Bone最新文献

{"title":"Clinical characteristics of patients with bone marrow edema syndrome, transient osteoporosis or migratory osteoporosis: a scoping review","authors":"Eivind Hasvik ,&nbsp;Anne Julsrud Haugen ,&nbsp;Lars Grøvle","doi":"10.1016/j.bone.2025.117535","DOIUrl":"10.1016/j.bone.2025.117535","url":null,"abstract":"<div><div>Bone marrow edema syndrome (BMES), transient osteoporosis of the hip (TOH), and regional migratory osteoporosis (RMO), along with numerous variants of these terms, are used inconsistently to describe spontaneous pain, typically in the lower extremity, accompanied by bone marrow edema on MRI and/or bone demineralization. In the present review, we aimed to determine whether these designations represent distinct conditions or varying manifestations of a shared pathology. We employed a scoping review methodology, following a preregistered protocol, utilizing a comprehensive systematic search of electronic databases. Eligible publications reported on patients designated with BMES, TOH, RMO, or related terms. A total of 2924 patients, across 561 studies, were included. Data extraction focused on demographics, clinical features and imaging results. Descriptive statistics and meta-analytic methods were used to synthesize the data. Our results show that patients described by terms related to bone marrow edema syndrome, or transient or migratory osteoporosis, displayed similar demographic and clinical profiles. Our findings strongly suggest that these various designations refer to the same clinical entity. Bone marrow edema syndrome appears to be the most suitable term to describe this condition, facilitating a more standardized approach to future diagnosis, management and research.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"198 ","pages":"Article 117535"},"PeriodicalIF":3.5,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144089968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding the variation of volumetric bone mineral density in the femur and tibia in a paediatric population","authors":"Julie Choisne ,&nbsp;Jannes Brüling ,&nbsp;Yidan Xu","doi":"10.1016/j.bone.2025.117534","DOIUrl":"10.1016/j.bone.2025.117534","url":null,"abstract":"<div><div>Childhood and adolescence are crucial time for bone mineral accumulation with 25 % of bone mineral density (BMD) being laid during puberty. BMD development during growth was found to be correlated with the development of osteoporosis later in life. Mapping the variation of BMD in a paediatric population is important to understand how BMD change with age and sex. Therefore, the aim of this study was to evaluate the variation of BMD in the long bones for a paediatric population. CT-scans of 333 children and adolescents aged from 4 to 18 years were used to reconstruct 657 femora and 652 tibiae. Volumetric meshing and material mapping was performed for all bones with a CT-calibration phantom. Volumetric BMD was calculated for each femur and tibia and analysed by regions of interest, femur and tibia proximal and distal epiphysis, shaft, femoral head, neck and greater trochanter. A statistically significant interaction between the effects of age and sex were found in all regions of the femur and tibia with a significant simple main effect associated with age between male and female and with sex at age 11 and 14. Correlation between vBMD and participants' age, height and weight were mostly found in the distal tibia and tibial shaft. Interestingly, the vBMD at the femoral head, neck and greater trochanter did not increase with age. This study is the first to report on the variation of vBMD with age and sex from children and adolescents aged from 4 to 18 years.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"198 ","pages":"Article 117534"},"PeriodicalIF":3.5,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144089969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of aging on the immune and periosteal response to fracture injury","authors":"Justin S. King ,&nbsp;Matthew Wan ,&nbsp;Adam Kim ,&nbsp;Shagun Prabhu ,&nbsp;Sanja Novak ,&nbsp;Ivo Kalajzic ,&nbsp;Anne M. Delany ,&nbsp;Archana Sanjay","doi":"10.1016/j.bone.2025.117524","DOIUrl":"10.1016/j.bone.2025.117524","url":null,"abstract":"<div><div>Aging predisposes individuals to reduced bone mass and fragility fractures, which are costly and linked to high mortality. Understanding how aging affects fracture healing