JBMR Plus最新文献

{"title":"Are machine learning models superior to logistic regression models to predict 30-day mortality post-hip fracture surgery?","authors":"Zeinab Issa, Fouad Trad, Ryan Yammine, Caline Rhayem, Aya Ghosn, Joudie Alwan, Hani Tamim, Rachid Haidar, Ali Chehab, Ghada El-Hajj Fuleihan","doi":"10.1093/jbmrpl/ziag079","DOIUrl":"10.1093/jbmrpl/ziag079","url":null,"abstract":"<p><p>Hip fractures represent a significant global health burden, with high mortality rates. Accurate prediction of 30-d postoperative mortality is instrumental to optimize patient care. This study aimed to validate previously developed logistic regression and machine learning (ML) models for predicting 30-d mortality after hip fracture surgery measured from the date of the index operation (counting deaths occurring in-hospital or within 30 d after surgery) and compare their performance against one established calculator. We included 47 276 patients aged ≥65 yr who underwent hip fracture surgery, excluding cancer, atypical, pathologic, and stress fractures. We applied previously derived logistic regression and ML equations from the 2011 to 2017 National Surgical Quality Improvement Program (NSQIP) dataset, to the updated 2018-2020 dataset. We developed 2 models for each, one derived on admission and one taking into account operative course. For each of these models, we also developed a full model and a parsimonious counterpart. We assessed discrimination using the area under the curve (AUC) metric. We compared AUCs for models with the DeLong test. We developed an online calculator for our most highly performing model. We also benchmarked our preoperative logistic and ML calculators against a previously published preoperative model. The logistic models demonstrated acceptable to good discrimination with AUCs as follows: preoperative full of 0.756, preoperative parsimonious of 0.748, postoperative full of 0.829, and postoperative parsimonious of 0.817. Machine learning models maintained good discrimination performance: preoperative full, 0.772; preoperative parsimonious, 0.751; postoperative full, 0.865; and postoperative parsimonious, 0.838. Machine learning models were slightly superior to logistic regression models. A previously published model by Harris et al. had more variables and demonstrated no significant superiority. Both logistic regression and ML approaches offer clinically useful predictions for 30-d mortality after hip fracture surgery. Prospective validation in other populations and then integration of the parsimonious models into clinical practice may enhance perioperative decision-making and possibly patient outcomes.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 7","pages":"ziag079"},"PeriodicalIF":3.0,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13267897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148264448","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":"Development of bone alkaline phosphatase-specific monoclonal antibodies and immunoassay exhibiting low cross-reactivity to liver isoform.","authors":"Tatsuji Kimura, Shiomi Ojima, Kosuke Doi","doi":"10.1093/jbmrpl/ziag080","DOIUrl":"10.1093/jbmrpl/ziag080","url":null,"abstract":"<p><p>Tissue-nonspecific alkaline phosphatase (TNSALP) is an enzyme that catalyzes the hydrolysis of phosphomonoesters and promotes mineralization of bone. Tissue-nonspecific alkaline phosphatase contains 5 N-glycosylation sites: N140, N230, N271, N303, and N430. Bone alkaline phosphatase (BALP) and liver alkaline phosphatase (LALP) are isoforms of TNSALP. Despite sharing identical amino acid sequences derived from the single gene <i>ALPL</i>, these isoforms exhibit different glycosylation patterns. As osteoblasts express BALP, serum BALP levels reflect osteoblastic activity and are used as markers of bone formation. However, distinguishing serum BALP from coexisting LALP is challenging, as the 2 isoforms differ only in carbohydrate composition. Moreover, while BALP-specific immunoassays using BALP-selective mAbs are currently used in clinical laboratories, they exhibit significant cross-reactivity with LALP, highlighting the need for more selective assays for BALP. In the present study, we developed mAbs against BALP with minimal cross-reactivity to LALP. Using these mAbs, we generated an in-house BALP-specific immunoassay that exhibited high correlation with a clinically approved BALP test kit. Using a series of single N-glycosylation site mutants of TNSALP, we found that all 6 clones of BALP-selective mAbs recognized an epitope relevant to N303-linked glycans. These mAbs could facilitate the development of improved BALP assays with reduced cross-reactivity to LALP, enabling a more accurate diagnostic evaluation, particularly in patients with liver disease.