JBMR Plus最新文献

{"title":"A rare coexistence: Ollier disease and primary hyperparathyroidism-mere coincidence or expanding the spectrum of Ollier disease?","authors":"Justine Luciano, Astrid Dauchez, Beatrix Cochand-Priollet, Antonin Ginguay, Charlotte Melot, Caroline Michot, Mevyn Nizard, Sophie Monnot, Frédéric Sailhan, Valérie Cormier-Daire, Eugénie Koumakis","doi":"10.1093/jbmrpl/ziag034","DOIUrl":"10.1093/jbmrpl/ziag034","url":null,"abstract":"<p><p>Ollier disease (OD) is the most common form of multiple enchondromatosis. It is an extremely rare disorder characterized by the development of multiple benign cartilaginous tumors, known as enchondromas. The prognosis is mainly determined by the risk of malignant transformation, which occurs in approximately 50% of patients within the first 30 yr of life. The disease is caused by somatic gain-of-function mutations in the <i>IDH1</i> and <i>IDH2</i> genes, identified in around 80% of cases of enchondromas and chondrosarcomas. Primary hyperparathyroidism (PHPT) is a common endocrine disorder characterized by excessive secretion of PTH, resulting in dysregulation of calcium levels. It predominantly affects postmenopausal women and may result in complications, primarily involving the bones and kidneys, such as fractures and nephrolithiasis. We report the first case of a patient with OD in whom PHPT was diagnosed and associated with the presence of an <i>IDH1</i> mutation detected in a parathyroid adenoma. This observation suggests a possible role of <i>IDH1</i> mutations in parathyroid tumorigenesis in OD and underscores the need to consider endocrine manifestations in this condition.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 5","pages":"ziag034"},"PeriodicalIF":3.0,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13050500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rethinking race-based interpretation in pediatric densitometry: a scoping review.","authors":"Amira Ramadan, Zakora Moore, Usman A Ahmed, Nessa Tantivit, Dhriti Aiylam, Chloe Rotman, Alicia Pendleton, Carter R Petty, Mali DiMeo, Amanda Grice, Valerie L Ward, Christina M Jacobsen, Nora E Renthal","doi":"10.1093/jbmrpl/ziag028","DOIUrl":"10.1093/jbmrpl/ziag028","url":null,"abstract":"<p><p>As pediatric populations in the United States (US) become increasingly diverse, current practices for interpreting bone density using DXA in children warrant reevaluation. The International Society for Clinical Densitometry currently recommends adjusting pediatric bone density Z-scores by race, sex, and age. However, race-based adjustments risk reinforcing disparities and perpetuating systemic inequities in pediatric bone health assessment. We conducted a scoping review of studies examining racial and ethnic differences in BMD among healthy US children, identifying 3960 records across 4 databases, of which 54 met inclusion criteria. Across these studies, reporting of race and ethnicity was inconsistent: although nearly all relied on self- or parent-report, none provided explicit definitions, and only 13% confirmed concordance across grandparents. Fifty percent of studies reported statistically significant racial differences in BMD, yet most did so without comprehensive covariate adjustment. By contrast, studies that accounted for height, lean mass, and pubertal status frequently found that differences attenuated or disappeared. These findings underscore the need to critically reconsider race-based adjustments in pediatric DXA interpretation. Developing and validating race-neutral reference standards, with attention to structural determinants and biologically relevant measures, such as stature, body composition, and pubertal timing, is essential for achieving a more equitable and clinically meaningful assessment of pediatric bone health.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 4","pages":"ziag028"},"PeriodicalIF":3.0,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13007872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147512266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The therapeutic window: timing dentoalveolar surgery to minimize MRONJ risk in denosumab-treated osteoporotic patients.","authors":"Daya Masri, Eli Rosenfeld, Shaked Adut, Gavriel Chaushu, Gloria Tsvetov, Gal Avishai, Omar Ghanaiem, Ehud Jonas, Ayelet Zlotogorski-Hurvitz, Daniel Muchnik","doi":"10.1093/jbmrpl/ziag038","DOIUrl":"10.1093/jbmrpl/ziag038","url":null,"abstract":"<p><p>Osteoporosis patients treated with denosumab (Dmab) remain at risk for medication-related osteonecrosis