Calcified Tissue International最新文献

{"title":"Fracture Risk Stratification by REMS: A 5 Years Prospective Longitudinal Multicentre Study.","authors":"Carla Caffarelli, Maria Luisa Brandi, Giuseppe Girasole, Andrea Giusti, Maurizio Muratore, Stefano Gonnelli","doi":"10.1007/s00223-026-01610-x","DOIUrl":"https://doi.org/10.1007/s00223-026-01610-x","url":null,"abstract":"<p><p>Osteoporosis is a skeletal disorder characterized by low bone mass and deterioration of bone microarchitecture. Current predictive tools, mainly based on DXA-BMD, do not full capture all the factors contributing to bone deterioration. By combining information on bone quantity (T-score) and skeletal fragility (Fragility Score, FS), the Radiofrequency Echographic Multi-Spectrometry provides an integrated measure of fracture susceptibility known as fracture risk stratification. We aimed To evaluate the ability of REMS fracture risk stratification through a 5 years prospective longitudinal multicentre study. A non-parametric Mann-Whitney test was used to assess differences of REMS T-score and FS between fractured and non-fractured patients. Additionally, Chi-squared tests, Cochran-Armitage trend tests, class-specific unadjusted logistic regressions and standardized residual analyses were performed to evaluate the proposed stratification model. A total of 4443 female patients was recruited and n = 4017 underwent REMS scans. The Chi-squared and the Cochran-Armitage trend tests showed that the distribution of fractured patients differed across the 7 risk classes with a strong positive monotonic trend at lumbar spine (Z = 47.83; p < 0.0001) and femoral neck (Z = 75.41; p < 0.0001). From a clinical perspective, both Class-specific binary logistic regression and standardized residuals clearly identified two opposite risk profiles: patients belonging to the low-risk classes exhibited a significantly reduced probability of fracture, whereas those in the high-risk classes showed a markedly increased fracture risk. This 5-year longitudinal study supports the clinical consistency of a REMS composite approach for fracture risk stratification based on the integration of REMS BMD T-score and Fragility Score.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calcitonin Gene-Related Peptide (CGRP) in Bone Repair and Musculoskeletal Pain: A Scoping Review of Skeletal Regeneration, Joint and Tendon Involvement, and CGRP-Targeted Therapies.","authors":"Surakshya Baral, Sanyam Kulshrestha, Vibhu Krishnan Viswanathan, Vijay Kumar Jain, Karthikeyan P Iyengar, Anil Regmi","doi":"10.1007/s00223-026-01619-2","DOIUrl":"10.1007/s00223-026-01619-2","url":null,"abstract":"<p><p>Calcitonin gene-related peptide (CGRP) is a sensory neuropeptide with established roles in vasodilation and nociception and increasing relevance to musculoskeletal biology. While CGRP-targeted therapies are widely used for migraine prevention, emerging experimental evidence suggests that CGRP also plays important roles in bone remodeling, fracture healing, angiogenesis, and musculoskeletal pain, raising questions about the skeletal implications of modulating the CGRP pathway. This scoping review aimed to systematically map the existing evidence on CGRP signaling in orthopaedic and musculoskeletal contexts, focusing on bone repair, cartilage and tendon biology, pain modulation, and potential clinical implications of CGRP-targeted therapies. The review was conducted in accordance with the PRISMA-ScR guidelines. PubMed, Embase, and Scopus were searched from inception to December 2025 for in vitro, animal, and human studies evaluating CGRP signaling in musculoskeletal conditions. Data were charted and synthesized descriptively across musculoskeletal surgery domains. Preclinical studies consistently demonstrate that CGRP promotes osteogenesis, inhibits osteoclast activity, enhances angiogenesis, and supports fracture healing. In contrast, genetic or pharmacological inhibition of CGRP signaling impairs callus formation and biomechanical recovery. CGRP also contributes to peripheral nociceptive sensitization in osteoarthritis and tendinopathy, highlighting a pain-repair paradox. In cartilage, effects are context-dependent: CGRP is anabolic in healthy chondrocytes but pro-apoptotic and pro-senescent in osteoarthritic chondrocytes, and antagonism of the CGRP receptor attenuated cartilage degeneration in a murine osteoarthritis model. A randomized clinical trial of the anti-CGRP antibody galcanezumab did not reduce signs or symptoms of knee osteoarthritis. Human evidence remains limited to short-term biomarker studies, rare case reports, and ongoing clinical trials, with no definitive data on fracture healing, osseointegration, or long-term bone outcomes. CGRP plays a biologically significant role in musculoskeletal repair and pain modulation. While routine modification of anti-CGRP therapy in musculoskeletal patients is not currently supported by clinical evidence, important translational gaps remain. Prospective studies evaluating orthopaedic outcomes are urgently needed.