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 6","pages":"ziag080"},"PeriodicalIF":3.0,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13184525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147981816","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":"Transcutaneous vagal nerve stimulation improves post-traumatic osteoarthritis pain in mice.","authors":"Shivmurat Yadav, Lynsie Morris, Taylor Conner, Jessica Lumry, Sanique M South, Emmaline Prinz, Vladislav Izda, Gabby Dyson, Montana Barrett, Pratibha Dube, Nicholas Hanebutt, Cindy Brawner, Stavros Stavrakis, Matlock A Jeffries, Timothy M Griffin, Mary Beth Humphrey","doi":"10.1093/jbmrpl/ziag078","DOIUrl":"10.1093/jbmrpl/ziag078","url":null,"abstract":"<p><p>Vagus nerve stimulation (VNS) has been shown to improve chronic pain, including fibromyalgia, migraine headaches, and gastrointestinal pain, as well as inflammation in RA. Here, we investigated the efficacy of transcutaneous VNS (tVNS) in providing pain relief in a mouse model of post-traumatic osteoarthritis (PTOA). Destabilization of the medial meniscus (DMM) surgery was performed in 16-wk-old female and male mice. Beginning at 4 wk post-injury, mice were randomized to receive tVNS (10 min daily, 5 d per wk) delivered via the tragus of the ear or sham stimulation for 8 wk. Mechanical hyperalgesia, as measured using an algometer, and weight distribution were monitored at 3 time points: (1) pre-VNS, (2) 4-wk treatment, and (3) 8-wk treatment (end point of the study). Compared to the sham treatment, 4 wk of tVNS reduced mechanical hyperalgesia in female mice, and 8 wk of tVNS improved weight-bearing in male and female mice. tVNS altered serum pro-inflammatory cytokine and chemokine levels in a sex-dependent manner. Eight weeks of tVNS improved the lateral femur compartment of the DMM-affected joints in males. Our results reveal that tVNS improves PTOA-related pain and suppresses pro-inflammatory cytokine production, making it a promising, non-addictive intervention for chronic OA pain.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 6","pages":"ziag078"},"PeriodicalIF":3.0,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13184521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147981827","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":"Design and validation of a perfusion bioreactor for long-term human bone explant culture.","authors":"Mahsa Zojaji, Annelise G Pageau, Teodora Maluckov, Johannes Eichwalder, Mariya Peskova, Corey Smith, George S Athwal, Maud Gorbet, Louis M Ferreira, Nikolas Knowles","doi":"10.1093/jbmrpl/ziag081","DOIUrl":"10.1093/jbmrpl/ziag081","url":null,"abstract":"<p><p>Ex vivo bone cultures offer a unique platform to study mechanobiology by preserving bone cells and marrow within their native extracellular matrix. We present a 3D-printable modified ZetOS bioreactor for long-term ex vivo culture of human osteoarthritic trabecular bone. Computational fluid dynamics simulations guided design optimization and supported improved average flow velocity and shear stress throughout the central region of the bone construct in the modified bioreactor design. Humeral head osteotomies from four osteoarthritic patients (age: 65-77 yr, 1 female, 3 males) were prepared within 2 h of surgery. Trabecular bone cores ([Formula: see text]9.15 ± 0.14 [Formula: see text] 9.5 ± 2.0 mm) were cultured under static conditions (<i>n</i> = 6) or perfused at 252 μL/min (dynamic I, <i>n</i> = 7) or 752 μL/min (dynamic II, <i>n</i> = 9). Cellular metabolic activity, alkaline phosphatase (ALP), and lactate dehydrogenase levels were monitored on 4 time-points. Genomic content (DNA and cell viability) were assessed during the culture period, and micro-CT (μCT)-based morphometric analysis was performed after completion of the culture. Perfused cores maintained high metabolic activity and showed significantly higher ALP activity compared with static culture, indicating that fluid shear stress alone promotes osteogenic differentiation. Lactate dehydrogenase release decreased more rapidly in dynamic cultures, suggesting reduced cellular stress under perfusion. DNA content was higher in perfused cores with showed no significant differences. Morphometric analysis from μCT showed no significant differences, likely due to small sample size and inter-donor variability. Power analysis indicated that the current sample sizes were adequate for identifying large changes within groups but were insufficient to reliably detect small between-group differences. The modified ZetOS bioreactor proved biocompatible for long-term ex vivo culture of human trabecular bone tissue, preserving cell viability and enhancing osteogenic activity, while providing a robust platform to evaluate potential biomarkers and guide the development of bone-targeted therapies.