Journal of Bone and Mineral Research最新文献

{"title":"Enhanced fatty acid oxidation in osteoprogenitor cells provides protection from high-fat diet induced bone dysfunction.","authors":"Ananya Nandy, Ron C M Helderman, Santosh Thapa, Sun H Peck, Alison Richards, Shobana Jayapalan, Nikita Narayani, Michael P Czech, Clifford J Rosen, Elizabeth Rendina-Ruedy","doi":"10.1093/jbmr/zjae195","DOIUrl":"https://doi.org/10.1093/jbmr/zjae195","url":null,"abstract":"<p><p>Bone homeostasis within the skeletal system is predominantly maintained by bone formation and resorption. Where formation of new bone involves maturation of stromal cells to mineral and matrix secreting mature osteoblasts, which requires cellular energy or adenosine triphosphate (ATP). Alterations in systemic metabolism can influence osteoblast functioning. In line with this, type 2 diabetes mellitus (T2DM), a common metabolic disorder is also associated with reduced bone formation and increased risk of fracture. Impairment in lipid metabolism is one of the key features associated with T2DM-related pathologies in multiple tissues. Therefore, we tested the hypothesis that the reduced bone formation reported in obese murine models of impaired glucose tolerance is a function of disrupted lipid metabolism in osteoblasts. We first confirmed that mice fed a high fat diet have reduced bone microarchitecture along with lower bone formation rates. Interestingly, osteoblasts from obese mice harbor higher numbers of cytosolic lipid droplets along with decreased bioenergetic profiles compared to control cells. Further supporting this observation, bone tibia cortex demonstrated higher total lipid content in high fat diet fed mice compared to control-fed mice. As a further proof of principle, we generated a novel murine model to conditionally delete Plin2 in osteoblast-progenitor cells using Prrx1-Cre, to enhance lipid droplet breakdown. Our data demonstrate that knocking down Plin2 in an osteoprogenitor specific manner protects from high-fat diet induced osteoblast dysfunction. Furthermore, the mechanism of action involves enhanced osteoblast fatty acid oxidation. In conclusion, the current studies establish that high fat diet induced glucose intolerance leads to perturbations in osteoblast lipid metabolism, thus causing lower bone formation, which can be protected against by increasing fatty acid oxidation.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805754","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":"Macrophages regulate angiogenesis-osteogenesis coupling induced by mechanical loading through the Piezo1 pathway.","authors":"Hongzhi Liu, Hang Zhou, Yuanhao Fan, Jiawei Li, Ziyu Guo, Qiuchi Xu, Yang Liu, Kun Gao, Neima Ait Lahcine, Jianing Zhang, Jingjing Zhou, Fengjin Guo, Chao Liu","doi":"10.1093/jbmr/zjae198","DOIUrl":"https://doi.org/10.1093/jbmr/zjae198","url":null,"abstract":"<p><p>Bone is a mechanosensitive organ, and its regeneration also depends on the ability of bone cells to perceive and react to mechanical stimuli. Macrophages are indispensable for bone formation, regeneration, and maintenance. Depletion of macrophages resulted in poor bone development, due to impaired vessels formation and osteogenesis. However, how mechanical stimulation stimulates macrophages during bone regeneration is unclear. As in many cell types, Piezo1 is part of the mechanotransduction in macrophages, and modulates macrophage activity. Here, we utilized conditional knockout of Piezo1 in LysM+ myeloid cells and in vivo mechanical loading to investigate the mechanoregulation of macrophages and their contribution to bone repair. We found that mechanical loading increased the ratio of CD206+ macrophages, angiogenesis-osteogenesis coupling, and cell proliferation within defect region, leading to enhanced bone regeneration. However, all the loading-induced upregulation were blunted by conditional knockout of Piezo1 in macrophages. Furthermore, we implanted wildtype bone marrow-derived macrophages into defect area in Piezo1 knockout mice. Wildtype macrophages rescued mechanosensitive angiogenesis-osteogenesis coupling and promoted bone regeneration in Piezo1 knockout mice. Together, our data showed that Piezo1 in macrophages is indispensable for loading-induced bone regeneration by stimulating macrophage polarization into the CD206+ phenotype, thereby facilitating the angiogenesis-osteogenesis coupling, promoting cell proliferation, and finally resulting in enhanced bone regeneration.