Journal of Bone and Mineral Research最新文献

{"title":"Prediction of hip fracture by high-resolution peripheral quantitative computed tomography in older Swedish women.","authors":"Raju Jaiswal, Aldina Pivodic, Michail Zoulakis, Kristian F Axelsson, Henrik Litsne, Lisa Johansson, Mattias Lorentzon","doi":"10.1093/jbmr/zjaf020","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf020","url":null,"abstract":"<p><p>The socioeconomic burden of hip fractures, the most severe osteoporotic fracture outcome, is increasing and the current clinical risk assessment lacks sensitivity. This study aimed to develop a method for improved prediction of hip fracture by incorporating measurements of bone microstructure and composition derived from high-resolution peripheral quantitative computed tomography (HR-pQCT). In a prospective cohort study of 3028 community-dwelling women aged 75 to 80, all participants answered questionnaires and underwent baseline examinations of anthropometrics and bone by dual x-ray absorptiometry (DXA) and HR-pQCT. Medical records, a regional x-ray archive, and registers were used to identify incident fractures and death. Prediction models for hip, major osteoporotic fracture (MOF), and any fracture were developed using Cox proportional hazards regression and machine learning algorithms (neural network, random forest, ensemble, and XGBoost). In the 2856 (94.3%) women with complete HR-pQCT data at 2 tibia sites (distal and ultra-distal), the median follow-up period was 8.0 years, and 217 hip, 746 MOF, and 1008 any type of incident fracture occurred. In Cox regression models adjusted for age, BMI, clinical risk factors (CRF), and femoral neck bone mineral density (FN BMD) the strongest predictors of hip fracture were tibia total volumetric BMD and cortical thickness. The performance of the Cox regression-based prediction models for hip fracture was significantly improved by HR-pQCT (time-dependent AUC; area under receiver operating characteristic curve at 5 years of follow-up 0.75 [0.64-0.85]), compared to a reference model including CRFs and FN BMD (AUC = 0.71 [0.58-0.81], p<.001) and a FRAX risk score model (AUC = 0.70 [0.60-0.80], p<.001). The Cox regression model for hip fracture had a significantly higher accuracy than the neural network-based model, the best-performing machine learning algorithm, at clinically relevant sensitivity levels. We conclude that the addition of HR-pQCT parameters improves the prediction of hip fractures in a cohort of older Swedish women.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Probability of Achieving Bone Mineral Density Treatment Goals with Denosumab Treatment in Postmenopausal Women with Osteoporosis.","authors":"Felicia Cosman, Zhenxun Wang, Xiaodong Li, Steven R Cummings","doi":"10.1093/jbmr/zjaf014","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf014","url":null,"abstract":"<p><p>Bone mineral density (BMD) levels achieved on osteoporosis treatment are predictive of subsequent fracture risk, and T-score > -2.5 has been proposed as a minimum treatment target for women with osteoporosis. Knowing the likelihood of attaining target T-scores with different medications for different baseline BMD levels can help determine appropriate initial treatment for individual patients. In this post hoc analysis, we estimated the probability of achieving a non-osteoporotic T-score (> -2.5 or ≥ -2.0) at the total hip (TH) or lumbar spine (LS) in postmenopausal women >60 years old treated with denosumab for either 3 or 10 years in the FREEDOM trial and its long-term extension. In women with baseline TH T-scores of -2.7, -3.0, and -3.5, the probabilities of achieving target T-scores > -2.5 with 3 years of denosumab were 71%, 12%, and 0.1%, respectively. At LS, for baseline T-scores of -2.7, -3.0, and -3.5, the probabilities were 86%, 59%, and 11%, respectively. Longer treatment duration of up to 10 years increased the probability of achieving target T-scores. The baseline T-scores that permitted at least 50% of women to achieve a target T-score > -2.5 was -2.8 at TH and -3.1 at LS after 3 years and -3.0 at TH and -3.7 at LS after 10 years of treatment. To achieve higher treatment targets (T-scores ≥ -2.0), overall probabilities were lower at both skeletal sites, particularly for TH, even with longer treatment duration. Our results demonstrate that the probability of achieving T-score targets with denosumab is dependent on baseline BMD, skeletal site, and treatment duration. Knowing the probability of achieving treatment targets for different baseline TH and LS T-scores can help determine whether denosumab is an appropriate first choice of treatment in individual patients.