JBMR Plus最新文献

{"title":"Micro-CT-based analysis of the murine osteochondral unit: a review and recommendations for standardized subchondral bone assessment.","authors":"Cecilia Liberati, G Harry van Lenthe","doi":"10.1093/jbmrpl/ziag068","DOIUrl":"10.1093/jbmrpl/ziag068","url":null,"abstract":"<p><p>Micro-CT enables high-resolution, 3D, and non-destructive visualization of bone microarchitecture in small preclinical animal models. It is widely applied to assess mineralized tissues in joints, making it a valuable tool for monitoring disease progression. Murine models are particularly prevalent in joint research due to their cost-effectiveness and disease tunability. Established guidelines for murine bone microstructure assessment provide a standardized framework for morphometric analysis and facilitate cross-study comparisons. However, these recommendations were developed for trabecular and cortical bone in long bones, and may not fully address the unique characteristics of mineralized tissues within joints. This review focuses on murine studies, and aims to: (1) examine reported methodologies for volume of interest selection; (2) outline commonly evaluated parameters; and (3) propose adaptations to expand existing guidelines for quantitative analysis of the osteochondral unit. In the absence of specific guidelines for osteochondral unit analysis, reported volumes of interest vary considerably and are influenced by anatomical differences across strains, sexes, ages, and disease stages. Many studies target the subchondral bone plate (SBP); however, the spatial resolution of desktop microCT is insufficient to distinguish SBP from calcified cartilage; hence, they are measured as 1 entity. To enhance reproducibility and comparability, we recommend standardized volumes of interest that include all mineralized tissues from the articular surface to the growth plate. Given the structural differences between SBP and subchondral trabecular bone, a consistent method for defining their boundary is strongly recommended. Data should be reported using robust, easily implementable metrics such as volume and thickness, with additional parameters (eg, porosity, mineral density) included as appropriate. Commonly used metrics such as SBP thickness and volume should continue to be used. When SBP and calcified cartilage cannot be distinguished, we recommend using the subchondral mineralized plate nomenclature.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 7","pages":"ziag068"},"PeriodicalIF":3.0,"publicationDate":"2026-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13313321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148351960","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":"Influencing factors and early warning indicators for nonvertebral fractures in patients with Duchenne muscular dystrophy.","authors":"Changping Yan, Sen Kou, Shu Zhang, Pei Zhang, Yuandai Mao, Yang Liu, Shaoxia Wang, Ye Lin, Shanshan Kong, He Zhao, Sai Gao, Shengyuan Yu, Shiwen Wu","doi":"10.1093/jbmrpl/ziag098","DOIUrl":"10.1093/jbmrpl/ziag098","url":null,"abstract":"<p><p>Nonvertebral fractures (NVFs) in patients with Duchenne muscular dystrophy (DMD) are often associated with an unfavorable prognosis. However, the influencing factors and early warning indicators for NVFs remain unclear. To address this knowledge gap, a retrospective cohort study was conducted across 2 centers involving 295 DMD patients who were evaluated between August 2013 and February 2022. Data collection included telephone callback records and outpatient face-to-face assessments. Among the 295 patients, 30 (10.2%) had experienced at least 1 NVF. The overall NVF incidence rate was 91.8 (95% CI, 62.4-130.3) per 10 000 person-years, representing a rate more than 5 times higher than that of traumatic NVFs in boys aged 0-14 yr. This finding underscores the significant burden of NVFs in DMD patients. Subsequent analysis investigated the association between the occurrence of the first NVF and various factors, including ambulant status, glucocorticoid (GC) regimen, and dystrophin isoform expression. Multivariate analysis revealed that ambulation was a significant risk factor for the first NVF, with an increased risk of 29.2-fold (95% CI, 3.9-217.3, <i>p <</i> .001). In contrast, a longer GC-naïve duration exhibited a protective effect against the first NVF, reducing the risk to 0.804-fold per year (95% CI, 0.691-0.936, <i>p =</i> .005). In patients aged 8-13 yr, motor function parameters 1 yr before the first NVF, including the 6-min walking distance (6MWD), the 10-m walking test time (10mWT), and the time from supine to standing (TSS), were significantly worse compared with those without NVF. Specifically, the 6MWD was shorter (<i>p</i> = .007), while 10mWT and TSS were longer (<i>p</i> = .025 and <i>p</i> = .020, respectively). Receiver operating characteristic curves indicated that a 6MWD of 248.2 m and a 10mWT of 9.85 s were the optimal cut-off values for predicting the onset of the first NVF, suggesting that a decline in the 6MWD to ~250 m and an increase in the 10mWT to ~10 s may serve as early warning indicators.