JBMR Plus最新文献

{"title":"An ex vivo appositional growth model to study periosteal activity and associated BMP signaling.","authors":"Gavin Chen, Jillian Scott, Ana Garcia Castineiras, Laura Gamer, Vicki Rosen, Emily R Moore","doi":"10.1093/jbmrpl/ziag061","DOIUrl":"10.1093/jbmrpl/ziag061","url":null,"abstract":"<p><p>The periosteum is an osteogenic tissue containing periosteal stem and progenitor cells (PSPCs) that form and repair bones. Much is known about how the periosteum regulates fracture repair, but its key role in bone accrual during postnatal growth and adult load-induced formation remains a significant knowledge gap. The periosteal activity that drives bone formation and repair can be studied using existing mouse models, but traditional in vivo techniques are not feasible for investigating appositional growth, or widening of the bones, in young mouse pups. We therefore developed an ex vivo appositional growth model that combines existing in vitro fluid flow approaches and a custom support to secure mouse femur explants in a culture system. We observed that femurs widen after daily exposure to fluid flow, and this coincides with expansion of the periosteum and activation of BMP signaling, which is essential for periosteal osteogenesis. We further validated our system by recapitulating an in vivo thin-bone phenotype in mice that exhibit a lack of periosteal activity due to disrupted BMP signaling. Using our device, we were able to partially recover the thin-bone phenotype by supplementing culture media with recombinant BMP2. This ex vivo appositional growth model is an important step in obtaining a more holistic understanding of how the periosteum and its resident PSPCs drive bone formation and repair. Furthermore, we anticipate this apparatus can be used to interrogate the periosteum's osteogenic capabilities and motivate future bone anabolism treatments for skeletal diseases and the prevention of fractures or enhancement of repair.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 6","pages":"ziag061"},"PeriodicalIF":3.0,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13198797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015540","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":"An osteoporotic bone model: developing and validating an ex-vivo bone demineralization protocol.","authors":"Fahad Alabdah, Adel Alshammari, Araida Hidalgo-Bastida, Glen Cooper","doi":"10.1093/jbmrpl/ziag069","DOIUrl":"10.1093/jbmrpl/ziag069","url":null,"abstract":"<p><p>Studies estimate that there are 500 million osteoporotic patients worldwide. Osteoporosis leads to 2.7 million hip fractures annually. These fractures usually require synthetic implants known as total hip replacement. Orthopedic implant development is an ongoing process, which requires numerous tests to evaluate their feasibility, in addition to the International Standards Organization regulatory tests. These tests require human cadaveric bones and animal in vivo experiments, which are associated with high costs, are time-consuming and limited through regulations, which poses a challenge. Following the replacement, reduction and refinement principle in animal testing (3Rs), this study aims to develop and evaluate a protocol where osteoporotic samples are prepared through ex vivo procedure using sheep bones from the food chain, given their availability and size, which is considerably similar to human cadaveric bones. Sheep femurs were demineralized using hydrochloric acid at different time intervals, resulting in changes in the bone architecture, mineral density, and mechanical properties. Demineralized specimens exhibited progressive reductions in mechanical performance and trabecular integrity with increasing demineralization time. Young's modulus decreased from 110.7 ± 28.8 MPa in Control group to 88.7 ± 16.0 MPa and 57.7 ± 6.0 MPa in the 48H and 96H groups, respectively, accompanied by corresponding reductions in failure load. Trabecular microstructure was significantly altered, with trabecular thickness decreasing and trabecular separation and porosity increasing, reaching an approximately 30% higher porosity in the 96H group compared with Control group. Volumetric BMD (vBMD) was significantly reduced by both demineralization treatments (33% relative decrease). Despite the limited sample size, consistent trends indicate meaningful changes with demineralization. The observed structural and mechanical properties fall within reported ranges for human osteoporotic trabecular bone, supporting the use of demineralized sheep bone as a cost-effective ex vivo model for osteoporotic studies and preliminary orthopedic device evaluation.