Journal of Bone and Mineral Research最新文献

{"title":"Prediction of hip fracture by high-resolution peripheral quantitative computed tomography in older Swedish women.","authors":"Raju Jaiswal, Aldina Pivodic, Michail Zoulakis, Kristian F Axelsson, Henrik Litsne, Lisa Johansson, Mattias Lorentzon","doi":"10.1093/jbmr/zjaf020","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf020","url":null,"abstract":"<p><p>The socioeconomic burden of hip fractures, the most severe osteoporotic fracture outcome, is increasing and the current clinical risk assessment lacks sensitivity. This study aimed to develop a method for improved prediction of hip fracture by incorporating measurements of bone microstructure and composition derived from high-resolution peripheral quantitative computed tomography (HR-pQCT). In a prospective cohort study of 3028 community-dwelling women aged 75 to 80, all participants answered questionnaires and underwent baseline examinations of anthropometrics and bone by dual x-ray absorptiometry (DXA) and HR-pQCT. Medical records, a regional x-ray archive, and registers were used to identify incident fractures and death. Prediction models for hip, major osteoporotic fracture (MOF), and any fracture were developed using Cox proportional hazards regression and machine learning algorithms (neural network, random forest, ensemble, and XGBoost). In the 2856 (94.3%) women with complete HR-pQCT data at 2 tibia sites (distal and ultra-distal), the median follow-up period was 8.0 years, and 217 hip, 746 MOF, and 1008 any type of incident fracture occurred. In Cox regression models adjusted for age, BMI, clinical risk factors (CRF), and femoral neck bone mineral density (FN BMD) the strongest predictors of hip fracture were tibia total volumetric BMD and cortical thickness. The performance of the Cox regression-based prediction models for hip fracture was significantly improved by HR-pQCT (time-dependent AUC; area under receiver operating characteristic curve at 5 years of follow-up 0.75 [0.64-0.85]), compared to a reference model including CRFs and FN BMD (AUC = 0.71 [0.58-0.81], p<.001) and a FRAX risk score model (AUC = 0.70 [0.60-0.80], p<.001). The Cox regression model for hip fracture had a significantly higher accuracy than the neural network-based model, the best-performing machine learning algorithm, at clinically relevant sensitivity levels. We conclude that the addition of HR-pQCT parameters improves the prediction of hip fractures in a cohort of older Swedish women.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of femoral neck width and hip Axis length on incident hip fracture risk: a registry-based cohort study.","authors":"Fatima Zarzour, Sajjad Aftabi, William D Leslie","doi":"10.1093/jbmr/zjaf019","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf019","url":null,"abstract":"<p><p>Bone mineral density (BMD) measured with dual-energy X-ray absorptiometry (DXA) is widely used in clinical practice to assess fracture risk and guide management. DXA can also assess hip geometry, including femoral neck width (FNW) and hip axis length (HAL), which have both been associated with increased risk for hip fracture independently from BMD. Our objective was to assess if FNW predicts hip fracture independently from other factors including HAL. We performed a retrospective cohort study using the Province of Manitoba BMD registry. The study population comprised 75 095 individuals (90.8% women), mean age 64.7 years, with baseline hip BMD and hip geometry parameters. Linked health records were used to ascertain subsequent hospitalization with hip fracture as a primary diagnosis. During a mean follow up of 8.3 (SD 5.1) years, 2341 incident hip fractures were recorded. Each SD increase in age- and sex-adjusted FNW was associated with incident hip fracture (HR 1.15, 95% CI 1.10-1.19) which was unchanged after adjustment for height, weight, femoral neck BMD and clinical risk factors. However, FNW showed a significant positive correlation with HAL (r = 0.68). When further adjusted for HAL, FNW was no longer associated with increased risk for hip fracture (HR 0.98, 95% CI 0.94-1.03). A similar pattern was seen for femoral neck, intertrochanteric and non hip fractures. In contrast, increased risk of hip fracture was consistently seen with each SD increase in HAL even after adjustment for all covariates including FNW (HR 1.35, 95% CI 1.28-1.42). In conclusion, FNW is a risk factor for hip fracture before but not after adjustment for HAL. HAL, on the other hand, robustly and independently predicts hip fracture, including both femoral neck and trochanteric fractures.