Yu ZD, Zang HB, Zhu YJ
… +7 more, Yu XH, Tang CH, Cao HW, Huang XL, Bo L, Lei SF, Deng FY
J Bone Miner Metab
· 2026 Jan · PMID 41193836
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INTRODUCTION: Facial skin aging (FSA) is a very easily observable indicator of aging, but whether FSA is associated with osteoporosis is still unknown. MATERIALS AND METHODS: Based on the individual-level datasets from U...INTRODUCTION: Facial skin aging (FSA) is a very easily observable indicator of aging, but whether FSA is associated with osteoporosis is still unknown. MATERIALS AND METHODS: Based on the individual-level datasets from UK Biobank, this study calculated the PhenoAge (an accurate aging parameter), genetic risk score (GRS) and PhenoAge_advance, and performed multiple linear correlation analyses and Cox regression analyses. Based on the summary data from genome-wide association Studies (GWAS), linkage disequilibrium regression (LDSC), pleiotropic analysis under composite null hypothesis (PLACO) and Mendelian randomization (MR) analysis were performed to reveal shared genetic components and infer causal effects, respectively. RESULTS: Higher degrees of FSA were associated with lower eBMD (p < 0.001), and FSA was positively associated with the risks of osteoporosis (HR = 1.852, p < 0.001) and fracture (HR = 1.501, p < 0.001). However, FSA was not genetically associated as well as causally associated with all studied osteoporosis-related traits. In addition, we found significant phenotypic and genetic correlations between FSA and PhenoAge (rp = -0.137, p < 0.05) as well as between PhenoAge and fractures (rg = 0.092, p < 0.05). CONCLUSION: FSA, PhenoAge and osteoporosis are three aging-related parameters that coexist with aging, and the aging process is accompanied by FSA and osteoporosis. FSA may serve as a marker for the onset of osteoporosis. These findings provide clues for early detection of bone loss in at-risk populations and for OP diagnosis using accurate clinical tools.
Koide M, Yamashita T, Kobayashi Y
… +3 more, Yasuda H, Nakamura M, Udagawa N
J Bone Miner Metab
· 2025 Nov · PMID 41160106
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INTRODUCTION: Administration of an anti-sclerostin antibody enhances Wnt/β-catenin signaling, resulting in a significant increase in bone mass by stimulating bone formation and suppressing bone resorption. Wnt/β-catenin...INTRODUCTION: Administration of an anti-sclerostin antibody enhances Wnt/β-catenin signaling, resulting in a significant increase in bone mass by stimulating bone formation and suppressing bone resorption. Wnt/β-catenin signaling upregulates the expression of osteoprotegerin (Opg), a key regulator that inhibits osteoclast differentiation and suppresses bone resorption. However, sclerostin-knockout (Sost-KO) mice exhibit increased bone formation without a corresponding suppression of bone resorption. Therefore, the role of Opg in Sost deficiency remains unclear. MATERIALS AND METHODS: To determine whether the osteogenic effects of Sost deficiency depend on the presence of Opg, we compared femoral bone mass among Sost/Opg double-knockout (DKO), Sost-KO, Opg-KO, and C57BL/6 (WT) mice. RESULTS: High-resolution imaging and histological analysis revealed that cortical bone mass was significantly higher in DKO mice compared with WT and Opg-KO mice. In contrast, trabecular bone mass was reduced in DKO mice compared with WT mice, and the number of TRAP-positive osteoclasts and serum CTX levels, a bone resorption marker, were significantly higher in DKO mice compared with Sost-KO mice. To further examine the role of bone resorption in DKO mice, an anti-RANKL antibody was administered to these mice. This treatment markedly increased both trabecular and cortical bone mass. Bone resorption was almost completely suppressed in antibody-treated DKO mice compared with vehicle-treated mice, while bone formation markers, including the mineral apposition rate, were maintained at approximately one-third the levels of vehicle-treated mice. CONCLUSION: These findings indicate that the enhanced bone formation in DKO mice primarily increases cortical bone mass without inhibiting bone resorption. The osteogenic effects of Sost deficiency are independent of Opg.
