Journal of Bone and Mineral Research最新文献

{"title":"Geometry of the proximal femur during growth and its contribution to childhood fractures in healthy children.","authors":"Babette S Zemel, Jonathan A Mitchell, Andrea Kelly, David R Weber, Shana E McCormack, Joan M Lappe, Sharon E Oberfield, Dana L Duren, John A Shepherd, Devon Cataldi, Struan F A Grant, Heidi J Kalkwarf","doi":"10.1093/jbmr/zjag079","DOIUrl":"https://doi.org/10.1093/jbmr/zjag079","url":null,"abstract":"<p><p>Hip structural analysis (HSA) of proximal femur scans by dual energy X-ray absorptiometry estimates hip geometry and structural strength, but little is known about how these parameters change during peak bone mass development. We describe age-related changes, precision and long-term stability, and sex and race/ethnic identity differences in hip geometry measures by HSA, and test whether HSA measures predict childhood fractures in healthy children. We used data from the Bone Mineral Density in Childhood Study, a multi-center, longitudinal cohort study of 2,014 healthy U.S. children, ages 5-23y, with up to 7 annual visits. HSA measures included cortical thickness, cross-sectional area, cross-sectional moment of inertia, section modulus, buckling ratio, and bone width at the narrow neck and femoral shaft, and hip axis length. Additional measures included self-identified race and ethnicity, Z-scores for height, BMIZ, appendicular lean soft tissue mass index and fat mass index, and self-reported physical activity, calcium intake, Tanner stage and fractures. Results indicated age-related trends and sex differences in hip geometry. Reference ranges were generated and HSA Z-scores were adjusted for height-for-age Z-score. Femoral shaft measures showed better precision (CV: 1.1 to 3.7%) than narrow neck measures (CV: 2.2 to 7.4%); buckling ratio (both sites) was the least precise. HSA Z-scores tracked well over one year (0.77 to 0.94). Narrow neck buckling ratio (HR 1.16 [95% CI: 1.02, 1.31]) and hip axis length Z-scores (HR 1.20 [95% CI: 1.00, 1.44]) associated with fracture risk. When adjusted for covariates (BMD Z-score, BMIZ, Tanner stage, sex), narrow neck cross-sectional area, cross-sectional moment of inertia, section modulus and bone width, and femoral shaft cross-sectional area and section modulus Z-scores positively associated with fractures (e.g., section modulus Z-score associated with 44% increased fracture risk). These findings provide the foundation for evaluating hip geometry as an indicator of bone strength in children.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855724","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":"Mechanical loading-induced bone formation is associated with increased blood velocity and vascular canal bone porosity, with localized vascular adaptation.","authors":"Taylor deVet, Mahmoud S Moussa, Hanna Gonzalez, Paul Zaslansky, Lorraine E Chalifour, Svetlana V Komarova, Bettina M Willie","doi":"10.1093/jbmr/zjag076","DOIUrl":"https://doi.org/10.1093/jbmr/zjag076","url":null,"abstract":"<p><p>Bone is a highly vascularized tissue, which is required for the metabolically demanding process of remodeling. Blood vessels are important in fluid movement occurring during bone mechanoadaptation. We hypothesized that in-vivo mouse tibial loading, which does not involve muscle contraction and exercise-associated cardiovascular effects, would lead to acute and chronic changes in femoral, saphenous, and popliteal artery structure and function, as well as bone vascular porosity coincident with adaptive bone (re)modeling. Sixteen, 26-wk-old female C57BL/6 J mice received two weeks of once, daily in vivo cyclic loading to the left tibia, resulting in increased cortical bone formation with minimal changes to trabecular bone. In vivo microCT-based timelapse morphometry revealed that most formation occurred on the endocortical surface. Ultrasonography showed changes to blood velocity after each loading episode (days 1, 3, 7, and 9) in saphenous and popliteal arteries, with the femoral artery adapting later. Chronic changes to blood velocity (Δ from baseline) were seen only in the femoral and popliteal vessels closely associated with the loaded tibia. Microfil contrast