Journal of Bone and Mineral Research最新文献

{"title":"Refractory hypocalcemia from combined autosomal dominant hypocalcemia type 2 and postsurgical hypoparathyroidism.","authors":"Melda Sonmez Ince, Nazanene H Esfandiari, Fadil M Hannan, Mehboob A Hussain, Thomas J Giordano, Megan R Haymart, Rajesh V Thakker, Gregory A Clines","doi":"10.1093/jbmr/zjag043","DOIUrl":"10.1093/jbmr/zjag043","url":null,"abstract":"<p><p>A 49-year-old female with a history of chronic hypocalcemia had serum calcium concentrations that ranged between 6.4 and 8.5 mg/dL (nl, 8.6-10.3 mg/dL) with inappropriately low to low-normal parathyroid hormone (PTH) concentrations. She did not report symptoms of hypocalcemia. A thyroid nodule was discovered, and the patient underwent total thyroidectomy for papillary thyroid cancer. Parathyroid autotransplantation was not performed since parathyroid glands were not identified during the surgery. After total thyroidectomy, the patient developed a more severe symptomatic, refractory hypocalcemia with undetectable PTH concentrations. Postoperative pathologic examination identified a single hypercellular parathyroid gland. Despite medical treatment, including frequent and regular calcium gluconate infusions, serum calcium concentrations remained persistently low. A genetic evaluation identified a pathogenic GNA11 variant (c.178C>T, p.Arg60Cys), consistent with autosomal dominant hypocalcemia type 2 (ADH2). This case expands the understanding of ADH2 and raises important questions about optimal treatment strategies in patients with coexisting genetic and postsurgical hypoparathyroidism.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"934-939"},"PeriodicalIF":6.5,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147300477","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":"Diagnosis, treatment, and management recommendations for cleidocranial dysplasia: A modified Delphi panel.","authors":"Julie Hoover-Fong, Cheryl Anderson-Cermin, Frank Artinian, Stella Chaushu, Mike Harrison, Suzanne M Jan de Beur, Klane K White, Kelly Wosnik, Nnenna Ene, M Elizabeth Wegman, Marielle Brown, Ilana M Zinn","doi":"10.1093/jbmr/zjag004","DOIUrl":"10.1093/jbmr/zjag004","url":null,"abstract":"<p><p>Cleidocranial dysplasia is a rare genetic condition negatively impacting skeletal development. Clinical guidelines for patients, their family members, and clinicians on the diagnosis, treatment, and management of this disease are lacking. The aim of this study was to align expert opinion on standard of care (SoC) medical recommendations for patients with cleidocranial dysplasia, primarily for adults and children (≥2 yrs of age). A modified Delphi panel comprised of a 3-round survey was used to determine consensus among a multidisciplinary team of 13 experts with experience treating patients with cleidocranial dysplasia. Statements for Round 1 were generated from a targeted literature review and received input from a steering committee of 2 experts within the panel. Expert discussion held after Round 2 helped refine statements for Round 3; the steering committee also reviewed statements before dissemination in each round. The consensus threshold was pre-defined as ≥70% agreement or disagreement for Likert-scale statements or ≥70% of experts selecting the same response for a multiple-choice option. For statements wherein consensus was measured, 79% (n/N = 26/33), 91% (n/N = 21/23), and 100% (n/N = 12/12) of statements reached consensus, respectively, in Round 1, Round 2, and Round 3. Overall, consensus was reached on 37 SoC recommendations for patients with cleidocranial dysplasia: 9 regarding diagnosis, 24 regarding treatment and management, consisting of 7 dental/orthodontic and 17 other medical (non-dental/orthodontic), and 4 regarding care providers. The expert consensus reached in this panel informs the first comprehensive best practice guidelines for patients, their family members, and healthcare providers to diagnose, treat, and manage the dental/orthodontic and other medical complications of cleidocranial dysplasia.