JBMR Plus最新文献

{"title":"Uncemented hip arthroplasty and denosumab: increased postoperative dipeptide concentrations and identification of potential new bone turnover biomarkers.","authors":"Kim Kultima, Saman Hosseini Ashtiani, Ida Erngren, Payam Emami Khoonsari, Henrik Carlsson, Stephanie Herman, Eva Freyhult, Hans Mallmin, Nils P Hailer","doi":"10.1093/jbmrpl/ziaf091","DOIUrl":"10.1093/jbmrpl/ziaf091","url":null,"abstract":"<p><p>Denosumab is a potent antagonist of RANKL and is widely used to treat severe postmenopausal osteoporosis. Using high-resolution mass spectrometry (HRMS), we aimed to identify molecular mediators associated with the rapid reactivation of osteoclasts following discontinuation of denosumab. In a previously reported randomized controlled trial, 64 patients undergoing uncemented total hip arthroplasty were randomized to receive 2 doses of 60 mg denosumab or placebo, administered 1-3 d and 6 mo postoperatively. Serum samples were analyzed using untargeted HRMS coupled with liquid chromatography, and bone turnover markers were assessed. Data were evaluated using linear mixed-effects models and machine learning techniques. After surgery, 83 metabolite features showed significant concentration changes (<i>p</i> < .0001). Denosumab-treated patients exhibited increased levels of the dipeptides di-L-phenylalanine, phenylalanylleucine, and alpha-Asp-Phe, and decreased levels of fibrinopeptide A and related peptides 24 mo after surgery. The oxidized peptide AP(Ox)GDRGEP(Ox)GPP(Ox)GP, derived from the collagen type I alpha 1 chain (COL1A1) and referred to as COL1A1-OxP, showed a strong correlation with the bone formation marker procollagen type 1 amino-terminal propeptide (P1NP) (<i>p</i> = 4.4E^-83). Similarly, the tripeptide DL-alpha-aspartyl-DL-valyl-DL-proline (DVP) correlated highly with the bone resorption marker carboxy-terminal telopeptide of type 1 collagen (CTX) (<i>p</i> = 1.1E^-222). P1NP and CTX levels were suppressed at 3, 6, and 12 mo postoperatively but exceeded baseline levels by 24 mo. Global metabolic shifts were observed postoperatively, with distinct profiles between treatment groups. The observed increase in specific dipeptides may reflect mechanisms contributing to rebound bone loss following denosumab withdrawal. Fibrinopeptide A and its analogs may play a protective role, while COL1A1-OxP and DVP represent potential new markers of bone turnover. These findings suggest metabolomics-based biomarkers could aid clinical decision-making by allowing earlier detection of rebound effects and guiding individualized treatment strategies after denosumab therapy. <b>Clinical trial registration number:</b> ClinicalTrials.gov, NCT01630941 (URL: https://clinicaltrials.gov/); European Union Clinical Trials Register (EU CTR), EudraCT No. 2011-001481-18 (https://www.clinicaltrialsregister.eu/).</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 7","pages":"ziaf091"},"PeriodicalIF":3.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528007","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":"McCune-Albright syndrome: a case of an adult with fibrous dysplasia, severe cardiopulmonary complications, acromegaly, and chronic myeloid leukemia.","authors":"Amanda Ji, Anna McLean, Ashim Sinha","doi":"10.1093/jbmrpl/ziaf090","DOIUrl":"10.1093/jbmrpl/ziaf090","url":null,"abstract":"<p><p>McCune-Albright syndrome (MAS) is a rare mosaic disorder characterized by the classic triad of fibrous dysplasia of bone (FD), café-au-lait skin macules, and hyperfunctioning endocrinopathies. MAS is caused by a postzygotic mutation in the G-protein alpha subunit (GNAS) gene resulting in G-protein α-subunit somatic activation. There is no approved treatment for MAS. We present the case of a 43-yr-old male carpenter with severe polyostotic FD and adult-onset growth hormone (GH) excess who was treated with denosumab and somatostatin analog, complicated with a diagnosis of chronic myeloid leukemia (CML). The patient had multiple skeletal lesions, resulting in pain on movement and neurovascular compromise of the left arm. A forequarter amputation was considered to treat a large clavicular lesion, however, involvement of his thoracic cage resulted in significant cardiopulmonary impairment, including restrictive lung disease, and the surgery was deemed too risky. Denosumab was commenced after failed intravenous bisphosphonate for pain management, resulting in alleviation of pain. Screening of endocrinopathy revealed GH excess with an elevated Insulin-like Growth Factor-1 (IGF-1) level and 7 mm pituitary adenoma. Lanreotide was commenced as a medical therapy, resulting in a reduction in IGF-1 levels. Over 9 mo into the denosumab treatment, the patient was diagnosed with CML in the context of routine full blood examination. The patient achieved a hematological remission with imatinib. Polyostotic FD can lead to serious complications from deformities of the skeleton, including cardiopulmonary complications. This case represents a patient with a severe spectrum of MAS/FD with a diagnosis of CML. We postulate that CML is unlikely due to the MAS, as the two have different pathogenic pathways. Denosumab is effective in pain management, however, it should be used with caution, and there are no large studies to guide long-term management. Evaluation and management of MAS should also include detailed endocrinopathy assessment and screening, even in adulthood.