of the jaw (MRONJ), particularly after dentoalveolar surgery. Optimizing surgical timing may reduce this risk while avoiding complications related to prolonged drug interruption. This retrospective cohort study evaluated 258 osteoporotic patients receiving Dmab and examined both patient-level data and intervention-level data from 91 patients who underwent 185 dentoalveolar procedures. Multivariable logistic regression and generalized estimating equations (GEE) were applied to identify factors associated with MRONJ development. Medication-related osteonecrosis of the jaw occurred in 5.43% of the total cohort. All MRONJ cases at the intervention level were observed when dentoalveolar procedures were performed within 3 mo of a Dmab injection. A longer interval between the last Dmab dose and dentoalveolar intervention demonstrated a strong protective effect against MRONJ (OR 0.35, <i>p</i> = .0089). In addition, prolonged previous antiresorptive drug intake was identified as a significant independent risk factor at the patient level. No specific type of dentoalveolar procedure showed a statistically significant association with MRONJ development. These findings confirm that surgical timing is a critical determinant of MRONJ risk in Dmab-treated osteoporotic patients. Avoiding dentoalveolar interventions during the early post-injection period, particularly within the first 3 mo, may substantially reduce risk. A delay of at least 4 mo after the last Dmab administration appears to be a clinically important preventative strategy, balancing MRONJ avoidance with the need to minimize fracture risk resulting from prolonged discontinuation of therapy. Additional prospective studies are warranted to refine surgical timing recommendations and guide individualized patient care.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 5","pages":"ziag038"},"PeriodicalIF":3.0,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13050504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impaired bone matrix maturation and mineralization are prevalent in adolescent end-stage kidney disease.","authors":"Nadja Fratzl-Zelman, Renata C Pereira, Stéphane Blouin, Markus A Hartmann, Kathleen Noche, Isidro B Salusky, Katherine Wesseling-Perry","doi":"10.1093/jbmrpl/ziag036","DOIUrl":"10.1093/jbmrpl/ziag036","url":null,"abstract":"<p><p>Children and adolescents with end-stage kidney disease (ESKD) have a high prevalence of bone deformities and fractures, even when bone histomorphometric measures of bone formation, mineralization, and volume are within normal range. We postulated that bone matrix quality and osteocyte differentiation are impaired in ESKD in ways which might be not reflected by alterations in surface-based cell activity. We assessed bone turnover, mineralization, and volume by traditional histomorphometry in bone biopsy cores from 24 adolescent patients with ESKD. We stained sequential sections of the same cores for apoptosis (TUNEL staining) and for osteocyte-specific maturation markers (sclerostin, DMP1, and FGF23). We then performed quantitative backscattered electron imaging (qBEI) to assess bone mineralization density distribution on the whole bone surface and additionally in bone packets containing FGF23-expressing osteocytes. Increased amounts of osteoid (OV/BV > 4.7%) and a true defect in bone surface mineralization (O.Th > 10 μm combined with MLT > 27.1 d) were detectable by histomorphometry in 29% and 17% of bone samples, respectively. By contrast, qBEI detected an excess in primary mineralizing bone (TbCaLow > 6.8%) in 88% of samples and abnormally low bone matrix mineralization (TbCaMean < 22.1 wt% calcium) in 75% of samples. Osteocyte lacunar density and size were within normal range. Unexpectedly, higher numbers of FGF23-expressing osteocytes and a more elongated osteocyte lacunar shape were found in bone samples with greater matrix mineralization. In conclusion, matrix mineralization defects, which are not detected by traditional histomorphometry, are highly prevalent in ESKD bone and reflect poor bone matrix maturation. High numbers of FGF23-expressing osteocytes are found in bone with the most appropriate matrix maturation characteristics. This differs from the bone characteristics of individuals with normal kidney function, in whom large amounts of FGF23 result in low circulating phosphate levels, which in turn triggers severe osteomalacia and hypomineralized periosteocytic lesions.