Journal of Bone and Mineral Research最新文献

{"title":"Abnormal position of a GNAS methylation regulatory element causes autosomal dominant pseudohypoparathyroidism type 1B (PHP1B).","authors":"Andreea Apetrei, Nicolas Richard, Yorihiro Iwasaki, Harald Jüppner, Magali Demoor, Nicolas Gruchy, Hélène Bony, Rachel Desailloud, Arnaud Molin","doi":"10.1093/jbmr/zjag107","DOIUrl":"https://doi.org/10.1093/jbmr/zjag107","url":null,"abstract":"<p><p>The parental imprinted GNAS complex locus encodes the α-subunit of the stimulatory G protein. Pseudohypoparathyroidism type Ib (PHP1B) is characterized by renal resistance to parathormone and is caused by epigenetic anomalies, ie, at least the loss of methylation (LOM) at the A/B differentially methylated region (DMR). LOM or gain of methylation (GOM) may also affect other DMRs and different transcripts expressions within the locus (NESP, exon H, AS1, XLαs, A/B). Most PHP1B are sporadic and result from abnormal methylation of all DMRs in the regulatory region of GNAS. Autosomal dominant PHP1B (AD-PHP1B) is usually caused by a recurrent STX16 gene microdeletion in the maternal allele which leads to isolated LOM at the A/B DMR. In this study, we investigated an AD-PHP1B family without STX16 deletion using whole genome sequencing (WGS). The two affected siblings presented a LOM at the A/B DMR and the half telomeric portion of the XLαs DMR and their healthy mother presented a partial GOM at the AS1 DMR and the half centromeric portion of the XLαs DMR. The WGS analysis revealed a 140-kb paracentric inversion with breakpoints located in the NPEPL1 gene and XLαs DMR. We identified the first inversion involving the regulatory region of GNAS locus leading to a maternally inherited AD-PHP1B. This observation provides additional insight into the methylation regulatory elements in the GNAS locus on both alleles, especially on NESP and exon H transcription-mediated methylation. This study will help design subsequent strategies for further studies.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148402988","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":"Ossification of the Posterior Longitudinal Ligament - Novel findings from Pandora's box of ENPP1 Deficiency.","authors":"Lothar Seefried","doi":"10.1093/jbmr/zjag106","DOIUrl":"https://doi.org/10.1093/jbmr/zjag106","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148387157","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":"Editorial on \"Evidence-based classification of genes implicated in skeletal disorders using the ClinGen curation framework\".","authors":"Eric T Rush","doi":"10.1093/jbmr/zjag035","DOIUrl":"10.1093/jbmr/zjag035","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"697-698"},"PeriodicalIF":6.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146224822","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":"Activation of the noncanonical inflammasome-GSDMD pathway triggers pyroptosis in bone marrow and promotes periosteal bone formation.","authors":"Wei Zou, Chun Wang, Yongjia Li, Wentong Jia, Steven L Teitelbaum, Gabriel Mbalaviele","doi":"10.1093/jbmr/zjaf197","DOIUrl":"10.1093/jbmr/zjaf197","url":null,"abstract":"<p><p>Evidence indicating that inflammation is commonly associated with ectopic osteogenesis in certain autoimmune and infectious conditions challenges the dogma that inflammatory responses always suppress bone formation. In this study, we find that systemic administration of lipopolysaccharide (LPS) to mice causes not only inflammation in bone marrow, as expected, but also stimulates periosteal bone formation. This response can be reproduced in vitro as bone marrow supernatants from LPS-treated mice induce robust osteogenesis of osteoprogenitors compared to supernatants from PBS-treated counterparts. Periosteal bone accrual is partly dependent on periosteal leptin receptor-positive (LepR)+ osteoprogenitors but not bone marrow LepR+ or adiponectin (Adq)+ osteoprogenitors and correlates with pyroptosis within bone marrow. Consistent with the dependence of periosteal osteogenesis on pyroptosis, this response is slightly attenuated in Nlrp3-/- or caspase-1-/- mice but significantly inhibited in caspase-11-/-, caspase-1-/-;caspase-11-/-, or Gsdmd-/- mice. Our study reveals a novel role for pyroptosis in which lysed cells release intracellular contents that stimulate osteoprogenitors and promote osteogenic differentiation within the periosteal compartment.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"772-783"},"PeriodicalIF":6.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13321126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145772931","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":"Combined treatment with a C-type natriuretic peptide analog and bisphosphonate enhances bone growth in growing mice with osteogenesis imperfecta: a pilot study.","authors":"Jack E Mulcrone, Ketsia Seide, Jonathan Chacko, Erin M Carter, Nancy Pleshko, Chloe E Derocher, Cathleen L Raggio","doi":"10.1093/jbmr/zjaf190","DOIUrl":"10.1093/jbmr/zjaf190","url":null,"abstract":"<p><p>Osteogenesis imperfecta (OI) is a heterogeneous type 1 collagenopathy characterized by recurrent fractures, decreased bone mass, and short stature. Bisphosphonates reduce fracture incidence in children with OI, but do not improve growth velocity. C-type natriuretic peptide (CNP) is produced in the growth plate (also in the brain and heart), and it positively regulates linear bone growth; people with OI have been shown to have reduced serum levels of CNP. This pilot study evaluated whether a CNP analog combined with alendronate (ALN) improves growth and BMD in