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osteosarcopenia: More Than the Sum of Its Parts? A Community-Based Study Across Sarcopenia Definitions.","authors":"Radmila Matijevic, Milan Tosic, Filip Lazetic, Nikola Vukosav, Milan Majkic, Branko Baljak, Dora Selesi","doi":"10.1007/s00223-026-01611-w","DOIUrl":"https://doi.org/10.1007/s00223-026-01611-w","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Osteosarcopenia, the co-existence of osteoporosis and sarcopenia, is described as a geriatric syndrome arising from shared determinants of muscle and bone. We asked how far the prevalence of sarcopenia and osteosarcopenia depends on the definition of low muscle mass, whether osteoporosis and sarcopenia co-occur more often than expected under statistical independence, and whether the muscle-bone relationship is expressed in areal bone mineral density (BMD) or in femoral geometry. Cross-sectional study of 649 community-dwelling adults aged 65 years and over (72% women; mean age 71.5 years; mean body mass index (BMI) 29.6 kg/m&lt;sup&gt;2&lt;/sup&gt;) assessed with dual-energy X-ray absorptiometry (GE Lunar iDXA), grip dynamometry (Jamar Hydraulic Hand Dynamometer) and the Short Physical Performance Battery. Osteoporosis followed World Health Organization criteria. Sarcopenia was classified according to EWGSOP2, and low muscle mass was defined three ways (appendicular lean mass (ALM)/height2; absolute ALM; and the Foundation for the National Institutes of Health (FNIH) ALM/BMI index). Observed co-occurrence was compared with the value expected under independence (Fisher exact test, odds ratios (OR) with 95% confidence intervals (CI)); for the best-powered analysis the two one-sided tests (TOST) equivalence procedure using pragmatic equivalence bounds of OR 0.5 to 2.0. Hip structural analysis provided section modulus and cross-sectional area. Low muscle mass ranged from 3.7 to 15.7%, and confirmed sarcopenia from 1.4 to 4.2%, according to the metric. Osteoporosis prevalence was 17.6% (95% CI 14.9 to 20.8). Under none of the sarcopenia definitions was there statistically significant evidence of excess co-occurrence (Fisher p = 0.50 to 1.00), although observed overlap under the absolute-ALM definition was slightly above the independence expectation. For probable sarcopenia (low grip strength), the best-powered comparison, the OR was 0.89 (95% CI 0.47 to 1.67) and equivalence within broad OR bounds of 0.5 to 2.0 was supported (90% CI 0.52 to 1.51; TOST p = 0.037); equivalence was not supported under narrower bounds. Appendicular lean mass was not associated with areal BMD after adjustment for body size (femoral neck standardised β = 0.03, 95% CI - 0.18 to 0.24) but was associated with femoral section modulus substantially more strongly in men than women (globally standardised interaction Δβ = 0.30, 95% CI 0.15 to 0.44, p &lt; 0.001). In this community sample, there was no statistically significant evidence that osteoporosis and sarcopenia co-occurred more often than expected under statistical independence, across several sarcopenia definitions, although estimates for confirmed sarcopenia were imprecise. The muscle-bone association was more apparent for femoral geometry than areal BMD and was seen predominantly in men. These findings do not support assuming that low bone mass and low muscle mass identify the same individuals, but they concern statistical co-occur","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Divergent trajectories of structural accrual and matrix-level mechanical properties during alveolar bone maturation.","authors":"Jun Zhou, Xiaoling Liao, Jingxiao Zhong, Li Zhou, Chie Watanabe, Reina Tanaka, Lu Sun, Yasutaka Sugamori, Jiaming Zhang, Yo Shibata, Zailing Gong","doi":"10.1007/s00223-026-01615-6","DOIUrl":"https://doi.org/10.1007/s00223-026-01615-6","url":null,"abstract":"<p><p>Alveolar bone, a highly dynamic tissue supporting dentition, undergoes a poorly characterized transition from growth to maturity that is critical for orthodontic treatment and periodontal risk assessment. We integrated micro‑CT (μCT), nanoindentation creep modeling, and RNA sequencing to define structural, mechanical, and transcriptomic signatures of this transition in rats at 12 and 24 weeks, using the molar‑bearing alveolar region (M1) and the mandibular notch as a non‑alveolar reference. μCT revealed progressive cortical and trabecular bone accrual at 24 weeks, with trabeculae shifting from