J Bone Miner Metab
· 2025 Nov · PMID 41148286
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BACKGROUND: Dialysis patients are at increased risk of fractures, particularly in the proximal femur where cortical bone predominates. Effective treatments targeting cortical bone are therefore essential. Romosozumab is...BACKGROUND: Dialysis patients are at increased risk of fractures, particularly in the proximal femur where cortical bone predominates. Effective treatments targeting cortical bone are therefore essential. Romosozumab is a monoclonal antibody that simultaneously promotes bone formation and inhibits bone resorption. It is administered monthly in a clinical setting and continued for one year, offering a treatment regimen acceptable to patients. In dialysis patients, romosozumab has been shown to significantly increase bone mineral density not only in the lumbar spine but also in the proximal femur and femoral neck. However, since dialysis patients are at higher risk of cardiovascular events, the risks and benefits of romosozumab require careful consideration. KEY MESSAGES: Romosozumab effectively improves both trabecular and cortical bone mass in dialysis patients. Cardiovascular safety concerns necessitate cautious patient selection. Romosozumab offers medical and economic advantages over teriparatide.
J Bone Miner Metab
· 2026 Jan · PMID 41148285
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INTRODUCTION: Hip fractures in older adults lead to high mortality and reduced quality of life, requiring effective outcome prediction tools. The Geriatric Nutritional Risk Index (GNRI) evaluates nutritional status, whil...INTRODUCTION: Hip fractures in older adults lead to high mortality and reduced quality of life, requiring effective outcome prediction tools. The Geriatric Nutritional Risk Index (GNRI) evaluates nutritional status, while inflammatory markers such as the Systemic Immune-Inflammation Index (SII), pan-immune-inflammation value (PIV), and c-reactive protein-to-lymphocyte ratio (CLR) serve as potential predictors. This study assesses the combined effectiveness of GNRI and these markers in forecasting post-hip fracture surgery outcomes. MATERIALS AND METHODS: This retrospective cohort study included geriatric hip fracture patients treated from 2020 to 2022. Biomarkers including GNRI, SII, PIV, and CLR were calculated from pre-operative laboratory data. GNRI was based on serum albumin and body weight, while inflammatory indices were derived from neutrophil, lymphocyte, platelet, monocyte counts, and CRP levels measured via hospital analyzers. Time-dependent ROC curves were used to identify optimal cutoff values, and Cox regression was applied to examine associations with overall survival. RESULTS: A total of 159 patients aged ≥ 60 years were included. In single-index analyses, a high GNRI (HR 0.95, 95% CI 0.91-0.98) was significantly associated with improved overall survival (OS), while a high SII (HR 1.002, 95% CI 1.0006-1.0034) was associated with reduced OS. Combination analyses revealed that low GNRI and elevated CLR significantly associated with risk of postoperative mortality (HR 4.92, 95% CI 2.25-10.92). Combining GNRI with CLR predicted mortality within 3 months post-hip surgery with 90% accuracy. CONCLUSION: Combining GNRI and CLR effectively predicts mortality risk in elderly hip fracture patients, particularly during the high-risk first 3 months after surgery.
Nishikawa A, Kawao N, Mizukami Y
… +2 more, Goto K, Kaji H
J Bone Miner Metab
· 2025 Nov · PMID 41045359
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INTRODUCTION: Postmenopausal osteoporosis is a critical task in the clinical management of older individuals. Numerous studies have proposed various pathophysiological mechanisms for postmenopausal osteoporosis. Tmem119...INTRODUCTION: Postmenopausal osteoporosis is a critical task in the clinical management of older individuals. Numerous studies have proposed various pathophysiological mechanisms for postmenopausal osteoporosis. Tmem119 is a crucial factor for osteoblastic bone formation, and we previously clarified its contribution to the bone anabolic effects of various osteotropic factors. However, the roles of Tmem119 in postmenopausal osteoporosis and the effects of estrogen on bone remain unknown. Therefore, we herein investigated the roles of Tmem119 in bilateral ovariectomized mice with or without Tmem119 deficiency and/or the administration of estrogen. MATERIALS AND METHODS: Wild-type and Tmem119-deficient mice underwent bilateral ovariectomy (OVX) and subcutaneous injections of 17β-estradiol for 6 weeks. We measured bone parameters in the femurs of mice using micro-computed tomography. RESULTS: OVX reduced the uterine weight and trabecular bone parameters, which were increased by estrogen administration. Tmem119 deficiency significantly blunted estrogen-induced increases in uterine weight, trabecular bone volume, and trabecular thickness in OVX mice. Tmem119 deficiency also significantly blunted estrogen-induced increases in alkaline phosphatase activity in mouse osteoblasts. CONCLUSION: Our data indicated that Tmem119 is partly involved in the effects of estrogen on trabecular osteopenia induced by estrogen deficiency presumably by affecting osteoblasts in female mice.