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826574","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":"Verifying the effectiveness of romosozumab re-administration on bone mineral density.","authors":"Tomonori Kobayakawa, Yukio Nakamura","doi":"10.1093/jbmr/zjae196","DOIUrl":"https://doi.org/10.1093/jbmr/zjae196","url":null,"abstract":"<p><p>Upon completing romosozumab therapy for osteoporosis, sequential treatment with other agents is required. However, for patients at high fracture risk despite such therapy, re-administration of romosozumab might be a potent option for subsequent medication to prevent additional fractures. Currently, there is still insufficient real-world clinical data verifying the efficacy of romosozumab re-administration, therefore, this study aimed to evaluate its efficacy. We enrolled 72 osteoporosis patients who remained at high risk of fractures after a 12-month course of romosozumab, followed by sequential therapy either with bisphosphonates, denosumab, or teriparatide. Patients were re-administered another 12-month romosozumab to assess changes in bone mineral density and the percentages of patients achieving a T-score >-2.5 at the completion. Our result exhibited that bone mineral density at the lumbar spine and femoral neck increased significantly through the re-administration phase (P<0.001). The percentage of patients achieving a T-score >-2.5 in the lumbar spine, total hip and femoral neck increased significantly compared to before initial romosozumab therapy, with the greatest improvement seen after re-administration (all P<0.001). Bone formation markers increased significantly (P<0.001) during re-administration, while bone resorption markers showed no significant change (P=0.408). The impact of prior sequential therapy was also evaluated. Bone mineral density increased significantly at all sites for patients who received bisphosphonates as sequential therapy (P<0.05). After denosumab therapy, significant bone mineral density increases were observed only in the lumbar spine (P<0.01), while the total hip and femoral neck showed no significant change. After teriparatide therapy, bone mineral density temporarily decreased during the sequential period but increased significantly after romosozumab re-administration, especially in the lumbar spine and femoral neck (both P<0.001). In conclusion, romosozumab re-administration is an effective treatment. Furthermore, its efficacy varies depending on the sequential therapy used, with the highest effectiveness seen in the order of teriparatide, bisphosphonates, and denosumab.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826593","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":"Romosozumab Improves Microarchitecture as Assessed by Tissue Thickness-Adjusted Trabecular Bone Score in Postmenopausal Women with Osteoporosis.","authors":"Michael R McClung, Donald Betah, Benjamin Z Leder, David L Kendler, Mary Oates, Jen Timoshanko, Zhenxun Wang","doi":"10.1093/jbmr/zjae194","DOIUrl":"https://doi.org/10.1093/jbmr/zjae194","url":null,"abstract":"<p><p>Bone mineral density (BMD) is only one of several bone strength determinants affected by osteoporosis therapies. Trabecular Bone Score (TBS), a gray-level texture index determined from lumbar spine (LS) dual-X-ray absorptiometry scans, is an indirect measure of bone microarchitecture independent of and complementary to BMD and clinical risk factors. In the ARCH study, monthly subcutaneous romosozumab 210 mg for 12 months followed by 24-month open-label weekly oral alendronate 70 mg (romosozumab-to-alendronate) significantly reduced fracture risk compared to 36-month alendronate alone in postmenopausal women with osteoporosis and prior fracture. This analysis evaluated tissue thickness-adjusted TBS (TBSTT) in a subgroup of patients from ARCH who had post-hoc TBS measurements at baseline and at least one post-baseline visit at Months 12, 24, and 36. Baseline characteristics were similar between romosozumab-to-alendronate (n = 190) and alendronate alone (n = 188). Romosozumab led to significantly greater gains in TBSTT vs alendronate at Month 12 (least squares mean difference, 3.6%), with greater gains maintained after transition to alendronate and persisting at Months 24 (2.9%) and 36 (2.3%; all P < 0.001). Romosozumab-to-alendronate increased the percentage of individual patients with \"normal\" TBSTT from 28.9% at baseline to 48.1%, 