Lau TC, Chang DG, Chen CH
… +8 more, Huang S, Lau EMC, Law SW, Lee YK, Tolman C, Canals L, Yeo SH, Ebeling PR
J Bone Miner Metab
· 2026 Jun · PMID 42307760
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INTRODUCTION: To compare 24-month persistence and compliance of denosumab with alendronate in postmenopausal women with osteoporosis across 5 Asia-Pacific territories. MATERIALS AND METHODS: This prospective cohort study...INTRODUCTION: To compare 24-month persistence and compliance of denosumab with alendronate in postmenopausal women with osteoporosis across 5 Asia-Pacific territories. MATERIALS AND METHODS: This prospective cohort study included women aged ≥ 50 years from Australia, Taiwan, South Korea, Hong Kong, and Singapore. Participants received either a bi-annual denosumab injection or weekly oral alendronate as osteoporosis treatment, based on physician judgment. Multivariable logistic regression assessed whether therapy (denosumab or alendronate) was significantly associated with treatment persistence and compliance over 24 months of follow-up. The models were adjusted for age, fracture history, baseline bone mineral density (BMD), prior osteoporosis therapy, and prior oral glucocorticoid treatment. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated. RESULTS: Among 687 enrolled patients, 549 completed their 24-month visit (295 in denosumab and 254 in alendronate group). Patients in the denosumab group were older and a higher proportion previously received osteoporosis treatment. Overall treatment persistence and compliance were 74.9% and 56.6%, respectively. Patients prescribed with denosumab exhibited higher persistence (86.1% vs. 61.8%; P < 0.001) and compliance (62.4% vs. 50.0%; P = 0.004), compared with those on alendronate. Regression results also demonstrated that patients receiving denosumab were more likely to be persistent (aOR = 3.91; 95% CI 2.52-6.08), and compliant (aOR = 1.61; 95% CI 1.12-2.31). BMD T-scores improved in both the treatment groups after 24 months with no significant association between treatment type and change in T-score. No significant difference was also observed in the occurrence of adverse events between the two treatment cohorts. Patients on alendronate reported gastrointestinal issues more frequently, whereas those on denosumab had a higher incidence of bone and joint injuries. CONCLUSION: Postmenopausal women with osteoporosis were more likely to be persistent and compliant with a bi-annual denosumab injection, compared with weekly oral alendronate.
Jiang Y, Zeng Y, Xin L
… +14 more, Chen W, Xu Y, Tian S, Wang Q, Li J, Chen S, Lin X, Ying Q, Chiba S, Yamagiwa C, Yamaguchi T, Ke Z, Xia W, Takeuchi Y
J Bone Miner Metab
· 2026 Jun · PMID 42303801
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INTRODUCTION: Eldecalcitol is an active vitamin D derivative approved for the treatment of osteoporosis in Japan and postmenopausal osteoporosis in China. However, the impact of concomitant calcium supplementation on its...INTRODUCTION: Eldecalcitol is an active vitamin D derivative approved for the treatment of osteoporosis in Japan and postmenopausal osteoporosis in China. However, the impact of concomitant calcium supplementation on its safety profile is unclear. MATERIALS AND METHODS: This was a prospective, observational, non-interventional post-marketing drug intensive monitoring study in Chinese postmenopausal women with osteoporosis (NCT05433207). Data were collected using an electronic case report form at baseline, before initial eldecalcitol dosing, and during routine clinical visits over a 1-year follow-up period. RESULTS: One thousand patients were enrolled from 29 Chinese clinical sites; 958 received eldecalcitol (853 without/105 with calcium supplementation). The mean age (standard deviation [SD]) of patients was 65.6 (9.0) years and mean (SD) time since osteoporosis diagnosis was 2.7 (3.8) years. Adverse drug reactions (ADRs) affected 39.2% and 42.9% of patients in the without and with calcium supplementation groups, respectively. 22 (2.3%) patients developed hypercalcemia including 17 (1.99%) and 5 (4.76%) in the without and with calcium supplementation groups, respectively. Multivariable logistic regression analyses indicated that those receiving calcium were more likely to experience hypercalcemia (adjusted odds ratio [OR] 3.07, 95% confidence interval [CI] 1.16, 8.10, P = 0.02) than those not receiving calcium. ADRs of urolithiasis were experienced by three patients (0.35%) in the without calcium supplementation group. CONCLUSION: This study confirmed the real-world safety profile of eldecalcitol in a large population of Chinese women with postmenopausal osteoporosis. Hypercalcemia incidence was higher in patients with compared to without calcium supplementation, indicating that concomitant eldecalcitol and calcium should be carefully considered.