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 8","pages":"ziag098"},"PeriodicalIF":3.0,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13332812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148390449","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":"Enamel matrix acidification caused by loss of amelogenin phosphorylation disrupts ameloblast pH-regulatory machinery.","authors":"Ai Thu Bui, Lasya Bhogadi, Henry C Margolis, Elia Beniash","doi":"10.1093/jbmrpl/ziag096","DOIUrl":"10.1093/jbmrpl/ziag096","url":null,"abstract":"<p><p>Amelogenin (AMELX), the predominant extracellular enamel matrix protein, contains a single phosphorylation site at serine16 (S16). To investigate the functional significance of AMELX phosphorylation, we generated a knock-in (KI) mouse model (<i>Amelx^S16A</i> ) in which S16 is substituted with alanine, preventing AMELX phosphorylation. These KI mice exhibited hypoplastic, hypomineralized enamel lacking a characteristic rod structure, demonstrating that AMELX phosphorylation is critical for dental enamel formation. Mineralization analysis revealed accelerated formation of carbonated hydroxyapatite (CHA) and rapid transformation of amorphous calcium phosphate to CHA during the secretory stage, resulting in enamel acidification. Based on these findings, we hypothesized that excessive acidity disrupts pH regulation in KI ameloblasts. To test this hypothesis, we examined the mRNA and protein expression of 3 carbonic anhydrases (CAs) involved in pH regulation: intracellular CA2, transmembrane CA9, and extracellular CA6, localized their distribution; and measured total CA enzymatic activity in enamel organs (EOs) and matrix lysates. Additionally, we assessed the mRNA expression of 4 ion transporters (Slc4a4, Slc24a3, Slc24a4, and Cftr) involved in pH regulation. Our results revealed significant downregulation of all studied genes during the secretory stage in KI vs WT mice, with a general trend of reduced expression during maturation. Consistent with these findings, CA activity was markedly lower in KI EOs. Collectively, these data indicate that AMELX phosphorylation supports ameloblast function by stabilizing enamel pH during the secretory stage of amelogenesis through its capacity to slow the rate of enamel mineral formation and prevent enamel acidification. In the absence of AMELX phosphorylation, excessive acidity overwhelms ameloblast pH regulation, leading to dysregulation and defective enamel. This study provides evidence that the loss of biological control over extracellular mineralization can lead to cellular disruption, highlighting a critical link between protein phosphorylation, mineralization kinetics, and pH regulation.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 8","pages":"ziag096"},"PeriodicalIF":3.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13332813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148390475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The current state of computed tomography in osteoarthritis research.","authors":"Ryo Yoshikawa, Abhinav Boddu, Tom D Turmezei, Neil A Segal","doi":"10.1093/jbmrpl/ziag095","DOIUrl":"10.1093/jbmrpl/ziag095","url":null,"abstract":"<p><p>CT has evolved into a complementary tool for three-dimensional (3-D) structural assessment in OA research. This review highlights advances across key domains of CT-based OA imaging: structural features, shape modeling, alignment, contact stress modeling, bone morphometry and BMD, articular cartilage, meniscus, and combination with other modalities. CT's high-resolution bone visualization enables accurate quantification of osteophytes, subchondral bone cysts, and sclerosis, as well as precise measurement of joint space width (JSW). The high geometric fidelity of CT also facilitates 3-D bone shape modeling. Additionally, CT supports dynamic evaluation of joint mechanics, including articular contact stress estimates. Weight-bearing CT enables functional assessment of joint alignment and JSW under physiologic loads. QCT, HR-pQCT, and micro-CT support detailed analysis of periarticular bone morphometry and BMD, capturing microarchitectural changes linked to OA severity. CT arthrography provides high-contrast visualization of articular cartilage and has shown superior sensitivity over MRI for detecting cartilage and meniscal defects. Dual-energy CT enables material differentiation, offering a noninvasive alternative to arthrocentesis. Spectral photon-counting CT combines ultra-high spatial resolution with multi-energy tissue characterization, improving the accuracy of compositional and structural assessment. Moreover, CT provides the anatomical framework for hybrid imaging modalities, such as PET CT and SPECT CT, which can assess bone metabolic activity. Together, these emerging CT modalities allow detailed 3-D analysis of bone geometry and subchondral changes, as well as evaluation of cartilage thickness and meniscal integrity, alongside accurate 3-D alignment measurements. These advances establish CT as a versatile platform for developing OA imaging biomarkers, monitoring disease progression, and enhancing clinical trial outcomes. Insights gained from these technologies will continue to inform future OA research and guide clinical decision-making.