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Probability of Achieving Bone Mineral Density Treatment Goals with Denosumab Treatment in Postmenopausal Women with Osteoporosis.","authors":"Felicia Cosman, Zhenxun Wang, Xiaodong Li, Steven R Cummings","doi":"10.1093/jbmr/zjaf014","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf014","url":null,"abstract":"<p><p>Bone mineral density (BMD) levels achieved on osteoporosis treatment are predictive of subsequent fracture risk, and T-score > -2.5 has been proposed as a minimum treatment target for women with osteoporosis. Knowing the likelihood of attaining target T-scores with different medications for different baseline BMD levels can help determine appropriate initial treatment for individual patients. In this post hoc analysis, we estimated the probability of achieving a non-osteoporotic T-score (> -2.5 or ≥ -2.0) at the total hip (TH) or lumbar spine (LS) in postmenopausal women >60 years old treated with denosumab for either 3 or 10 years in the FREEDOM trial and its long-term extension. In women with baseline TH T-scores of -2.7, -3.0, and -3.5, the probabilities of achieving target T-scores > -2.5 with 3 years of denosumab were 71%, 12%, and 0.1%, respectively. At LS, for baseline T-scores of -2.7, -3.0, and -3.5, the probabilities were 86%, 59%, and 11%, respectively. Longer treatment duration of up to 10 years increased the probability of achieving target T-scores. The baseline T-scores that permitted at least 50% of women to achieve a target T-score > -2.5 was -2.8 at TH and -3.1 at LS after 3 years and -3.0 at TH and -3.7 at LS after 10 years of treatment. To achieve higher treatment targets (T-scores ≥ -2.0), overall probabilities were lower at both skeletal sites, particularly for TH, even with longer treatment duration. Our results demonstrate that the probability of achieving T-score targets with denosumab is dependent on baseline BMD, skeletal site, and treatment duration. Knowing the probability of achieving treatment targets for different baseline TH and LS T-scores can help determine whether denosumab is an appropriate first choice of treatment in individual patients.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143035477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trabecular bone deficits predominate in the appendicular skeleton of midlife women living with HIV: findings from a cross-sectional study in Zimbabwe.","authors":"Mícheál Ó Breasail, Tafadzwa Madanhire, Cynthia Kahari, Peter R Ebeling, Victoria Simms, Lisa K Micklesfield, Rashida A Ferrand, Celia L Gregson, Kate A Ward","doi":"10.1093/jbmr/zjaf021","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf021","url":null,"abstract":"<p><p>HIV-related mortality has fallen due to scale-up of antiretroviral therapy (ART), so more women living with HIV (WLH) now live to reach menopause. Menopausal estrogen loss causes bone loss, as do HIV and certain ART regimens. However, quantitative bone data from WLH are few in Africa. A cross-sectional study of women aged 40-60 years (49% WLH) was conducted in Harare, Zimbabwe. Menopause status, fracture history, HIV status and treatment, and anthropometry were collected, and radial/tibial peripheral Quantitative Computed Tomography (pQCT) scans performed. pQCT outcomes were: distal radius and tibia trabecular volumetric bone mineral density (vBMD), total area, and compressive bone strength (BSIc); proximal radius and tibia cortical vBMD, bone mineral content (BMC), cortical thickness, bone area, and stress-strain index (SSI). Linear regression determined differences by HIV status, minimally adjusted for age and menopause status, and further adjusted for height and fat mass. Relationships between pQCT parameters and major osteoporotic fracture history were explored using univariate logistic regression. In WLH, linear regression assessed associations between HIV and ART durations on pQCT measures. 