43.9%, and 45.4% at Months 12, 24, and 36, respectively, and decreased the percentage of individual patients with degraded TBSTT from 52.6% to 33.3%, 36.0%, and 33.5%, respectively (all P < 0.001). A similar but much smaller trend was observed with alendronate alone from baseline through Month 36 (P ≤ 0.012). Percent changes in TBSTT and LS BMD were largely unrelated from baseline to Month 12 (romosozumab-to-alendronate, r2 = 0.065; alendronate alone, r2 = 0.021) and Month 36 (r2 = 0.058; r2 = 0.057, respectively). In postmenopausal women with osteoporosis and prior fracture, 12-month romosozumab followed by 24-month alendronate significantly improved bone microarchitecture estimated by TBSTT more than 36-month alendronate alone.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826586","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":"Risk Factors for Osteonecrosis of the Jaw in Patients with Chronic Kidney Disease: A Nested Case-Control Study.","authors":"Ken Iseri, Noriko Hida","doi":"10.1093/jbmr/zjae193","DOIUrl":"https://doi.org/10.1093/jbmr/zjae193","url":null,"abstract":"<p><p>Osteonecrosis of the jaw (ONJ) is a severe disease leading to decreased quality of life, but risk factors for ONJ in chronic kidney disease (CKD) patients remain unclear. We conducted a nested case-control study using a large Japanese administrative database to investigate. CKD patients were identified based on estimated glomerular filtration rate (eGFR) measurements, and ONJ cases were identified using ICD-10 codes and diagnostic terms. Controls were matched 1:4 by age and sex. Among 597 026 CKD patients, 75 ONJ cases were identified during a median follow-up of 2.9 years (incidence rate: 3.27 per 100 000 patient-years). A total of 375 patients (250 males, 66.7%) with a median age of 72 years (IQR, 64-78) were included after matching controls. The use of bisphosphonates and denosumab for tumor-related disorders in the case group was significantly higher compared to the control group. There was no significant association between kidney functions and the ONJ risk. Multivariate analysis revealed that anti-resorptive drugs for tumor-related disorders (OR: 74.74, 95% CI: 8.81-634.39, P<.001) and oral corticosteroids (OR: 13.23, 95% CI: 3.34-52.33, P<.001) were significantly associated with increased ONJ risk, while anti-resorptive drugs for osteoporosis and injectable corticosteroid use were not. Other relevant factors such as diabetes, liver disease, anabolic drugs, and radiation therapy did not have a significant association with ONJ risk. When stratified by indications for bisphosphonate use (known to be eliminated by renal excretion), bisphosphonate use for tumor-related disorders showed a significant association with ONJ risk (OR: 27.80, 95% CI: 2.47-313.29, P<.01), while bisphosphonates use for osteoporosis did not (OR: 0.74, 95% CI: 0.19-2.92, P=.67). These findings suggest that anti-resorptive drugs for tumor-related disorders and oral corticosteroids are associated with ONJ risk in CKD patients. Heightened surveillance may be necessary for CKD patients receiving these treatments to prevent or detect ONJ early.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826580","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":"Prevalence of incomplete atypical femoral fractures using single energy absorptiometry after long term anti-resorptive therapy.","authors":"Jessica Abou Chaaya, Ghada El-Hajj Fuleihan, Angela M Cheung, Hiba Abou Layla, Asma Arabi","doi":"10.1093/jbmr/zjae174","DOIUrl":"https://doi.org/10.1093/jbmr/zjae174","url":null,"abstract":"<p><p>Atypical femur fractures (AFFs) have been reported with long term use of anti-resorptive drugs. Early identification is crucial because it allows early intervention to stop the progression to complete fracture, thus potentially reducing the ensuing burden. It has been shown that extending the scan image to take a full-length image of the femur (FFI) using single energy (SE) X-rays at the time of a dual-energy X-ray absorptiometry (DXA) scan can detect findings in the spectrum of AFF. Following the International Society for Clinical Densitometry (ISCD) recommendations, FFI by SE X-ray is being performed for all patients who present to the Calcium Metabolism and Osteoporosis program at AUBMC for BMD measurement by DXA, if they have received anti-resorptive drug for, a cumulative period of 3 years or more. Patients can be currently on anti-resorptive drug or have