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 6","pages":"ziag069"},"PeriodicalIF":3.0,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13160424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147929633","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":"Rare disease care pathways profile in France: leveraging hospital big data to characterize natural history in osteogenesis imperfecta.","authors":"Julia Herrou, Nathanael Beeker, Valerie Cormier Daire, Martine Cohen Solal, Christian Roux, Martin Biosse-Duplan, Frédéric Sailhan, Philippe Anract, Hina Simonnet, Genevieve Baujat, Karine Briot, Eugénie Koumakis","doi":"10.1093/jbmrpl/ziag030","DOIUrl":"10.1093/jbmrpl/ziag030","url":null,"abstract":"<p><p>Rare bone disease referral centers (RBDCs) were established to improve the diagnosis and management of rare diseases. The objective of this retrospective observational study was to characterize real-life care pathways of patients with osteogenesis imperfecta (OI) in the Paris region. Patient data were extracted from the Assistance Publique-Hôpitaux de Paris (AP-HP) health data warehouse (Entrepôt de Données de Santé). Patients were identified using the ICD-10 code for OI (Q78.0) and keyword searches. Inclusion criteria were age ≥15 yr and at least one hospital visit between January 1, 2016 and March 1, 2021. After exclusion of unconfirmed diagnoses and patients younger than 15 yr, 472 patients with OI were included (mean age 39.5 ± 16.2 yr; 64.6% women). Of these patients, 78% (<i>N</i> = 368) were cared for in one of Paris RBDC, the majority in a single center (76% (<i>N</i> = 280)), while 104 patients (22%) were not seen within RBDCs in AP-HP data. The most frequent specialties involved were rheumatology (74.9%, <i>N</i> = 326), orthopedics (17.6%, <i>N</i> = 76), and otorhinolaryngology (12.9%, <i>N</i> = 56). The proportion of patients seen in rheumatology increased after the transition age of 25 yr (81.8% before vs 90% after, <i>p</i> = .04), whereas consultations in orthopedics and genetics decreased (29.5% vs 17.8%, <i>p</i> = .02, and 22.7% vs 6.8%, <i>p</i> < .0001, respectively). Orthopedic surgery during follow-up was performed in 6.2% of patients followed in RBDCs and 8.6% of those not seen within RBDCs. Although 78% (<i>N</i> = 368) of patients with OI in the Paris region were followed within RBDCs, nearly one quarter were not (22%), suggesting persistent gaps in access to specialized care. These findings provide a real-life description of hospital-based care pathways for OI but do not allow assessment of the effectiveness of the referral center model.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 5","pages":"ziag030"},"PeriodicalIF":3.0,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13188994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147987575","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":"Spatial transcriptomic profiling of decalcified murine musculoskeletal samples via Xenium Prime 5K.","authors":"Lindsey Lammlin, Huong X Tran, Aanya Mohan, Michael D Newton, Scarlet C Howser, Stephen J Redding, Christina A Capobianco, Kurt D Hankenson, Alexander J Knights, Tristan Maerz","doi":"10.1093/jbmrpl/ziag070","DOIUrl":"10.1093/jbmrpl/ziag070","url":null,"abstract":"<p><p>Successful generation of high-quality spatial transcriptomics data from murine musculoskeletal tissues has been impeded by the challenge of preserving RNA integrity through the harsh tissue processing steps required for histological sectioning. In particular, the need to thoroughly fix and decalcify mineralized tissues has proven problematic. We detail a comprehensive sample processing pipeline for 3 common murine musculoskeletal tissue samples, enabling high-quality transcript detection via imaging-based spatial transcriptomics using the Xenium Prime 5K platform from 10x Genomics. Our protocol outlines methodological details for transcardiac perfusion, fixation, decalcification, paraffin processing, and a sample co-embedding strategy facilitating anatomically consistent and simultaneous