Journal of Bone and Mineral Metabolism最新文献

{"title":"Nationwide database study of postoperative sequelae and in-hospital mortality in super-elderly hip fracture patients.","authors":"Yu Mori, Kunio Tarasawa, Hidetatsu Tanaka, Naoko Mori, Kiyohide Fushimi, Toshimi Aizawa, Kenji Fujimori","doi":"10.1007/s00774-024-01564-w","DOIUrl":"https://doi.org/10.1007/s00774-024-01564-w","url":null,"abstract":"<p><strong>Introduction: </strong>The risk of postoperative sequelae and in-hospital mortality in Japanese patients aged 90 years and older with hip fractures is unexplored. This study aims to use a comprehensive medical claims database in Japan to compare super-elderly patients aged 90 years and older with elderly aged 65-89 and clarify the risk of sequelae and in-hospital mortality in super-elderly patients.</p><p><strong>Materials and methods: </strong>We retrospectively analyzed the Diagnosis Procedure Combination (DPC) database for all of Japan from April 2016 to March 2022. Medical records from approximately 1100 DPC-related hospitals were provided with consistent consent during this period. In this study, we focused on super-elderly patients and examined the association with the risk of postoperative pneumonia, pulmonary embolism, myocardial infarction, urinary tract infection, acute renal dysfunction, subsequent cognitive dysfunction, and in-hospital mortality after one-to-one propensity score matching.</p><p><strong>Results: </strong>After performing propensity score matching based on sex and comorbidities, 129,953 pairs of patients were identified. These pairs were compared to elderly and super-elderly patients. The results of this study showed that compared with hip fractures in the elderly, hip fractures in the super-elderly were associated with an increased risk of pneumonia, urinary tract infection, acute renal dysfunction, subsequent cognitive dysfunction, and in-hospital mortality after adjustment for confounders. The odds ratio of in-hospital mortality was 2.190 (95% CI 2.062-2.325).</p><p><strong>Conclusion: </strong>As it has been shown that super-elderly patients with hip fractures are at greater risk of respiratory and urinary tract infections and increased in-hospital mortality, careful attention should be required for perioperative management.</p>","PeriodicalId":15116,"journal":{"name":"Journal of Bone and Mineral Metabolism","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604483","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":"Aromatase inhibitors, bone microstructure, and estimated bone strength in postmenopausal women with breast cancer: a 5-year prospective study.","authors":"Sayaka Kuba, Ko Chiba, Kounosuke Watanabe, Megumi Matsumoto, Michi Morita, Momoko Akashi, Aki Yukutake, Yuki Hara, Ayako Fukushima, Eiko Inamasu, Ryota Otsubo, Kosho Yamanouchi, Kengo Kanetaka, Makoto Osaki, Keitaro Matsumoto, Susumu Eguchi","doi":"10.1007/s00774-024-01560-0","DOIUrl":"https://doi.org/10.1007/s00774-024-01560-0","url":null,"abstract":"<p><strong>Introduction: </strong>Aromatase inhibitors (AIs) are the standard treatment for early breast cancer (EBC) and are typical causative agents of cancer treatment-induced bone loss. However, the effects of long-term treatment with these drugs on bone microstructure remain unclear.</p><p><strong>Materials and methods: </strong>This prospective, single-arm observational study included postmenopausal, non-osteoporotic women with hormone receptor-positive EBC. Patients who underwent dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT), and tartrate-resistant acid phosphatase-5b (TRACP-5b) or procollagen type I N-terminal propeptide levels were compared at baseline and at 60 months after commencing AI treatment.</p><p><strong>Results: </strong>Fifteen women were included in the study, with a median age of 58 years and a quartile range of 56.5-62.5 years. At 60 months, HR-pQCT revealed that the cortical area and thickness decreased with increased cortical porosity in the cortical bone. In addition, the number of trabeculae decreased and trabecular separation increased trabecular bones decreases, and trabecular bone separation opens, resulting in a decrease in the trabecular bone volume fraction. Total bone mineral density (BMD), trabecular volumetric BMD, and cortical volumetric BMD, and estimated bone strength significantly decreased. DXA BMD values significantly decreased in the total hip and femoral neck but not the lumbar spine. TRACP-5b values after 5 years of AI treatment showed a significant negative correlation with the rate of change in the total volumetric BMD in the distal tibia.