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 5","pages":"ziag036"},"PeriodicalIF":3.0,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13050508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Follistatin-like protein 1 (FSTL1) modulates bone remodeling and attenuates bone loss in a mouse model of postmenopausal osteoporosis.","authors":"Hao Yuan, Bao-Rui Chen, Fu-Xing Han, Kai Huang, Zhi-Hao Jia, Ying-Ying Dong, Lin Bo","doi":"10.1093/jbmrpl/ziag037","DOIUrl":"10.1093/jbmrpl/ziag037","url":null,"abstract":"<p><p>This study systematically delineates the expression dynamics of follistatin-like protein 1 (FSTL1) in postmenopausal osteoporosis (PMOP) and elucidates its role in skeletal homeostasis. Integrated analyses of clinical serum samples and the GTEx database revealed a pronounced reduction in circulating FSTL1 levels in PMOP patients. In vivo, Fstl1^+/- ovariectomized mice displayed exacerbated bone loss-evidenced by diminished BMD and trabecular volume-together with impaired osteoblastic activity and heightened osteoclast activation. Complementary in vitro experiments showed that FSTL1 over-expression markedly enhanced osteogenic differentiation, as reflected by increased alkaline phosphatase activity and matrix mineralization, whereas FSTL1 knockdown produced the opposite effect. Conversely, FSTL1 over-expression suppressed osteoclastogenesis, while its silencing facilitated the formation of tartrate-resistant acid phosphatase-positive osteoclasts. Therapeutic administration of recombinant FSTL1 protein in vivo significantly attenuated OVX-induced bone loss and improved trabecular architecture, stimulated osteoblast differentiation, and curtailed osteoclast function. Collectively, these findings position FSTL1 as a down-regulated mediator in PMOP that modulates bone remodeling by simultaneously promoting osteogenesis and restraining osteoclastogenesis, supporting a potential association of FSTL1 with PMOP and its possible relevance as a biomarker and therapeutic target.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 5","pages":"ziag037"},"PeriodicalIF":3.0,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13050501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histomorphometric bone analysis in premenopausal women with longstanding rheumatoid arthritis and osteoporosis.","authors":"Mariana O Perez, Lucas P Sales, Vanda Jorgetti, Valeria F Caparbo, Luciene M Dos Reis, Ana C Medeiros-Ribeiro, Karina R Bonfiglioli, Andrea Y Shimabuco, Vinícius F Plantz, Camille P Figueiredo, Rosa M R Pereira, Eduardo F Borba, Diogo S Domiciano","doi":"10.1093/jbmrpl/ziag012","DOIUrl":"10.1093/jbmrpl/ziag012","url":null,"abstract":"<p><p>Data on bone microarchitecture in premenopausal women with RA are scarce and have not been evaluated using histomorphometry. We assessed bone fragility in premenopausal RA women through static and dynamic histomorphometric parameters, compared to age- and sex-matched controls. Eighty patients were screened, and iliac crest biopsies were performed in those with fragility fractures or low BMD (Z-score ≤ -2.0). All analyses focus exclusively on the 12 women who underwent bone biopsy. Among these 12 premenopausal women with longstanding RA, mean age was 41.8 ± 6.6 yr and disease duration was 10.8 ± 5.8 yr. Bone volume (BV/TV) was numerically lower in RA patients compared with controls (<i>p</i> = .064). Thus, a reduction in bone volume cannot be excluded, given the limited statistical power. RA patients demonstrated reduced trabecular thickness, increased cortical porosity, and higher osteoclastic surface. Dynamic evaluation showed markedly lower mineralizing surface (MS/BS) and greater variability in mineralization lag time (Mlt). However, Mlt values remained within the physiological range and do not meet histological criteria for osteomalacia. Four patients (33%) showed absent tetracycline labeling. Osteoid indices correlated positively with disease activity, and MS/BS correlated inversely with glucocorticoid dose. In this selected group of premenopausal women with longstanding RA and osteoporosis by clinical criteria, bone fragility appears to result from a combination of trabecular thinning, cortical porosity, and disturbances in mineralization kinetics rather than from classic histomorphometric osteoporosis or osteomalacia.