384 women mean(SD) age 49.7(5.8) years had pQCT data. WLH had lower absolute pQCT measures at all sites. Overall, HIV-related deficits were robust to adjustment for age, menopause status, height, and fat mass: WLH had lower trabecular vBMD (radius -7.3 [-12.5; -2.0]%, tibia -5.4 [-9.1; -1.7]%), and cortical vBMD (radius -3.5 [-5.9; -1.1]%, tibia -1.1[-1.6; -0.5]%). Strength estimates were lower in WLH and of similar magnitude at the radius and tibia. Longer HIV duration was associated with lower radius bone area, BMC, estimates of bone strength, independent of ART duration. Trabecular deficits predominate in WLH, though with age cortical compartment bone loss may increase in importance. This is particularly concerning as these differences were observed at the radius, a common site of postmenopausal osteoporotic fracture.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143035478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epiregulin ameliorates ovariectomy-induced bone loss through orchestrating the differentiation of osteoblasts and osteoclasts.","authors":"Yuan Dong, Xiaowen Wu, Yinglong Hao, Wei Liu, Xingli Hu, Jie Zhou, Xiaoxia Li, Baoli Wang","doi":"10.1093/jbmr/zjaf017","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf017","url":null,"abstract":"<p><p>Epiregulin plays a role in a range of biological activities including malignancies. This study aims to investigate the potential contribution of epiregulin to bone cell differentiation and bone homeostasis. The data showed that epiregulin expression was upregulated during osteogenesis but downregulated during adipogenesis. Functionally, epiregulin promoted osteoblast differentiation while inhibiting adipocyte differentiation from mesenchymal progenitor cells. Epidermal growth factor receptor (EGFR), one of the two known receptors for epiregulin, exerted opposing effects compared to epiregulin. Intriguingly, silencing EGFR almost completely abolished the dysregulation of osteoblast and adipocyte differentiation induced by epiregulin, suggesting that EGFR is indispensable for mediating epiregulin function. Further mechanistic exploration indicated that epiregulin/EGFR signaled via the inactivation of mechanistic target of rapamycin complex 1 (mTORC1) pathway. Moreover, epiregulin downregulated receptor activator of nuclear factor-κB ligand (RANKL) expression in BMSCs and inhibited the differentiation of bone marrow osteoclast precursor cells into osteoclasts. Treatment of ovariectomized female mice with recombinant epiregulin increased osteoblasts and bone formation, decreased osteoclasts and bone resorption, and ameliorated cancellous bone loss. Consistently, epiregulin treatment improved the potential of BMSCs to differentiate into osteoblasts. Collectively, this study has identified a critical role of epiregulin in regulating osteoblast differentiation through EGFR-mediated inactivation of mTORC1 pathway, as well as osteoclast differentiation via a mechanism associated with RANKL signaling. Additionally, it highlights the potential of epiregulin as a strategy for combating osteoporosis.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143035476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-invasive quantification of bone (re) modeling dynamics in adults with osteogenesis imperfecta treated with Setrusumab using timelapse HR-pQCT.","authors":"Seyedmahdi Hosseinitabatabaei, Isabela Vitienes, Maximillian Rummler, Annette Birkhold, Frank Rauch, Bettina M Willie","doi":"10.1093/jbmr/zjaf013","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf013","url":null,"abstract":"<p><p>Timelapse imaging using high-resolution peripheral quantitative computed tomography (HR-pQCT) has emerged as a noninvasive method to quantify bone (re)modelling. However, there is no consensus on how to perform the procedure. As part of the ASTEROID phase-2b multicenter trial, we used 29 same-day repeated scans from adults with osteogenesis imperfecta (OI) to identify a method that minimized measurement error. We evaluated input image type, registration method, segmentation mask, and for grayscale images various values for the voxel density difference considered formed or resorbed, minimum formation/resorption cluster size, and Gaussian smoothing sigma. We verified the accuracy of our method and then used it on longitudinal scans (baseline, 6, 12, 18 and 24 month) from 78 participants to assess bone formation and resorption induced by an anabolic (setrusumab) and anti-catabolic (zoledronic acid) treatments as part of the ASTEROID trial. Regardless of image registration method, binary input images resulted in large errors ~13% and ~ 8% for first- and