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"972-987"},"PeriodicalIF":6.5,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13525201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145931532","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 clinical utility of imaging in osteoarthritis and its importance in future prediction of total hip replacement; a nested case-control study within the AGES-Reykjavik cohort.","authors":"Kenneth E S Poole, Ilya S Burkov, Graham M Treece, Andrew H Gee, Fjola Johannesdottir, Simona D'Amore, Stephen K Kaptoge, Sigurdur Sigurdsson, Thor Aspelund, Tamara B Harris, Helgi Jonsson, Vilmundur Gudnason, Thomas D Turmezei","doi":"10.1093/jbmr/zjaf202","DOIUrl":"10.1093/jbmr/zjaf202","url":null,"abstract":"<p><p>Current guidelines are split on the role that imaging has in the clinical assessment of osteoarthritis (OA), yet clinical CT imaging has now revealed how a 3D approach can improve prediction of TH replacement (THR) over 2D measures alone. We applied 2D grading and measurement along with 3D cortical bone mapping to ordinary clinical CT imaging of the pelvis in a cohort of healthy older people, aiming to discover which of these features had clinical utility in predicting THR within 8 yr and which were related to baseline hip pain. Using a nested case-control design in the Age, Gene/Environment Susceptibility-Reykjavik (AGES-Reykjavik) study, 74 future THR cases were age and sex-matched with 184 controls from the cohort (age 74 ± 5 yr). Baseline assessment involved a validated hip pain questionnaire and pelvic CT. The following were performance-tested using receiver operating characteristics analysis and clinical utility index: (1) hip pain, (2) Kellgren and Lawrence grade (K&L grade), (3) minimum joint space width, and (4) 3D cortical bone thickness (CTh). The clinical utility index for prediction of future THR from baseline pain was poor at 0.28, with the inclusion of imaging improving this to 0.79 (K&L grade) and 0.82 (3D CTh). Self-reported hip pain at baseline was also a poor-to-marginal predictor of THR (AUC = 0.63), but 3D cortical thickening at the femoral head was predictive of future THR (0.81). Having radiographic OA strongly predicted THR irrespective of hip pain (0.85). Combining hip pain, K&L grade, and 3D CTh gave optimal prediction (0.88). Ascertainment bias may have occurred, if primary care physicians requested their own radiographs of their patients' hips. Imaging features from standard clinical CT identifies patients at high risk of progression to surgery for OA, regardless of baseline pain.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"963-971"},"PeriodicalIF":6.5,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13525202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846250","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":"Bone phenotype in patients with kidney failure with and without type 2 diabetes.","authors":"Sabina Chaudhary Hauge, Hanne Skou Jørgensen, Kathleen Claes, Anja Verhulst, Etienne Cavalier, Ditte Hansen, Pieter Evenepoel","doi":"10.1093/jbmr/zjag019","DOIUrl":"10.1093/jbmr/zjag019","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) is common in patients with chronic kidney disease (CKD). Both conditions are associated with an increased fracture risk, with the proposed etiology including impaired bone quantity and quality. This cross-sectional study examined the bone phenotype in patients with T2DM and kidney failure and explored the role of glycemic control on the bone phenotype. To do so, laboratory parameters of mineral metabolism (including sclerostin) and bone turnover markers (BTM) (bone-specific alkaline phosphatase [BALP], trimeric pro-collagen type I N-terminal propeptide [intact P1NP], and tartrate-resistant acid phosphatase isoform 5b [TRACP5b]) were assessed in 647 patients with kidney failure, of which 102 had T2DM (median hemoglobin A1c [HbA1c] of 6.2%), at the time of kidney transplantation. Patients with type 1 DM were excluded. BMD (n = 555) by densitometry, and bone histomorphometry (n = 188) were available for subsets, and correlations between HbA1c and both BTM and BMD were examined. This study found that intact P1NP was lower (68 vs 82 μg/L, p = .03) while sclerostin was higher (2.1 vs 1.8 ng/mL, p = .04) in T2DM versus non-T2DM in an unadjusted analysis. BMD at the lumbar spine (Z-score: -0.066 vs -0.760, p < .001) and femoral neck (Z-score: -0.680 vs -0.965, p = .04) were higher in T2DM, and T2DM was in multivariable regression analysis identified as a significant determinant of lumbar spine BMD, independent of age, sex, and BMI. Bone histomorphometric parameters did not differ between groups. A correlation between HbA1c and BTM and BMD was present, but only in non-T2DM (BALP [ρ = -0.12, p = .007], intact P1NP [ρ = 0.14, p = .002], TRACP5b [ρ = -0.13, p = .003], BMD at the lumbar spine [ρ = 0.12, p = .008], femoral neck [ρ = 0.11, p = .02], and total hip [ρ = 0.17, p < .001]). In conclusion, patients with kidney failure and T2DM have preserved BMD compared with patients without diabetes. Our findings suggest a role for hyperglycemia as a determinant of the bone phenotype.