Jang SA, Heo SJ, Kwon SJ
… +3 more, Kim CS, Park SW, Kim KM
J Bone Miner Metab
· 2025 Nov · PMID 41044438
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INTRODUCTION: Despite the increasing number of anti-osteoporotic medications for improving bone mineral density (BMD) and reducing fracture risk, some patients show unsatisfactory responses. MATERIALS AND METHODS: We ret...INTRODUCTION: Despite the increasing number of anti-osteoporotic medications for improving bone mineral density (BMD) and reducing fracture risk, some patients show unsatisfactory responses. MATERIALS AND METHODS: We retrospectively analyzed 2134 patients who received anti-osteoporotic medications between March 2020 and October 2024. BMD percentage changes at the lumbar spine, femoral neck, and total hip were assessed after 1 year. Patients were categorized as "non-BMD gainers" (<3% increase at all sites) or "BMD gainers" (≥3% increase at any site). Multivariable logistic regression was used to evaluate associations with non-BMD gainer status, including age, body mass index, baseline T-score, and medication class. RESULTS: 578 patients (27.1%) were classified as non-BMD gainers. The observed rates of non-BMD gainer varied across medication classes in this real-world cohort, with selective estrogen receptor modulators (SERMs) showing the highest non-BMD gain rate (46.0%), followed by bisphosphonates (32.2%), teriparatide (35.1%), denosumab (19.5%), and romosozumab (5.6%). Non-BMD gainers had high baseline BMD and low bone turnover markers, and were more likely to have a history of osteoporosis treatment. In multivariable logistic regression analysis, older age (≥75 years), SERM use, and high baseline BMD T-scores were independently associated with increased risk of non-BMD gainer status. Conversely, low T-scores (≤-3.0) were associated with a significantly reduced likelihood of being a non-BMD gainer. CONCLUSION: Approximately 25% of patients did not achieve BMD gain after 1 year of treatment. Older age, higher baseline BMD T-scores, and SERM use were associated with an increased probability of non-BMD gainer status in this observational study.
Torii A, Yamada Y, Ono-Uruga Y
… +9 more, Sato Y, Kaneko Y, Nakamura S, Iwamoto T, Matsubara Y, Matsumoto M, Nakamura M, Sato K, Miyamoto T
J Bone Miner Metab
· 2026 Jan · PMID 41042331
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INTRODUCTION: Tendinopathy, a disease that causes inflammation and pain and limits patients' activities of daily living, is considered particularly important to treat during the acute inflammatory phase to prevent the tr...INTRODUCTION: Tendinopathy, a disease that causes inflammation and pain and limits patients' activities of daily living, is considered particularly important to treat during the acute inflammatory phase to prevent the transition to chronic degeneration. Recently, platelet-rich plasma (PRP) has been used to treat tendinopathy; however, it is not clear whether platelets themselves, which are the active component of PRP, could be effective in treating tendinopathy. MATERIALS AND METHODS: We made rat Achilles tendinopathy models by incision of the calcaneal attachment and administrated platelet-like cells derived from adipose-derived mesenchymal stem cells (ASCL-PLCs) to the injury site and investigated the anti-inflammatory effect. RESULTS: ASCL-PLCs significantly inhibits the inflammatory cytokine expression and inflammatory cell infiltration in acute tendonitis in a rat Achilles tendon injury model in vivo. Interestingly, we observed no xeno-reaction when human-derived ASCL-PLCs were administered to wild-type rats in vivo. Moreover, IL-6 expression and phosphorylation seen in NIH3T3 fibroblasts treated with IL-6 plus soluble IL-6 receptor were both significantly suppressed by ASCL-PLCs in vitro. CONCLUSION: ASCL-PLC has advantages over existing PRP therapies, including the ability to be cryopreserved after quality checks, and homogeneous populations of ASCL-PLCs can be prepared in large quantity. We conclude that in the future ASCL-PLCs may serve as an allogeneic transplant effective to treat tendinopathy.
J Bone Miner Metab
· 2025 Oct · PMID 41032119
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Qi et al. presented a prognostic model for hip refracture survival, identifying age, comorbidities, lymphocyte count, and surgery as key predictors. Although clinically relevant, the model lacks external validation and u...Qi et al. presented a prognostic model for hip refracture survival, identifying age, comorbidities, lymphocyte count, and surgery as key predictors. Although clinically relevant, the model lacks external validation and uses suboptimal predictor handling. The selection bias and underpowered subgroup analysis limit the generalizability of the results. Further robust multicenter studies are needed to refine risk stratification in this high-risk population.