is essential for developing therapies to enhance bone regeneration in older adults. During the inflammatory phase of fracture healing, immune cells are recruited to the injury site as periosteal skeletal stem/progenitor cells (pSSPCs) rapidly proliferate and differentiate into osteochondral lineages, allowing for fibrocartilaginous callus formation and, subsequently, complete bone healing. Irrespective of age, how periosteal mesenchymal and immune cells interact during early fracture healing is incompletely understood, limiting our ability to modulate this process. To address this, we directly analyzed, in parallel, at a single-cell level, isolated murine CD45(+) and CD45(−) periosteal cells dissected from intact and fractured bones, collected three days after injury. Comprehensive analysis, corroborated by bulk RNA-sequencing, flow cytometry, and histology, demonstrated that aging decreased pSSPC proliferation, markedly reduced expression of genes required for callus formation, and increased senescence signature. During the regeneration phase, at 14 days post injury, aged mice demonstrated reduced mineralization of the callus, accompanied by elevated Sox9 expression and increased cartilage content, suggesting delayed repair. We also found that the chemokine <em>Cxcl9</em> was highly upregulated in aged intact Prrx1+ pSSPCs, which has the potential to directly regulate other pSSPCs, and was associated with increased recruitment of CD8+ T cells at the fracture site. Cell-to-cell communication analysis provided further appreciation of the complex interactions among the many mesenchymal and hematopoietic cell types regulating fracture healing and highlighted the impact of aging on these interactions. Together, these results provide insight into age-induced alterations in early fracture healing, which could facilitate the development of improved therapeutic approaches for fracture repair in the elderly.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"198 ","pages":"Article 117524"},"PeriodicalIF":3.5,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative effectiveness of romosozumab versus teriparatide for fracture prevention: A new-user, active comparator design","authors":"Ryoji Tominaga ,&nbsp;Tatsuyoshi Ikenoue ,&nbsp;Ryosuke Ishii ,&nbsp;Kakuya Niihata ,&nbsp;Tetsuro Aita ,&nbsp;Tadahisa Okuda ,&nbsp;Sayaka Shimizu ,&nbsp;Noriaki Kurita ,&nbsp;Masataka Taguri","doi":"10.1016/j.bone.2025.117523","DOIUrl":"10.1016/j.bone.2025.117523","url":null,"abstract":"<div><h3>Background</h3><div>Comparative evidence on the effectiveness of romosozumab and teriparatide in preventing osteoporotic fractures remains limited. This study evaluated their effectiveness in fracture prevention.</div></div><div><h3>Methods</h3><div>This observational new-user cohort study used the DeSC Healthcare database, a nationwide claims database in Japan. Patients aged ≥40 years with osteoporosis, defined by International Classification of Diseases, 10th Revision codes or prior fragility fractures, who newly initiated romosozumab or teriparatide between March 2019 and August 2021 were included. The primary outcome was the major osteoporotic fractures within 1 year. Secondary outcomes included 2-years fracture incidence and individual fracture types. Cox proportional hazards models, weighted by inverse probability-of-treatment derived from propensity scores, were used to estimate hazard ratios (HRs) with 95 % confidence intervals (CIs), accounting for patient- and facility-level confounders.</div></div><div><h3>Results</h3><div>Among 35,547 observations (romosozumab: 9603; teriparatide: 25,944), the mean ages were 80.3 and 80.0 years, 85.2 % and 81.3 % were women, and 64.4 % and 71.9 % had a history of fragility fracture, respectively. The 1-year incidences of major osteoporotic fractures were 10.14 per 100 person-years (teriparatide) and 7.01 per 100 person-years (romosozumab) (HR: 0.80, 95 % CI: 0.71, 0.89). Romosozumab was also associated with lower rates of composite fractures over 2 years (HR: 0.81, 95 % CI: 0.72, 0.90); vertebral fractures over 1 and 2 years; and proximal humeral, distal forearm, and proximal femoral fractures over 1 year.</div></div><div><h3>Conclusions</h3><div>In this nationwide Japanese cohort, romosozumab use was associated with a lower incidence of major osteoporotic fractures compared to teriparatide over both 1- and 2-year follow-up periods among high-risk patients with osteoporosis.