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143035477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative cardiovascular safety of romosozumab versus bisphosphonates in Japanese patients with osteoporosis: a new-user, active comparator design with instrumental variable analyses.","authors":"Ryoji Tominaga, Tatsuyoshi Ikenoue, Ryosuke Ishii, Kakuya Niihata, Tetsuro Aita, Tadahisa Okuda, Sayaka Shimizu, Masataka Taguri, Noriaki Kurita","doi":"10.1093/jbmr/zjaf010","DOIUrl":"10.1093/jbmr/zjaf010","url":null,"abstract":"<p><p>This study analyzed the association of romosozumab, a human monoclonal antibody with bone-forming and bone resorption-inhibiting effects, and bisphosphonates with the development of cardiovascular disease among patients with osteoporosis. A new-user design was employed to address selection bias, and instrumental variable analysis was used to address confounding by indication. Japanese patients aged ≥40 years, diagnosed with osteoporosis or experienced a fragility fracture, were admitted to medical facilities covered by a commercial administrative claims database, and newly prescribed romosozumab or bisphosphonates after the commercialization of romosozumab in Japan (March 4, 2019) were included based on verification of a 180-day washout period. Cardiovascular disease (myocardial infarction or stroke) was identified based on information regarding diagnosis, medical procedures, and drug codes. Facility-level prescription preference for romosozumab was used as an instrumental variable, defined as the proportion of romosozumab prescribed at the patient's facility within 90 days prior to the index date. Of the 59 694 included prescriptions, 8808 were for romosozumab and 50 886 were for bisphosphonates. The mean age in the romosozumab group was higher than that in the bisphosphonates group (80.5 vs. 78.2 years, respectively), and most patients were females (85.3 vs. 80.2%, respectively). The incidence of cardiovascular disease within 1 year of prescription was 12.3 per 100 person-years for romosozumab versus 11.4 for bisphosphonates (unadjusted incidence rate ratio: 1.08, 95% confidence interval: 1.00-1.18). An instrumental variable analysis using the two-stage residual inclusion method yielded a hazard ratio of 1.30 (95% confidence interval: 0.88-1.90) for romosozumab compared with bisphosphonates over 1 year. Although possibly underpowered, this study showed that no definitive evidence of increased cardiovascular risk associated with romosozumab use compared with bisphosphonates was observed in patients with osteoporosis. These findings should be further validated by larger pharmacoepidemiological studies to alleviate clinicians' concerns about romosozumab's safety.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time-lapse HR-pQCT reliably assesses and monitors local bone turnover in patients with chronic kidney disease.","authors":"Minhao Zhou, Saghi Sadoughi, Lauren Go, Gabriella Ramil, Isabel Yu, Isra Saeed, Bo Fan, Po-Hung Wu, Isidro B Salusky, Thomas L Nickolas, Joachim H Ix, Galateia J Kazakia","doi":"10.1093/jbmr/zjaf006","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf006","url":null,"abstract":"<p><p>Bone turnover assessment and monitoring are essential for chronic kidney disease (CKD)-associated bone care. Patients with CKD suffer from significantly elevated fracture risk due to abnormally high or low bone turnover, which requires diametrically opposite treatments informed by patient-specific bone turnover data. However, a reliable, accessible, non-invasive bone turnover assessment and monitoring tool remains an unmet clinical need. Combining time-lapse (TL) analysis with high-resolution peripheral quantitative computed tomography (HR-pQCT) scans obtained over time allows for in vivo temporospatial bone remodeling assessment. This study aimed to evaluate the feasibility of applying TL HR-pQCT to assess and monitor local bone formation and resorption in patients with CKD. A customized TL HR-pQCT pipeline was developed on a second-generation HR-pQCT platform and