Kokubu Y, Obi A, Kimura Y
… +14 more, Hattori A, Nemoto H, Matsuda Y, Oki Y, Amamiya R, Ogine K, Misawa M, Shimaoka T, Hirose K, Ando Y, Kurashige T, Marusugi K, Kaneyama S, Kawaguchi H
J Bone Miner Metab
· 2025 Nov · PMID 41032116
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INTRODUCTION: Timely surgical intervention for hip fractures is essential for improving outcomes in older adults. Japan's Ministry of Health, Labour and Welfare (MHLW) recently introduced a reimbursement policy to incent...INTRODUCTION: Timely surgical intervention for hip fractures is essential for improving outcomes in older adults. Japan's Ministry of Health, Labour and Welfare (MHLW) recently introduced a reimbursement policy to incentivize hip fracture surgery within 48 h. However, the impact and sustainability of this policy remain unclear. MATERIALS AND METHODS: This retrospective cohort study included 498 patients aged ≥ 75 years with hip fractures at a single Japanese hospital from 2022 (pre-policy) to 2024 (post-policy year 2). We performed univariate and multivariate logistic regression analyses of the rate of early surgery (≤ 48 h) to identify predictors of surgical delay. RESULTS: The early surgery rate rose from 42.4% in 2022 to 52.7% in 2023 but declined to 45.1% in 2024. The reimbursement policy was associated with reduced surgical delay in its first year (2023; OR = 0.58, p = 0.024), but this effect was not sustained. Key structural and clinical predictors of delay included nursing home residence, refusal at other hospitals, weekend admission, and multi-specialty consultation. The frequency of off-hours surgery decreased in 2024, possibly due to the 'Workstyle Reform for Physicians' policy. Interaction analysis showed a suggestive inverse effect of off-hours surgery on delay. CONCLUSION: Japan's reimbursement policy was initially effective, but its impact was transient and ultimately reversed by the competing national workstyle reform policy. Our findings underscore that to achieve sustained improvements in timely surgical care, future strategies must not only ensure coordinated policy design but also address persistent structural barriers, including weekend service gaps and fragmented regional coordination.
Bahadoran Z, Hadaegh F, Azizi F
… +1 more, Ghasemi A
J Bone Miner Metab
· 2025 Nov · PMID 41032115
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INTRODUCTION: The association between serum zinc (SZn) concentration and fracture risk in postmenopausal women was investigated. MATERIALS AND METHODS: Women (n = 851) with a history of natural, premature, or surgical me...INTRODUCTION: The association between serum zinc (SZn) concentration and fracture risk in postmenopausal women was investigated. MATERIALS AND METHODS: Women (n = 851) with a history of natural, premature, or surgical menopause who had completed data, including SZn concentrations at baseline (2009-2011), were included and followed through March 2018 for the incidence of any fracture requiring inpatient care. Potential non-linear and dose-response associations between SZn and fracture risk were assessed using a restricted cubic spline model (RCS) in Cox regression with the likelihood ratio test (LRT). Multivariable Cox proportional hazard models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of fractures across the categories of SZn [< 86, 86-135 (as reference), and ≥ 135 μg/dL]. RESULTS: During a median follow-up period of 8.8 years (interquartile range: 8.1-9.2 years), 4.3% of postmenopausal women (with a mean age of 61.4 ± 8.6 years) experienced a new incident fracture. The mean of baseline SZn concentration was 113 ± 39.3 μg/dL. The LRT indicated no significant non-linear association (P = 0.176) and no evidence of a dose-response relationship (P = 0.448) between SZn and fracture risk. Using the categorical approach, the multivariable-adjusted Cox model showed that postmenopausal women with SZn concentrations below 86 μg/dL had a significantly increased risk of fracture compared to those within the reference range (86-135 μg/dL), with an HR of 2.29 (95% CI = 1.02-5.16, P = 0.044). SZn concentrations exceeding the reference range (≥ 135 μg/dL) were not associated with risk of fractures (HR = 1.47, 95% CI = 0.61-3.58). CONCLUSIONS: Suboptimal SZn levels, indicative of inadequate zinc status, may contribute to an increased risk of bone fractures in postmenopausal women.
Takada J, Iba K, Takebayashi T
… +3 more, Hanaka M, Akatsuka T, Teramoto A
J Bone Miner Metab
· 2025 Nov · PMID 40987997
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We appreciate the valuable suggestions and comments that Drs. Caroline Francis, Koyel Roy, and Gujar Anantkumar Jotiram provided regarding this study, "Probability of Achieving Treatment Goals with Twice-Weekly Teriparat...We appreciate the valuable suggestions and comments that Drs. Caroline Francis, Koyel Roy, and Gujar Anantkumar Jotiram provided regarding this study, "Probability of Achieving Treatment Goals with Twice-Weekly Teriparatide Followed by Bisphosphonate in Japanese Postmenopausal Osteoporosis".
