J Bone Miner Metab
· 2026 Mar · PMID 41454032
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Arthritis represents a group of chronic joint diseases characterised by persistent inflammation, pain, and progressive tissue damage. Despite advances in therapeutic management, many patients experience incomplete sympto...Arthritis represents a group of chronic joint diseases characterised by persistent inflammation, pain, and progressive tissue damage. Despite advances in therapeutic management, many patients experience incomplete symptom relief, highlighting the need to better understand the underlying mechanisms that sustain inflammation and pain. Emerging evidence indicates that neuroimmune interactions within the joint microenvironment play a central role in the pathogenesis of arthritis. The synovium, a thin membrane that lines the joint cavity, is the primary site of pathology in arthritis and serves as a dynamic interface integrating immune, vascular, and neural components. Under physiological conditions, tissue-resident macrophages, fibroblasts, and sensory nerve fibres maintain joint homeostasis. However, during arthritis, the synovium undergoes extensive remodelling, including hyperplasia, angiogenesis, and nerve fibre sprouting, which together amplify inflammatory and nociceptive signalling. Distinct macrophage subsets within the synovium exhibit specialised roles in mediating inflammation and communicating with neurons. Macrophage-derived cytokines such as IL-1β, IL-6, and TNF-α can directly sensitise nociceptors, whilst chemokines like CCL2 engage neuronal receptors to enhance excitability. Conversely, activated sensory neurons release neuropeptides such as calcitonin gene-related peptide (CGRP) and substance P (SP), which can modulate immune cell behaviour. Sympathetic signalling further contributes to immune modulation and correlates with disease severity. Together, these studies reveal that arthritis progression and chronic pain are shaped by reciprocal signalling between the nervous and immune systems. Understanding these complex pathways offers new perspectives for therapeutic intervention, suggesting that targeting neuroimmune crosstalk could provide dual benefits-reducing inflammation whilst alleviating chronic pain in arthritic disease.
Radulescu A, Hopkinson M, Chang Y
… +3 more, Azfer A, Ralston S, Chenu C
J Bone Miner Metab
· 2026 Jan · PMID 41447410
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INTRODUCTION: Osteoporosis can cause chronic pain, but the mechanisms are unclear. This study investigates pain behaviours in mouse models of osteoporosis and fracture together with nociceptive markers expression in bone...INTRODUCTION: Osteoporosis can cause chronic pain, but the mechanisms are unclear. This study investigates pain behaviours in mouse models of osteoporosis and fracture together with nociceptive markers expression in bone and dorsal root ganglia (DRGs). It also quantifies nerve markers in serum of patients with or without osteoporotic fractures and pain. MATERIAL AND METHODS: Ovariectomy (OVX) or Sham surgery (Sham-OVX) of C57/Bl6 mice was performed (n = 10/group) and evoked and spontaneous pain behaviours assessed. In another experiment, OVX or Sham-OVX mice underwent a femoral osteotomy or sham osteotomy (n = 8/group) and pain behaviours measured. Gene expression of pain markers in bone and DRGs was quantified by RT-PCR. Nerve markers were quantified in serum of osteoporotic patients with or without fractures and pain using specific ELISAs. RESULTS: OVX did not cause changes in pain behaviours nor alter nociceptive gene expression in bone and DRGs. Osteotomy and Sham osteotomy both affected pain behaviours in mice compared to non-operated controls but did not significantly change nociceptive gene expression in bone and DRGs. OVX before osteotomy worsens weight-bearing compared to Sham-OVX. Fracture and pain did not affect nerve markers expression levels in serum of osteoporotic patients. CONCLUSION: This study demonstrates that OVX and subsequent bone loss in mice are insufficient to induce pain behaviours but may intensify pain after fracture. Our clinical analysis does not show a correlation between circulating nerve markers and fracture pain reported by the patients but suggests possible sex differences in pain markers that need to be further investigated.