optimized using ex vivo cadaveric phantom and in vivo scan-rescan HR-pQCT images. The annualized least significant change in bone formation and resorption were evaluated using in vivo longitudinal reproducibility images. Finally, the feasibility of the TL HR-pQCT pipeline in assessing and monitoring bone turnover was evaluated in patients with end stage kidney disease (ESKD; n = 9). We found that a 2-month time-lapse period was sufficient for the TL HR-pQCT pipeline to reliably assess and monitor local bone turnover in a cohort of patients with ESKD. We also demonstrated the importance of characterizing TL HR-pQCT precision metrics using longitudinal baseline/follow-up rather than short-term scan-rescan datasets. The TL HR-pQCT pipeline assessed a range of bone formation metrics consistent with the gold standard histomorphometric bone formation reported in the literature for patients with CKD and ESKD. Our findings highlight that TL HR-pQCT holds promise as a \"virtual bone biopsy\" that reliably assesses and monitors local bone turnover for CKD bone care. Subsequent work will focus on validating this TL HR-pQCT pipeline against the gold standard bone biopsy with quantitative histomorphometry.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of calcium supplementation on bone calcium balance and calcium and bone metabolism during load carriage in women: a randomised controlled crossover trial.","authors":"Charlotte V Coombs, Julie P Greeves, Christina D Young, Alice S Irving, Anton Eisenhauer, Ana Kolevica, Alexander Heuser, Jonathan C Y Tang, William D Fraser, Thomas J O'Leary","doi":"10.1093/jbmr/zjaf004","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf004","url":null,"abstract":"<p><p>Calcium supplementation before exercise attenuates the decrease in serum calcium and increase in PTH and bone resorption. This study investigated the effect of calcium supplementation on calcium and bone metabolism during load carriage in women. Forty-eight women completed two load carriage sessions (load carriage 1 n = 48; load carriage 2 n = 40) (12.8 km in 120 min carrying 20 kg) 60 min after consuming either 1000 mg calcium (Calcium) or nothing (Control) in a randomised order. Pre- and post-exercise urine samples were analysed for calcium isotope ratio (δ44/42Ca). Fasted blood samples were taken before (pre-exercise), during (0, 20, 40, 60, 80, 100, 120 min), and after (+15, +30, +60, +90 min) exercise and analysed for markers of calcium and bone metabolism. There was no effect of load carriage or supplementation on urine δ44/42Ca (P≥.110). Serum δ44/42Ca did not change with load carriage in Control (P=.617) but increased in Calcium (P=.003) and was higher at 120 min in Calcium vs Control (P=.018). Ionised calcium (iCa) decreased from pre-exercise to all exercise time-points (P<.001); iCa was higher in Calcium than Control throughout (P<.001). PTH increased from pre-exercise to 120 min in Control (P<.001) but decreased from pre-exercise to all time-points in Calcium (P<.001). PTH was higher in Control than Calcium from 0 to +90 min (P<.001). βCTX decreased from pre-exercise to 20 to +15 min in Control (P≤.004); βCTX decreased from pre-exercise to 0 to +90 min in Calcium (P<.001). βCTX was lower in Calcium than Control from 20 to +90 min (P≤.036). A 1000 mg calcium supplement before load carriage promotes bone calcium balance and prevents disruptions to bone and calcium homeostasis.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thrombopoietic agents enhance bone healing in mice, rats, and pigs.","authors":"Paul J Childress, Jeffery J Nielsen, Thomas B Bemenderfer, Ushashi C Dadwal, Nabarun Chakraborty, Jonathan S Harris, Monique Bethel, Marta B Alvarez, Aamir Tucker, Alexander R Wessel, Patrick D Millikan, Jonathan H Wilhite, Andrew Engle, Alexander Brinker, Jeffrey D Rytlewski, David C Scofield, Kaitlyn S Griffin, W Christopher Shelley, Kelli J Manikowski, Krista L Jackson, Stacy-Ann Miller, Ying-Hua Cheng, Joydeep Ghosh, Patrick L Mulcrone, Edward F Srour, Mervin C Yoder, Roman M Natoli, Karl D Shively, Aarti Gautam, Rasha Hammamieh, Stewart A Low, Philip S Low, Todd O McKinley, Jeffrey O Anglen, Jonathan W Lowery, Tien-Min G Chu, Melissa A Kacena","doi":"10.1093/jbmr/zjae191","DOIUrl":"10.1093/jbmr/zjae191","url":null,"abstract":"<p><p>Achieving bone union remains a significant clinical dilemma. The use of