首页 > 最新文献

Journal of Bone and Mineral Research最新文献

英文 中文
Romosozumab improves microarchitecture as assessed by tissue thickness-adjusted trabecular bone score in postmenopausal women with osteoporosis. 罗莫司单抗可改善绝经后骨质疏松症女性的微结构,以组织厚度调整后的骨小梁评分来评估。
IF 5.1 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-02-02 DOI: 10.1093/jbmr/zjae194
Michael R McClung, Donald Betah, Benjamin Z Leder, David L Kendler, Mary Oates, Jen Timoshanko, Zhenxun Wang

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 Active-Controlled Fracture Study in Postmenopausal Women with Osteoporosis at High Risk (ARCH), monthly subcutaneous romosozumab 210 mg for 12 mo followed by 24-mo open-label weekly oral alendronate 70 mg (romosozumab-to-alendronate) significantly reduced fracture risk compared to 36-mo 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<.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<.001). A similar but smaller trend was observed with alendronate alone from baseline through month 36 (p ≤.012). 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-mo romosozumab followed by 24-mo alendronate significantly improved bone microarchitecture estimated by TBSTT more than 36-mo alendronate alone.

骨矿密度(BMD)只是受骨质疏松症疗法影响的几个骨强度决定因素之一。骨小梁评分(TBS)是通过腰椎(LS)双 X 射线吸收扫描确定的灰度纹理指数,它是骨微结构的一种间接测量方法,独立于骨密度和临床风险因素,并与之互补。在 ARCH 研究中,对于患有骨质疏松症并曾发生骨折的绝经后妇女,每月皮下注射 Romosozumab 210 毫克,持续 12 个月,然后每周开放标签口服阿仑膦酸钠 70 毫克,持续 24 个月(romosozumab-to-阿仑膦酸钠),与单独服用阿仑膦酸钠 36 个月相比,能显著降低骨折风险。这项分析评估了 ARCH 患者亚组的组织厚度调整 TBS (TBSTT),这些患者在基线时进行了事后 TBS 测量,并至少在基线后第 12、24 和 36 个月进行了一次随访。罗莫索单抗对阿仑膦酸钠(n = 190)和单独使用阿仑膦酸钠(n = 188)的基线特征相似。在第 12 个月,Romosozumab 与阿仑膦酸钠相比,TBSTT 的改善幅度明显更大(最小二乘均方差,3.6%),在转用阿仑膦酸钠后,改善幅度更大,并持续到第 24 个月(2.9%)和第 36 个月(2.3%;P 均为 0.05)。
{"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":"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 Active-Controlled Fracture Study in Postmenopausal Women with Osteoporosis at High Risk (ARCH), monthly subcutaneous romosozumab 210 mg for 12 mo followed by 24-mo open-label weekly oral alendronate 70 mg (romosozumab-to-alendronate) significantly reduced fracture risk compared to 36-mo 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<.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<.001). A similar but smaller trend was observed with alendronate alone from baseline through month 36 (p ≤.012). 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-mo romosozumab followed by 24-mo alendronate significantly improved bone microarchitecture estimated by TBSTT more than 36-mo alendronate alone.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"193-200"},"PeriodicalIF":5.1,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11789382/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Novel therapeutic options for hypophosphatasia.
IF 5.1 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-02-02 DOI: 10.1093/jbmr/zjaf023
Wolfgang Högler, Lothar Seefried
{"title":"Novel therapeutic options for hypophosphatasia.","authors":"Wolfgang Högler, Lothar Seefried","doi":"10.1093/jbmr/zjaf023","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf023","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078263","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}
引用次数: 0
Epidural steroid injections and fracture incidence among older individuals with radiculopathy. 硬膜外类固醇注射与患有神经根病的老年人的骨折发生率。
IF 5.1 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-02-02 DOI: 10.1093/jbmr/zjae162
Huifeng Yun, Ye Liu, Jeffrey R Curtis, Kenneth Saag, Giavanna D'Erasmo, Katherine Haseltine, Emily M Stein