rod‑like to plate‑like configurations via lateral expansion. Nanoindentation revealed a site-specific decreasing trend in elastic modulus at M1, which was absent at the mandibular notch, suggesting a regional divergence of local mechanics from bulk mineralization. Time‑dependent creep analysis demonstrated that fast retardation time τ₁ tended to increase at the notch but remained stable at M1, while long‑timescale τ₂ showed a similar upward tendency at the notch, suggesting a viscosity‑related shift in viscoelastic behavior confined to the notch. Transcriptomically, 24‑week alveolar bone exhibited downregulation of genes related to bone matrix assembly and mineralization, alongside observed enrichment of senescence and inflammatory pathways. These molecular changes offer biological context for the observed divergence between continued structural bone accrual and altered matrix-level mechanical quality. Collectively, our findings demonstrate that alveolar bone maturation involves distinct trajectories of structural accrual and site-specific matrix alterations, providing important considerations for the biomechanical assessment of dynamic skeletal tissues.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Equivalent Twelve-Month Bone Mineral Density Response to Romosozumab in Patients Aged ≥ 85 Years and  < 85 Years: A Multi-center Real-World Cohort Study (n = 417) from Northern Japan.","authors":"Ryo Nakano, Atsushi Suzuki, Hiroki Iwasaki, Akira Fukuda","doi":"10.1007/s00223-026-01600-z","DOIUrl":"10.1007/s00223-026-01600-z","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Patients aged ≥ 85 years are systematically under-represented in pivotal romosozumab trials, yet bear the highest absolute fracture burden in aging societies. Whether romosozumab achieves equivalent bone mineral density (BMD) gains in this population remains unproven. We conducted a multi-center retrospective cohort study at two hospitals in Aomori Prefecture, Japan (Mutsu General Hospital and Towada City Hospital). All adult patients who initiated subcutaneous romosozumab 210 mg monthly for osteoporosis between April 2019 and April 2025 were included. The primary outcome was the percentage change in lumbar spine BMD (LS-BMD) at 12 months, compared between patients aged ≥ 85 years and &lt; 85 years. Equivalence was prospectively assessed using two one-sided tests (TOST) with margins of ± 5 and ± 3% points. Pre-specified secondary analyses included 12-month bone turnover markers (P1NP and TRACP-5b), age × prior treatment interaction, and a concomitant vitamin D subgroup analysis. The analytic cohort comprised 417 patients (Mutsu 315, Towada 102; 346 aged &lt; 85 years and 71 aged ≥ 85 years). Approximately 50% of patients in each stratum received a concomitant active vitamin D analog (&lt; 85: 50.6%; ≥85: 53.5%). The median LS-BMD percentage change at 12 months was + 11.1% [IQR 6.3 to 17.5] in patients aged &lt; 85 years (n = 337 with paired data) and + 10.9% [IQR 6.2 to 20.0] in patients aged ≥ 85 years (n = 69) (Mann-Whitney P = 0.926). The 90% confidence interval of the between-group difference lay entirely within both pre-specified equivalence margins (TOST P = 0.0009 at ± 5% points; P = 0.031 at ± 3% points). Total hip BMD change was also equivalent (TOST at ± 5 pp, P = 0.012). Bone turnover markers decreased similarly in both age strata (P1NP median - 16.4% vs. - 19.6%, P = 0.928; TRACP-5b - 32.1% vs. - 33.1%, P = 0.746). Concomitant vitamin D use did not modify the LS-BMD response in either stratum (both between-group P ≥ 0.27). A borderline age × prior-treatment interaction was observed (β = + 5.60 pp, P = 0.082): prior treatment attenuated the response in patients &lt; 85 years (naïve + 14.6% vs. pretreated + 7.5%, P &lt; 0.001) but not in patients ≥ 85 years (+ 10.7% vs. + 11.2%, P = 0.59). On-treatment fragility fracture rates were 5.2% (18/345) in &lt; 85-year patients and 7.0% (5/71) in ≥ 85-year patients (Fisher P = 0.57), with similar renal function and calcium profiles. In this multi-center real-world cohort, twelve-month romosozumab response was statistically equivalent between patients aged ≥ 85 years and &lt; 85 years at both pre-specified equivalence margins. The equivalence was robust to concomitant vitamin D status, was consistent at the total hip, and was corroborated by comparable bone turnover marker changes. The attenuating effect of prior treatment observed in &lt; 85-year patients appeared to be absent in patients ≥ 85 years, a pattern that may reflect incomplete carry-over suppression of bone remodeling by prior therapy in the very elderly","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low Prevalence of Exploratory Biochemical Patterns Compatible with Osteomalacia in a Large