discontinued it within the past 5 years prior to scan, instead of the 1 year, as recommended by the ISCD. The primary aim of this retrospective study was to assess the prevalence of findings in the spectrum of AFF using FFI by SE X-rays. We collected data on demographic factors, clinical risk factors for osteoporosis, and bone densitometry parameters. Out of the 948 patients, 18 patients were found to have findings in the spectrum of AFF, 14 underwent subsequent imaging studies to investigate and confirm these abnormalities. One patient out of 948 patients was found to have an incomplete AFF confirmed by CT scan. Studying the prevalence of the signs of AFF on FFI in other studies and assessing the specificity of this technique by comparing its findings to more established methods, is important. Future ISCD task forces may need to re-assess efficacy and cost effectiveness of its recommended guidance on using SE femur in patients to prevent adverse outcomes.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823479","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":"Patella fractures are associated with bone fragility - a retrospective study.","authors":"Isabella Rosillo, Carmen Germosen, Sanchita Agarwal, Ragyie Rawal, Ivelisse Colon, Mariana Bucovsky, Nayoung Kil, Elizabeth Shane, Marcella Walker","doi":"10.1093/jbmr/zjae165","DOIUrl":"10.1093/jbmr/zjae165","url":null,"abstract":"<p><p>Patella fractures are not typically considered osteoporotic fractures. We compared bone mineral density (BMD) and microstructure in elderly women from a multiethnic population-based study in New York City with any history of a patella fracture (n = 27) to those without historical fracture (n = 384) and those with an adult fragility forearm fracture (n = 28) using dual energy x-ray absorptiometry (DXA) and high resolution peripheral quantitative computed tomography (HR-pQCT). Compared to those without fracture, women with patella fracture had 6.5% lower areal BMD (aBMD) by DXA only at the total hip (p=.007), while women with forearm fracture had lower aBMD at multiple sites and lower trabecular bone score (TBS), adjusted for age, body mass index, race and ethnicity (all p<.05). By HR-pQCT, adjusted radial total and trabecular (Tb) volumetric BMD (vBMD) and Tb number were 10%-24% lower while Tb spacing was 12-23% higher (all p<.05) in the fracture groups versus women without fracture. Women with a forearm, but not a patella, fracture also had lower adjusted radial cortical (Ct) area and vBMD and 21.8% (p<.0001) lower stiffness vs. women without fracture. At the tibia, the fracture groups had 9.3%-15.7% lower total and Tb vBMD (all p<.05) compared to the non-fracture group. Women with a forearm fracture also had 10.9, and 14.7% lower tibial Ct area and thickness versus those without fracture. Compared to women without fracture, tibial stiffness was 9.9% and 12% lower in the patella and forearm fracture groups, respectively (all p<.05). By HR-pQCT, the patella vs. forearm fracture group had 36% higher radial Tb heterogeneity (p<.05). In summary, women with patella fracture had Tb deterioration by HR-pQCT associated with lower tibial mechanical competence that was similar to those with fragility forearm fracture, a more universally accepted \"osteoporotic\" fracture. These data suggest patella fractures are associated with skeletal fragility and warrant skeletal evaluation.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"1752-1761"},"PeriodicalIF":5.1,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11638554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386745","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":"Association of vertebral fractures with worsening degenerative changes of the spine: a longitudinal study.","authors":"Carrie Ye, William D Leslie, Mary L Bouxsein, Alyssa B Dufour, Ali Guermazi, Daniel Habtemariam, Mohamed Jarraya, Douglas P Kiel, Pradeep Suri, Elizabeth J Samelson","doi":"10.1093/jbmr/zjae172","DOIUrl":"10.1093/jbmr/zjae172","url":null,"abstract":"<p><p>Vertebral compression fractures (VFs) and spinal degeneration are both common causes of back pain, particularly in older adults. Previous cross-sectional studies have shown a potential association between these entities, but there is limited evidence on the role of VFs in spinal degeneration. In this longitudinal study, we evaluated the association between prevalent VFs and the subsequent progression of facet joint