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"198 ","pages":"Article 117523"},"PeriodicalIF":3.5,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monitoring denosumab therapy using the calcium isotope marker (CIM) technology","authors":"Anton Eisenhauer ,&nbsp;Sönke Sönnichsen ,&nbsp;Agustina Hastuti ,&nbsp;Rukshana Shroff ,&nbsp;Alexander Heuser ,&nbsp;Ana Kolevica ,&nbsp;Amarin Lubnow ,&nbsp;Burkard Brandt ,&nbsp;Michael Müller","doi":"10.1016/j.bone.2025.117522","DOIUrl":"10.1016/j.bone.2025.117522","url":null,"abstract":"<div><div>Denosumab provides a well-established therapy for osteoporosis. Dual-energy X-ray absorptiometry (DXA) and bone turnover markers (BTMs) track changes in bone mineral density (BMD) and turnover. Calcium (Ca) Isotope Markers (CIM), which measure naturally occurring variations in stable Ca isotope ratios in serum (CIM_serum) and urine (CIM_urine), offer a potentially more sensitive and individualized approach for monitoring bone health and therapy responsiveness. In this pilot study, 13 postmenopausal women with DXA-confirmed osteoporosis were initiated on denosumab. Over 24 weeks, serial measurements of CIM_serum, CIM_urine, BMD, BTMs, and parathyroid hormone (PTH) were obtained. CIM thresholds distinguishing net bone Ca uptake from net bone Ca efflux were applied. Baseline CIM values, adjusted for Ca supplement intake (average CIM_serum: −1.09±0.15 ‰ and CIM_urine: 0.00±0.22 ‰), indicated net bone Ca loss. After 60 mg denosumab injection, all patients showed substantial increases in CIM_serum and CIM_urine values by ∼ +0.4 ‰ after one week. Peak values were reached in week 4 (CIM_serum: ∼ −0.8 ‰) to 8 (CIM_serum: ∼ −0.7 ‰). CIM_serum and CIM_urine values correlated positively to PTH. Some patients´ CIM values quickly rose above threshold levels, while others showed more modest or transient changes. Although DXA indicated an increase in the lumbar and hip T-score values after 24 weeks, DXA primarily confirmed group-level gains. BTMs did not reflect individual variations in CIM response. While further validation in larger, controlled cohorts is warranted, these findings highlight CIM's potential to enhance osteoporosis management through personalized treatment monitoring.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"198 ","pages":"Article 117522"},"PeriodicalIF":3.5,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rest-activity circadian rhythms and osteoporosis: A prospective cohort and Mendelian randomization study","authors":"Hanhan Zhao ,&nbsp;Jiacheng Wang ,&nbsp;Yi Zheng ,&nbsp;Zhenqiu Liu ,&nbsp;Yanfeng Jiang ,&nbsp;Chen Suo ,&nbsp;Xingdong Chen ,&nbsp;Kelin Xu","doi":"10.1016/j.bone.2025.117521","DOIUrl":"10.1016/j.bone.2025.117521","url":null,"abstract":"<div><h3>Background</h3><div>Disruptions in rest-activity circadian rhythms (RAR) have been shown to be associated with an increased risk of osteoporosis. However, there remains a scarcity of prospective studies examining this association.</div></div><div><h3>Methods</h3><div>This longitudinal cohort study utilized data from the UK Biobank, including 90,029 participants who were initially free of OP and had reliable accelerometer data at baseline, with a median follow-up time of 8.1 years. Participants newly lost to follow-up within the first two years were excluded. We assessed the associations of eleven RAR variables including nonparametric variables relative amplitude (RA), most active 10-h period counts (M10), least active 5-h period counts (L5), interdaily stability (IS), and intradaily variability (IV), and parametric variables amplitude, mesor, pseudo-F statistic, acrophase, alpha, and beta with the risk of OP using Cox models adjusted for multiple confounders. Mediation analyses were conducted to determine whether inflammatory markers mediated the associations between RAR variables and OP incidence. Additionally, two-sample MR analyses were conducted to infer causality.</div></div><div><h3>Results</h3><div>In this study, 1702 new-onset OP cases were documented. Higher RA(adjusted hazard ratio 0.87 [95 % CI 0.83–0.92]) and M10 (0.73 [0.60–0.89]) were associated with a lower risk of osteoporosis, while higher L5 (1.09 [1.04–1.15]) was associated with an increased risk. The associations between these three RAR variables and osteoporosis risk were possibly mediated by leukocyte count and platelet-to-lymphocyte ratio, with mediation proportions ranging from 6.06 % to 13.84 %. Higher alpha of parametric variables (0.92 [0.88–0.97]) were associated with a lower risk of osteoporosis. Two-sample MR analyses suggested potential significant associations between RA, L5, pseudo-F and femoral neck bone mineral density, consistent with observational results.