agent perfused into the vasculature showed minimal loading-induced changes in overall limb vascularity and confirmed targeted popliteal adaptation. Synchrotron tomography revealed greater cortical bone vascular canal porosity in the metaphysis, but not mid-diaphysis of loaded versus non-loaded tibiae. We measured an increased osteocyte lacunar number density surrounding blood vessels in loaded limbs, with no increase found in the canalicular density. Overall, loading led to both temporal and spatially dependent adaptation in the vasculature in the hindlimb and the bone tissue at the level of the primary limb arteries, intracortical bone blood vessels, as well as the osteocyte lacunocanalicular network architecture surrounding the blood vessels. These results highlight the critical role of local vascular dynamics in orchestrating bone adaptation, with implications for developing precision therapies that modulate the vasculature to enhance skeletal resilience.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831543","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":"HR-pQCT skeletal phenotype clustering associated with muscle function in older men and women: The Study of Muscle, Mobility and Aging (SOMMA).","authors":"Morgan W Bolger, Kerri S Freeland, Megan M Marron, Nina Z Heilmann, Lauren S Roe, Nicole M Sekel, Kristen J Koltun, Katelyn Guerriere Aaron, Julie M Hughes, Bradley C Nindl, Ashley A Weaver, Paolo Caserotti, Anne B Newman, Jane A Cauley, Elsa S Strotmeyer","doi":"10.1093/jbmr/zjag068","DOIUrl":"https://doi.org/10.1093/jbmr/zjag068","url":null,"abstract":"<p><p>Age-related changes to BMD, morphometry, and microarchitecture do not occur uniformly across the population and the common skeletal phenotypes beyond BMD are not well defined. Additionally, the associations between bone and muscle are critical to understanding fall and fracture risk. We hypothesized that unsupervised clustering of High Resolution-peripheral Quantitative Computed Tomography (HR-pQCT) measures at the distal tibia (DT) and radius (DR), separately, would reveal unique skeletal phenotypes; and certain phenotypes would be associated with worse muscle function. In the Study of Muscle, Mobility and Aging (SOMMA; first annual follow-up visit), a cohort of community-dwelling older women and men (61% women; 87% White), HR-pQCT parameters acquired at the DT (N = 321; 76.3 ± 4.6 yr) and DR (N = 295; 76.1 ± 4.5 yr) were standardized within-sex then combined to form clusters. This resulted in 3 phenotypic clusters, (C1) high total BMD (Tt.BMD) and cortical area (Ct.Ar); (C2) medium Tt.BMD, Ct.Ar and low trabecular BMD (Tb.BMD); and (C3) low Tt.BMD, and Ct.Ar. DT C2 and C3 exhibited lower micro finite element analysis failure loads, with the cortical load fraction higher in C2 and lower in C3. C2 and C3 both had a similar proportion of osteoporotic and osteopenic/low bone density individuals, highlighting the novel granularity of HR-pQCT clusters vs. aBMD clinical cutoffs. In linear regression models for women, DT C3 was associated with lower leg power (p < .05). For men, DT C3 was associated with lower stair climb and leg power (p < .05). No significant difference was found in grip strength between DT clusters. For DR, no significant difference or association was found between muscle function and clusters for women and men. These findings suggest the concept of bone phenotypic-specific associations with lower but not upper extremity muscle function and have possible implications for the interaction between skeletal phenotypes and muscle function as potential contributory factors to fracture risk.