</p><p><strong>Conclusion: </strong>Postmenopausal women who received AIs for 5 years for EBC experienced significant deterioration in the bone microstructure, BMD, and estimated bone strength.</p>","PeriodicalId":15116,"journal":{"name":"Journal of Bone and Mineral Metabolism","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604278","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":"Association between the Sp1-binding-site polymorphism in the collagen type I alpha 1 (COLIA1) gene and bone phenotypes: the Dubbo Osteoporosis Epidemiology Study.","authors":"Ngoc Huynh, Krisel De Dios, Thach S Tran, Jacqueline R Center, Tuan V Nguyen","doi":"10.1007/s00774-024-01558-8","DOIUrl":"https://doi.org/10.1007/s00774-024-01558-8","url":null,"abstract":"<p><strong>Introduction: </strong>Polymorphisms within the collagen 1 alpha 1 gene (COLIA1) have been shown to be associated with bone mineral density (BMD). This study aimed to test the hypothesis that COLIA1 polymorphisms are associated with bone loss and fragility fractures.</p><p><strong>Materials and methods: </strong>The study involved 809 postmenopausal women aged 60 years and above in the Dubbo Osteoporosis Epidemiology Study who had COLIA1 genotypes and at least two BMD measurements over a 30-year period. BMD at the lumbar spine (LSBMD) and femoral neck (FNBMD) was measured biennially by dual-energy X-ray absorptiometry (GE-Lunar Prodigy). Fragility fracture has been ascertained by X-ray reports between 1990 and 2020. The G-> T polymorphism at the Sp1-binding site in the COLIA1 gene (rs1800012) was determined by the PCR-based method, and coded as GG, GT, and TT.</p><p><strong>Results: </strong>Women homozygous for the minor allele (TT) tended to have greater bone loss (-0.72%/year) than those with GT (-0.58%/year) or GG (-0.56%/year) though the difference did not achieve statistical significance (P = 0.84). Women of the TT genotype were associated with a two-fold greater risk of any fracture (adjusted hazard ratio: 2.21; 95%CI 1.42-3.46) and almost fourfold greater risk of hip fracture (3.78; 1.83-7.82) than those with either GG or GT genotype.</p><p><strong>Conclusions: </strong>Polymorphisms at the Sp1 site in the COLIA1 gene are associated with fracture risk, independent of bone loss.</p>","PeriodicalId":15116,"journal":{"name":"Journal of Bone and Mineral Metabolism","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590650","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":"Incidence of four major osteoporotic fragility fractures among older individuals in Sado, Japan, in 2020.","authors":"Norio Imai, Asami Nozaki, Yugo Shobugawa, Kentaro Higuchi, Yoshihiro Suda, Takeo Oinuma, Hayato Suzuki, Yoji Horigome, Hiroyuki Kawashima","doi":"10.1007/s00774-024-01529-z","DOIUrl":"10.1007/s00774-024-01529-z","url":null,"abstract":"<p><strong>Introduction: </strong>This study compared the 2020 incidence of fragility fractures in Sado City with those from 2004 to 2015.</p><p><strong>Materials and methods: </strong>Data from patients aged ≥ 60 years living in Sado City with fragility fractures in the hip, vertebral, distal radius, and proximal humerus between January 1 and December 31, 2020, were collected. We examined the number and incidence of four types of osteoporotic fractures in the older population aged ≥ 60 years living in Sado City in 2020. We compared the results with those of the 2004, 2010, and 2015 surveys, examining the temporal change and trend in the incidence of the four fracture types in this population. We investigated the use rate of anti-osteoporotic medications and the relationship between their administration and the occurrence of fragility fractures.</p><p><strong>Results: </strong>The age-specific incidence of hip fractures slightly decreased from 2015. However, the incidence of the other three fractures slightly increased, although the difference was not statistically significant. The incidence of hip fractures markedly increased in the 80 s. In 2020, the percentage of patients taking anti-osteoporotic agents before the occurrence of fractures decreased to 12.4% from 14.5% in 2015; it increased from 4% in 2004 to 7.6% in 2010.</p><p><strong>Conclusion: </strong>The 2020 incidence of the four fractures did not decrease, and the percentage of patients receiving anti-osteoporotic agents did not increase. A higher frequency of osteoporosis treatment is necessary to reduce the incidence of fragility fractures. We recommend using anti-osteoporotic agents to prevent hip fractures among individuals in their mid-70 s and above.