Cohort of Participants with Low Serum 25-Hydroxyvitamin D Levels.","authors":"Rolf Jorde, Per Medbøe Thorsby, Guri Grimnes","doi":"10.1007/s00223-026-01612-9","DOIUrl":"10.1007/s00223-026-01612-9","url":null,"abstract":"<p><p>The threshold for vitamin D deficiency is mainly based on osteomalacia prevention. Osteomalacia is diagnosed by bone biopsy, but may potentially also be identified biochemically. Our objective was to examine the prevalence of exploratory biochemical patterns compatible with osteomalacia in a population with low vitamin D status, as well as the effect of vitamin D supplementation on the biochemical parameters. The study was cross-sectional followed by a randomized controlled trial (trial registration number: NCT02750293). The participants were recruited from the population-based Tromsø study. Plasma parathyroid hormone, serum calcium, alkaline phosphatase and bone-specific alkaline phosphatase were measured. 423 participants were included in the cross-sectional part and 382 completed the randomized controlled trial (194 given vitamin D (100,000 IU as a loading dose followed by 20,000 IU per week for four months) and 188 given placebo). The mean serum 25-hydroxyvitamin D level in the cohort was 34 nmol/L. None of the participants had a combination of high (above reference range) serum parathyroid hormone, high alkaline phosphatase, and low (below reference range) serum calcium. With the most permissive exploratory biochemical pattern the prevalence was 8.3%. In the intervention study vitamin D significantly reduced plasma parathyroid hormone and alkaline phosphatase and increased serum calcium as compared to placebo. In conclusion, the prevalence of the explored biochemical patterns compatible with ostemalacia was low and strongly dependent on the analytical thresholds applied. In the absence of validation against bone histomorphometry, these findings cannot determine the prevalence of osteomalacia or establish an appropriate serum 25OHD threshold.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Somatic Mosaicism Modulating Clinical Severity in COL2A1-Related Skeletal Dysplasia: A Case of Profound Skeletal Asymmetry.","authors":"Rukiye Sena Turk Yilmaz, Lisa Cruz, Cemre Robinson, Allen E Bale, Thomas O Carpenter","doi":"10.1007/s00223-026-01599-3","DOIUrl":"10.1007/s00223-026-01599-3","url":null,"abstract":"<p><p>Type II collagenopathies represent a broad spectrum of skeletal dysplasias caused by pathogenic variants in the COL2A1 gene, ranging from perinatally lethal achondrogenesis type II to milder phenotypes such as spondyloepiphyseal dysplasia congenita and Stickler syndrome. Although specific mutations may suggest certain phenotypic trends, the genotype-phenotype relationship is not fully clarified. We describe a patient with marked skeletal asymmetry due to somatic mosaicism for a pathogenic COL2A1 variant (c.G1537A; p.G513S) previously associated with lethal phenotypes. The mutation, identified in mosaic form with an alternative allele ratio of 36:17, likely accounts for the asymmetric and nonlethal presentation. We also included a review of previously reported mosaic cases in the literature, highlighting the underrecognized role of mosaicism in modulating disease severity and laterality in COL2A1-related skeletal dysplasias.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osteoporosis and Skeletal Fragility in non-Metastatic Pheochromocytomas and Paragangliomas: The Adrenergic-Skeletal Axis.","authors":"Alberto Vassallo, Filippo Raggini","doi":"10.1007/s00223-026-01607-6","DOIUrl":"https://doi.org/10.1007/s00223-026-01607-6","url":null,"abstract":"<p><p>Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors arising from chromaffin cells, characterized by excessive catecholamines secretion. Traditionally, the clinical burden of PPGLs has been attributed to cardiovascular, neurological and metabolic complications, including hypertension, arrhythmias, insulin resistance, and increased cardiovascular mortality. However, growing evidence suggests that chronic catecholamine excess may also exert clinically relevant effects on skeletal health. Over the last decade, few clinical studies have demonstrated increased bone turnover, reduced bone mineral density (BMD), impaired trabecular bone quality, and a higher prevalence of vertebral fractures (VFs) in patients with PPGLs. These clinical manifestations are supported by a strong biological rationale, as bone tissue is richly innervated by sympathetic fibers and expresses functional adrenergic receptors (AR) that modulate bone remodeling. Although skeletal involvement remains underrecognized in routine clinical practice, the accumulating evidence suggests that PPGLs may be associated with an adverse skeletal phenotype with increased skeletal fragility. This review summarizes current knowledge regarding the pathophysiological mechanisms, clinical features, and management implications of PPGL-induced bone loss. Crucially, it explores the distinct impacts of catecholamine secretion profiles and discusses the emerging, yet speculative, role of genetic backgrounds-specifically VHL and SDHx mutations-as novel modulators of the skeletal phenotype. Furthermore, this work aims to raise awareness among clinicians involved in PPGLs management in order to implement early screening and prevention strategies.