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 7","pages":"ziag095"},"PeriodicalIF":3.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13298875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148345303","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":"A single site, multi-operator precision study for second-generation HR-pQCT.","authors":"Joshua R Stapleton, Nina Z Heilmann, Kristin Cattell, Andrew J Burghardt, Daniel P Beavers, Diana A Madrid, Kambrie M Brandt, S Delanie Lynch, Ashley A Weaver","doi":"10.1093/jbmrpl/ziag097","DOIUrl":"10.1093/jbmrpl/ziag097","url":null,"abstract":"<p><p>As HR-pQCT increases in popularity for studying bone dynamics, it becomes increasingly important to quantify the factors that impact rigor and reproducibility in research, particularly for longitudinal studies. Previously reported data for HR-pQCT precision primarily use first-generation HR-pQCT, and focus on single operators, with narrow study populations that reflect the population of a larger research question. This study at a single academic imaging center with standardized, single-analyst post-processing was designed to investigate how operator characteristics in scan acquisition and participant demographics influence measurement precision. In total, 45 adults (58% female; 22-82 yr; BMI 18.4-44.8 kg/m²) underwent same-day repeat HR-pQCT scanning of the distal tibia and radius, with 3 imaging technologists each acquiring 15 participant scan pairs, and registration was applied in post-processing to accurately depict the standard workflow at the center. The root-mean-square coefficient of variation was ≤1.3% for BMD measures and <2% for area measures in both the radius and tibia. Trabecular microarchitecture ranged from 1.22% to 2.24% in the radius and from 1.14% to 2.82% in the tibia, while cortical thickness precision was calculated as 1.99% in the radius and 1.57% in the tibia. Cortical porosity was much higher, at 24.66% in the radius and 20.90% in the tibia. Significant differences were not found when analyzed by technologists, or in statistical modeling of participant demographics as potential covariates. While final image quality scores varied among technologists, it did not influence precision outcomes. These results offer reference values for the least significant change and demonstrate that standardized technologist training can yield consistent scan-rescan precision across operators.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 7","pages":"ziag097"},"PeriodicalIF":3.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13283432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148301685","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":"Effectiveness, safety, and pharmacokinetics of burosumab in Chinese children with X-linked hypophosphatemia: an open-label, single-arm phase 4 study.","authors":"Wei Wu, Yan Jiang, Zhenlin Zhang, Li Liu, Wenjuan Qiu, Ying Ji, Maiko Sugimoto, Chinwei Yung, ChenRui Qiu, Masaaki Kuriki, Xiaoping Luo, Weibo Xia","doi":"10.1093/jbmrpl/ziag094","DOIUrl":"10.1093/jbmrpl/ziag094","url":null,"abstract":"<p><p>Burosumab has shown benefits in treating X-linked hypophosphatemia (XLH), a rare genetic bone disorder that causes rickets among pediatric patients. However, data in Chinese children with XLH are lacking. Therefore, we evaluated the effectiveness, safety, and pharmacokinetics of burosumab among Chinese children (aged 1-12 yr) with XLH in this open-label, multi-center, single-arm, phase 4 study. Of the 28 patients enrolled (12 male, 16 female), 27 completed the study. All patients received s.c. injections of burosumab at a starting dose of 0.8 mg/kg every 2 wk for 64 wk. The mean ± SD patient age was 5.68 ± 3.07 yr. Burosumab treatment increased the serum phosphorus level by 0.96 ± 0.27 mg/dL from baseline during the burosumab dose cycles (average of week 2, 4, 8, 12, 16, 24, 32, 40, 52, and 64). The improvement from baseline (2.33 ± 0.24 mg/dL) to week 64 (3.29 ± 0.30 mg/dL) was significant (<i>p</i> < .05). The Radiograph Global Impression of Change was significantly improved at week 64 (1.90 ± 0.48; <i>p</i> < .0001 vs baseline), and the percentage predicted 6-min walking test among patients aged ≥5 yr with post-baseline values (<i>n</i> = 16) was significantly increased from 67.32% ± 8.27% at baseline to 71.91% ± 8.25% at week 64 <i>(p</i> < .05). All patients experienced treatment-emergent adverse events; most were mild to moderate. In conclusion, burosumab treatment in Chinese children with XLH corrected serum phosphorus levels and improved clinical parameters with tolerable safety profiles.