J Bone Miner Metab
· 2026 Jun · PMID 42295423
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PURPOSE: This review examines the role of marrow adipose tissue fatty acid composition in skeletal homeostasis, focusing on osteoporosis. To avoid conceptual confusion, we define evidence tiers: human studies assessing e...PURPOSE: This review examines the role of marrow adipose tissue fatty acid composition in skeletal homeostasis, focusing on osteoporosis. To avoid conceptual confusion, we define evidence tiers: human studies assessing endogenous marrow lipid profiles; mechanistic studies applying exogenous fatty acids in vitro and in vivo; indirect MRI-based surrogates of marrow fat quantity; and direct ex vivo measurements of fatty acid composition via GC-MS, LC-MS, and lipidomics. We also clarify the distinction between marrow fat quantity and fatty acid quality. RESULT: Human data reveal disease-, age-, and site-related alterations in marrow lipid saturation and unsaturation; however, findings vary by skeletal site, marrow compartment, fracture status, analytical platform, and study population. Experimental evidence demonstrates that saturated fatty acids (e.g., palmitic acid) induce lipotoxicity and osteoblast dysfunction, whereas unsaturated fatty acids (e.g., oleic acid and n-3 polyunsaturated fatty acids) exert protective effects via modulation of mesenchymal stem cell differentiation, osteoclastogenesis, ferroptosis, autophagy, and mitochondrial metabolism. Collectively, current evidence supports an association between marrow fatty acid biology and osteoporotic bone loss. CONCLUSION: Causal, diagnostic, and therapeutic implications remain preliminary. This review's main contribution is a fatty-acid-centered framework that integrates evidence tiers, molecular categories, and skeletal-site heterogeneity, guiding future research.
Tuna MM, Engin İ, Uzun Ö
… +16 more, Fırat SN, Kimyon Ö, Güneş E, Karatoprak K, Özbay ÜN, Üç ZA, Yeşiltepe A, Güneş Ş, Zuhur SS, Yağcı H, Bozkur E, Gül ÖÖ, Oğuz A, Duran C, Cansu BG, Gül N
J Bone Miner Metab
· 2026 May · PMID 42105121
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INTRODUCTION: Normocalcemic primary hyperparathyroidism (NPHPT) is thought to be an early form of hypercalcemic primary hyperparathyroidism (PHPT). However, some studies have shown that the adverse effects on bone and ki...INTRODUCTION: Normocalcemic primary hyperparathyroidism (NPHPT) is thought to be an early form of hypercalcemic primary hyperparathyroidism (PHPT). However, some studies have shown that the adverse effects on bone and kidney health are similar in both conditions. MATERIALS AND METHODS: This is a nationwide, multicentre, retrospective study. Data from centres, including 404 patients with NPHPT and 723 patients with mild PHPT from different regions of Turkey, were included in this study. All laboratory parameters, dual-energy X-ray absorptiometry, and renal ultrasounds were performed locally at each centre. The prevalence of adverse bone and kidney outcomes and metabolic and cardiovascular comorbidities were the main outcome measures. RESULTS: Patients with NPHPT had lower calcium and PTH levels. Skeletal outcomes revealed 29% osteoporosis and 42% osteopenia, while the prevalence of nephrolithiasis was 12.4%, which is similar to that observed in patients with mild PHPT. Hypertension was more prevalent in patients with mild PHPT than in those with NPHPT (44.4% vs. 34.9%, p = 0.002), as was diabetes mellitus (27.9% vs. 13.2%, p < 0.001). The prevalence of cardiovascular disease was similar (11.5% vs. 9.5%, p = 0.306). CONCLUSION: Patients with NPHPT experience significant skeletal complications and nephrolithiasis but have lower rates of hypertension and diabetes.