sectioning of multiple samples onto the spatial transcriptomics slide. Rigorous quality control demonstrates high-quality tissue-specific outcomes across intact knee joints, tibiae, and lumbar spines from adult mice. Our pipeline enabled 70%-91% high-quality transcripts across synovium, meniscus, patellar tendon, articular cartilage, subchondral bone, cortical bone, bone marrow, muscle, fracture callus, and dorsal root ganglion (DRG) tissues. The average number of detected transcripts varied markedly between tissue types: soft tissues, such as synovium, patellar tendon, muscle, bone marrow, and callus exhibited ~200 to 400 transcript per cell; mineralized tissues, such as subchondral bone, meniscus, and cortical bone exhibited ~13 to 150 transcripts per cell; and highly active neuronal tissues, such as DRG neurons yielded 750-1100 transcripts per cell. Canonical cell markers within each tissue confirmed successful identification and representation of key cell types. Through rigorous sample quality assessment at multiple stages of processing, this protocol yields high-quality RNA transcript detection while preserving critical anatomical context and will serve as a valuable tool enabling spatial transcriptomic profiling of intact musculoskeletal tissue samples.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 6","pages":"ziag070"},"PeriodicalIF":3.0,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13160414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147929673","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":"DXA-derived biofidelic finite element models for quantifying the efficacy of hip protectors.","authors":"Dheeraj Jha, Yijun Zhou, Anitha D Praveen, Ellie S Galliker, Preeti Gupta, Ecosse L Lamoureux, Namki Hong, Yumie Rhee, Halldór Pálsson, Stephen J Ferguson, Benedikt Helgason","doi":"10.1093/jbmrpl/ziag067","DOIUrl":"10.1093/jbmrpl/ziag067","url":null,"abstract":"<p><p>We aimed to develop a tool to predict the probability of hip fracture given a fall, using biofidelic finite element models (FEMs) built from DXA scans. Additionally, we evaluated the effectiveness of hip protectors, assuming full compliance, by quantifying the reduction in relative risk in-silico. This study included 700 subjects (325 males and 375 females) from the Population Health and Eye Disease Profile in Elderly Singaporeans (PIONEER) cohort, consisting of Chinese, Indian, and Malay ethnicities. The probability of hip fracture was calculated using DXA-based biofidelic FEMs by simulating various falls. The relative risk was determined by comparing fracture probabilities between falls with and without hip protectors. The overall probability of hip fracture in the cohort (mean age: 71.5 yr) was 4.49% (SD: 4.71). Chinese males had a significantly higher fracture risk, with odds ratios of 3.15 (95% CI: 1.81-5.49) compared to Malay males, and 4.57 (95% CI, 2.21-9.44) compared to Indian males. Similarly, Chinese females had a higher fracture risk, with odds ratios of 2.22 (95% CI, 1.16-4.24) compared to Malay females, and 7.70 (95% CI, 2.30-25.76) compared to Indian females. The relative risk with hip protectors was 0.38 (SD: 0.28) for males overall, with subgroup values of 0.42 (SD: 0.29) for Chinese, 0.33 (SD: 0.29) for Indians, and 0.38 (SD: 0.26) for Malays. For females, the overall relative risk was 0.43 (SD: 0.28), with subgroup values of 0.41 (SD: 0.21) for Chinese, 0.37 (SD: 0.32) for Indian, and 0.51 (SD: 0.29) for Malay, with no significant differences between ethnicities. In conclusion, we have developed an in-silico tool to assess hip fracture risk and evaluate the effectiveness of hip protectors using clinical DXA scans. These findings support the adoption of hip protectors as a preventive measure to reduce fracture risk.