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 7","pages":"ziag094"},"PeriodicalIF":3.0,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13376143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148578714","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 index of net bone formation relative to resorption is associated with incident fracture during the menopause transition and postmenopause.","authors":"Albert Shieh, Arun S Karlamangla, Fatma Gossiel, Richard Eastell, Sherri-Ann Burnett-Bowie, Gail A Greendale","doi":"10.1093/jbmrpl/ziag092","DOIUrl":"10.1093/jbmrpl/ziag092","url":null,"abstract":"<p><p>We previously created a bone balance index (BBI) that combines bone resorption and formation markers (CTX and PINP, respectively) to estimate bone balance. The bone balance index quantifies net bone formation relative to resorption; greater values indicate a more favorable balance. This study examined the association of the BBI with incident fracture across the menopause transition and tested each individual bone turnover marker (BTM) (either CTX or PINP) as a separate predictor of fracture. We included 451 participants from the Study of Women's Health Across the Nation (SWAN) cohort study, with 2667 longitudinal observations from pre-, early peri-, late peri-, or post-menopause. Participants did not report fractures or the use of bone-active medications before their BTM assessments. Using repeated measures Cox proportional hazards regression, we examined the associations of the BBI, CTX, or PINP with 2 different fracture outcomes: incident fracture at any site or incident fracture at a major osteoporotic fracture (MOF) site (spine, hip, radius, or humerus). Women were censored at the first use of bone-beneficial medications during follow-up. Covariates were age, BMI, race/ethnicity, family history of hip fracture, cigarette use, diabetes mellitus, bone-detrimental medication use, menopause transition stage, FN BMD, and SWAN study site. The mean age across the BBI, CTX, and PINP assessments was 52 yr. Seventy-eight women sustained an incident fracture over a 15.1 yr of follow-up. Adjusted for covariates, each SD increment in the BBI was associated with a 20% smaller hazard for fracture at any site (hazard ratio [HR] [95% CI]: 0.80 [0.67, 0.97], <i>p</i> = .02) or a 25% lesser hazard for fracture at a MOF site (HR [95% CI]: 0.75 [0.61, 0.85]), <i>p</i> = .01). In contrast, when considered singly in adjusted analyses, neither CTX (<i>p</i> > .2) nor PINP (<i>p</i> > .1) was related to either fracture outcome. We conclude that BBI predicts fracture, independent of clinical and densitometric fracture risk factors.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 7","pages":"ziag092"},"PeriodicalIF":3.0,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13271363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148271367","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":"Quantitative traits of early-stage osteochondrosis lesions in porcine distal femurs are consistent with skeletal developmental age.","authors":"Brittney P Kokinos, Pamela J Lang, Laura A Amundson, Matthew A Halanski, Thomas D Crenshaw","doi":"10.1093/jbmrpl/ziag091","DOIUrl":"10.1093/jbmrpl/ziag091","url":null,"abstract":"<p><p>Early-stage osteochondrosis (OC) lesions are focal failures of endochondral ossification in the physeal and epiphyseal regions. Lesions are initially detected and quantified as ossification variants using non-invasive imaging methods. The etiology of OC lesions is not understood, as early-stage lesions are rarely imaged in children or animals until symptoms advance to stages that require intervention. The distal femur, a common site for OC lesions, provides an easily accessible, anatomical location to study early-stage development. Non-invasive CT and MRI techniques for distinguishing early-stage lesions were compared in images collected from Cross-sectional and Longitudinal Studies. Osteochondrosis lesion traits in the physeal and epiphyseal regions of swine distal femurs were quantified. Cross-sectional subjects were randomly selected from asymptomatic, crossbred swine at 7, 12, and 24 wk of age. A longitudinal cohort was repeatedly imaged at 6, 12, and 18 wk of age. Subsets of femurs from each age group were selected for histological analysis. Ossification variants defined as abnormal physeal widths without defined OC lesions, were observed at 7 wk. At 12 wk, 2.7 ± 1.8 physeal lesions per pig with an average volume = 9.8 ± 10.0 mm³ were quantified but no epiphyseal lesions were detected. At 24 wk, similar numbers (2.1 ± 1.4) of epiphyseal and physeal lesions were observed. Epiphyseal lesions had greater volumes (44.5 ± 53.5 mm³). At 24 wk, atypical ossification variants not previously characterized, were unexpectedly observed in over 40% of the femurs. These large, undefined regions characterized by extreme undulations and irregular mineralization without physeal widening were labeled irregular physeal lesions. Although the quantitative outputs differed, both CT and MRI methods yielded consistent inferences regarding the developmental age and location (primary vs secondary centers of ossification) of OC lesion progression across Cross-sectional and Longitudinal Studies. These outcomes support future research efforts to identify pivotal molecular signals controlling the initiation, progression, and regression of early-stage lesion development.