osteoarthritis (FJOA) and intervertebral disc height narrowing (DHN), using data from the Framingham Heart Study Offspring and Third Generation Multi-Detector Computed Tomography study. Summary indices representing the total burden of each spinal parameter (VFs, DHN, and FJOA) were calculated for each individual. We hypothesized that prevalent VFs are associated with worsening spinal degeneration. Three hundred and seventy (31%) of 1197 participants had a baseline (prevalent) VF. The change in summary index of DHN over the follow-up period was significantly higher in those with vs without prevalent VF (difference in change in DHN 0.38, 95% CI 0.18 to 0.59, p<.001), but the change in summary index of FJOA was similar between those with and without prevalent VF. However, once adjusted for age, sex, cohort, smoking status, BMI, and baseline DHN, the change in summary index of DHN did not differ by prevalent VF status. There was a modestly higher change in the FJOA summary index in those with prevalent VFs compared to those without in the fully adjusted model (difference in change in FJOA 0.62, 95% CI -0.01 to 1.24, p = .054), driven primarily by those with severe (grade 3) VF (difference in change in FJOA 4.48, 95% CI 1.99-6.97). Moreover, there was greater change in the summary index of FJOA with increasing severity of prevalent VF (linear trend p = .005). Beyond the established morbidity and mortality associated with VFs, our study suggests that VFs may also lead to worsening spine osteoarthritis.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"1744-1751"},"PeriodicalIF":5.1,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11638720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454262","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":"Expression of Concern: CYP4A22 loss-of-function causes a new type of vitamin D-dependent rickets (VDDR1C).","authors":"","doi":"10.1093/jbmr/zjae168","DOIUrl":"10.1093/jbmr/zjae168","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"1839"},"PeriodicalIF":5.1,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680054","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":"Longitudinal changes in BMD in adults with cystic fibrosis.","authors":"Reem Jad, Xiayi Ma, Sanja Stanojevic, Abarnaa Illango, Elizabeth Tullis, Julie Gilmour, Christopher H Goss, Lisa J Strug, Anne L Stephenson","doi":"10.1093/jbmr/zjae139","DOIUrl":"10.1093/jbmr/zjae139","url":null,"abstract":"<p><p>Improved survival in people with cystic fibrosis (pwCF) presents new complexities of care, including CF-related bone disease, a common complication in older pwCF. The trajectory of bone loss with age in this population remains unclear. The objective of this study was to estimate the average rate of change in BMD in adults with CF. This retrospective study included adults with CF, aged 25-48 yr, followed between January 2000 and December 2021. Subjects with at least one DXA scan were included. Scans obtained posttransplantation, after the initiation of bisphosphonates or cystic fibrosis transmembrane conductance regulator modulator therapy was excluded. The primary outcome was BMD (g/cm2) at the LS and FN. A linear mixed-effects model with both random intercept and random slope terms was used to estimate the average annual change in BMD. A total of 1502 DXA scans in 500 adults (average age 28.4 y) were included. There was a statistically significant annual decline in BMD of -0.008 gm/cm2/yr (95% CI, -0.009 to -0.007) at the FN and -0.006 gm/cm2/yr (95% CI, -0.007 to -0.004) at the LS. Relative to BMD at age 25, there was a 18.8% decline at the FN by age 48 yr and a 11% decline at the LS. Pancreatic insufficient subjects had a faster rate of decline in BMD compared with pancreatic sufficient subjects. After adjusting for markers of disease severity, the annual rate of decline remained significant. Individuals with CF experience bone loss at an age when it is not anticipated, thereby entering early adulthood, where further bone loss is inevitable especially with the decrease in estrogen during menopause, with suboptimal BMD. As the CF population ages, it will become very important to consider interventions to maximize bone health.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"1716-1721"},"PeriodicalIF":5.1,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11637762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102673","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}