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations Between Peripheral Blood Inflammatory and Immune Markers and Osteoporotic and Fragility Fractures: A Systematic Review and Meta-Analysis.","authors":"Chenyang Li, Chenbing Zhao, Ruhui Fu, Shangkun Zhong, Qiang Yuan, Peifeng Li, Yanan Fan, Ying Zhang","doi":"10.1007/s00223-026-01606-7","DOIUrl":"10.1007/s00223-026-01606-7","url":null,"abstract":"<p><p>Chronic low-grade inflammation and osteoimmune dysregulation may contribute to skeletal fragility, but evidence across circulating markers and fracture outcomes remains heterogeneous. We evaluated associations between peripheral blood inflammatory or immune markers and osteoporotic or fragility fractures. This PRISMA 2020-compliant systematic review and meta-analysis was registered in PROSPERO (CRD420261441126). Five databases were searched from inception to 25 June 2026. Eligible observational studies evaluated serum, plasma, or whole-blood inflammatory or immune markers in relation to observed osteoporotic, fragility, low-energy, or site-specific fractures. Reported ratio estimates were synthesized within marker-outcome-contrast units using random-effects models, with effect-type sensitivity analyses. Evidence certainty was assessed using GRADE. Forty-eight studies were included. C-reactive protein/high-sensitivity C-reactive protein-related (CRP/hsCRP-related) exposures were associated with hip fracture (pooled ratio estimate 1.39, 95% CI 1.17-1.67) and vertebral fracture (2.16, 95% CI 1.47-3.18). Interleukin-6 was associated with hip fracture (1.40, 95% CI 1.15-1.71), as were tumor necrosis factor-alpha or soluble TNF receptors (1.81, 95% CI 1.34-2.44). Certainty was low. Findings for blood-count-derived indices were less stable, and temporally unclear studies could support only associations with fracture status. Observational evidence supports marker- and site-specific associations, but heterogeneity in design, temporality, populations, bone mineral density adjustment, and covariates precludes causal or established predictive interpretation. These markers should not replace established fracture-risk assessment.Trial registration PROSPERO, CRD420261441126.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-osteoporotic Pharmacotherapy and Muscle Outcomes in Osteosarcopenia: a Source-Verified Translational Evidence Map.","authors":"Dong-Ju Lim, Min Kue Kang","doi":"10.1007/s00223-026-01608-5","DOIUrl":"https://doi.org/10.1007/s00223-026-01608-5","url":null,"abstract":"<p><p>Anti-osteoporotic drugs are increasingly discussed as candidate dual bone-muscle therapies in osteosarcopenia, yet clinical claims often conflate biological plausibility, observational signals, and randomized efficacy. We conducted a source-verified scoping evidence map and translational review, updated through 25 July 2026 using PubMed/MEDLINE, Europe PMC, and citation tracking. Evidence was classified as primary randomized evidence, secondary randomized analysis, observational human evidence, mechanistic/preclinical rationale, or review-level context; quantitative pooling was avoided because no drug-outcome pair had a sufficiently homogeneous randomized evidence base. Denosumab has the most coherent translational rationale through RANKL/RANK/NF-kB signaling, but randomized long-term-care data were neutral for muscle mass, strength, and performance despite bone mineral density improvement. Long-term-care context may reduce anabolic reserve, but a drug-by-exercise interaction remains unproven. Early pamidronate data in severe pediatric burns support prevention of resorption-linked muscle catabolism rather than reversal of established age-related sarcopenia. Bisphosphonates and teriparatide have preclinical or secondary signals; romosozumab and abaloparatide lack direct clinical muscle-efficacy evidence. Nandrolone is retained only as a historical positive control. Future trials should distinguish prevention from reversal and use factorial or rigorously standardized exercise designs with prespecified strength, muscle-mass, physical-performance, and pathway endpoints.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}