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 4","pages":"ziag012"},"PeriodicalIF":3.0,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12981667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147463228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prolyl 3-hydroxylase 1 (P3H1) deficient osteogenesis imperfecta with vascular malformations: a rare disorder with atypical features.","authors":"Cherie Chua, Yi Shan Ang, Angeline Lai, Kenneth Wong, Mei Yoke Chan, Mark Koh, Sylvia Kam, Rashida Farhad Vasanwala","doi":"10.1093/jbmrpl/ziag035","DOIUrl":"10.1093/jbmrpl/ziag035","url":null,"abstract":"<p><p>Osteogenesis imperfecta (OI) is a genetic disorder characterized by skeletal fragility with increased susceptibility to fractures, alongside various extra-skeletal manifestations. It has a wide spectrum of clinical presentations and varying degree of severity. Over the years, the classification of OI has expanded, and new pathogenic variants are being identified in genes involved in the regulation of collagen synthesis. We describe a case of a 4-yr-old boy who first presented with right eye swelling, redness, proptosis, and limitation in extraocular movements. Further investigation revealed presence of large left sphenoid vascular malformation (VM). He was treated with repeated embolization and oral propranolol. A year later, he suffered a pathological fracture of the left proximal femur. This was followed by recurrent fractures over a period of 5 yr. Radiographs and MRI showed multiple osteolytic lesions in his skull and extremities, and he had low BMD. Genetic testing identified biallelic variants in the <i>P3H1</i> gene. Intravenous zoledronate therapy was commenced and improvement in BMD and remodeling of bones were seen after 4 doses. There was concurrent development of a right sphenoid VM and widespread intraosseous slow-flow VMs seen on serial MRI. He was treated with oral sirolimus for 5 yr and 5 mo duration. There was eventual resolution of sphenoid VMs, while intraosseous VMs remained stable. This is a case of P3H1 deficient OI with atypical clinical features, and the presence of vascular malformations that may or may not be related to underlying collagen defects but may have implications on his treatment and surveillance.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 5","pages":"ziag035"},"PeriodicalIF":3.0,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13188992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147987538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The orally available SIK2/SIK3 inhibitor SK-124 increases bone mass in hypogonadal male mice.","authors":"Roy B Choi, Sung-Hee Yoon, Parthena E Kotsalidis, Caroline H Houghton, Majd George, Daniel J Brooks, Yingshe Zhao, Mary L Bouxsein, Marc N Wein","doi":"10.1093/jbmrpl/ziag032","DOIUrl":"10.1093/jbmrpl/ziag032","url":null,"abstract":"<p><p>At present, there are no FDA-approved orally-available bone anabolic agents to treat osteoporosis. PTH stimulates bone formation through an intracellular signaling cascade that involves the inhibition of salt-inducible kinase (SIK) isoforms 2 and 3. Therefore, direct small molecule SIK2/SIK3 inhibitors may represent a strategy to mimic PTH actions to treat different forms of osteoporosis. We previously described the synthesis and characterization of SK-124, a pharmacologic SIK2/SIK3 inhibitor that increases trabecular bone formation in eugonadal mice. However, the efficacy of this agent in osteoporosis mouse models remains unknown. Hypogonadism is an important cause of age-related bone loss. In this study, we investigated the therapeutic potential of SK-124 in a male hypogonadal bone loss model (orchiectomy, ORX) in BALB/c mice. Radiographic and histological analyses revealed that SK-124-treated ORX mice showed reduced bone loss compared to the vehicle-treated ORX mice. Serum bone turnover markers demonstrated that SK-124 treatment increased bone turnover, suggesting that SK-124 acts in a PTH-like manner in ORX mice. Bone RNA-sequencing analysis demonstrated novel pathways associated with increased bone formation in response to SK-124 treatment. These findings indicate that SK-124 prevents bone loss in a hypogonadal bone loss model and holds potential as an orally available therapeutic for treating osteoporosis due to testosterone deficiency.