population (1.6 %). Impaired self-care ability was observed in 33.2, 40.6, and 23.8 % of overall, hip fracture, and vertebral fracture group, respectively. The overall diagnosis rate of osteoporosis was 56.8 %, and bone mineral density (BMD) measurement had never been conducted in 42.0 % among these women. After the index fracture, 69.6 % of them received supplements and/or anti-osteoporotic medications, among which 39.6 % only received calcium with/without vitamin D supplementation. Conclusions: The osteoporotic hip and vertebral fractures caused excess mortality rates in this population of Mainland China. The current diagnosis and medical treatment following the fragility fractures is still insufficient in Mainland China. [ABSTRACT FROM AUTHOR]

Summary: This study compares efficacy of ALN/D5600 versus that of calcitriol in osteoporotic Chinese postmenopausal women. ALN/D5600 produced greater bone mineral density (BMD) increases, greater bone turnover marker decreases, and less vitamin D insufficiency. This study provided detailed clinical information regarding ALN/D5600 treatment versus calcitriol 0.25 μg/day. The study did not evaluate fracture risk. Introduction: The aim of this study is to investigate efficacy of alendronate 70 mg/vitamin D 5600 IU combination tablets (ALN/D5600) versus calcitriol in osteoporotic Chinese postmenopausal women. Methods: This study is a 6-month, randomized, open-label, active-comparator study with 6-month extension (clinicaltrials.gov number NCT01350934) in postmenopausal women aged >55 years with osteoporosis (low bone mineral density (BMD) with/without prior fragility fracture). Patients were randomized to ALN/D5600 once weekly or calcitriol 0.25 μg daily. The primary efficacy end point of the base study was percent change from baseline in lumbar spine BMD (month 6). Hypercalcemia and hypercalciuria were safety events of special interest. Results: A total of 219 patients (ALN/D5600 n = 111, calcitriol n = 108) were randomized. Baseline characteristics were similar, 30.3 % baseline 25-hydroxyvitamin D (25(OH)D) ≤15 ng/mL. At months 6 and 12, changes in lumbar spine BMD from baseline were 3.5 versus 1.6 % and 5.2 versus 2.3 % for ALN/D5600 versus calcitriol (between-group differences p < 0.001), respectively. Between-group differences for ALN/D5600 versus calcitriol were significant ( p < 0.001) at months 6 and 12 for change from baseline in procollagen type 1 N-terminal propeptide (−59.1 versus −16.8 %, −68.1 versus −17.0 %) and serum C-telopeptides (−79.2 versus −27.2 %, −76.2 versus −24.2 %). Drug-related adverse events (AEs) and discontinuations due to drug-related AEs occurred in 15 (14.0 %) versus 8 (7.4 %) patients and 3 (2.8 %) versus 0 patients in the ALN/D5600 and calcitriol group, respectively. Hypercalciuria 12-month incidence (24-h urine Ca >300 mg) was 8.4 (ALN/D5600) versus 13.9 % (calcitriol) ( p > 0.05). One patient (calcitriol) had hypercalcemia. Conclusions: ALN/D5600 produced greater increases in lumbar spine BMD and greater decreases in bone turnover markers versus calcitriol in osteoporotic Chinese women. It is not known whether the greater increase in BMD results in fewer fractures. ALN/D5600 was generally well tolerated in Chinese patients. [ABSTRACT FROM AUTHOR]