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 7","pages":"ziaf090"},"PeriodicalIF":3.4,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528005","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":"High prevalence of laboratory abnormalities indicative of secondary osteoporosis detected by systematic testing.","authors":"Nandi Shah, Hayley Galitzer, Swaytha Yalamanchi, Deborah E Sellmeyer","doi":"10.1093/jbmrpl/ziaf089","DOIUrl":"10.1093/jbmrpl/ziaf089","url":null,"abstract":"<p><p>Osteoporosis treatment guidelines recommend assessment for potential causes of secondary osteoporosis, however, there are limited data evaluating the yield of laboratory tests recommended for routine screening. The purpose of this study was to quantify the frequency of abnormal laboratory results indicative of secondary osteoporosis in patients referred to a Metabolic Bone Clinic with a diagnosis of low bone density or fracture. A retrospective chart review was conducted on 890 consecutive patients at a tertiary academic medical center from October 2018 to December 2021. Upon referral, patients were asked to complete a standardized set of laboratory tests, including comprehensive metabolic panel, 25OHD, PTH, thyroid testing, complete blood count, phosphorus, tissue transglutaminase antibodies, and 24-h urine calcium with creatinine. Among 890 patients, 67% of subjects had at least one laboratory abnormality. The most common abnormalities were of 25OHD and PTH with 22.4% and 19.1% of each test respectively showing abnormal results. Over 99% of serologic testing was completed; however, urine calcium testing was completed in only 34% of subjects. Among individuals who completed 24-h urine calcium testing (<i>n</i> = 304), 26.5% had hypocalciuria (<100 mg/24 h), and 25.2% had hypercalciuria (>250 mg/24 h). Subjects with a Z-score <-2.0 were more likely to have abnormal laboratory results. This study demonstrates that laboratory abnormalities indicating secondary osteoporosis are very common among patients with low bone density and fracture. Systematic laboratory testing with a circumspect number of tests is appropriate in all patients with skeletal fragility.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 7","pages":"ziaf089"},"PeriodicalIF":3.4,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528003","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":"Atenolol, alone or in combination with PTH, has a modest effect on bone in female C57BL/6J mice.","authors":"Rebecca L Fontaine, Daniel J Brooks, Deborah Barlow, Ryan J Neilson, Christine W Lary, Karen L Houseknecht, Katherine J Motyl","doi":"10.1093/jbmrpl/ziaf087","DOIUrl":"10.1093/jbmrpl/ziaf087","url":null,"abstract":"<p><p>Atenolol is a β1-selective β-adrenergic receptor antagonist (a.k.a. β-blocker) and is under investigation in a clinical trial to prevent osteoporosis in postmenopausal women. The effects of atenolol on rodent bone are unknown, which limits research investigating mechanisms or modeling human treatment effects. However, propranolol, a non-selective β-blocker, has been widely used in rodent models. Propranolol co-treatment with intermittent truncated PTH improves a serum marker of bone formation, P1NP, while blocking the PTH-induced increase in CTX-I-MMP, a serum marker of bone resorption. To determine whether atenolol has similar properties as propranolol during co-treatment, we tested the combined effects of atenolol and PTH in female C57BL/6J mice. Atenolol exposure was confirmed in both serum and marrow at clinically relevant levels. Atenolol had little effect on femoral or L5 vertebra microarchitecture, either on its own or in combination with PTH, which improved trabecular microarchitecture as expected. However, co-treatment with PTH significantly increased P1NP levels past that of PTH alone, suggesting longer treatment may improve bone density by increasing bone formation. In summary, we found little effect of atenolol alone or in combination with PTH, which may be related to relative selectivity of atenolol for β1AR over β2AR, the predominant βAR in bone. Future studies should test whether longer term atenolol may improve microarchitectural parameters with PTH co-treatment.