oim/oim (OIM) mice, a model of moderate-to-severe Type III OI. Two-wk-old OIM and WT mice received weekly ALN and 1 of 3 CNP regimens: 10 μg/kg 3 d/wk (low), 20 μg/kg 3 d/wk (medium), or 20 μg/kg 5 d/wk (high). Controls received saline. Faxitron images were taken at 2, 8, and 14 wk (sacrifice) to assess fracture incidence and measure femoral length and vertebral height. MicroCT was used to assess bone microstructural parameters of the femur ex vivo. The high-dose group had no fractures post-sacrifice, while 1 fracture each was observed in the low and medium dose groups. Femoral length increased in all treated groups, with the high dose-group showing the greatest increase (8.2% and significant) in OIM mice. Vertebral height increased in all treated groups; low and high dose groups had greater and comparable increases than the medium group in OIM mice. All treated groups showed increased trabecular BMD. Cortical tissue mineral density, BMD, and thickness were also elevated in all treated groups compared to the controls. In conclusion, CNP analog adjuvant treatment enhanced linear growth and bone quality without compromising fracture reduction, providing benefits not seen with bisphosphonates alone. These results will inform optimal dosing for future studies. A full murine study is planned to further evaluate the therapeutic potential for translation to humans.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"762-771"},"PeriodicalIF":6.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145720140","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":"Marrow pyroptosis ignites the periosteal reaction.","authors":"Masayuki Tsukasaki","doi":"10.1093/jbmr/zjag015","DOIUrl":"10.1093/jbmr/zjag015","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"703-704"},"PeriodicalIF":6.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146049819","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":"Correction to: Suppression of Bone Resorption by miR-141 in Aged Rhesus Monkeys.","authors":"","doi":"10.1093/jbmr/zjag061","DOIUrl":"10.1093/jbmr/zjag061","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"789-790"},"PeriodicalIF":6.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721215","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":"Editorial: aging and bone-muscle unit.","authors":"Keiichi Ozono","doi":"10.1093/jbmr/zjag010","DOIUrl":"10.1093/jbmr/zjag010","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"699-700"},"PeriodicalIF":6.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145987362","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":"Adding to the cytomegalovirus crime sheet? Editorial on \"Osteonecrosis of the femoral head is associated with cytomegalovirus reactivation\".","authors":"Matthew Reeves","doi":"10.1093/jbmr/zjag016","DOIUrl":"10.1093/jbmr/zjag016","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"701-702"},"PeriodicalIF":6.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146045893","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":"Lonafarnib clinical trials demonstrate uncoupling of the muscle-bone unit in Hutchinson-Gilford Progeria Syndrome.","authors":"Raymond J Kreienkamp, Leslie B Gordon, Rachel Ehrbar, Alicia Pendleton, Daniel J Schiferl, Asya Lyass, Monica E Kleinman, Brian D Snyder, Catherine M Gordon","doi":"10.1093/jbmr/zjaf184","DOIUrl":"10.1093/jbmr/zjaf184","url":null,"abstract":"<p><p>Hutchinson-Gilford Progeria Syndrome (HGPS) is a devastating, ultrarare genetic premature aging disease resulting in early atherosclerosis and death during adolescence due to heart failure. Structures of mesenchymal origin, including bone, fat, and muscle, create a progressive skeletal dysplasia, lifelong failure to thrive, and a unique bone phenotype. Characterizing the interaction between muscle and bone has emerged as a powerful tool for defining drivers of bone disease in other conditions but has not been previously explored in HGPS. We examined the \"muscle-bone unit\" using radial pQCT in youth with HGPS aged 2-18 yr before and after treatment with lonafarnib, a farnesyltransferase inhibitor that extends HGPS lifespan. Untreated radii displayed highly abnormal shapes in 70% of individuals spanning all ages. Compared to controls, HGPS forearm muscle and radial area were lower (p < .001) and grew more slowly (muscle β = 1.4 cm2/yr vs 0.3 cm2/yr in HGPS; radius β = 5.8 mm2/yr vs 0.5 mm2/yr in HGPS). Fat area decreased with age (β = -.2 cm2/yr, p < .001) and muscle area, normalized for either BMI or radial length, was reduced in HGPS (p = .02 and p ≤ .001, respectively). These normalized outcomes were similar to controls at younger ages but diverged as patients aged. Radial architectural changes were present even before changes in muscle area and represent a pattern distinct from the normal aging process and other muscle-wasting pediatric conditions. Lonafarnib therapy did not normalize the muscle-bone phenotype after 24 mo, although some individuals (25%) had partial normalization of radial shape. These results demonstrate that the muscle-bone unit is uncoupled in children with HGPS. Normal muscle mass for body size at younger ages implies that there is an opportunity for early treatment to avoid impending pathology. New strategies are needed to ameliorate this phenotype in HGPS, and this study provides a benchmark for gauging future therapies.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"740-750"},"PeriodicalIF":6.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12751024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145666395","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}