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 6","pages":"ziag067"},"PeriodicalIF":3.0,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13156511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147867872","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":"From farm to lab: gene-edited sheep transforming bone research.","authors":"Raine Lunde-Young, Shannon Huggins, Jane H Pryor, Mark E Westhusin, Ken Muneoka, William J Murphy, Larry J Suva, Charles R Long, Dana Gaddy","doi":"10.1093/jbmrpl/ziag064","DOIUrl":"10.1093/jbmrpl/ziag064","url":null,"abstract":"<p><p>For more than half a century, mice have been the workhorse of biomedical research. Their small size, rapid reproduction, and well-characterized genetics make them ideal disease models, and genome editing has enabled transgenic, knock-out, and knock-in lines that mimic numerous human conditions. These advances transformed modern biology, yielding fundamental insights into cancer, metabolism, immunity, and more. Their strengths notwithstanding, mouse models have important limitations, as biology does not scale neatly across species. Differences in physiology, size, and metabolism can obscure-or even distort-experimental outcomes. Nowhere is this clearer than in musculoskeletal research. Human bones are dynamic tissues that undergo Haversian remodeling, whereas mice exhibit limited Haversian remodeling and display distinct temporal growth trajectories. Moreover, mice have monophyodont dentition and craniofacial development diverges in ways that impact maxillofacial studies, and aging timelines differ. These differences limit our ability to understand human bone disorders from murine models alone. Biotechnology offers a new path forward: advances in genome sequencing, assembly and molecular engineering enable precise DNA editing in larger domesticated species-sheep, goats, and pigs-whose skeletal size, biomechanics, growth patterns, and remodeling dynamics more closely mirror humans. By introducing targeted, patient-relevant mutations, large-animal models can replicate mechanisms difficult to capture in mice and support longitudinal, clinically-relevant phenotyping-imaging, histomorphometry, serum biomarkers, and functional testing-in a translatable human-like context. The implications are profound. Large-animal models can validate disease pathways, refine biomarkers, and evaluate drugs, biologics, and implants, potentially improving treatment strategies and reducing clinical failures and costs. This shift does not diminish the value of mice, whose genetic tractability and cost-effectiveness ensure a central and continued important role in discovery. Rather, it adds a complementary strategy: expand to gene-edited large-animal models when human skeletal-like biology matters and where mice fall short, thereby bridging the gap between fundamental research and clinical reality.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 7","pages":"ziag064"},"PeriodicalIF":3.0,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13232629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148163194","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":"Efficacy, pharmacodynamics, pharmacokinetics, safety, and immunogenicity of Bmab 1000 vs reference denosumab: 78-wk results from a randomized, double-blind, multicenter, parallel-arm Phase 3 trial (DEVOTE) in women with postmenopausal osteoporosis.","authors":"Richard Eastell, Eric Orwoll, Felicia Cosman, Rafal Plebanski, Kuldeep Kumar, Ashwani Marwah, Sarika S Deodhar, Elena Wolff-Holz, Subramanian Loganathan","doi":"10.1093/jbmrpl/ziag062","DOIUrl":"10.1093/jbmrpl/ziag062","url":null,"abstract":"<p><p>This randomized, double-blind, multicenter Phase 3 trial evaluated the efficacy, safety, pharmacodynamics (PD), pharmacokinetics (PK), and immunogenicity of Bmab 1000 vs reference denosumab in 479 women with postmenopausal osteoporosis. Participants (mean age 66.6 yr; lumbar spine T-score ≤-2.5 to ≥-4.0) were randomized 1:1 to receive 60 mg Bmab 1000 (<i>n</i> = 238) or reference denosumab (<i>n</i> = 241) subcutaneously. The study comprised 2 parts: Part 1 (weeks 0-52) evaluated therapeutic and PD equivalence between Bmab 1000 and reference denosumab using percentage change from baseline (%CfB) in lumbar spine bone mineral density (BMD) at week 52 and area under the effect curve (AUEC) of serum C-terminal telopeptide of Type 1 collagen (sCTX) from baseline to 26 wk following dosing on day 1 and week 26. Part 2 (weeks 52-78) re-randomized those on reference denosumab to either continue or switch to Bmab 1000 (<i>n</i> = 104 each), while those on Bmab 1000 continued treatment (<i>n</i> = 218). Part 2 monitored the safety of Bmab 1000 and reference denosumab after transition from reference denosumab to Bmab 1000 vs continuing reference denosumab. Secondary analyses included additional efficacy, PD, PK, safety, and immunogenicity parameters. At week 52, the confidence intervals (CIs) for