Horii C, Tanaka S, Iidaka T
… +9 more, Fujiwara S, Iki M, Oshima Y, Muraki S, Oka H, Kawaguchi H, Nakamura K, Akune T, Yoshimura N
J Bone Miner Metab
· 2026 May · PMID 42071064
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INTRODUCTION: Osteoporosis is a major public health concern, particularly in the aging population, where fragility fractures significantly impact quality of life and mortality. Despite the importance of early detection,...INTRODUCTION: Osteoporosis is a major public health concern, particularly in the aging population, where fragility fractures significantly impact quality of life and mortality. Despite the importance of early detection, screening rates for osteoporosis in Japan remain low. The Osteoporosis Self-Assessment Tool for Asians (OSTA) and Fracture Risk Assessment Tool (FRAX) are noninvasive screening tools. This study aimed to develop an efficient method for screening osteopenia using these tools. MATERIALS AND METHODS: We analyzed data from 1060 Japanese women aged 40-74 years from the Research on Osteoarthritis/Osteoporosis Against Disability (ROAD) study. The OSTA and FRAX scores, as well as individual FRAX risk factors, were assessed for their ability to detect osteopenia. As FRAX score calculations are not publicly available, we evaluated the discriminative ability of the seven risk factors individually. Prior fragility fractures were deemed the most critical, and all 64 possible combinations of the remaining six risk factors were analyzed. RESULTS: OSTA had the highest discriminative ability (AUC = 0.81), followed by FRAX-Hip (AUC = 0.79) and FRAX-Major (AUC = 0.77). The sensitivity and specificity of OSTA ≤ -1 were 83.7% and 62.6%, respectively. The most effective criterion was OSTA ≤ -1 or at least one FRAX risk factor, achieving a sensitivity of 90.4%, specificity of 47.2%, and positive predictive value of 63.3%. CONCLUSION: A simple, noninvasive osteopenia screening method combining OSTA ≤ -1 and FRAX risk factors identified at-risk individuals effectively. This approach could enhance osteoporosis screening in Japan and facilitate early intervention and fracture prevention.
J Bone Miner Metab
· 2026 May · PMID 42069997
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INTRODUCTION: Proximal femoral fractures are highly prevalent in Japan, with over 200,000 cases annually and a rising trend. Fracture liaison service (FLS) interventions improve osteoporosis treatment initiation and redu...INTRODUCTION: Proximal femoral fractures are highly prevalent in Japan, with over 200,000 cases annually and a rising trend. Fracture liaison service (FLS) interventions improve osteoporosis treatment initiation and reduce refracture rates. The content of FLS interventions varies by institution, and the effectiveness of our intervention remains unclear. The aim of this study was to evaluate the effectiveness of our FLS intervention in preventing fragility fractures within 1 year after proximal femoral fracture surgery. MATERIALS AND METHODS: A retrospective case-control study was performed on patients aged ≥ 50 undergoing surgery for proximal femoral fracture between February 2021 and January 2024. Patients were divided into non-FLS (pre-August 2022) and FLS groups. Data including demographics, comorbidities, fracture type, medication initiation, and refracture occurrence within 1 year were extracted. Statistical analyses involved Mann-Whitney U, χ2 tests, and Cox proportional hazards modeling. RESULTS: Among 521 eligible patients, osteoporosis medication initiation within 3 months improved from 14% in the non-FLS group to 100% in the FLS group (p < 0.05). Time to medication initiation decreased from 20 to 12 days (p < 0.05). The refracture rate was significantly lower in the FLS group (1.8% vs. 5.7%, p < 0.05). Multivariate analysis showed FLS intervention significantly reduced refracture risk (HR 0.32, 95% CI 0.12-0.89, p = 0.03) and robust in sensitivity analyses for cognition, walking ability, and discharge destination. CONCLUSIONS: FLS intervention effectively reduced fragility fractures within 1 year postoperatively by enhancing early osteoporosis treatment initiation. Continued FLS programs and long-term follow-up are recommended to sustain benefits.
J Bone Miner Metab
· 2026 May · PMID 42068345
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INTRODUCTION: Medication-related osteonecrosis of the jaw (MRONJ) is a serious complication of antiresorptive therapy. Although surgical intervention is increasingly recommended, the optimal extent of mandibular resectio...INTRODUCTION: Medication-related osteonecrosis of the jaw (MRONJ) is a serious complication of antiresorptive therapy. Although surgical intervention is increasingly recommended, the optimal extent of mandibular resection-particularly indications for marginal versus segmental mandibulectomy-remains controversial. Conventional staging systems may not capture qualitative CT patterns that could be associated with surgical outcomes. MATERIALS AND METHODS: This retrospective observational study included 76 patients with mandibular MRONJ who underwent surgical treatment between January 2018 and March 2024. Preoperative computed tomography (CT) images were evaluated for osteolysis, periosteal reaction, and osteosclerosis, and lesions were classified into three imaging-based types (A-C). Treatment outcomes and prognostic factors were analyzed separately for marginal and segmental mandibulectomy. RESULTS: Marginal mandibulectomy was performed in 46 patients and segmental mandibulectomy in 30 patients. Healing was achieved in 43.5% after marginal mandibulectomy and in 80.0% after segmental mandibulectomy. In the marginal mandibulectomy group, higher imaging-based MRONJ types (Types B and C), denosumab use, malignancy, and absence of sequestrum separation were associated with lower healing rates. In contrast, in the segmental mandibulectomy group, younger age and periosteal reaction were associated with improved healing. CONCLUSIONS: This study suggests that radiological patterns of mandibular MRONJ are associated with surgical outcomes and may complement conventional staging. Although segmental mandibulectomy showed numerically higher healing, interpretation is limited by confounding by indication. CT-based imaging assessment may help anticipate the risk of delayed or incomplete healing after limited resection and support individualized selection of surgical extent. Future prospective studies incorporating standardized imaging evaluation and radiologic-pathologic correlation are warranted.