</div></div><div><h3>Conclusions</h3><div>Our findings suggest that circadian rhythm disruption, as indicated by impaired RAR variables, was associated with higher osteoporosis risk. Circadian rhythm disruption may be a modifiable risk factor that could be targeted for osteoporosis prevention.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"198 ","pages":"Article 117521"},"PeriodicalIF":3.5,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter: Sex-specific association between dietary carbohydrate intake and bone mineral density in adolescents","authors":"Cheng Xue","doi":"10.1016/j.bone.2025.117518","DOIUrl":"10.1016/j.bone.2025.117518","url":null,"abstract":"","PeriodicalId":9301,"journal":{"name":"Bone","volume":"198 ","pages":"Article 117518"},"PeriodicalIF":3.5,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Different effects of moderate tibial loading and Yoda1 on breast cancer-induced osteolysis in aged mice","authors":"Murtaza Wasi ,&nbsp;Shubo Wang ,&nbsp;Rosa M. Guerra ,&nbsp;Tiankuo Chu ,&nbsp;Rory Kooker ,&nbsp;Kimberly Seaman ,&nbsp;Xin (Suzie) Song ,&nbsp;Amel Sassi ,&nbsp;Xuehua Li ,&nbsp;Jinhu Xiong ,&nbsp;Lidan You ,&nbsp;Liyun Wang","doi":"10.1016/j.bone.2025.117517","DOIUrl":"10.1016/j.bone.2025.117517","url":null,"abstract":"<div><div>Elderly breast cancer patients and survivors are at high risk of bone loss but experience obstacles to harness the known benefits of exercise due to aging, cancer, and cancer treatment. Previously, we and others showed that moderate mechanical loading suppressed breast cancer-induced osteolysis in young adult mice. To overcome the mechano-transduction deficits in aged skeletons, we recently tested a dual therapy combining mechanical and Yoda1 activation of mechanosensitive Piezo1 channels. We found that the dual therapy was more effective in mitigating bone loss due to aging and doxorubicin in mature mice than the individual interventions. In the present study, we further tested the hypothesis that dual therapy combining moderate tibial loading and Yoda1 protects aged skeleton from breast cancer-induced osteolysis better than individual treatments. Aged female C57BL/6 J mice (~74-week-old) receiving Py8119 breast cancer cells in both tibiae were assigned to the four experimental groups (<em>n</em> = 5–8 per group) to examine the effects of 4-week Yoda1 (dose 5 mg/kg, 5 times/week) and moderate tibial loading (4.5 N peak load, 4 Hz, 300 cycles per day, 5 days/week), individually or combined on bone structural integrity. At the end of 4 weeks' experiments, the dual therapy group had the lowest incidence of osteolytic perforation (56 %) compared to the non-treated group (80 %), loading only group (70 %), and Yoda1 only group (100 %). The relative drop of cortical polar moment of inertia (Ct.pMOI), calculated as [(Week 4- Week 0)/Week 0, %], were analyzed at the proximal end, mid-diaphysis, and tibial-fibular junction of the tibia. The average values over the three locations were − 12.7 %, −3.2 %, −24.0 %, −4.2 % for the non-treated, loading only, Yoda1 only, and dual therapy groups, respectively. Furthermore, the % of samples with decreased Ct.pMOI (indication of structural deterioration) was suppressed in the dual therapy group (33 %), compared with nontreated (100 %), loading only (80 %), and Yoda1 only (100 %) groups. Each treatment differentially affected the osteoclast activity, tumor proliferation, and apoptosis of osteocytes, marrow cells and tumor cells, revealing the complex interactions of bone, tumor, and mechanical stimulations. In summary, the dual therapy resulted in skeletal benefits comparable to or slightly better than loading only treatment. However, the exacerbated bone loss and cortical perforation associated with Yoda1 call for further investigation on safe and effective treatments of skeletal damages caused by metastatic breast cancers.