Homma F, Iwasaki R, Tateyama M
… +5 more, Soma T, Morita M, Kashio M, Nakagawa T, Miyamoto T
J Bone Miner Metab
· 2026 Jan · PMID 41369694
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INTRODUCTION: Osteoclasts and foreign body giant cells (FBGCs) are multi-nuclear cells established by fusion of their mono-nuclear forms. Multi-nucleation via cell-cell fusion is a common characteristic of osteoclasts an...INTRODUCTION: Osteoclasts and foreign body giant cells (FBGCs) are multi-nuclear cells established by fusion of their mono-nuclear forms. Multi-nucleation via cell-cell fusion is a common characteristic of osteoclasts and FBGCs, and Dendritic Cell-Specific Transmembrane Protein (DC-STAMP) and Osteoclast Stimulatory Transmembrane Protein (OC-STAMP) are both required for the process. Thus, it is thought that DC-STAMP and OC-STAMP interaction likely induces this fusion, but details of these mechanisms are not clear. MATERIALS AND METHODS: We crossed DC-STAMP knockout (KO) with OC-STAMP KO mice to obtain DC-STAMP/OC-STAMP doubly deficient (DKO) mice. Osteoclasts and FBGC common progenitors were isolated from wild-type (WT), DC-STAMP KO, OC-STAMP KO or DKO mice. We then set up 4 co-culture systems: (1) WT with DC-STAMP KO cells, (2) WT with OC-STAMP KO cells, (3) WT with DKO cells, and (4) DC-STAMP KO with OC-STAMP KO cells to induce osteoclast or FBGC formation. We evaluated osteoclast and FBGC formation by TRAP and May-Gruenwald Giemsa staining, respectively. Finally, we performed bone morphometric analysis of WT, DC-STAMP KO, OC-STAMP KO, and DKO mice. RESULTS: Cell-cell fusion occurs normally in co-cultures of DC KO with WT cells, OC KO with WT cells, and DKO with WT cells in both osteoclast and FBGC-inducing conditions. By contrast, co-cultures of DC-STAMP KO with OC-STAMP KO cells did not show cell-cell fusion. Bone morphometric analysis revealed enhanced bone formation in DKO mice. CONCLUSION: DC-STAMP and OC-STAMP cooperate to promote osteoclast and FBGC cell-cell fusion. DC-STAMP and OC-STAMP doubly deficient mice exhibit increased osteogenesis.
Prasad TN, Sharma LR, Bhansali A
… +8 more, Bhadada SK, Aggarwal N, Singh T, Sachdeva N, Konsam BD, Tiwari VP, Baruah MM, Walia R
J Bone Miner Metab
· 2026 Jan · PMID 41366030
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BACKGROUND: A significant proportion of bone loss per year occurs starting around 1-3 years before menopause. A number of fractures occur in the osteopenic range of bone mineral density (BMD). There are no recommendation...BACKGROUND: A significant proportion of bone loss per year occurs starting around 1-3 years before menopause. A number of fractures occur in the osteopenic range of bone mineral density (BMD). There are no recommendations for the treatment of osteopenic peri-menopausal women. We conducted this study to explore the utility of zoledronic acid in preserving bone health in this population. MATERIALS AND METHODS: This is a prospective single-blinded randomized controlled trial. A total of 60 peri-menopausal women and 30 postmenopausal women with osteopenia were enrolled. The peri-menopausal women were randomized to receive either zoledronic acid or placebo in a 1:1 ratio. All postmenopausal osteopenic women received zoledronic acid. Participants were followed up for 12 months. BMD and bone turnover markers (BTM) were assessed. RESULTS: At the end of 12 months, there was a significant increase in lumbar spine BMD in the peri-menopausal and postmenopausal groups which received zoledronic acid. On further subcategorizing the T-score, the improvement in BMD was statistically significant in the group with a T-score of - 1.75 to - 2.5. In peri-menopausal women with osteopenia with a T-score of - 1.75 to - 2.5, a single infusion of zoledronic acid increased lumbar spine and femoral neck BMD and suppressed the high bone turnover. Zoledronic acid thus could be used for preserving bone density and preventing the risk of osteoporosis and fragility fractures in the future.