Korkmaz N, Yardımcı G, Özgen ANK
… +2 more, Köroğlu Ö, Yılmaz B
J Bone Miner Metab
· 2025 Nov · PMID 40960694
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INTRODUCTION: Bone loss is most common around the knee region in spinal cord injury (SCI) population. However, bone mineral density (BMD) measurement and T score in the knee region, which indicate osteoporosis, are not c...INTRODUCTION: Bone loss is most common around the knee region in spinal cord injury (SCI) population. However, bone mineral density (BMD) measurement and T score in the knee region, which indicate osteoporosis, are not clear. This study aimed to examine BMD, T and Z scores at hip and knee including femoral neck (FN), total hip (TH), proximal tibia (PT), and distal femur (DF) in individuals with SCI, to investigate the relationship between BMD of the knee and hip, and to define DF and PT T scores thresholds that predict osteoporosis at the hip. MATERIALS AND METHODS: This cross-sectional study used dual-energy x-ray absorptiometry to assess BMD in 94 SCI individuals. The medial and lateral parts of the PT and DF were defined as PT-1 and PT-2, DF-1 and DF-2, respectively. T and Z scores of PT and DF were calculated with a tool recommended by ISCD. RESULTS: All knee BMD values showed positive correlations with the hip BMD. Applying a PT-1 T-score threshold of - 1.55, the overall specificity was 83.9% and the sensitivity was 84.2% in detecting osteoporosis at FN or TH. CONCLUSION: Low hip BMD values are associated with low knee BMD values in SCI individuals. A T score of -1.55 in PT-1 probably indicates osteoporosis of the hip. However, there is a prompt need for standardization of the T-cut off value in the knee region, where the risk of fracture risk is high. Body mass index, time since injury, wheelchair use, and injury severity were associated with bone loss in the PT-1.
Koto R, Yoshida S, Nakajima A
… +2 more, Miwa T, Miyakoshi N
J Bone Miner Metab
· 2025 Nov · PMID 40960693
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INTRODUCTION: This study aimed to investigate perioperative treatment and postoperative outcomes in osteoporotic patients with vertebral fractures (VFs), categorized by the type of spine surgery. MATERIALS AND METHODS: P...INTRODUCTION: This study aimed to investigate perioperative treatment and postoperative outcomes in osteoporotic patients with vertebral fractures (VFs), categorized by the type of spine surgery. MATERIALS AND METHODS: Patients aged ≥ 40, diagnosed with VFs and osteoporosis, with initial spine surgery between April 2015 and February 2021, were analyzed using a Japanese claims database. Time-to-event analysis was conducted for postoperative outcome. Outcome-related factors were explored with a multivariable Cox proportional hazards model. RESULTS: The study population (n = 4870) consisted of 2675 patients in the percutaneous vertebroplasty (PVP) group and 2195 in the spine fusion surgery (SFS) group. Most patients had lumbar VFs, and posterior spinal fusion was common in the SFS group. Approximately 20% of patients did not receive prescriptions for osteoporosis medications during the perioperative period. Most reoperations and subsequent fractures occurred within 90 days after PVP or SFS. In the PVP group, degenerative spine disease (adjusted hazard ratio 1.34 [95% CI, 1.03-1.76]), psychotropic drugs (1.34 [1.03-1.76]), and glucocorticoid prescriptions with a mean dose of ≥ 5 to < 7.5 mg/day (2.35 [1.04-5.34]) (vs. < 1 mg/day) were associated with reoperation. In post hoc subgroup analysis by year of spine surgery, anabolic agents were associated with a lower risk of reoperation (0.48 [0.30-0.75]) in 2019 and later. In the SFS group, hyperparathyroidism and Parkinson's disease were associated with reoperation (2.14 [1.03-4.44] and 2.10 [1.31-3.37], respectively). CONCLUSION: Perioperative osteoporosis medication may be suboptimal. Factors associated with postoperative outcomes must be considered, with the strategic goal of improving patient outcomes.
J Bone Miner Metab
· 2025 Nov · PMID 40957939
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This commentary evaluates the study by Takada et al. on sequential teriparatide bisphosphonate therapy in postmenopausal osteoporosis. While lumbar spine bone mineral density (BMD) targets are frequently met, the clinica...This commentary evaluates the study by Takada et al. on sequential teriparatide bisphosphonate therapy in postmenopausal osteoporosis. While lumbar spine bone mineral density (BMD) targets are frequently met, the clinical validity of total hip BMD thresholds, especially in Asian populations, remains uncertain. We emphasize the need for fracture-based endpoints and caution against over-reliance on surrogate BMD targets in pre-treated patients.