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 6","pages":"ziag081"},"PeriodicalIF":3.0,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13192549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015485","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- and site-specific reference data for size-invariant properties using multi-stack HRpQCT.","authors":"Simone Poncioni, Dominique Lüscher, Michael Indermaur, Daniela A Frauchiger, Christian Meier, Philippe Zysset, Kurt Lippuner","doi":"10.1093/jbmrpl/ziag077","DOIUrl":"10.1093/jbmrpl/ziag077","url":null,"abstract":"<p><p>HRpQCT is emerging as a promising evolution to DXA for longitudinal assessment of bone properties and strength estimation beyond FN aBMD, as it provides a detailed 3D representation and separate quantification of trabecular and cortical compartments. Reference data exist for thin single stacks of 10<i>.</i>2 mm in second-generation HRpQCT, but these sections may not fully capture clinically relevant fracture locations and pose challenges for longitudinal monitoring due to their limited thickness. Reported parameters are mainly size-dependent properties susceptible to bias from skeletal dimensions, potentially concealing changes in bone quality at the material level. Moreover, microstructural parameters are derived from densitometric information, making them partially redundant. This study provides the first age-, sex-, and site-specific reference data for a novel multi-stack on second-generation HRpQCT at the distal radius and tibia in 381 healthy participants (144F, 237M) from a primarily Caucasian population aged 20-92 yr and identifies the size-independent parameters most sensitive to age for improved bone health assessment. Six size-independent parameters relevant for estimated mechanical properties or exhibiting short trend assessment intervals were selected as candidates for improved bone health assessment: 2 densitometric properties (total volumetric BMD, cortical volumetric BMD), 1 size-independent geometrical property (relative cortical thickness), 2 microstructural properties (trabecular degree of anisotropy, trabecular bone volume over total volume), and 1 mechanical property (apparent yield stress [^app <i>σ</i> _y]) estimated by homogenized finite elements. Intensive mechanical properties provided more sensitive follow-up estimations. Cortical volumetric BMD, especially in the weight-bearing tibia in women, was the most sensitive with age. Matched comparisons with single-stack counterparts demonstrated good agreement between densitometric and microstructural properties, supporting potential cross-study and cross-protocol comparisons. The present work proposes an alternative set of size-independent variables for multi-stack HRpQCT, which may offer a refined assessment of bone health and longitudinal monitoring.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 6","pages":"ziag077"},"PeriodicalIF":3.0,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13198809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015482","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 alterations of the femoral geometry in a mouse model of Marfan syndrome.","authors":"Gina Agostini-Walesch, Tyler Gallagher, Brian Tibble, Anna Stimpson, Mitra Esfandiarei","doi":"10.1093/jbmrpl/ziag072","DOIUrl":"10.1093/jbmrpl/ziag072","url":null,"abstract":"<p><p>Marfan syndrome (MFS), caused by mutations in the <i>Fbn1</i> gene, is associated with skeletal fragility; yet, the geometric and mechanical consequences for long bones remain underexplored. We examined femoral geometry and rigidity in male and female <i>Fbn1^C1041G/+</i> (MFS) and WT <i>C57BL/6 J</i> (littermate control) mice (<i>n</i> = 5/sex/genotype) at 6 mo of age using high-resolution micro-CT. Femur length, cortical and medullary areas, cross-sectional circularity, and derived rigidity indices (<i>I</i> _MAX, <i>I</i> _MIN) were quantified across 3 diaphyseal locations. Marfan syndrome mice had significantly longer femora than controls, with more circular cross-sections regardless of sex. Male MFS mice displayed endosteal expansion, reduced cortical bone (-18% to 30%), and lower bending rigidity, indicating weakened structural resistance. In contrast, female MFS mice maintained or exceeded control rigidity values despite geometric alterations. These findings reveal pronounced sex-dependent skeletal effects in MFS, suggesting that cortical bone loss and estimated mechanical weakening are male-biased features, potentially linked to hormonal influences and altered bone remodeling. Such differences may contribute to differential fracture risk and have implications for targeted interventions in connective tissue disorders.