Sunayama M, Omi N, Nishiyama T
… +8 more, Otani T, Nakagawa-Senda H, Nagaya T, Nagaya K, Kato M, Shibata K, Yamada T, Suzuki S
J Bone Miner Metab
· 2025 Nov · PMID 41364368
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INTRODUCTION: Body size is known to influence bone mass and fracture risk throughout life; however, the critical period at which body size most strongly affects later fracture risk remains unclear. Herein, we investigate...INTRODUCTION: Body size is known to influence bone mass and fracture risk throughout life; however, the critical period at which body size most strongly affects later fracture risk remains unclear. Herein, we investigated whether body size in adolescence or early adulthood is more strongly associated with future fracture risk, hypothesizing a stronger association for adolescence. MATERIALS AND METHODS: Participants included health examination attendees in the Okazaki region of the Japan Multi-Institutional Collaborative Cohort Study aged 35-79 years. Overall, 2152 males (mean age 58.5 ± 10.9 years) and 1900 females (54.9 ± 10.2 years) were analyzed. In the primary survey (2007-2011), participants recalled body size in junior high school and their 20 s. In the secondary survey, conducted approximately 5 years later, participants self-reported fracture history in the past year. Associations between recalled body size and fracture risk were examined using logistic regression. RESULTS: Females with a thin body size in junior high school had a higher fracture risk than those with a normal body size (OR 2.29; 95% CI 1.10-4.76). However, a thin body size in the 20 s showed no association (OR 0.83; 95% CI 0.33-2.06). Additionally, no significant associations were observed for overweight females or males in either period. CONCLUSION: In females, a thin body size in adolescence may be more strongly associated with future fractures than in early adulthood. Our findings provide a basis for future research confirming these associations with objective measures and longer follow-up.
Boonrod A, Kittipongphat N, Piyaprapaphan P
… +2 more, Theerakulpisut D, Boonrod A
J Bone Miner Metab
· 2026 Jan · PMID 41361106
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INTRODUCTION: To diagnose osteoporosis, assess the risk of fragility fracture, and determine the necessity for treatment, bone mineral density (BMD) is mostly measured from dual energy X-ray absorptiometry (DXA) as a gol...INTRODUCTION: To diagnose osteoporosis, assess the risk of fragility fracture, and determine the necessity for treatment, bone mineral density (BMD) is mostly measured from dual energy X-ray absorptiometry (DXA) as a gold standard. Due to the limited resources of DXA, we proposed the deep learning models to screen for osteoporosis and measure its accuracy on osteoporosis detection from lumbar spine radiographs. MATERIALS AND METHODS: The models were developed from the training data set (2244 anteroposterior and 2368 lateral lumbar spine radiographs). We categorized patients into two groups based on DXA BMD T-score: non-osteoporosis (T > - 2.5) and osteoporosis (T ≤ - 2.5). A two-class models were trained to classify non-osteoporosis and osteoporosis. Model performance was tested with the test data set (963 AP and 1018 lateral images) to evaluate the accuracy. RESULTS: The results showed that, for AP images, the ResNet-18 model diagnosing osteoporosis achieved an area under the curve (AUC) of 0.79 (95% confidence interval [CI] 0.76-0.82) with a concomitant sensitivity of 79.7% (95% CI 74.4-85.0%) and specificity of 66.5% (95% CI 63.1-69.9%). For lateral images, the DarkNet-19 model yielded the highest AUC at 0.82 (95% CI 0.80-0.85) with the highest sensitivity for lateral data set at 87.5% (95% CI 83.1-91.9%) and specificity of 79.4% (95% CI 76.6-82.2%). CONCLUSIONS: Deep learning models may have the efficacy to anticipate osteoporosis screening based on lumbar spine radiographs which would be helpful as a readily available tool for assessing the risk and determining treatment.