osteoinductive agents, specifically bone morphogenetic proteins (BMPs), has gained wide attention. However, multiple side effects, including increased incidence of cancer, have renewed interest in investigating alternatives that provide safer, yet effective bone regeneration. Here we demonstrate the robust bone healing capabilities of the main megakaryocyte (MK) growth factor, thrombopoietin (TPO), and second-generation TPO agents using multiple animal models, including mice, rats, and pigs. This bone healing activity is shown in two fracture models (critical-sized defect [CSD] and closed fracture) and with local or systemic administration. Our transcriptomic analyses, cellular studies, and protein arrays demonstrate that TPO enhances multiple cellular processes important to fracture healing, particularly angiogenesis, which is required for bone union. Finally, the therapeutic potential of thrombopoietic agents is high since they are used in the clinic for other indications (eg, thrombocytopenia) with established safety profiles and act upon a narrowly defined population of cells.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"125-139"},"PeriodicalIF":5.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-duration type 1 diabetes is associated with deficient cortical bone mechanical behavior and altered matrix composition in human femoral bone.","authors":"Shannon R Emerzian, Jarred Chow, Ramina Behzad, Mustafa Unal, Daniel J Brooks, I-Hsien Wu, John Gauthier, Surya Vishva Teja Jangolla, Marc Gregory Yu, Hetal S Shah, George L King, Fjola Johannesdottir, Lamya Karim, Elaine W Yu, Mary L Bouxsein","doi":"10.1093/jbmr/zjae184","DOIUrl":"10.1093/jbmr/zjae184","url":null,"abstract":"<p><p>Type 1 diabetes (T1D) is associated with an increased risk of hip fracture beyond what can be explained by reduced bone mineral density, possibly due to changes in bone material from accumulation of advanced glycation end-products (AGEs) and altered matrix composition, though data from human cortical bone in T1D are limited. The objective of this study was to evaluate cortical bone material behavior in T1D by examining specimens from cadaveric femora from older adults with long-duration T1D (≥50 yr; n = 20) and age- and sex-matched nondiabetic controls (n = 14). Cortical bone was assessed by mechanical testing (4-point bending, cyclic reference point indentation, impact microindentation), AGE quantification [total fluorescent AGEs, pentosidine, carboxymethyl lysine (CML)], and matrix composition via Raman spectroscopy. Cortical bone from older adults with T1D had diminished postyield toughness to fracture (-30%, p = .036), elevated levels of AGEs (pentosidine, +17%, p = .039), lower mineral crystallinity (-1.4%, p = .010), greater proline hydroxylation (+1.9%, p = .009), and reduced glycosaminoglycan (GAG) content (-1.3%, p < .03) compared to nondiabetics. In multiple regression models to predict cortical bone toughness, cortical tissue mineral density, CML, and Raman spectroscopic measures of enzymatic collagen crosslinks and GAG content remained highly significant predictors of toughness, while diabetic status was no longer significant (adjusted R2 > 0.60, p < .001). Thus, the impairment of cortical bone to absorb energy following long-duration T1D is well explained by AGE accumulation and modifications to the bone matrix. These results provide novel insight into the pathogenesis of skeletal fragility in individuals with T1D.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"87-99"},"PeriodicalIF":5.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11700620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"One day at a time: understanding how 24-hr physical activity, sedentary behavior and sleep patterns influence falls and fracture risk.","authors":"Costas Glavas, David Scott","doi":"10.1093/jbmr/zjae188","DOIUrl":"10.1093/jbmr/zjae188","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"1-2"},"PeriodicalIF":5.