</p>","PeriodicalId":15116,"journal":{"name":"Journal of Bone and Mineral Metabolism","volume":" ","pages":"647-652"},"PeriodicalIF":2.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558831","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":"Gender differences between smoking and the risk of hip fracture.","authors":"Yilun Tang, Yan Xu, Jinhui Song, Chen Zhang, Run Tian, Kunzheng Wang, Pei Yang","doi":"10.1007/s00774-024-01546-y","DOIUrl":"10.1007/s00774-024-01546-y","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to estimate the relation between cigarette smoking and hip fracture in men compared with women using a meta-analytic approach.</p><p><strong>Methods: </strong>On March 1, 2024, prospective cohort studies were searched from PubMed, Embase and Cochrane library systems. The gender difference in the relationship between smoking and hip fracture risk was evaluated by random effect model.</p><p><strong>Results: </strong>Eleven prospective cohort studies involving data from 2,689,620 individuals were selected for meta-analysis. The ratio of relative risk (RRR) of hip fractures in current smokers was significantly higher in men than in women (RRR: 1.10; 95%CI: 1.00 - 1.20; P = 0.047), while no evidence of sex differences in former smoking and hip fracture risk (RRR: 0.98; 95%CI: 0.88 - 1.10; P = 0.759).</p><p><strong>Conclusions: </strong>The male-to-female RRR of hip fractures increased in current smokers, whereas no sex difference was found in the relationship between former smoking and the risk of hip fractures.</p>","PeriodicalId":15116,"journal":{"name":"Journal of Bone and Mineral Metabolism","volume":" ","pages":"623-632"},"PeriodicalIF":2.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347229","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":"Effect of bisphosphonate and denosumab treatment on TBS in Japanese breast cancer patients with AIBL.","authors":"Emi Onuma, Shin Saito, Taku Tsuburai, Hiromi Yoshikata, Shoko Adachi, Shinya Yamamoto, Kazutaka Narui, Tomonari Hayama, Mariko Murase, Taichi Mizushima, Etsuko Miyagi, Hideya Sakakibara, Ryoko Asano","doi":"10.1007/s00774-024-01542-2","DOIUrl":"10.1007/s00774-024-01542-2","url":null,"abstract":"<p><strong>Introduction: </strong>Bisphosphonates and denosumab increase bone mineral density (BMD) for osteoporosis treatment in patients with aromatase inhibitor-associated bone loss (AIBL). This study aimed to directly compare bisphosphonates with denosumab in treating patients with AIBL and to determine the effect of denosumab on the trabecular bone score (TBS).</p><p><strong>Materials and methods: </strong>Thirty-nine patients with AIBL receiving osteoporosis treatment (21 in the bisphosphonates group and 18 in the denosumab group) were retrospectively evaluated for changes in lumbar spine and femoral BMD, lumbar spine bone quality (assessed by TBS), and blood bone metabolic markers. The Mann-Whitney and Wilcoxon tests were used for statistical evaluation.</p><p><strong>Results: </strong>After 24 months of treatment, the lumbar spine BMD change rate was 5.82 ± 1.10% with bisphosphonates and 10.49 ± 1.20% with denosumab, with the change rate of denosumab significantly increasing over that of bisphosphonates. The change rate in femoral BMD was 2.69 ± 1.16% with bisphosphonates and 2.95 ± 1.26% with denosumab, with no significant difference between the two groups. The rate of decrease in tartrate-resistant acid phosphatase isoform 5b was significantly higher in the denosumab group. The change rate in TBS at 24 months of treatment was 0.53 ± 1.26% in the bisphosphonates group and 1.08 ± 1.33% in the denosumab group, with no significant difference between the two groups. After 24 months, TBS remained stable.</p><p><strong>Conclusion: </strong>Both bisphosphonates and denosumab may increase BMD, improve bone metabolism, and inhibit bone quality loss in patients with AIBL.</p>","PeriodicalId":15116,"journal":{"name":"Journal of Bone and Mineral Metabolism","volume":" ","pages":"699-709"},"PeriodicalIF":2.