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 6","pages":"ziag072"},"PeriodicalIF":3.0,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13171039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147941324","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":"Examining the association between sagittal craniosynostosis and midline cephalohematoma.","authors":"Taylor deVet, Abdulrahman Almansouri, Marco Dallavalle, Bettina M Willie, Roy W R Dudley","doi":"10.1093/jbmrpl/ziag071","DOIUrl":"10.1093/jbmrpl/ziag071","url":null,"abstract":"<p><p>We describe a case with sagittal craniosynostosis accompanied by a midline cephalohematoma. Preoperative CT revealed fusion of the center of the sagittal suture, under the cephalohematoma. Postoperative micro-CT of en bloc specimen confirmed a fused suture along cephalohematoma, with thicker more mature outer layer of bone compared to the inner layer. Histological analysis revealed suture present in both superior and inferior bone layers surrounding the hematoma. We conclude craniosynostosis gave rise to the midline cephalohematoma.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 6","pages":"ziag071"},"PeriodicalIF":3.0,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13160416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147929602","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":"Knowledge, skills, and attitudinal gaps in fibrodysplasia ossificans progressiva diagnosis and management in the United States.","authors":"Patrice Lazure, Matthew T Drake, Michelle Davis, Corrie J Crowe, Zvi Grunwald, Lu Fan, Suzanne Murray","doi":"10.1093/jbmrpl/ziag076","DOIUrl":"10.1093/jbmrpl/ziag076","url":null,"abstract":"<p><p>Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare and disabling disease. Preventing unnecessary and/or harmful medical procedures to patients requires early and accurate diagnosis, multidisciplinary care, and access to specialists with FOP expertise. This study aims to assess the needs of healthcare providers (HCPs) when providing care to patients with FOP. Knowledge, confidence, and management practices were measured through a short awareness survey, completed by 400 HCPs from different specialties who may encounter patients with FOP. Complementary qualitative data were obtained from a dialogue session about FOP. Quantitative data was analyzed using descriptive and inferential analysis, while qualitative data underwent thematic coding. Results indicate a need for enhanced knowledge and confidence regarding identifying clinical manifestations of FOP, referral to FOP specialists and subsequent patient management. Only 8.8% of HCPs correctly identified FOP from an open-ended question showing malformed great toes, a classical clinical manifestation of FOP, and only 31.8% correctly identified FOP from a multiple-choice question showing heterotopic ossification on a child's back, another classical clinical manifestation of FOP. Structural and system-level issues were also identified as barriers to optimal patient care pathways, with limited access to FOP specialists reported as a prominent concern. These results document a need for improvements in HCP knowledge in addition to local care collaboration and healthcare system optimization to meet the needs of patients with rare diseases. Given that FOP is an ultra-rare disease, educational interventions are recommended to focus on rare disease recognition, with FOP included as one topic. In addition, greater team collaboration and system-level approaches to assist HCPs in overcoming barriers that impede patient access to care and ongoing management, as well as interventions to enhance patients' capacity to have informed communication with their HCPs, are needed.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 6","pages":"ziag076"},"PeriodicalIF":3.0,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13171035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147941306","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":"Effects of comorbid chronic kidney disease on late-onset hypophosphatasia mice under treatment with asfotase alfa.","authors":"Cintia Tokuhara, Flavia Amadeu de Oliveira, Sonoko Narisawa, Elis J Lira Dos Santos, Brian L Foster, Jose Luis Millan","doi":"10.1093/jbmrpl/ziag074","DOIUrl":"10.1093/jbmrpl/ziag074","url":null,"abstract":"<p><p>Hypophosphatasia (HPP) is a rare bone disorder caused by loss-of-function mutations in the <i>ALPL</i> gene, leading