second-generation scanners, respectively. For the grayscale input images, errors were smaller for 3D compared to matched angle registration. For both scanner generations, a density threshold of 200mgHA/cm3 combined with Gaussian noise reduction resulted in errors <1%. We verified the method was accurate by showing that similar regions of bone formation and resorption were identified when comparing each scan from the same-day repeated scans with a scan from another timepoint. Timelapse analysis revealed a dose-dependent increase in bone formation and resorption with setrusumab treatment. Zoledronic acid altered bone changes in favor of formation, although no changes reached statistical significance. This study identifies a timelapse method that minimizes measurement error, which can be used in future studies to improve the uniformity of results. This noninvasive imaging biomarker revealed dose dependent bone (re) modeling outcomes from one year of setrusumab treatment in adults with OI.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the Effects of Immune Checkpoint Inhibitors on Bone Utilizing Machine Learning-assisted Opportunistic Quantitative Computed Tomography.","authors":"Bryn E Matheson, Jacob L Jaremko, Alexandra Dowhanik, Jasmine Gill, Cassandra Gallant, John Walker, Nathan Armani, William D Leslie, Michael Kolinsky, Steven K Boyd, Carrie Ye","doi":"10.1093/jbmr/zjaf009","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf009","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICI) are widely used in cancer treatment, yet their impact on bone health remains unclear. This study aimed to perform a retrospective cohort study utilizing routine computed tomography (CT) scans from patients with melanoma to perform opportunistic quantitative CT (QCT) analysis to investigate the effects of ICI treatment on skeletal health, including volumetric bone mineral density (vBMD) measurements and osteoarthritis (OA) parameters. A previously established machine-learning assisted opportunistic QCT pipeline was used to estimate lumbar spine vBMD from baseline and 12-month follow-up CT scans in patients with melanoma treated with ICI therapy and those not treated with ICI therapy. Facet joint OA, osteophyte formation and endplate sclerosis was also graded. Independent and paired t tests were used to determine any differences in vBMD and OA parameters between ICI users and non-ICI users. Multivariable linear regression models were used to control for confounding variables. Non-ICI users had a significant decrease in vBMD of -6.96 mg/cm3 from baseline to follow-up, whereas the ICI users had no significant change. There was a significant difference in change in vBMD from baseline to follow-up between the two groups, with the non-ICI users experiencing a 11.22 mg/cm3 larger decrease in vBMD. After adjusting for baseline age, sex, baseline vBMD and change in OA parameters, this difference remained significant at -13.04 mg/cm3. Among the ICI users, those who had a decline in vBMD had a lower baseline vBMD compared to those who increased vBMD. Neither group showed a significant change in OA parameters over the follow-up period, nor a difference in change between ICI and non-ICI users, even after adjusting for sex, age and baseline OA parameters. While the effects of ICI treatment on vBMD may vary based on baseline bone health, ICIs do not significantly impact OA parameters in the short term.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms to explain the overshoot in bone remodeling markers after denosumab discontinuation: Are we there yet?","authors":"Sabashini K Ramchand, Michelle M McDonald","doi":"10.1093/jbmr/zjaf007","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf007","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early and multiple doses of zoledronate mitigates rebound bone loss following withdrawal of RANKL inhibition.","authors":"Albert S Kim, Victoria E Taylor, Ariel Castro-Martinez, Suraj Dhakal, Amjad Zamerli, Sindhu T Mohanty, Ya Xiao, Marija K Simic, Alyssa Pantalone, Julian Chu, Tegan L Cheng, Peter I Croucher, Jacqueline R Center, Christian M Girgis, Michelle M McDonald","doi":"10.1093/jbmr/zjaf008","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf008","url":null,"abstract":"<p><p>Rebound bone loss following denosumab discontinuation is an important barrier in the effective long-term treatment of skeletal disorders. This