the difference in least square means (LSMs) in %CfB in lumbar spine BMD between Bmab 1000 and reference denosumab were contained within the predefined margins (±1.45; LSM diff: 0.610, 95% CI: -0.095, 1.316), indicating therapeutic equivalence. The sCTX AUEC up to 26 wk for Bmab 1000 and reference denosumab were similar (geometric LSM ratio: 104.14; 95% CI: 97.76, 110.95). The secondary results were comparable among all groups up to week 78, including after transitioning to Bmab 1000 from reference denosumab. In conclusion, Bmab 1000 demonstrated equivalent efficacy and PD to reference denosumab, with similar PK, safety, and immunogenicity profiles. There was no effect of transitioning from reference denosumab to Bmab 1000. Clinical trial registration: EudraCT number: 2021-006545-36, CT.gov number: NCT05345691.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 6","pages":"ziag062"},"PeriodicalIF":3.0,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13156503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147868077","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":"Sex-dependent mechanisms of temporomandibular joint osteoarthritis.","authors":"Dimitri Sokolowskei, Aaron W James, Cong-Qiu Chu, Robert J Tower, Ginny C-Y Hsu","doi":"10.1093/jbmrpl/ziag063","DOIUrl":"10.1093/jbmrpl/ziag063","url":null,"abstract":"<p><p>Temporomandibular joint osteoarthritis (TMJ OA) is a prevalent degenerative disease characterized by chronic pain and impaired jaw function. Similarly to other OA affected limb joints, TMJ OA has shown increased prevalence across several demographic and biological factors. These risk factors include sex, with female patients reporting twice the incidence rate and suffering from greater symptom severity compared to male patients. However, due to a lack of relevant preclinical models, there is limited knowledge related to how sex differences impact TMJ OA pathophysiology. With increasing attention in women's health, we aim to understand the molecular mechanisms underlying sexually-dimorphic TMJ OA pathogenesis. Using the burn-synovectomy mouse model to induce TMJ OA, which mimics the elevated inflammatory cytokines associated with chronic stressors and local TMJ derangement, we observed more severe cartilage and subchondral bone abnormalities in females consistent with findings in patients. Single-cell RNA sequencing (scRNA-seq) and histology revealed that females had an increased inflammatory response, both in terms of immune cell abundance as well as in their inflammatory gene signature, compared to male animals. Additional analyses also showed that female mice downregulated major morphogenetic pathways, such as WNT, BMP TGF-β, and FGF, within osteochondral cell populations, while simultaneously increasing expression of extracellular matrix remodeling enzymes. These results demonstrate the sexual-dimorphisms in disease initiation and progression leading to the differentially observed TMJ OA phenotypes. The data herein may explain the incident tendency and symptom severity in female patients and suggest sex-dependent treatment strategies for future patient care.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 6","pages":"ziag063"},"PeriodicalIF":3.0,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13156496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147868338","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":"Delayed diagnosis of mucopolysaccharidosis type I in a patient with spinopelvic instability, short stature, and skeletal dysplasia.","authors":"Oskar Windels, Mona Lindschau, Felix Boschann, Ralf Oheim, Nicole Muschol","doi":"10.1093/jbmrpl/ziag065","DOIUrl":"10.1093/jbmrpl/ziag065","url":null,"abstract":"<p><p>Pathogenic variants in <i>IDUA</i>, encoding α-L-iduronidase (IDUA), cause the autosomal recessive lysosomal storage disorder mucopolysaccharidosis type I (MPS I). Deficiency of α-L-iduronidase leads to the accumulation of partially degraded glycosaminoglycans in various tissues, including the musculoskeletal system. Clinically, typical skeletal manifestations are dysostosis multiplex, joint contractures, and low BMD. Mucopolysaccharidosis type I represents a spectrum of disease severity. Especially in attenuated disease, establishing an accurate diagnosis and initiating disease-specific therapy, including enzyme replacement therapy (ERT) and