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HR-pQCT reveals marked trabecular and cortical structural deficits in women with pregnancy and lactation-associated osteoporosis (PLO).","authors":"Sanchita Agarwal, Dany El-Najjar, Ananya Kondapalli, Nayoung Kil, Mafo Kamanda-Kosseh, Mariana Bucovsky, Ivelisse Colon, Joan M Lappe, Julie Stubby, Robert R Recker, X Edward Guo, Elizabeth Shane, Adi Cohen","doi":"10.1093/jbmr/zjae167","DOIUrl":"10.1093/jbmr/zjae167","url":null,"abstract":"<p><p>Pregnancy and lactation-associated osteoporosis (PLO) is a rare presentation of early-onset osteoporosis characterized by low trauma and spontaneous fractures during late pregnancy/lactation. Herein, we report areal BMD (aBMD) by DXA and volumetric BMD (vBMD), microarchitecture, and strength at the distal radius and tibia by HR-pQCT in 59 women with PLO-in comparison to both healthy premenopausal controls (n = 28) and premenopausal women with idiopathic osteoporotic fractures not associated with pregnancy/lactation (non-PLO IOP; n = 50). Women with PLO (aged 34 ± 6 yr) had a more severe clinical presentation than non-PLO IOP: 80% had vertebral and 92% had multiple fractures (p<.001). They had lower DXA aBMD at all sites vs Controls (all p<.001) and non-PLO IOP (all p<.05). By HR-pQCT, PLO had deficits in all radial/tibial density and most microarchitecture parameters and lower bone strength than controls (all p<.001). Compared to non-PLO IOP, PLO had lower total and trabecular density at radius and tibia (all p ≤ .01) and significant deficits in trabecular microstructure and cortical thickness at the radius only. We studied PLO subgroups with clinical factors potentially related to bone physiology: Within PLO, women with vertebral fractures had lower spine aBMD and higher tibial cortical porosity but were otherwise structurally similar to the nonvertebral group. Those with prior heparin exposure had larger bone size and trabecular area, and those with renal stones had smaller bone size and lower 1/3 radius aBMD. We also compared groups based on postpartum timing: Recent PLO (n = 25) evaluated ≤12 M postpartum, before expected recovery of pregnancy/lactation bone loss, had significantly lower aBMD than distant PLO (n = 34) evaluated >12 M postpartum. However, radial/tibial HR-pQCT measures did not differ, suggesting pre-existing and/or persistent structural deficits. This structural study increases our mechanistic understanding of the severe bone fragility presentation that characterizes PLO and also highlights areas of potential mechanistic heterogeneity that require additional investigation.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"38-49"},"PeriodicalIF":5.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12034093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new Col1a1 conditional knock-in mouse model to study osteogenesis imperfecta.","authors":"Milena Dimori, Mahtab Toulany, Lira Samia Sultana, Melda Onal, Jeff D Thostenson, John L Carroll, Charles A O'Brien, Roy Morello","doi":"10.1093/jbmr/zjae189","DOIUrl":"10.1093/jbmr/zjae189","url":null,"abstract":"<p><p>Osteogenesis imperfecta (OI) constitutes a family of bone fragility disorders characterized by both genetic and clinical heterogeneity. Several different mouse models reproduce the classic features of OI, and the most commonly studied carry either a spontaneous or genetically induced pathogenic variant in the Col1a1 or Col1a2 gene. When OI is caused by primary alterations of type I collagen, it represents a systemic connective tissue disease that, in addition to the skeleton, also affects several extra-skeletal tissues and organs, such as skin, teeth, lung, heart, and others, where the altered type I collagen is also expressed. Currently, existing mouse models harbor a disease-causing genetic variant in all tissues and do not allow assessing the primary vs secondary consequences of the mutation on a specific organ/system. Here, we describe the generation of the first conditional knock-in allele for Col1a1 that can express a severe OI-causing glycine substitution (p.Gly1146Arg) in the triple helical region of α1(I) but only after Cre-driven recombination in the tissue of choice. We called this new dominant allele Col1a1G1146R-Floxed/+ and introduced it into the murine model. We describe its validation by crossing mice carrying this allele with EIIA-Cre expressing mice and showing that offspring with the recombined allele reproduce the classic features of a severe form of OI. The new mouse model will be useful to study the tissue-specific impact of this severe mutation on organs, such as the lung, the heart, and others.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"114-124"},"PeriodicalIF":5.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}