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 7","pages":"ziaf087"},"PeriodicalIF":3.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12161496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144284375","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":"Thermoneutral housing has limited effects on social isolation-induced bone loss in male C57BL/6J mice.","authors":"Rebecca V Mountain, Rebecca L Peters, Audrie L Langlais, Julia Patrizia Stohn, Christine W Lary, Katherine J Motyl","doi":"10.1093/jbmrpl/ziaf088","DOIUrl":"10.1093/jbmrpl/ziaf088","url":null,"abstract":"<p><p>Social isolation stress has numerous known negative health effects, including increased risk for cardiovascular disease, dementia, as well as overall mortality. The impacts of social isolation on skeletal health, however, have not been thoroughly investigated. We previously found that 4 wk of social isolation through single housing led to a significant reduction in trabecular and cortical bone in male, but not female, mice. One possible explanation for these changes in male mice is thermal stress due to sub-thermoneutral housing and sex differences in thermal physiology. Single housing at room temperature (~20 to 25 °C)-below the thermoneutral range of mice (~26 to 34 °C)-may lead to cold stress, which has known negative effects on bone. Therefore, the aim of this study was to test the hypothesis that housing mice near thermoneutrality, thereby ameliorating cold-stress, will prevent social isolation-induced bone loss in male C57BL/6J mice. 16-wk-old mice were randomized into social isolation (1 mouse/cage) or grouped housing (4 mice/cage) at either room temperature (~23 °C) or in a warm temperature incubator (~28 °C) for 4 wk (<i>N</i> = 8/group). As seen in our previous studies, isolated mice at room temperature had significantly reduced bone parameters, including femoral bone volume fraction (-35% BV/TV), bone mineral density (-27% BMD), and cortical thickness (-12%). Contrary to our hypothesis, these negative effects on bone were not fully ameliorated by thermoneutral housing. There was no significant effect of housing or temperature on serum turnover markers. Social isolation increased glucocorticoid-related gene expression in bone and <i>Ucp1</i> and <i>Pdk4</i> expression in BAT across temperatures, while thermoneutral housing increased percent lipid area and decreased <i>Ucp1</i> and <i>Pdk4</i> expression in BAT across housing conditions. Overall, our data suggest thermal stress from single housing cannot fully explain social isolation-induced bone loss and provide a key insight into the mechanism mediating the effects of isolation on skeletal health.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 7","pages":"ziaf088"},"PeriodicalIF":3.4,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505723","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":"Assessment and treatment of osteoporosis in a patient with a neurodevelopmental disorder caused by a <i>RNU4-2</i> pathogenic variant (ReNU syndrome).","authors":"Tess Holling, Simon von Kroge, Laura Hecher, Michael Amling, Thorsten Schinke, Kerstin Kutsche, Ralf Oheim","doi":"10.1093/jbmrpl/ziaf084","DOIUrl":"10.1093/jbmrpl/ziaf084","url":null,"abstract":"<p><p>A 16-yr-old male with a genetically undiagnosed neurodevelopmental disorder (NDD) was admitted to our outpatient clinic for skeletal assessment. DXA and HR-pQCT showed a severely reduced BMD and a pronounced reduction of trabecular and cortical bone mass. Lateral vertebral assessment identified multiple previously unrecognized vertebral fractures of the thoracic and lumbar spine. Laboratory tests indicated an activated bone turnover, which was confirmed by an increased number of osteoclasts and osteoblasts in an undecalcified tibia biopsy of the patient. Treatment of the severe osteoporosis was initiated with neridronate. Trio exome sequencing in the patient and healthy parents did not uncover a genetic cause of the disease. Importantly, however, targeted sequencing of the <i>RNU4-2</i> gene, which encodes the U4 small nuclear RNA (a major component of the splicing machinery), identified a heterozygous causative variant in the patient. This led to the molecular diagnosis of ReNU syndrome. <i>RNU4-2</i> pathogenic variants underlie a NDD with multisystemic involvement, including skeletal abnormalities. Therefore, this case not only underlines the relevance of osteologic assessment and therapy in individuals with NDDs, but also highlights the necessity of future research efforts to elucidate the bone pathologies in ReNU syndrome.