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758343","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":"Validating Fracture Risk After Stoke: A Call to Action to Optimize Skeletal Health After Stroke?","authors":"Robert A Wermers","doi":"10.1093/jbmr/zjag075","DOIUrl":"https://doi.org/10.1093/jbmr/zjag075","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758276","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":"Comparative bone histomorphometry effects of combined denosumab and teriparatide vs monotherapy in postmenopausal women with osteoporosis: a randomized controlled trial.","authors":"Sabashini K Ramchand, Joy N Tsai, Yingshe Zhao, Stuart H Hershman, Daniel G Tobert, Hang Lee, Janaina S Martins, Natalie L David, Grace Sassana-Khadka, Savannah Ryan, Marie B Demay, Benjamin Z Leder","doi":"10.1093/jbmr/zjaf152","DOIUrl":"10.1093/jbmr/zjaf152","url":null,"abstract":"<p><p>Combined treatment with PTH receptor stimulation (teriparatide 20-μg) and RANKL inhibition (denosumab 60-mg) increases spine and hip BMD and improves estimates of bone strength to a greater extent than either monotherapy. The mechanisms underlying the enhanced efficacy of this combination, however, are not fully defined. In this randomized, 3-arm interventional trial, postmenopausal women with osteoporosis were randomized to receive denosumab 60-mg (n = 9), teriparatide 20-μg (n = 13), or both (n = 12) for 3 mo. Participants received double fluorochrome labeling and underwent a single iliac crest bone biopsy at month 3. A total of 26 bone biopsies were suitable for histomorphometry. Fluorescence microscopy was utilized to differentiate remodeling-based from modeling-based bone formation in the cancellous and endocortical envelopes by identifying the morphology of underlying cement lines as either scalloped or smooth, respectively. Within-subject 3-mo changes from baseline were compared among the 3 treatment groups using one-way ANOVA. At 3 mo, teriparatide significantly increased histomorphometric indices of bone formation (BFR/BS, MS/BS, and dLS/BS) compared to denosumab or combination therapy, consistent with its greater effect on bone formation markers. Although both remodeling- and modeling-based bone formation increased in the combination group, denosumab attenuated the teriparatide-induced increases bone in formation, except for modeling-based bone formation in the endocortical envelope. These findings suggest that the greater increases in BMD observed with combined denosumab and teriparatide in the Denosumab and Teriparatide Administration study may result from the net effect of denosumab-mediated remodeling suppression which leads to a reduction in cortical porosity and enables secondary mineralization of the preserved bone volume and teriparatide-induced bone formation.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"497-506"},"PeriodicalIF":5.9,"publicationDate":"2026-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342335","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":"Journal of Bone and Mineral Research (JBMR) 40th anniversary celebration: the third decade (part 2).","authors":"Juliet E Compston","doi":"10.1093/jbmr/zjag047","DOIUrl":"https://doi.org/10.1093/jbmr/zjag047","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":"41 5","pages":"469-473"},"PeriodicalIF":5.9,"publicationDate":"2026-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809054","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":"miR-433 targets BMP and Indian hedgehog signaling to coordinate murine postnatal growth plate dynamics.","authors":"Prachi Thakore, Spenser S Smith, Sangita Karki, Rosa Guzzo, Anne M Delany","doi":"10.1093/jbmr/zjaf182","DOIUrl":"10.1093/jbmr/zjaf182","url":null,"abstract":"<p><p>The postnatal growth plate undergoes dynamic morphogenetic changes essential for endochondral bone formation. While morphogen signaling in this context is well studied, microRNA-mediated post-transcriptional control is poorly understood. Here, we identify microRNA-433-3p (miR-433-3p; miR-433) as a key regulator of chondrocyte proliferation and hypertrophy, acting in part through direct targeting of vital chondrocyte genes. miR-433 is evolutionarily conserved and prominently expressed in precursor chondrocytes embryonically and in the proliferating zone of the growth plate postnatally. To interrogate miR-433 function in vivo, we generated a conditional miR-433 tough decoy (TuD) (competitive inhibitor) mouse model to decrease endogenous miR-433 activity in a lineage-restricted manner. Male and female mice expressing miR-433 TuD in Prrx1-expressing skeletal progenitors and their progeny exhibited shortened and narrower femurs, while a significantly decreased trabecular bone volume was only apparent in males. Male miR-433 decoy mice had disorganized