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"988-997"},"PeriodicalIF":6.5,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146058187","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":"Progress towards drug treatment for melorheostosis.","authors":"B Paul Wordsworth","doi":"10.1093/jbmr/zjag044","DOIUrl":"10.1093/jbmr/zjag044","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"911-912"},"PeriodicalIF":6.5,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147388943","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":"A novel model to study the impact of gender-affirming therapy on bone in young male mice.","authors":"Lieve Verlinden, Sandra Calvo Blanco, Toke Liekens, Ingrid Stockmans, Karen Moermans, Dieter Schollaert, Chris Vercruysse, Tom Fiers, Tim Reyns, Nick Narinx, Tom De Waal, Leen Antonio, Ruslan I Dmitriev, Frank Claessens, Dirk Vanderschueren, Geert Carmeliet, Vanessa Dubois, Steve Stegen","doi":"10.1093/jbmr/zjag009","DOIUrl":"10.1093/jbmr/zjag009","url":null,"abstract":"<p><p>Transgender individuals are increasingly seeking gender-affirming therapy. For children and adolescents, this typically involves puberty suppression followed by hormone treatment. However, potential long-term adverse effects on the growing skeleton remain poorly characterized, largely due to the lack of appropriate preclinical animal models. Existing models often rely on surgical puberty suppression and, in the case of estradiol (E2) administration, cause a high bone mass-phenotype that is not observed in the clinical setting. To address this, we developed a novel preclinical mouse model that mimics the medical approach used in transgirls and analyzed the effects of gender-affirming therapy on bone. Four-week-old male mice were treated with the gonadotropin-releasing hormone analogue degarelix (DGX) for pharmacological puberty suppression. After 4 wk, E2 was administered at different doses, and bone properties were analyzed after an additional 8 wk. DGX treatment effectively suppressed sex steroid signaling, leading to reduced bone mass and strength, which were dose-dependently restored by E2. While high E2 doses resulted in an excessive increase in bone mass, thereby precluding further mechanistic study, lower doses resulted in a bone phenotype resembling that of native females. At the cellular level, DGX-mediated puberty suppression resulted in increased bone resorption that exceeded bone formation, and also caused an accumulation of marrow adipocytes. Subsequent low-dose E2 administration reduced bone resorption, stimulated bone formation, and prevented the increase in bone marrow adiposity. In summary, we established and validated a mouse model that accurately mimics gender-affirming therapy initiated during early puberty and enables the study of its effects on bone.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"1027-1038"},"PeriodicalIF":6.5,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13525205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145987396","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":"QCT-based geometric, densitometric, and biomechanical properties of the aging human thoracolumbar spine.","authors":"Jianzhong Xu, Hossein Hemmatazad, Michael Indermaur, Alice Dudle, Alicia Feist, Rainer J Egli, Jasmin Wandel, Philippe Zysset","doi":"10.1093/jbmr/zjag008","DOIUrl":"10.1093/jbmr/zjag008","url":null,"abstract":"<p><p>Vertebral fractures represent a growing health issue in our aging societies. We performed a large-scale quantitative assessment of the geometric, densitometric, and biomechanical characteristics of the aging thoracolumbar spine using QCT and homogenized finite element (hFE) analysis. A total of 9298 intact vertebral bodies from T1 to L5 were evaluated across 629 radiologically healthy