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 7","pages":"ziag091"},"PeriodicalIF":3.0,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13318846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148368271","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":"Mechanisms limiting the long-term anabolic effects of teriparatide (PTH 1-34) on bone.","authors":"Clarissa Schmal, Joy Y Wu, Abbas Jafari","doi":"10.1093/jbmrpl/ziag093","DOIUrl":"10.1093/jbmrpl/ziag093","url":null,"abstract":"<p><p>Teriparatide, (recombinant human PTH 1-34) is an Food and Drug Administration (FDA)-approved anabolic therapy for osteoporosis. In patients with severe bone loss, daily teriparatide injections increase osteoblastic activity and bone turnover, leading to net gain in bone mass, increased BMD, and significantly reduced fracture risk. However, after 6-12 mo of treatment, its anabolic effects, reflected by increased serum bone turnover markers and LS-BMD gain, tend to diminish. Despite various efforts to address this challenge, the underlying mechanisms have remained poorly understood. This review discusses the main mechanisms proposed to limit teriparatide's bone anabolic potential, including osteoprogenitor depletion, changes in bone remodeling dynamics, counter-regulatory molecules (eg, Wnt inhibitors), the influence of mechanical loading, and downstream signaling adaptations. Understanding these mechanisms is important for optimizing osteoporosis therapy and developing strategies to extend teriparatide's \"anabolic window.\"</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 7","pages":"ziag093"},"PeriodicalIF":3.0,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13267908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148264418","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":"Crosstalk with bone marrow adipocytes, but not osteoblasts, drives a cortical bone resorption phenotype in female mice with adult-onset deletion of the glucocorticoid receptor in Osterix-expressing cells.","authors":"Jaeshia Lindsay, Husam Bensreti, Colby Gross, Alok Tripathi, David Maridas, Maribeth Johnson, Xingming Shi, Wendy B Bollag, Carlos M Isales, Meghan E McGee-Lawrence","doi":"10.1093/jbmrpl/ziag090","DOIUrl":"10.1093/jbmrpl/ziag090","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs) and heterogeneous bone marrow stromal cells (BMSCs) are multipotent progenitors that can differentiate into osteoblasts and bone marrow adipocytes (BMAd). The role of BMAd in skeletal homeostasis is not yet fully understood, in part due to a lack of reproducible in vitro models that faithfully mimic the biology and molecular signatures of BMAds to study their behavior. Here, we report the in vitro generation of murine BMSC- and MSC-derived Osterix-expressing BMAd-like cells via a trans-differentiation model (TD-BMAd), the development of a semi-automated analysis platform for quantification of lipid-laden cells, and the use of these models to interrogate the role of the glucocorticoid receptor (GR) in bone marrow adipose tissue (BMAT) as a regulator of osteoclastic bone resorption. The TD-BMAd cells stored intracellular lipids and robustly expressed BMAd-associated genes, such as <i>Sp7</i>/Osx, <i>Pparg</i>, and <i>Adipoq</i>. The pro-osteoclastogenic gene <i>Tnfsf11</i>/Rankl was comparably expressed between TD-BMAd and osteoblasts. We previously reported that female mice with adult-onset conditional KO (CKO) of the GR in Osx-expressing cells exhibited a low cortical bone mass and high BMAT phenotype. Here, we demonstrate that this phenotype was associated with an increase in the abundance of cortical bone osteoclasts in female but not male GR-CKO mice, but that surprisingly, GR-deficient osteoblasts from these mice did not express higher levels of pro-osteoclastogenic Rankl. Instead, TD-BMAd from female (but not male) GR-CKO mice expressed significantly higher levels of Rankl as compared to cells from GR-WT mice, suggesting that GR-deficient BMAT may be the source of the sexually dimorphic osteoclastogenic phenotype seen in vivo. Although this methodology is not intricate in nature, this simple culture technique and subsequent quantification platform may have broader utility for further studies of BMAd biology and lipid-laden cells.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 7","pages":"ziag090"},"PeriodicalIF":3.0,"publicationDate":"2026-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13249019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148217877","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}