growth plates with fewer resting zone cells, abnormal hypertrophic-like cells in the proliferative zone, and delayed secondary ossification center development. These defects were accompanied by elevated expression of Sox9, Ihh, PTHrP, Bmpr1a, as well as increased expression of validated miR-433 targets Runx2, Hdac6, and Hif1a. Tempering miR-433 activity increased proliferation in the resting zone at 1 and 3 weeks of age, and intensified SOX9 immunofluorescence throughout the growth plate, including the hypertrophic zone. The miR-433 target RUNX2 was ectopically expressed within the proliferating zone and showed increased expression in the hypertrophic zone, consistent with premature hypertrophic transition. Luciferase assays confirmed direct targeting of Bmpr1a and Ihh by miR-433. Given that BMP signaling induces Sox9 and Indian hedgehog promotes Runx2 expression, miR-433 may act as a molecular brake on both the BMP and hedgehog signaling axes, contributing to the spatial restriction of transcriptional programs driving chondrocyte maturation, thereby safeguarding orderly chondrocyte differentiation and bone elongation.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"551-564"},"PeriodicalIF":5.9,"publicationDate":"2026-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13078589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145666486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel brachydactyly type E syndrome caused by variants in helix 8 of the PTH1R.","authors":"Gavin Monahan, Jakob Höppner, Harald Jüppner, Audrey Rick, Elyshia McNamara, William Tee, Guillermo Lay-Son, Andy Contreras, Alejandro Martínez, Cristián García, Javiera Vildoso, Thomas J Gardella, Benjamin Kamien, Gianina Ravenscroft","doi":"10.1093/jbmr/zjaf134","DOIUrl":"10.1093/jbmr/zjaf134","url":null,"abstract":"<p><p>The parathyroid hormone receptor 1 (PTH1R) transmits stimuli provided by PTH and PTH-related protein (PTHrP) and thus plays key roles in calcium and phosphate homeostasis as well as skeletal development. Variants in PTH1R have been linked to several conditions, including Jansen metaphyseal chondrodysplasia, Blomstrand chondrodysplasia, primary failure of tooth eruption, and Eiken syndrome. Here, we report a novel skeletal phenotype identified in two unrelated families associated with PTH1R variants. The clinical features include brachydactyly type E, mild short stature, and dental anomalies. A novel heterozygous PTH1R substitution (p.E469K) was identified in affected members of Family 1, while the affected individual from Family 2 had a previously described heterozygous de novo substitution (p.E465K); these two mutated sites lie within helix 8 (H8) of the PTH1R. Cell-based assays revealed reduced cell surface expression, as well as impaired basal and PTH- or PTHrP-induced cAMP signaling responses for both mutants, as compared to WT-PTH1R. Introduction of the p.E469K substitution into humanized PTH1R mice resulted in mildly increased mineralization of bones in the paws as well as shortening of long bones. Our findings demonstrate a new skeletal phenotype associated with PTH1R variants and suggest that H8 of the receptor contributes to PTH1R expression and/or signaling during bone development.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"521-536"},"PeriodicalIF":5.9,"publicationDate":"2026-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Osteoporotic Fractures in Men study (MrOS): a 25-yr landmark study of skeletal health in older men.","authors":"Jane A Cauley, Peggy M Cawthon, Kristine Ensrud, Howard A Fink, Charles Ginsberg, Deborah M Kado, Lisa Langsetmo, John T Schousboe, Elsa S Strotmeyer, Steven R Cummings, Eric S Orwoll","doi":"10.1093/jbmr/zjag022","DOIUrl":"10.1093/jbmr/zjag022","url":null,"abstract":"<p><p>The Osteoporotic Fractures in Men study (MrOS) is among the largest and longest running, prospective cohort studies of older men. MrOS determined how fracture risk was related to bone mass, bone geometry, lifestyle, anthropometric and neuromuscular measures, comorbidity, biomarkers, and fall propensity. The cohort consisted of 5994 community-dwelling, ambulatory US men aged 65 yr or older recruited at 6 US academic clinical centers in 2000-2002 