Okamoto Y, Wakama H, Saika T
… +2 more, Tani K, Otsuki S
J Bone Miner Metab
· 2026 Jan · PMID 41339538
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INTRODUCTION: Osteosarcopenia-the coexistence of osteoporosis and sarcopenia-reflects a dual loss of bone and muscle integrity that contributes to frailty, falls, and functional decline in aging populations. While both o...INTRODUCTION: Osteosarcopenia-the coexistence of osteoporosis and sarcopenia-reflects a dual loss of bone and muscle integrity that contributes to frailty, falls, and functional decline in aging populations. While both osteoporosis and sarcopenia have been individually linked to postoperative recovery, their combined effect after major orthopedic procedures remains unclear. This study investigated whether osteosarcopenia independently predicts health-related quality of life after total hip arthroplasty (THA), as a model for older adults with musculoskeletal deficits. MATERIALS AND METHODS: A retrospective cohort of 214 patients aged ≥ 65 years who underwent unilateral THA was analyzed. Preoperative evaluations included dual-energy X-ray absorptiometry (osteoporosis: lumbar T-score < - 2.5) and sarcopenia was defined in accordance with the 2019 Asian Working Group for Sarcopenia consensus. Patients were grouped as osteosarcopenia, sarcopenia-only, osteoporosis-only, or normal. Multivariate logistic regression was conducted to identify predictors of achieving the minimum clinically important difference (MCID) in the Hip Disability and Osteoarthritis Outcome Score-Joint Replacement (HOOS-JR) at 24 months postoperatively. Propensity score matching was used to compare patients with osteosarcopenia with matched controls. RESULTS: Both osteoporosis (OR 0.71, 95%CI 0.60-0.83) and sarcopenia (OR 0.79, 95%CI 0.64-0.97) were independent predictors of failure to achieve MCID (> 18, 154/214). Post-matching, patients with osteosarcopenia (n = 25) had significantly lower HOOS-JR (P < 0.001), EuroQol 5-Dimension (P = 0.029), and satisfaction scores (P < 0.001) than controls (n = 50). CONCLUSION: Osteosarcopenia was associated with clinically inferior functional disability after THA. Preoperative identification of bone-muscle deficits could guide interventions-such as osteoporosis treatment and tailored rehabilitation-to enhance outcomes in older adults.
Mori Y, Tarasawa K, Tanaka H
… +5 more, Kanabuchi R, Mori N, Fushimi K, Aizawa T, Fujimori K
J Bone Miner Metab
· 2026 Jan · PMID 41291336
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INTRODUCTION: Hip fractures are common in elderly individuals and contribute to significant morbidity and mortality. Low body mass index (BMI) is associated with osteoporosis and frailty, yet its impact on postoperative...INTRODUCTION: Hip fractures are common in elderly individuals and contribute to significant morbidity and mortality. Low body mass index (BMI) is associated with osteoporosis and frailty, yet its impact on postoperative outcomes after hip fracture surgery remains unclear. MATERIALS AND METHODS: We conducted a retrospective cohort study using Japan's Diagnosis Procedure Combination (DPC) database. Patients aged ≥ 65 years undergoing surgery for hip fractures from April 2016 to March 2022 were included. Low BMI was defined as < 17.0 kg/m, and < 18.5 kg/m was used for sensitivity analyses. Patients < 65 years or treated non-operatively were excluded. Primary outcomes included venous thromboembolism (VTE), pneumonia, urinary tract infection, cognitive dysfunction, in-hospital mortality, transfusion volume, and length of stay. Propensity score matching (1:1) was performed, followed by logistic regression. RESULTS: Of 474,293 patients identified, 63,761 matched pairs were analyzed. Compared to the non-low BMI group, the low BMI group had higher rates of urinary tract infection (3.6% vs. 3.0%; OR 1.203, 95% CI 1.131-1.280), pneumonia (5.3% vs. 3.0%; OR 1.850, 95% CI 1.746-1.961), and in-hospital mortality (3.4% vs. 1.6%; OR 2.233, 95% CI 2.068-2.411). Perioperative transfusion volume was higher in the low BMI group, while VTE was less frequent. Sensitivity analyses using < 18.5 kg/m confirmed these findings. CONCLUSION: Low BMI is associated with increased complications and mortality following hip fracture surgery in the elderly. These findings emphasize the prognostic relevance of BMI in perioperative risk assessment.