is driven by increased osteoclastic bone resorption following the offset of RANKL inhibition, and sequential osteoclast-directed therapy has been utilised to mitigate this. However, current sequential treatment strategies intervene following the offset of RANKL inhibition and this approach fails to consistently prevent bone loss. Our previous work, using a mouse model of denosumab discontinuation, has shown that the processes that drive the rebound phenomenon occur earlier than when bone loss is detected, namely a rise and overshoot in serum TRAP. We identified that these changes in serum TRAP may provide an earlier window of opportunity to intervene with sequential therapy following RANKL inhibition withdrawal. Here, we show that early treatment with zoledronate (10 mg/kg, 3 weeks following the last dose of OPG:Fc), preceding the rise and overshoot in serum TRAP, effectively mitigates rebound bone density loss through preventing the overshoot in serum TRAP. Further, we show that multiple doses of zoledronate (early treatment and during anticipated BMD loss) is superior in consolidating bone density gains made with RANKL inhibition and preventing rebound BMD loss as measured by DXA. Importantly, we demonstrate the efficacy of early and multi-dose zoledronate strategy in preventing bone loss in both growing and skeletally mature mice. MicroCT analysis showed improved trabecular bone structure in both the femur and lumbar vertebrae with zoledronate treatment compared to control. These increases in bone mass translated to increased fracture resistance in skeletally mature mice. This work provides a novel approach of early and multi-dose sequential treatment strategy following withdrawal of RANKL inhibition, contributing valuable insight into the clinical management of patients who discontinue denosumab therapy.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preterm birth and risk of bone fractures during childhood and early adulthood.","authors":"Suvi Alenius, Maija E Miettinen, Markku Nurhonen, Samuli Salmi, Pieta Näsänen-Gilmore, Peija Haaramo, Marjaana Tikanmäki, Marja Vääräsmäki, Mika Gissler, Outi Mäkitie, Petteri Hovi, Eero Kajantie","doi":"10.1093/jbmr/zjaf011","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf011","url":null,"abstract":"<p><p>People born preterm have reduced bone mineral density, subnormal peak bone mass, and an increased risk of osteoporosis. Whether this translates to increased risk of bone fractures is uncertain. We assessed fracture risk from childhood to early adulthood in relation to gestational age and sex by conducting a nationwide register-linkage cohort study comprising all 223 615 liveborn (1/1987- 9/1990) singletons (9161, 4.1%, preterm) in Finland. Cox regression models provided hazard ratios (HR) for fracture diagnosis in public specialty healthcare in both first and recurrent event settings during the whole follow-up (0-29 yr), and during different age periods (0-4/5-9/10-29 yr). Gestational age was considered categorical (full-term, 39-41 weeks, reference). A total of 39 223 (17.5%) children or young adults had at least one fracture. In analyses not stratified by sex, only extremely preterm birth (<28 completed weeks' gestation) was associated with risk of bone fracture at 0-29 yr; adjusted HR (aHR) 0.46 (95% CI 0.28-0.74) compared with those born full-term. Among females, gestational age was unrelated to fracture risk at 0-29 yr. Among males, extremely and very preterm (28-31 weeks) birth was associated with lower risk of fracture at 0-29 yr compared with those born full-term: aHR 0.38 (CI 0.21-0.71) and 0.75 (CI 0.59-0.95) respectively. Restricting the analyses to the individuals without severe medical condition(s) attenuated the associations. However, the fracture risk varied according age and sex: at 10-29 yr moderately preterm (32-33wk) females, and extremely- and very preterm males had a lower risk: aHR 0.63 (0.43-0.94), 0.35 (0.17-0.69), and 0.74 (0.57-0.95) respectively, while late preterm birth (34-36wk) was associated to 1.6-fold higher risk among females at 0-5 yr, and 1.4-fold risk among males at 5-10 yr. Analyses on recurrent fractures showed similar pattern. Children and young adults, in particular males, born extremely or very preterm may have less bone fractures, this is partly explained by severe medical conditions in this group.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}