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 7","pages":"ziaf084"},"PeriodicalIF":3.4,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12161495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144284374","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":"Abaloparatide increases bone mass without affecting growth of bone-disseminated cancer cells.","authors":"Jeremy F Kane, Gwenyth J Joseph, Lawrence A Vecchi, Jade S Miller, Bradley T Ludington, Katherine N Gibson-Corley, Rachelle W Johnson","doi":"10.1093/jbmrpl/ziaf080","DOIUrl":"10.1093/jbmrpl/ziaf080","url":null,"abstract":"<p><p>Breast cancer cells frequently spread to the bone, causing osteoclast-mediated bone destruction and pathological fractures. Bone anabolic agents, such as abaloparatide, are used clinically to increase bone formation in osteoporotic patients, but their effectiveness against tumor-induced bone destruction is poorly understood. In this study, we present the first evaluation of abaloparatide in preclinical models of breast cancer cells disseminated to the bone marrow and demonstrate that intermittent abaloparatide dramatically increases trabecular bone volume in mice inoculated with triple negative breast cancer cells. Abaloparatide also increases BMD in a model of estrogen receptor positive breast cancer, despite elevated baseline bone volume due to estradiol supplementation. Importantly, abaloparatide does not increase tumor burden or incidence in bone or soft tissue sites in either model. These results suggest that abaloparatide may be effectively used to increase bone mass without stimulating growth of cancer cells in the bone marrow and may be beneficial for cancer patients with low bone mass.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 7","pages":"ziaf080"},"PeriodicalIF":2.4,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528002","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":"Reduced orthodontic tooth movement in <i>Ank</i> knockout mice.","authors":"Marta Rizk, Emily Yin Chu, Rogerio Bastos Craveiro, Merve Elmas, Sihem Brenji, Christian Niederau, Nikolaus Marx, Brian Lee Foster, Martha Joan Somerman, Michael Wolf","doi":"10.1093/jbmrpl/ziaf064","DOIUrl":"10.1093/jbmrpl/ziaf064","url":null,"abstract":"<p><p>Hypercementosis has been previously reported in mice lacking progressive ankylosis protein (<i>Ank</i> KO mice, or <i>Ank, KO - knockout, WT - wildtype</i>) due to decreased levels of the mineralization inhibitor inorganic pyrophosphate. However, the impact of hypercementosis on alveolar bone remodeling and periodontal ligament (PDL) maintenance from orthodontic forces during orthodontic tooth movement (OTM) remains unclear. To investigate the roles of ANK protein on tooth movement, PDL maintenance, alveolar bone remodeling, and tooth root resorption, we performed a split-mouth model of OTM induced by a closed-coil spring stretched between the maxillary first molar and maxillary incisors in <i>Ank</i> KO and WT mice (including both males and females). Micro-computed tomographic analysis revealed a 36.6% reduction in OTM in <i>Ank</i> KO mice compared with WT mice, although OTM-induced thickening of PDL was found to be similar in both groups. While reduced tissue mineral density (TMD) of the alveolar bone was observed in WT mice, TMD in <i>Ank</i> KO mice was maintained. Loss of <i>Ank</i> leads to wider roots with thicker cementum on the untreated, contralateral side, whereas a significant increase in OTM-induced root resorption was observed on the lateral tension side. Histologic analysis of root resorption confirmed these data and showed increased resorption lacunae located prevalently in the OTM tooth root cementum of <i>Ank</i> KO mice. Using a quantitative PCR array of bone-associated markers to interrogate total RNA harvested from PDL tissues along the root surface, we found alterations in gene expression from OTM in both WT and <i>Ank</i> KO mice, which included genes involved in bone remodeling, calciotropic hormones and receptors, cytokines, growth factors, and receptors. Our findings advance the understanding of the role of <i>Ank</i> in regulating mineralization in the periodontium as well as factors involved in root resorption.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 6","pages":"ziaf064"},"PeriodicalIF":3.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101108","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":"Expression of the aryl hydrocarbon receptor in Osterix-lineage cells regulates adult skeletal homeostasis in a compartment-specific manner.","authors":"Jennifer Dorn, Dima W Alhamad, Husam Bensreti, Christopher L Yearwood, Tate J Allen, Michaela Cushing, Joseph C Shaver, Colby Gross, William C Whichard, Caihong Dai, Kanglun Yu, Roger Zhong, Marion A Cooley, Maribeth H Johnson, Wendy B Bollag, Sadanand Fulzele, Carlos M Isales, Mark W Hamrick, William D Hill, Meghan E McGee-Lawrence","doi":"10.1093/jbmrpl/ziaf067","DOIUrl":"10.1093/jbmrpl/ziaf067","url":null,"abstract":"<p><p>Kynurenine (KYN), a tryptophan metabolite that increases with age, impairs osteoblast function. The aryl