and followed through November 2024. After enrollment, men were contacted by mail/phone every 4 mo to ascertain information on incident falls, fractures, and deaths/loss to follow-up. All fractures were confirmed by imaging reports. Over the 25-yr study, 95% of active surviving participants had complete follow-up. The MrOS study had 5 major clinic visits; while an ancillary sleep study had 2 additional clinic visits. MrOS has provided a comprehensive analysis of factors associated with areal (a) and volumetric (v) BMD and clinical risk factors for aBMD loss among men. Further analyses identified risk factors for hip, all non-spine, rib, wrist, and vertebral fractures. MrOS was the largest single cohort to estimate associations of aBMD with incident fractures in men and results indicated stronger associations in men than in women. MrOS also analyzed other structural features from DXA and both central and peripheral quantitative computed tomography in relationship to fractures in men. Serum, urine, and DNA were collected at clinic visits, and extensive analyses have been performed with respect to sex steroid and calciotropic hormones, bone turnover, and other novel measures of bone health. Several analyses evaluated the performance of formal tools in estimating the absolute risk of fractures in older men; however, findings indicated that better fracture prediction tools are needed. MrOS encourages outside investigators to make use of the publicly available data and to access the biospecimen bank at https://mrosonline.ucsf.edu.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"474-491"},"PeriodicalIF":5.9,"publicationDate":"2026-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13000919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New lens on congenital mild bone fragility: a novel Col1a1 knockout mouse model for osteogenesis imperfecta type 1.","authors":"Lidiia Zhytnik, Laura Ventura, Anastasia Sclocco, Matthjis Verhage, Astrid D Bakker, Jae-Hyuck Shim, Wissam Beaino, Pedro M Pereira, Myrthe E Hoogeland, Vivi M Heine, Huub Maas, Richard T Jaspers, Anja Niehoff, Frank Zaucke, Vivian de Waard, E Marelise W Eekhoff, Dimitra Micha","doi":"10.1093/jbmr/zjaf138","DOIUrl":"10.1093/jbmr/zjaf138","url":null,"abstract":"<p><p>Osteogenesis imperfecta (OI) is a genetic disorder characterized by bone fragility. It is one of the most prevalent rare skeletal dysplasias. The mildest form, OI type 1, predominantly results from collagen type I haploinsufficiency due to pathogenic variants in the COL1A1 gene, leading to reduced collagen type I. Despite OI type 1 representing approximately half of the OI population, the lack of an effective mouse model has hindered research and therapy development. To address this gap, we developed a genetically engineered mouse model harboring a heterozygous deletion of the Col1a1 allele using the CRISPR/Cas system. The bone phenotype was characterized in 8- and 24-wk-old mice, assessing transcriptomics and serum markers for bone formation (procollagen type I N-terminal propeptide) and resorption (tartrate-resistant acid phosphatase 5b). Bone volume, microarchitecture, and strength were evaluated by micro-CT, histomorphometry, and three-point bending test. We showed that the decreased Col1a1 to Col1a2 mRNA ratio determines reduced collagen type I production in OI mice bones as the underlying mechanism of haploinsufficient OI. This was supported by COL1A1 to COL1A2 mRNA ratio findings in human OI cell models, including fibroblasts and induced mesenchymal stem cells, as well as in induced pluripotent and mesenchymal stem cell models that were edited to carry a heterozygous COL1A1 allele. Our findings indicate for the first time that reduced bone volume and altered bone microarchitecture in haploinsufficient OI depends on the Col1a1 to Col1a2 mRNA ratio regulation. This novel mouse model faithfully recapitulates OI type 1 and provides a vital tool for investigating the disease mechanism and developing targeted therapeutic strategies for this large neglected OI patient population.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"565-580"},"PeriodicalIF":5.9,"publicationDate":"2026-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}