J Bone Miner Metab
· 2026 Mar · PMID 42018188
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INTRODUCTION: The periodontium is a dynamic composite tissue that anchors teeth to the alveolar bone and adapts continuously to mechanical loading and inflammatory challenges throughout life. Its development, homeostasis...INTRODUCTION: The periodontium is a dynamic composite tissue that anchors teeth to the alveolar bone and adapts continuously to mechanical loading and inflammatory challenges throughout life. Its development, homeostasis, and regeneration depend on diverse mesenchymal stem and progenitor cell populations derived from the dental follicle, apical papilla, and periodontal ligament. RESULTS: Recent advances in in vivo lineage-tracing studies have demonstrated that these progenitors are heterogeneous, and lineage restricted, rather than constituting a uniform stem cell pool. Distinct populations, including PTHrP⁺ dental follicle-derived progenitors and CXCL12⁺ apical papilla cells, contribute differentially to cementum, periodontal ligament, and alveolar bone formation during tooth root development and postnatal remodeling. The fate decisions of these progenitors are tightly regulated by coordinated signaling pathways, including Hedgehog-Foxf, Wnt/β-catenin, and BMP/TGF-β signaling, as well as by mechanotransducive cues. Spatially and temporally precise regulation of these pathways is essential for proper cementogenesis and alveolar bone formation, whereas their dysregulation leads to impaired periodontal regeneration and bone loss. This review summarizes current knowledge of periodontal stem cell biology with a particular emphasis on developmental origins and in vivo regulatory mechanisms and discusses emerging concepts that support endogenous stem cell-based approaches for periodontal regeneration and future therapeutic strategies.
INTRODUCTION: The health status of children born to mothers with pregnancy and lactation-associated osteoporosis (PLO) and impaired bone homeostasis remains unknown. This study aimed to investigate the effects of materna...INTRODUCTION: The health status of children born to mothers with pregnancy and lactation-associated osteoporosis (PLO) and impaired bone homeostasis remains unknown. This study aimed to investigate the effects of maternal PLO on child health, the PLO-predisposing factors related to such effects, and the incidence of the condition. MATERIALS AND METHODS: From a claims dataset comprising 172,730 mothers linked with their 210,124 children, mothers who developed fragility fractures between 5 months before and 12 months after delivery, along with their children, were defined as the PLO group. Healthy controls were randomly selected by matching maternal age and child sex. Body mass index (BMI), drug use, and maternal and pediatric diseases were compared between the two groups. RESULTS: Fifty-nine mothers and 65 children were included in the PLO group, and 11,556 mothers and 11,664 children served as the control group. The most common PLO fracture was a vertebral fracture, and delayed diagnosis was common. Maternal PLO had few adverse effects on child health. There were trends toward a higher frequency of birth asphyxia in singletons (P = 0.072) and low birth weight in twins (P = 0.070) in the case children, but with no significant differences. The incidence of PLO was estimated at 374 per million deliveries. Multiple delivery, maternal age ≥ 40 years, low BMI, heparin use, and ovulation disorder were identified as predisposing factors for PLO. CONCLUSION: There is little evidence that maternal PLO adversely affects child health. The predisposing factors for PLO suggest that caution is warranted regarding current advancements in reproductive technology.