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971189","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":"Efficacy of a single 5 mg zoledronic acid infusion in preventing bone loss and fracture in postmenopausal women with breast cancer.","authors":"Han-Sang Baek, Kabsoo Shin, Jinyoung Kim, Chaiho Jeong, Jeongmin Lee, Yejee Lim, Ki-Hyun Baek, Jeonghoon Ha","doi":"10.1007/s00774-024-01552-0","DOIUrl":"10.1007/s00774-024-01552-0","url":null,"abstract":"<p><strong>Introduction: </strong>Chemotherapy-induced bone loss (CTIBL) is common among breast cancer patients, requiring comprehensive assessment and intervention. Zoledronic acid, a strong inhibitor of bone resorption, is effective in CTIBL management, though information on dosing and intervals, particularly the efficacy of the 5 mg annual dose for osteoporosis in breast cancer patients, is limited.</p><p><strong>Materials and methods: </strong>In this 12-month prospective observational study, 85 breast cancer patients were divided into three groups: 17 received no treatment, 17 received tamoxifen, and 51 received anastrozole or letrozole (AI). Post-surgery, patients were administered a single 5 mg dose of zoledronic acid and monitored over 12 months for changes in bone mineral density (BMD), fracture rates, and biochemical markers.</p><p><strong>Results: </strong>Initially, the AI group was the oldest, averaging 59.1 ± 8.7 years. At baseline, no significant differences in variables, except age, were observed. After 12 months, BMD increased in all groups following a single zoledronic acid dose, with the smallest increase in the AI group at the lumbar spine: no treatment (2.4% ± 6.1%), tamoxifen (2.6% ± 3.4%), AI (0.6% ± 14.5%) (p = 0.778). CTx and P1NP levels were consistently suppressed up to 12 months post-treatment, with smaller reductions in the AI group. There were no significant differences in fracture or bone metastasis rates among groups.</p><p><strong>Conclusion: </strong>A single infusion of 5 mg zoledronic acid was effective in increasing bone density in breast cancer patients. However, AI-treated patients showed less improvement in vertebral bone mineral density and biochemical markers. Further long-term studies with larger cohorts are needed.</p>","PeriodicalId":15116,"journal":{"name":"Journal of Bone and Mineral Metabolism","volume":" ","pages":"720-727"},"PeriodicalIF":2.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347228","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":"Association of physical activity and sitting time with femoral bone health among older cancer survivors.","authors":"Ying Chen, Xinmin Meng, Kuan Yang, Hanfei Wang, Chongzhe Pei, Ningning Song","doi":"10.1007/s00774-024-01544-0","DOIUrl":"10.1007/s00774-024-01544-0","url":null,"abstract":"<p><strong>Introduction: </strong>Our primary goal was to investigate the independent and combined associations of physical activity (PA) and sitting time (ST) with femoral bone health among cancer survivors aged 60 or older.</p><p><strong>Materials and methods: </strong>This cross-sectional study included 1159 cancer survivors aged 60 years or older who underwent femur dual-energy X-ray absorptiometry (DXA) examination from continuous National Health and Nutrition Examination Survey data sets. PA and ST were assessed by self-report, and bone health included bone mineral density (BMD) at all femoral sub-regions, osteopenia/osteoporosis of femoral neck, and total fracture. The independent and combined associations of PA and ST with femoral bone health were determined using multivariable linear or logistic regression analyses.</p><p><strong>Results: </strong>More than 40% cancer survivors reported engaging in PA < 150 min/week with ST ≥ 6 h/d. PA solely showed no association with bone health at femur sites. Prolonged ST was associated with lower femur's BMD, higher prevalence of osteopenia/osteoporosis, and total fracture. Specifically, the negative association of prolonged ST and femur's BMD was shown in PA ≥ 150 min/week group, but not in PA < 150 min/week group. In combined analysis, prolonged ST with PA ≥ 150 min/week showed the strongest negative associations with femur's BMD.</p><p><strong>Conclusion: </strong>PA appears not to be directly associated with femoral bone health. Higher ST is associated with lower BMD and a higher incidence of total fractures, regardless of PA level, among cancer survivors aged 60 or older.</p>","PeriodicalId":15116,"journal":{"name":"Journal of Bone and Mineral Metabolism","volume":" ","pages":"710-719"},"PeriodicalIF":2.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912791","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":"Drug utilization pattern of romosozumab and other osteoporosis treatments in Japan, 2019-2021.","authors":"Satoshi Soen, Alex Wang, Etsuro Hamaya, Hsu-Chih Chien, Tzu-Chieh Lin","doi":"10.1007/s00774-024-01530-6","DOIUrl":"10.1007/s00774-024-01530-6","url":null,"abstract":"<p><strong>Introduction: </strong>Describe real-world treatment of osteoporosis and romosozumab treatment patterns in Japan.