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 4","pages":"ziag032"},"PeriodicalIF":3.0,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13019688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147573990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Thra</i> knockout protects male mice from hyperthyroidism-driven cortical bone loss by mitigating bone resorption.","authors":"Franziska Brinkmann, Eleonore Kreß, Christiane Schirm, Lorenz C Hofbauer, Martina Rauner, Elena Tsourdi","doi":"10.1093/jbmrpl/ziag033","DOIUrl":"10.1093/jbmrpl/ziag033","url":null,"abstract":"<p><p>Secondary osteoporosis is a major global health problem and can be caused by endocrine diseases, including hyperthyroidism. Of note, hyperthyroid mice exhibit both trabecular and cortical bone loss, accompanied by reduced bone strength, as a consequence of a high bone turnover in which bone resorption exceeds bone formation. Recently, we discovered that osteocytes in bones obtained from hyperthyroid mice develop osteoclast-like features. However, the role of thyroid hormone receptor α (TRα) in hyperthyroidism-driven bone resorption remains ill-defined. Here, we rendered male <i>Thra</i> ^0/0 mice (which lack all TRα isoforms) hyperthyroid, and comprehensively characterized their bone phenotype. <i>Thra</i> ^0/0 mice with L-thyroxine (T4) treatment displayed trabecular, but not cortical bone loss, and maintained bone strength, while T4-treated WT littermates showed overall reduced bone mass and strength. Serum levels of bone resorption marker tartrate-resistant acid phosphatase (TRAP) and numbers of TRAP-positive osteoclasts were elevated in hyperthyroid WT, but not <i>Thra</i> ^0/0 mice. We also detected increased numbers of TRAP-positive osteocytes in long bones of T4-treated WT mice. In line, the expression of osteoclast marker genes was upregulated with T4 in bone tissue from WT mice only. While thyroid hormones (THs) have been reported not to directly affect osteoclast activity, our in vitro studies using late osteoblasts/osteocytes derived from <i>Thra</i> ^0/0 and WT mice revealed that the TH-induced expression of osteoclast markers in these cells was <i>Thra</i>-dependent. Further, the <i>Rankl/Opg</i> ratio linking osteocytes to enhanced osteoclastogenesis was upregulated in hyperthyroid WT, but not <i>Thra</i> ^0/0 cells. Taken together, we demonstrate that <i>Thra</i> KO can preserve cortical bone mass and bone strength by obstructing an increase of bone-resorbing osteoclasts and osteocytes with osteoclast-like features in hyperthyroid male mice.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 5","pages":"ziag033"},"PeriodicalIF":3.0,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13050503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Growth differentiation factor 15 and the risk of hip fracture in older adults.","authors":"Lorenza Mattia, Sheena Patel, Katey Webber, Giuseppe Pugliese, Steven R Cummings, Richard Eastell","doi":"10.1093/jbmrpl/ziaf192","DOIUrl":"10.1093/jbmrpl/ziaf192","url":null,"abstract":"<p><p>Growth differentiation factor 15 (GDF15) is a protein that is produced by senescent cells during the aging process. Its level in blood increases with age and is associated with an increased risk of several age-related diseases and mortality. We measured GDF15 level in serum archived 1174 men and women aged between 70 and 79 yr in the Health Aging and Body Composition study who had measurements of BMD of the hip, markers of bone turnover (PINP and CTX) and tested for several physical functions (6 m gait speed, standing balance and grip strength, BMI, and appendicular lean mass) and falls, and were followed-up for incident fracture. Cox proportional hazard models were used to estimate hip fracture risk by increasing GDF15 quartiles. The mean GDF15 was significantly higher in men than in women (<i>p</i> < .0001) and the level significantly increased with age, slower gait speed, lower standing balance test time, and lower handgrip strength. During 11.5 (SD 4.5) yr of follow-up, 93 (8%) of the participants suffered a hip fracture and the risk was higher among women (<i>p</i> < .015), associated with older age, lower BMI, lower FN and TH BMD, lower appendicular lean mass, and weaker grip strength. In the unadjusted hazard model participants in the highest quartile of GDF15 had a 2-fold increased hip fracture risk (HR 2.12, <i>p</i> < .014) that remained significant after adjustment for age and sex (<i>p</i> < .037). However, the association was no longer statistically significant after adjusting for grip strength (HR 1.8, 95% CI: 0.97-3.34; <i>p</i> < .06). In conclusion, increased GDF15 is a predictor of hip fractures. This relationship might be partially mediated by muscle function and low lean mass but not BMD.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 4","pages":"ziaf192"},"PeriodicalIF":3.0,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12951078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147348330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}