hydrocarbon receptor (AhR) has been proposed to mediate KYN's actions in bone. To test whether deletion of AhR in osteoblasts is beneficial for bone, we established an adult-onset AhR conditional knockout (CKO) model using Osx-Cre and examined the effects of AhR CKO at 4.5 and 6 mo of age (representing ~6 and 12 wk of CKO). While BMSC-derived osteoblasts from WT mice demonstrated reduced matrix formation from KYN treatment, AhR CKO osteoblasts were unaffected by KYN. Kynurenine's harmful effects were most pronounced in the middle of an osteoblastic differentiation time course, and these effects could be rescued via the AhR antagonist BAY2416964. In vivo, AhR deletion in Osx-expressing cells promoted sex- and compartment-specific skeletal phenotypes. Trabecular bone was increased in the distal femur of male and female AhR CKO mice at both 4.5 and 6 mo of age, potentially driven by a net decrease in the ratio of trabecular osteoclasts to osteoblasts despite a reduction in mineral apposition rate at 6 mo of age. In contrast, cortical bone phenotypes induced by AhR deletion depended on age and sex. In males, cortical bone volume fraction (Ct.BV/TV) was elevated in AhR CKO mice vs WT littermates at 4.5 mo of age, but differences resolved by 6 mo of age. In contrast, cortical bone was reduced in female AhR CKO as compared to WT littermates at 6 mo of age. These results underscore the complexity of AhR signaling in skeletal biology that must be considered while exploring AhR as a therapeutic target for conditions like osteoporosis and musculoskeletal frailty. Future studies will be needed to test the effects of osteoblastic AhR deletion at advanced ages, when the endogenous AhR ligand KYN is elevated in the circulation and skeletal niche.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 6","pages":"ziaf067"},"PeriodicalIF":3.4,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150492","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":"How does bone recover in patients with tumor-induced osteomalacia? Long-term follow-up in a national cohort study.","authors":"María Belén Zanchetta, Fernando Jerkovich, Florencia Scioscia, Yamile Mocarbel, Analía Pignatta, Natalia Elías, Juan Manuel Roganovich, Carlos Vigovich, María Celeste Balonga, Ana Carolina Cohen, Giselle Mumbach, José Luis Mansur, Carolina Fux Otta, Walter Guillermo Douthat, Pilar Tartaglia, Griselda Cecchi, María Bastianello, Luisa Plantalech, Erich Fradinger, José Rubén Zanchetta","doi":"10.1093/jbmrpl/ziaf041","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziaf041","url":null,"abstract":"<p><p>Tumor-induced osteomalacia (TIO) is a rare disorder characterized by impaired bone mineralization due to phosphate wasting. Long-term changes in BMD and microarchitecture after surgical cure or medical therapy in TIO are not well understood. This study describes changes in BMD, microarchitecture, and bone strength in patients with TIO following surgical cure or medical therapy. A prospective cohort study included adults diagnosed with TIO from May 2018 to 2024, categorized into those with surgical cure and those on medical therapy. Follow-up assessments were classified as early (median 8 mo), intermediate (median 17 mo), and long-term (median 26 mo). Fifteen patients were included: seven achieved surgical cure, and eight remained on medical therapy. Lumbar spine BMD increased by +19% at early, +27% at intermediate, and +15% at long-term follow-up. Total hip BMD increased by +31%, +36%, and +31% at early, intermediate, and long-term assessments, respectively. All patients achieved a normal lumbar spine BMD, while 91% attained a normal total hip BMD. At the distal tibia, substantial increases in bone microarchitecture parameters-cortical area (Ct.Ar), cortical volumetric density (Ct.vBMD), and cortical thickness (Ct.Th)-were observed. Notably, Ct.Th improved to levels comparable to healthy controls. Bone strength improved by 13% but was not statistically significant, probably due to the small sample size. At the distal radius, most parameters remained stable. Patients with surgical cure showed more rapid and substantial improvements in BMD and cortical microarchitecture than non-cured patients, but these differences did not reach statistical significance. Overall, bone recovery in TIO is gradual, with gains in spine and hip BMD and significant improvements in tibial cortical parameters. However, some aspects of bone microarchitecture remained below control levels, underscoring the need for ongoing monitoring and individualized management strategies.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 5","pages":"ziaf041"},"PeriodicalIF":3.4,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12010155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001245","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}