</p><p><strong>Materials and methods: </strong>Data for patients initiating romosozumab or other antiosteoporotic medications between March 01, 2018, and May 31, 2022, were extracted from the Medical Data Vision (MDV) and Japan Medical Data Center (JMDC) databases. Patients were categorized into four cohorts: those who newly initiated romosozumab within the first (MDV: n = 4782; JMDC: n = 2578) or second (MDV: n = 3888; JMDC: n = 2446) year after launch and those who initiated teriparatide (TPTD; MDV: n = 14,576; JMDC: n = 8259) or non-TPTD antiosteoporotic medications within the first year of romosozumab launch (MDV: n = 352,142; JMDC: n = 185,785).</p><p><strong>Results: </strong>Mean age, sex, baseline cardiovascular history, comorbidities, and concomitant medications were similar across cohorts. In the MDV database, fracture history was higher in the romosozumab year-1 (59.3%), year-2 (64.1%), and TPTD (65.5%) cohorts versus the non-TPTD cohort (24.4%). Similar rates were identified in the JMDC database: romosozumab year-1 (64.7%), year-2 (66.6%), TPTD (67.5%), and non-TPTD (27.8%). Vertebral fractures were most common in all cohorts. 12-month romosozumab discontinuation varied between the year-1 and year-2 cohorts in MDV (62.4% and 58.8%) and JMDC (57.1% and 52.7%), whereas mean number of injections remained consistent (MDV: 9.7 and 9.8; JMDC: 7.3 and 7.8). Romosozumab persistence was lower in year-1 versus year-2 (MDV: 37.6% and 42.9%; JMDC: 41.2% and 47.3%).</p><p><strong>Conclusion: </strong>Patients initiating romosozumab and TPTD had a high fracture history. Given the dual effects of promoting bone formation and suppressing resorption, improving romosozumab adherence and persistence over time may be important for antiosteoporotic therapy.</p>","PeriodicalId":15116,"journal":{"name":"Journal of Bone and Mineral Metabolism","volume":" ","pages":"653-667"},"PeriodicalIF":2.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579757","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":"Enpp1 mutations promote upregulation of hedgehog signaling in heterotopic ossification with aging.","authors":"Zhongyuan He, Zhengya Zhu, Tao Tang, Fuan Wang, Peng Guo, Jianfeng Li, Nguyen Tran Canh Tung, Qian Liang, Shaoyu Liu, ManMan Gao, Xizhe Liu, Zhiyu Zhou","doi":"10.1007/s00774-024-01543-1","DOIUrl":"10.1007/s00774-024-01543-1","url":null,"abstract":"<p><strong>Introduction: </strong>Heterotopic ossification of the tendon and ligament (HOTL) is a chronic progressive disease that is usually accompanied by thickening and ossification of ligaments and high osteogenic activity of the surrounding ligament tissue. However, the molecular mechanism of maintaining the cellular phenotype of HOTL remains unclear.</p><p><strong>Materials and methods: </strong>We first constructed a model of HOTL, Enpp1^flox/flox/EIIa-Cre mice, a novel genetic mouse system. Imaging, histological, and cell-level analyses were performed to investigate the progressive ossification of the posterior longitudinal ligament, Achilles tendons, and degeneration joints caused by Enpp1 deficiency.</p><p><strong>Results: </strong>The results indicate that Enpp1 deficiency led to markedly progressive heterotopic ossification (HO), especially spine, and Achilles tendons, and was associated with progressive degeneration of the knees. The bone mass was decreased in the long bone. Furthermore, fibroblasts from Enpp1^flox/flox/EIIa-Cre mice had greater osteogenic differentiation potential following induction by osteogenesis, accompanied by enhanced hedgehog (Hh) signaling. In addition, fibroblast cells show senescence, and aggravation of the senescence phenotype by further osteogenic induction.</p><p><strong>Conclusion: </strong>Our study indicated that with increasing age, mutations in Enpp1 promote ectopic ossification of spinal ligaments and endochondral ossification in tendons and further aggravate knee degeneration by upregulating hedgehog signaling.</p>","PeriodicalId":15116,"journal":{"name":"Journal of Bone and Mineral Metabolism","volume":" ","pages":"681-698"},"PeriodicalIF":2.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11632054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142107751","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}