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"197 ","pages":"Article 117517"},"PeriodicalIF":3.5,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding the genetic spectrum of short rib polydactyly syndrome: Novel DYNC2H1 variants and functional insights","authors":"Bilgesu Ak ,&nbsp;Mete Akısü ,&nbsp;Asude Durmaz ,&nbsp;Mehmet Yalaz ,&nbsp;Demet Terek ,&nbsp;Ece Sönmezler ,&nbsp;Yavuz Oktay ,&nbsp;Haluk Akın ,&nbsp;Ayça Aykut","doi":"10.1016/j.bone.2025.117511","DOIUrl":"10.1016/j.bone.2025.117511","url":null,"abstract":"<div><h3>Introduction</h3><div>Short rib polydactyly syndrome (SRPS), with or without polydactyly, also known as Verma-Naumoff/Saldino-Noonan syndrome, is a type of skeletal ciliopathy. Initially, variants in the <em>IFT80</em> gene were implicated; however, approximately half of the SRPS cases are associated with variants in the <em>DYNC2H1</em> gene. Additionally, digenic variants involving <em>DYNC2H1</em> and <em>NEK1</em> can contribute to the syndrome.</div></div><div><h3>Materials and methods</h3><div>This case report describes a male patient presenting with characteristic SRPS features, including a constricted thorax and shortened limbs. Exome sequencing was performed to identify causative variants, followed by functional analyses to assess the pathogenicity of the identified variants, including a synonymous variant.</div></div><div><h3>Results</h3><div>Exome sequencing identified compound heterozygous variants in the <em>DYNC2H1</em> gene: a novel missense variant c.6439G&gt;T p.(Asp2147Tyr) and a synonymous variant c.6477G&gt;A p.(Gln2159=). Functional analyses confirmed that the synonymous variant triggers nonsense-mediated decay of the affected allele.</div></div><div><h3>Conclusion</h3><div>This study expands the spectrum of <em>DYNC2H1</em> variants associated with SRPS and emphasizes the importance of functional analyses in genetic diagnostics. Demonstrating pathogenicity for a synonymous variant highlights the necessity for comprehensive variant assessments to improve diagnostic accuracy and enable early intervention. These findings have significant implications for molecular diagnostics and personalized therapy strategies in skeletal ciliopathies.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"197 ","pages":"Article 117511"},"PeriodicalIF":3.5,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic, skeletal, and cartilage effects of a high-fat diet and the therapeutic impact of MGL3196 are age- and sex-dependent in mice","authors":"O. Perez ,&nbsp;G.A. Gomez ,&nbsp;C. Kesavan ,&nbsp;B. Edderkaoui ,&nbsp;A. Muralidharan ,&nbsp;S. Pourteymoor ,&nbsp;A. Quincey ,&nbsp;V.F. Sechriest ,&nbsp;S. Mohan","doi":"10.1016/j.bone.2025.117516","DOIUrl":"10.1016/j.bone.2025.117516","url":null,"abstract":"<div><div>Aged individuals with type 2 diabetes (T2D) may suffer from complications of common comorbid conditions like osteoporosis or osteoarthritis. MGL3196 (MGL) is a therapeutic thyroid hormone receptor beta (TRβ) agonist that has been shown to rescue non-alcoholic steatohepatitis by enhancing lipid metabolism. In a previous study, we demonstrated that MGL treatment protected against high-fat diet (HFD)-induced adiposity but increased HFD-induced trabecular bone loss in male mice. In this study, we explored the impact of MGL treatment on adiposity, bone, and cartilage in aged-21-month-old C57BL/6J mice after a 12-week HFD regimen. Our results show that MGL reduced body weight as well as adverse effects caused by HFD adiposity, in male mice only. Aged HFD-fed male mice experienced cortical bone loss, in contrast to the trabecular bone loss observed in adult male mice. Notably, MGL treatment further exacerbated the cortical bone loss. Mechanical testing of tibias from aged male mice by 3-point bending revealed a reduced maximum load and tibia stiffness with HFD and MGL treatment. Transcriptome analyses for cortical bone formation regulators unveiled a decreased expression of <em>Wnt16</em> and increased expression of the Wnt inhibitor, <em>Sost</em>, in the bones of HFD-fed male mice. Additionally, measurements of articular cartilage indicated that MGL treatment reduced articular cartilage degradation in both sexes, which was attributed to aging and a HFD. Our findings suggest tailored therapies are necessary to address the adverse effects of a HFD on fat, bone, and cartilage metabolism, specifically considering factors such as age and sex.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"198 ","pages":"Article 117516"},"PeriodicalIF":3.5,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}