JBMR Plus最新文献

{"title":"Longitudinal patient outcomes over 18 months following a hip, clinical vertebral, distal forearm, or proximal humerus fracture in the United States: results from the ICUROS US study.","authors":"Stuart Silverman, Deborah Gold, Michael Nichol, John Schousboe, Rebecca Smith, Anna Tosteson","doi":"10.1093/jbmrpl/ziaf077","DOIUrl":"10.1093/jbmrpl/ziaf077","url":null,"abstract":"<p><p>The longitudinal impact of fractures associated with osteoporosis on costs and health-related quality of life is not well understood. The objective of this study was to characterize these outcomes over an 18-mo period following 4 common fracture types. Patients aged over 50 yr at 7 study sites with a diagnosis of incident hip, distal radius, proximal humerus, or vertebral fracture were enrolled in the International Costs and Utilities Related to Osteoporotic Fracture Study US. Data collection by questionnaire occurred at baseline (within 6 wk of fracture), 4-, 12-, and 18-mo post-fracture. Direct, indirect, and total costs were estimated over an 18-mo period and are reported in 2020 US Dollars. Health utilities were measured using EuroQol EQ-5D and the SF-6D. We performed longitudinal regression models of estimated costs adjusted for age and sex. We enrolled 284 patients with single fragility fractures (58 hip, 50 distal radius, 32 proximal humerus, 144 vertebral). Mean ages were 68.1 yr for distal radius and proximal humerus and 76 yr for hip patients. Most participants were women (76%-84% women). Over the 18-mo study period, direct costs (Including initial fracture and fracture related follow-up costs) were $18 495 for hip, $3451 for distal forearm, $6009 for humerus, and $9274 for vertebral fracture. Mean indirect costs were $9250 for hip, $1772 for distal radius, $4195 for humerus, and $4084 for vertebral fracture. Adjusted mean EQ-5D differences (95% CI) at 18-mo for those surviving/reporting compared with baseline were: hip -0.162 (95% CI, -0.22 to -0.103), distal radius -0.017 (95% CI, -0.056 to 0.022), proximal humerus -0.064 (95% CI, -0.103 to -0.0248), and vertebral -0.044 (95% CI, -0.083 to -0.0048). Substantial direct and indirect costs are observed in the 18-mo following 4 common osteoporotic fractures. Significant changes in health utility persisted for all fractures other than distal radius fractures regardless of the health utility measure used.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 7","pages":"ziaf077"},"PeriodicalIF":3.4,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528004","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":"Correction to: Fracture discrimination capability of ulnar flexural rigidity measured via Cortical Bone Mechanics Technology: study protocol for The STRONGER Study.","authors":"","doi":"10.1093/jbmrpl/ziaf095","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziaf095","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/jbmrpl/ziad002.].</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 6","pages":"ziaf095"},"PeriodicalIF":3.4,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12123522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199146","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":"Bone phenotype in male and female mice after knockdown of transferrin receptor 1 in osterix-expressing cells.","authors":"Vanessa Passin, Maria G Ledesma-Colunga, Ulrike Baschant, Lorenz C Hofbauer, Martina Rauner","doi":"10.1093/jbmrpl/ziaf069","DOIUrl":"10.1093/jbmrpl/ziaf069","url":null,"abstract":"<p><p>Transferrin receptor 1 (Tfr1) plays a key role in mediating the cellular uptake of transferrin-bound iron. While Tfr1 is essential for iron uptake in erythroid cells and skeletal muscle, it is dispensable for iron acquisition in hepatocytes, intestinal epithelial, or endothelial cells. In this study, we investigated the significance of Tfr1 for iron uptake and cellular function in bone-forming osteoblasts. Therefore, we examined the bone characteristics of male and female Tfr1^fl/fl;Osx:cre^+/- (osteoprogenitors) conditional KO mice at 12 and 24 wk of age. Bone marrow-derived cells from Tfr1^fl/fl;Osx:cre^+/- mice were differentiated into osteoblasts in vitro to assess cellular iron status as well as cellular differentiation and function. Our findings indicate that Tfr1 deficiency in osteoprogenitors in male mice resulted in increased trabecular bone mass in the axial skeleton with decreased bone formation rate as well as decreased levels of serum bone turnover markers. Despite increased bone mass in the femur in females resulting from Tfr1 deficiency in osteoprogenitors, loss of bone mass following ovariectomy was not mitigated. Transferrin receptor 1-deficient osteoblasts showed mild changes in cytosolic iron levels and decreased mineralization. These results suggest a minor role of Tfr1 in osteoblasts differentiation and function but highlight distinct strategies for iron acquisition employed by bone cells to maintain cellular iron homeostasis.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 7","pages":"ziaf069"},"PeriodicalIF":3.4,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247908","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":"Sirtuin-3 promotes osteoclast maturation and bone loss by regulating mitochondrial ROS production during ionizing radiation exposure.","authors":"Gareeballah Osman Adam, Kimberly K Richardson, Ankita Chalke, Qiang Fu, Jeff D Thostenson, Hutomo Tanoto, Yuxiao Zhou, Nukhet Aykin-Burns, Ha-Neui Kim","doi":"10.1093/jbmrpl/ziaf092","DOIUrl":"10.1093/jbmrpl/ziaf092","url":null,"abstract":"<p><p>Ionizing radiation (IR) exposure leads to mitochondrial alterations in osteoclasts and osteoblasts, contributing to musculoskeletal disintegration. Despite this, the mechanisms controlling mitochondrial activity in bone cells during IR exposure-associated bone disorders remain underexplored. Sirtuin-3 (SIRT3), a NAD-dependent mitochondrial deacetylase, is essential for the enhanced mitochondrial function in osteoclasts and the increased bone resorption observed in osteoporosis. However, it is still unclear whether and how SIRT3 drives IR exposure-induced bone disorders. Here, we show that deletion of <i>Sirt3</i> greatly attenuated the IR exposure-induced loss of bone mass in young adult mice. This effect was associated with impaired osteoclast maturation and function, thus suppressing excessive bone resorption. IR exposure also increased mitochondrial activity and ROS production in osteoclasts. Deletion of <i>Sirt3</i> abrogated these effects of IR exposure. The levels of mitochondrial superoxide dismutase 2 (SOD2), a major component of the metabolic machinery that handles ROS in the mitochondrial matrix, were significantly increased in osteoclasts by RANKL with an identical pattern as SIRT3. Deacetylation of lysine 68 of SOD2 enhanced the formation of giant osteoclasts and increased mitochondrial ROS production, mimicking the effects of IR exposure. Inhibition of mitochondrial ROS production via Mito-TEMPO recapitulated the effects of <i>Sirt3</i> deletion on osteoclast maturation and mitochondrial activity during IR exposure. These findings demonstrate that SIRT3 plays an essential role in IR exposure-induced bone resorption by promoting deacetylation in osteoclast mitochondria. Understanding the mechanisms of mitochondrial quality control and protein acetylation in osteoclasts could pave the way for developing novel strategies to counteract IR exposure-associated bone disorders.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 7","pages":"ziaf092"},"PeriodicalIF":3.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528006","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":"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}