osteological treatment, is challenging. A 33-yr-old female patient presented with a history of juvenile idiopathic arthritis, persistent spinopelvic instability, and reduced BMD. Multiple surgical attempts to stabilize the spinopelvic nonunion had failed, thus osteological co-treatment with teriparatide to promote bone healing was recommended. Despite a significant BMD increase, spinopelvic nonunion persisted. Given the combination of short stature, joint contractures, and corneal clouding, a genetic skeletal dysplasia was suspected. Exome sequencing (ES) was inconclusive, whereas short-read genome sequencing (GS) revealed the combination of a 14 kb deletion and a promotor variant in <i>IDUA</i>. Thus, the diagnosis of MPS I in the attenuated form was made, and ERT was initiated. This case highlights the importance of considering MPS I in patients with short stature, joint contractures, skeletal dysplasia, and low BMD. Diagnosis can be overlooked in this attenuated form, underscoring the value of genetic testing, with GS offering advantages over ES. These findings emphasize the need for early diagnosis, systematic osteological evaluation, and individualized treatment strategies in patients with skeletal dysplasia.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 6","pages":"ziag065"},"PeriodicalIF":3.0,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13156509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147868428","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":"Wnt5a gain- and loss-of-function in bone have distinct craniofacial phenotypes.","authors":"Claire J Houchen, Portia Hahn Leat, Cassandra Delich, Jocelyn Vang, Sara Yingling-Haggard, Joseph L Roberts, Hicham Drissi, Erin E Bumann","doi":"10.1093/jbmrpl/ziag060","DOIUrl":"10.1093/jbmrpl/ziag060","url":null,"abstract":"<p><p>Robinow syndrome has characteristic craniofacial and dental features and can be caused by gain- or loss-of-function variants in Wnt family member 5A (<i>WNT5A</i>) non-canonical signaling. The craniofacial and dental manifestation of Robinow syndrome is heterogenous, as is the effect of altered <i>Wnt5a</i> in animal models. The relationship between <i>Wnt5a</i> and craniofacial and dental phenotypes is not fully understood. To investigate the role of <i>Wnt5a</i> in bone during craniofacial and dental development, we utilized a <i>Wnt5a</i> conditional loss-of-function (LOF: <i>Wnt5a^fl/fl;Ctsk^cre</i> ) and a <i>Wnt5a</i> conditional gain-of-function (GOF: <i>Rosa26-LSL-Wnt5a;Ctsk^cre</i> ) model to determine the effect of both LOF and GOF of <i>Wnt5a</i> in bone cells during craniofacial and dental development. Postnatal day 10 conditional LOF <i>Wnt5a</i>, GOF <i>Wnt5a</i>, and control skulls were scanned by micro-CT and assessed using traditional and geometric morphometrics. Mandibular bone apoptosis was further assessed by TUNEL staining. Conditional <i>Wnt5a</i> LOF resulted in midface hypoplasia, increased maxillary intermolar width, increased rostral basisphenoid width, and delayed molar eruption. <i>Wnt5a</i> LOF mandibles did not have altered BMD or bone microarchitecture unlike our previous study examining <i>Wnt5a</i> LOF femurs. In contrast, conditional <i>Wnt5a</i> GOF results in macrocephaly, shortened hard palate, increased zygomatic length, micrognathia, and mandibular process dysmorphology. The micrognathia and mandibular process dysmorphology in the <i>Wnt5a</i> GOF mice were not due to increased apoptosis. A partially penetrant snout deviation was present in both the <i>Wnt5a</i> LOF and GOF mice. Craniofacial and dental phenotype differed between mice with conditional GOF and LOF of <i>Wnt5a</i>, consistent with the craniofacial phenotype heterogeneity in <i>WNT5A</i>-associated Robinow syndrome. We detected tooth eruption delay, mandibular condyle dysmorphology, and facial asymmetry in mice with altered <i>Wnt5a</i> that have not been previously reported in patients with <i>WNT5A</i>-associated Robinow syndrome. Our data suggest precise regulation of <i>Wnt5a</i> is essential for proper craniofacial and dental development.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 6","pages":"ziag060"},"PeriodicalIF":3.0,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13156483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147868273","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}