to deficient tissue-nonspecific alkaline phosphatase (TNAP) activity and impaired skeletal/dental mineralization. Asfotase alfa (AA), the only FDA-approved therapy, improves survival and skeletal/dental mineralization. Because of its mineral-binding properties, AA also binds to sites of ectopic calcification, including vasculature. Overexpression of TNAP in either the vascular media or intima has been shown to induce severe calcification. Here, we examined what might occur if a disease that features medial artery calcification, such as CKD-mineral and bone disorder (CKD-MBD), were to develop in a subject with HPP undergoing AA treatment. Two-month-old <i>Alpl^Prx1/-</i> (HPP) or <i>Alpl^flox/-</i> (non-HPP control) mice were treated with s.c. AA injections (8.2 mg/kg, 3×/week) for 4 mo. After 3 mo of treatment, CKD was induced via a 0.2% adenine and 1.8% phosphorus diet. Mice were euthanized at 6 mo of age, and skeletal, renal, cardiac, and vascular tissues were analyzed. Alkaline phosphatase levels slightly increased with AA but significantly increased after inducing CKD in control and HPP female mice. In males, ALP activity was elevated in the AA and AA+CKD cohorts. Micro-CT analysis showed improved bone parameters in HPP under AA treatment. However, the improvements were dampened when CKD was induced, compared to non-CKD <i>Alpl^flox/-</i> . Immunohistochemistry of the kidney revealed increased TNAP immunolocalization in the AA+CKD cohort, in both females and males. Ectopic renal and vascular calcification was observed in the AA+CKD group. Gene expression profiling in the kidney revealed that AA treatment modulates the immune and mineral metabolism pathways, while CKD superimposition induces a shift toward pro-inflammatory and pro-fibrotic responses, compromising renal and skeletal homeostasis. These findings underscore the importance of carefully evaluating HPP patients under treatment with mineral-targeted TNAP at risk of developing comorbid conditions associated with ectopic calcification.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 6","pages":"ziag074"},"PeriodicalIF":3.0,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13171041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147941273","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":"11β-Hydroxysteroid dehydrogenase type 1 deficiency causes sexual dimorphism in body composition and bone mass in response to caloric restriction.","authors":"Iana M de Araújo, Phuong T Le, Caroline de Carvalho Picoli, Rowan Hardy, Ziru Li, Francisco José A de Paula, Clifford J Rosen","doi":"10.1093/jbmrpl/ziag075","DOIUrl":"10.1093/jbmrpl/ziag075","url":null,"abstract":"<p><p>Caloric restriction (CR) alters energy metabolism and increases systemic glucocorticoid production, contributing to bone loss and bone marrow adipose tissue (BMAT) expansion. The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) mediates the local amplification of glucocorticoids within these tissues, but its contribution to CR-induced skeletal alterations remains unclear. Eight-week-old male and female WT and global 11β-HSD1 KO mice were assigned to ad libitum feeding or 30% CR for 8 wk. Body composition was assessed by DXA, bone microarchitecture by micro-CT (μCT), biomechanics by 3-point bending, BMAT by histology, serum bone turnover markers, and corticosterone by ELISA. Caloric restriction reduced body weight and lean mass of both sexes and genotypes. Fat mass was decreased in males WT and KO but not in females, while bone mass was reduced significantly in WT and KO female CR. Micro-CT revealed trabecular and cortical deterioration in both WT and KO CR females. Bone marrow adipose tissue was increased in mice under CR in both sexes, regardless of genotype. KO mice exhibited elevated corticosterone during CR, suggesting compensatory hypothalamic-pituitary-adrenal activation. These results demonstrate that CR induces sex-dependent changes in mesenchymal tissues. Under CR, females preserved fat mass but lost bone mass, while males maintained bone mass despite fat loss. Both sexes experienced lean mass loss. The effects of 11β-HSD1 deletion were also sex-specific: female KO mice had higher trabecular and cortical parameters, and lean mass under ad libitum feeding, while male KO mice under CR showed increased lean mass and trabecular bone thickness. However, 11β-HSD1 deletion did not prevent BMAT expansion in either sex under CR.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 6","pages":"ziag075"},"PeriodicalIF":3.0,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13171033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147941330","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}