post-mortem spines (194 female, 435 male). We quantified vertebral height, cross-sectional area (CSA), BMC, BMD, synthetic areal BMD, and hFE-derived yield strength and applied a mixed linear regression model to investigate their dependence on age, sex, BMI, and spinal level. We found that vertebral height was greatest in the lumbar region, while CSA increased caudally and showed positive associations with both age and BMI. Both BMD and yield strength declined with advancing age, with significantly steeper reductions observed in females and in individuals with lower BMI. Interestingly, not yield force, but yield strength was found to be minimal at the thoracolumbar junction (T12-L1), which coincides with the highest occurrence of vertebral fractures. Despite inter-individual variability, BMD demonstrated strong segmental correlations, particularly between adjacent vertebrae, with correlation strength increasing with anatomical proximity. We established a robust power-law relationship (R2 = 0.91) between BMD and yield strength, which generalized across all vertebral levels. Collectively, these findings delineate spatial and demographic patterns in vertebral strength degeneration and provide normative QCT-based reference data for biomechanical modeling. The derived regression framework enables non-invasive estimation of vertebral yield strength, supporting future applications in fracture risk prediction and spine biomechanics research.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"951-962"},"PeriodicalIF":6.5,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13525206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145987405","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":"Complex clinical encounter series: glucagon-like peptide-1 receptor agonists-induced weight loss: are we paying attention to bone health?","authors":"Elena Ambrogini","doi":"10.1093/jbmr/zjag069","DOIUrl":"10.1093/jbmr/zjag069","url":null,"abstract":"<p><p>A 65-yr-old White woman with obesity class II, hypertension, hyperlipidemia, obstructive sleep apnea, osteoarthritis, and pre-diabetes was started on s.c. semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), for weight loss. Her DXA BMD, 3 mo prior to the initiation of semaglutide, showed osteopenia. She did not have personal or family history of fractures. She had gone into menopause at the age of 52 with no other risk factors for osteoporosis. She maintains an adequate intake of calcium and cholecalciferol, and she is active but does not exercise regularly. After 1 yr on semaglutide, she lost ~15% of her weight with improvement of blood pressure, lipid profile, and sleeping pattern. She reports 2 recent falls. The initial recommendation was to repeat DXA in 2-3 yr. However, recent evidence suggests that in elderly patients experiencing ~9% weight loss with semaglutide, monitoring bone remodeling markers and BMD after 1 yr of treatment is justified. Counseling on adequate protein intake and strengthening exercise to preserve muscle mass should also be provided.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"940-944"},"PeriodicalIF":6.5,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687296","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":"Sustained improvement in renal function with palopegteriparatide in adults with chronic hypoparathyroidism: 2-year results from the phase 3 PaTHway-trial.","authors":"Lars Rejnmark, Elvira O Gosmanova, Aliya A Khan, Stuart Sprague, Dolores M Shoback, Lynn Kohlmeier, Mishaela R Rubin, Andrea Palermo, Peter Schwarz, Claudia Gagnon, Elena Tsourdi, Yasuhiro Takeuchi, Noriko Makita, Yasuo Imanishi, Neil Gittoes, Juan J Díez, Caroline Prot-Bertoye, Bryant Lai, Carol Zhao, Jenny Ukena, Michael A Makara, Christopher T Sibley, Aimee D Shu","doi":"10.1093/jbmr/zjag085","DOIUrl":"10.1093/jbmr/zjag085","url":null,"abstract":"<p><p>The PaTHway clinical trial demonstrated sustained efficacy, safety, and tolerability of daily palopegteriparatide in the treatment of adults with hypoparathyroidism. Palopegteriparatide treatment was also associated with improvements in estimated glomerular filtration rate (eGFR) over 52 wk in a post hoc analysis, prompting further exploration of palopegteriparatide in the preservation of renal function. The current post hoc analysis evaluated the impact of palopegteriparatide treatment