J Bone Miner Metab
· 2026 Jan · PMID 41272310
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INTRODUCTION: Osteoporosis is highly prevalent in China and imposes a substantial economic burden. Early community-level management is pivotal and community health centers play an important role in prevention and managem...INTRODUCTION: Osteoporosis is highly prevalent in China and imposes a substantial economic burden. Early community-level management is pivotal and community health centers play an important role in prevention and management. As shared decision-making in medication expands, understanding public preferences can help improve community health services. This study investigated public preferences of osteoporosis community-level management in China, considering access to screening information, screening duration, service supplier, mode of administration, management approach and out-of-pocket costs. MATERIALS AND METHODS: A discrete choice experiment (DCE) was conducted in Shanghai among community-dwelling adults. We constructed a mixed logit model with a total of 14 levels of the above 6 attributes. Willingness-to-pay (WTP) and scenario predictions were performed. Exploratory subgroup analyses assessed heterogeneity by age, income, geographic location and self-reported osteoporosis. RESULTS: A total of 170 valid questionnaires were collected from 6 communities in Shanghai. OOP costs had the largest impact on utility, followed by screening duration, service supplier and access to screening information. Subgroup analyses revealed that shorter screening duration and specialist-provided screening services had greater positive impact on utility among suburban residents than among urban sample. Scenario predictions suggested that the combination of shorter screening duration, service supplied by tertiary-hospital specialists and management supplied by general practitioners meaningfully increased predicted participants' utility. CONCLUSION: Public preferences favored lower costs, convenient screening, clear information and specialist-led screening with general-practitioner-delivered management. Understanding the impact of attributes in community-level management strategies on residents' utility and willingness to pay is important for optimizing community-level management strategies.
Lau TC, Chang DG, Chen CH
… +9 more, Huang S, Lau EMC, Law SW, Lee YK, Tolman C, Canals L, Yeo SH, Yu J, Ebeling PR
J Bone Miner Metab
· 2026 Jan · PMID 41258429
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INTRODUCTION: To compare 12-month real-world treatment persistence and compliance in postmenopausal women prescribed denosumab or alendronate for osteoporosis in Asia-Pacific. MATERIALS AND METHODS: This prospective coho...INTRODUCTION: To compare 12-month real-world treatment persistence and compliance in postmenopausal women prescribed denosumab or alendronate for osteoporosis in Asia-Pacific. MATERIALS AND METHODS: This prospective cohort study enrolled women aged ≥ 50 years from Australia, Taiwan, South Korea, Hong Kong and Singapore between 2019-2021. Study participants were prescribed bi-annual denosumab injection or weekly alendronate, based on physicians' decision. Medication persistence and compliance were estimated over 12 months of follow-up. Multivariable logistic regression was used to determine if treatment type (denosumab or alendronate) was significantly associated with persistence and compliance, while adjusting for age, fracture history, baseline BMD, prior osteoporosis treatment, and prior treatment with oral glucocorticoids. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated. RESULTS: Among 686 enrolled women, 580 completed their 12-month visit (301 in denosumab and 279 in alendronate group). At baseline, those in the denosumab group were older and more likely to have received prior osteoporosis treatment. Overall treatment persistence and compliance were 72.4% and 70.7%, respectively. Patients receiving denosumab exhibited higher persistence (82.7% vs. 61.3%, P < 0.001) and compliance (86.0% vs. 54.1%, P < 0.001), versus those on alendronate. Regression results also showed that patients on denosumab were more likely to be persistent (aOR = 3.08; 95% CI 2.04-4.63) and compliant (aOR = 5.32; 95% CI 3.45-8.21) with treatment. Gastrointestinal disorders were more frequently reported in the alendronate group, while bone and joint injuries were more common in the denosumab group. CONCLUSION: Postmenopausal women with osteoporosis were more likely to be persistent and compliant with denosumab, compared with weekly oral alendronate.