INTRODUCTION: Diffuse idiopathic skeletal hyperostosis (DISH) primarily affects the axial skeleton, but its association with hip osteoarthritis (OA) remains unclear. We investigated the prevalence and 5 year progression...INTRODUCTION: Diffuse idiopathic skeletal hyperostosis (DISH) primarily affects the axial skeleton, but its association with hip osteoarthritis (OA) remains unclear. We investigated the prevalence and 5 year progression of hip OA in individuals with DISH and explored risk factors for progression. MATERIALS AND METHODS: This retrospective cohort study reviewed 694 asymptomatic individuals who underwent whole-body computed tomography (CT) for cancer screening (2016-2023) and had follow-up CT at ≥ 5 years. DISH was diagnosed using CT-based criteria. We identified 143 individuals with DISH and selected 143 age- and sex-matched controls without DISH (1:1). Hip OA was assessed using a CT-based composite score (0-14, bilateral). Radiographic hip OA was defined as a bilateral score ≥ 10, and progression as an increase of ≥ 2 points over 5 years. Multivariable regression analyses were performed to identify independent predictors of progression. RESULTS: The DISH group had higher total hip OA scores and a higher prevalence of radiographic hip OA than controls at baseline and follow-up. However, OA progression rates did not differ significantly between groups. Among individuals with DISH, the number of ankylosed vertebral segments was independently associated with hip OA progression. CONCLUSION: Individuals with DISH show a higher prevalence of radiographic hip OA. Extensive spinal ankylosis may increase the risk of hip OA progression, supporting the need for longitudinal monitoring of hip joint health in DISH.
Uesaka M, Hamada M, Tachiki T
… +18 more, Sato Y, Tsuda K, Kudo A, Kamiya K, Imai N, Nitta A, Tanaka M, Ohara K, Takashima N, Kitagawa J, Kouda K, Morita A, Uenishi K, Kajita E, Tamakoshi K, Kagamimori S, Tamaki J, Iki M
INTRODUCTION: Vertebral fractures are the most common osteoporotic fractures, yet approximately two-thirds of radiographically detectable fractures remain clinically unrecognized. The longitudinal impact of such subclini...INTRODUCTION: Vertebral fractures are the most common osteoporotic fractures, yet approximately two-thirds of radiographically detectable fractures remain clinically unrecognized. The longitudinal impact of such subclinical vertebral fractures on health-related quality of life (HRQOL) is not fully clarified. This study examined whether incident subclinical vertebral fractures were associated with subsequent changes in HRQOL. MATERIALS AND METHODS: This study was nested within the Japanese Population-based Osteoporosis (JPOS) Cohort. Community-dwelling women aged ≥ 50 years without clinical fractures were included. Incident subclinical vertebral fractures, assessed by single-energy X-ray absorptiometry-based vertebral fracture assessment with morphometry, were the primary exposure. HRQOL was evaluated using Japanese SF-36® v2. General linear models estimated associations between incident fractures and follow-up SF-36® subscale scores, adjusting for baseline HRQOL and prespecified covariates. Sensitivity analyses excluding participants with pre-baseline subclinical vertebral fractures or with anti-osteoporosis medication were performed. RESULTS: Of 344 participants, 53 (15.4%) developed incident subclinical vertebral fractures. Baseline SF-36® standardized subscale scores did not differ between groups. At follow-up, women with incident fractures had significantly lower physical functioning and social functioning scores. After multivariable adjustment, social functioning remained significantly lower in the fracture group (false discovery rate-adjusted p = 0.028). Social functioning declined progressively with increasing fracture number and was significantly lower in lumbar fractures. Sensitivity analyses yielded consistent results with primary analyses. CONCLUSIONS: Incident subclinical vertebral fractures among community-dwelling Japanese women were independently associated with clinically meaningful declines in social functioning, suggesting the importance of early identification to prevent deterioration in HRQOL.
Sun J, Ge M, Gao P
… +3 more, Zhang N, Huang T, Liu T
J Bone Miner Metab
· 2026 May · PMID 41954635
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Osteoporosis is a metabolic bone disease characterized by bone microstructural degeneration and increased fracture risk, primarily driven by an imbalance in bone homeostasis. Recent studies have revealed that lactate met...Osteoporosis is a metabolic bone disease characterized by bone microstructural degeneration and increased fracture risk, primarily driven by an imbalance in bone homeostasis. Recent studies have revealed that lactate metabolic remodeling and its derived lactylation modifications play a pivotal role in the dynamic balance between bone formation and resorption by regulating the metabolic-epigenetic network within the bone microenvironment. This review systematically examines the role of lactate metabolic pathways in the energy reprogramming of osteoblasts, analyzes the molecular mechanisms of lactylation in osteogenesis-osteoclastogenesis coupling, and discusses the challenges and future directions of novel therapeutic strategies targeting the lactate metabolism axis. By elucidating the critical role of lactate metabolism in the pathogenesis of osteoporosis, this review aims to enhance comprehensive understanding and facilitate the development of effective therapeutic interventions.