on renal function in adults with hypoparathyroidism through Week 104; as with prior analysis, changes in renal function were assessed using eGFR. At Week 104, 93% (76/82) of participants remained in the open-label extension. Of those, 82% had albumin-adjusted serum calcium levels in the normal range (8.3-10.6 mg/dL), 97% were independent from conventional therapy (≤600 mg/d of elemental calcium and no active vitamin D). Mean (SD) serum phosphate (3.5 (0.7) mg/dL) and albumin-adjusted calcium × phosphate product (30.7(5.1) mg2/dL2) levels were also within normal ranges. Palopegteriparatide treatment resulted in a mean (SD) increase in eGFR of 8.9 (11.0) mL/min/1.73m2 (p < .0001) from baseline to Week 52, which was sustained through Week 104, where it was 77.8 (14.8) mL/min/1.73 m2 with a mean (SD) change from baseline of 9.0 (10.3) mL/min/1.73 m2 (p < .0001). By Week 104, 45% and 34% of participants had an increase in eGFR of ≥5 mL/min/1.73 m2 and ≥10 mL/min/1.73 m2, respectively. Palopegteriparatide treatment normalized mean (SD) 24-h urine calcium within 26 wk and maintained levels below 250 mg/d through Week 104 (158.8 (90.5) mg/24 h). Most treatment-emergent adverse events were mild or moderate; no new safety signals or cases of treatment-related nephrolithiasis were reported. These findings demonstrate sustained renal safety of palopegteriparatide and suggest that PTH replacement therapy with palopegteriparatide preserves and may improve renal function in adults with chronic hypoparathyroidism after 104 wk of treatment.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"922-933"},"PeriodicalIF":6.5,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13525197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147979673","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":"CDK4 inhibition reduces proliferation and mineralization in MAP2K1+ melorheostosis: opening a pathway to treatment.","authors":"Jyotirindra Maity, Gourinandan Saravanan, Fatemeh Navid, Sarthak Gupta, Robert A Colbert, Timothy Bhattacharyya","doi":"10.1093/jbmr/zjaf186","DOIUrl":"10.1093/jbmr/zjaf186","url":null,"abstract":"<p><p>Melorheostosis is a rare disease where excessive bone overgrowth and exostoses cause deformity and pain. Somatic mutations of MAP2K1 result in hyperactivation of the ERK pathway in osteoblasts and increase in vitro mineralization. Currently, there is no effective treatment. Because melorheostosis-derived osteoblasts show increased expression of cell cycle proliferation-related molecules compared to controls, we hypothesized that rapid progression through the cell cycle contributes to the bony overgrowth. We used an induced pluripotent stem cell (iPSCs) model from unaffected and affected regions of patient skin fibroblasts. We then differentiated iPSCs into induced mesenchymal stromal cells (iMSCs), and then into osteoblasts. Using propidium iodide (PI) mediated cell cycle assay with flow cytometry, we recorded that affected iMSCs (and primary patient osteoblasts) have a higher proportion of proliferative cells than unaffected. We noticed that affected osteoblasts and iMSCs have elevated the expression of phospho-Rb-a crucial molecule for G1 to S phase transition. Immunofluorescence confirmed a significantly higher cell proliferation marker Ki-67 index in affected iMSCs. EdU incorporation assays validated higher percentage of S phase cells in affected populations. We applied the FDA-approved CDK4 inhibitor palbociclib to iMSCs and primary osteoblasts and found significant reduction of phospho-Rb. Palbociclib treated iMSCs and osteoblasts displayed elevated G0/G1 peak on flow cytometry and lowered EdU incorporation, thus confirming blockade of cell cycle progression by limiting S phase entry. Interestingly, palbociclib treatment for an initial 5 d of total 21 d of osteogenic stimulation restricts mineralization in affected cells to a greater extent than unaffected. This suggests that increased proliferation is contributing to the bone growth phenotype in patients. Thus, our data suggest that targeting cell cycle machinery can be a potential therapeutic approach for melorheostosis patients.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"998-1011"},"PeriodicalIF":6.5,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145754757","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}