Pandiar D, Krishnan RP, Gopinath D
… +3 more, Reddy SSP, Veeraiyan DN, Vijayakumar G
J Bone Miner Metab
· 2026 Jan · PMID 41249713
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BACKGROUND: Benign fibro-osseous lesions (BFOLs) are a heterogeneous group of bone-forming pathologies characterized by replacement of normal bone with fibrocellular stroma and mineralized tissue. Their overlapping clini...BACKGROUND: Benign fibro-osseous lesions (BFOLs) are a heterogeneous group of bone-forming pathologies characterized by replacement of normal bone with fibrocellular stroma and mineralized tissue. Their overlapping clinical, radiological, and histopathological features often complicate diagnosis. OBJECTIVE: This review summarizes the clinicopathologic characteristics and recent molecular insights of BFOLs to enhance diagnostic accuracy and classification. APPROACH: A narrative review of English-language literature available in electronic databases upto 2025 was performed, focusing on key clinical, radiologic, histologic, and molecular findings of BFOLs. FINDINGS: BFOLs encompass bone dysplasias including fibrous dysplasia and segmental odontomaxillary dysplasia, ossifying fibroma, and cemento-osseous dysplasia, each showing distinct biological behavior. Molecular studies have revealed GNAS mutations in fibrous dysplasia and HRPT2 alterations in ossifying fibroma, providing clues to their pathogenesis. CONCLUSION: Integrating molecular data with clinicopathologic assessment refines diagnosis, prevents misclassification, and supports more precise management of BFOLs.
Arakawa D, Tsukamoto M, Wang KY
… +9 more, Nabeshima T, Mano Y, Yamanaka Y, Suzuki H, Kawasaki M, Nakamura E, Azuma K, Yatera K, Sakai A
J Bone Miner Metab
· 2026 Jan · PMID 41247404
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INTRODUCTION: There are many risk factors for fractures in chronic obstructive pulmonary disease patients, and investigating the effects of any particular factor on bones is extremely difficult. We hypothesized that the...INTRODUCTION: There are many risk factors for fractures in chronic obstructive pulmonary disease patients, and investigating the effects of any particular factor on bones is extremely difficult. We hypothesized that the presence of pulmonary emphysema would delay the recovery of bone mass by reloading after unloading, and our study aimed to assess changes in bone metabolism dynamics in response to mechanical stress under pulmonary emphysema in model mice. MATERIALS AND METHODS: We used C57BL/6J mice, with or without emphysema, via intratracheal administration of elastase or vehicle. Half of these mice underwent 1 week of hindlimb unloading followed by reloading, with bone assessed by μCT and histomorphometry. RESULTS: Mice without emphysema exhibited transient bone loss, with bone mass fully recovering by week 3 after unloading, driven by a robust rebound in bone formation. Conversely, mice with emphysema showed a delay in the response of bone metabolism dynamics to mechanical stress; bone loss due to unloading were delayed by week 3 after unloading and bone recovery due to reloading by week 6. CONCLUSIONS: Slow changes in bone metabolism dynamics were observed during both unloading and reloading in mice with elastase-induced emphysema. The mechanism underlying these phenomena is unclear and requires further investigation.