Epidural steroid injections (ESIs) are a common and often effective treatment for radicular back pain. While oral glucocorticoids increase fracture incidence, little is known regarding fracture risk after ESI. This study investigated the incidence of fractures among individuals who received ESI and those who did not. We hypothesized that ESI exposure would be associated with an increased incidence of osteoporotic fractures and specifically vertebral fractures. Using 2005-2018 5% Medicare data, individuals with radicular pain who had ≥1 ESI and those who did not (non-ESI) were matched 1:10 by age, sex, and month of radicular pain diagnosis using exposure density sampling (EDS). Using a high-dimensional propensity score (HDPS) calculated based on the top 500 covariates across multiple data dimensions, ESI and non-ESI individuals were matched 1:1. Fractures were identified using validated ICD-9/10 diagnosis codes. Fracture incidence rate (IR) was calculated by group, and hazard ratios (HR) compared using Cox regression. 25 062 ESI patients and 221 735 non-ESI patients who met eligibility criteria were identified using EDS. Mean age was 76 yr (74% female). Among ESI-treated individuals, there were 2296 fractures, IR 49.1 (95% CI: 47.2-51.2) per 1000 person yr. For non-ESI individuals, there were 11 917 fractures, IR 35.2 (95% CI: 34.5-35.8). Individuals who received ESI had a greater hazard of fracture at typical osteoporotic sites, HR 1.39 (95% CI 1.33-1.46) by EDS and 1.32 (1.12-1.54) by HDPS, and a greater hazard of vertebral fracture, 1.54 (1.45-1.64) by EDS and 1.69 (1.38-2.07) by HDPS. Patients who received greater cumulative ESI doses (≥3 in 1 yr) had a higher risk of fractures within the first 6 mo of follow-up. ESI exposure in older individuals is associated with an increased risk of fracture, suggesting there may be lasting detrimental skeletal effects of ESI. Further research into strategies to reduce fracture risk in this population is warranted.

硬膜外类固醇注射(ESI)是治疗根性背痛的一种常见且通常有效的方法。虽然口服糖皮质激素会增加骨折的发生率,但人们对ESI后的骨折风险知之甚少。本研究调查了接受过 ESI 和没有接受过 ESI 的人的骨折发生率。我们假设,接受 ESI 会增加骨质疏松性骨折,尤其是椎体骨折的发生率。我们使用 2005-2018 年 5% 的医疗保险数据,通过暴露密度采样(EDS),按照年龄、性别和根性疼痛诊断月份,将接受过≥1 次 ESI 的根性疼痛患者与未接受过 ESI 的患者(非 ESI)进行 1:10 匹配。根据多个数据维度的前 500 个协变量计算出的高维倾向得分 (HDPS),ESI 和非 ESI 患者进行了 1:1 匹配。骨折是通过有效的 ICD-9/10 诊断代码确定的。按组别计算骨折发生率(IR),并使用 Cox 回归法比较危险比(HR)。通过 EDS 确定了符合资格标准的 25 062 名 ESI 患者和 221 735 名非 ESI 患者。平均年龄为 76 岁(74% 为女性)。在接受过 ESI 治疗的患者中,有 2296 例骨折,IR 为 49.1(95% CI:47.2-51.2)/1000 人年。在未接受ESI治疗的患者中,有11 917人发生骨折,IR值为35.2(95% CI:34.5-35.8)。接受ESI治疗的患者在典型的骨质疏松部位发生骨折的风险更大,根据EDS计算,HR为1.39(95% CI为1.33-1.46),根据HDPS计算,HR为1.32(1.12-1.54);发生脊椎骨折的风险更大,根据EDS计算,HR为1.54(1.45-1.64),根据HDPS计算,HR为1.69(1.38-2.07)。接受较多累积 ESI 剂量(1 年内≥3 次)的患者在随访的前 6 个月内发生骨折的风险较高。老年人接触 ESI 会增加骨折风险,这表明 ESI 可能会对骨骼产生持久的有害影响。有必要进一步研究降低这一人群骨折风险的策略。
{"title":"Epidural steroid injections and fracture incidence among older individuals with radiculopathy.","authors":"Huifeng Yun, Ye Liu, Jeffrey R Curtis, Kenneth Saag, Giavanna D'Erasmo, Katherine Haseltine, Emily M Stein","doi":"10.1093/jbmr/zjae162","DOIUrl":"10.1093/jbmr/zjae162","url":null,"abstract":"<p><p>Epidural steroid injections (ESIs) are a common and often effective treatment for radicular back pain. While oral glucocorticoids increase fracture incidence, little is known regarding fracture risk after ESI. This study investigated the incidence of fractures among individuals who received ESI and those who did not. We hypothesized that ESI exposure would be associated with an increased incidence of osteoporotic fractures and specifically vertebral fractures. Using 2005-2018 5% Medicare data, individuals with radicular pain who had ≥1 ESI and those who did not (non-ESI) were matched 1:10 by age, sex, and month of radicular pain diagnosis using exposure density sampling (EDS). Using a high-dimensional propensity score (HDPS) calculated based on the top 500 covariates across multiple data dimensions, ESI and non-ESI individuals were matched 1:1. Fractures were identified using validated ICD-9/10 diagnosis codes. Fracture incidence rate (IR) was calculated by group, and hazard ratios (HR) compared using Cox regression. 25 062 ESI patients and 221 735 non-ESI patients who met eligibility criteria were identified using EDS. Mean age was 76 yr (74% female). Among ESI-treated individuals, there were 2296 fractures, IR 49.1 (95% CI: 47.2-51.2) per 1000 person yr. For non-ESI individuals, there were 11 917 fractures, IR 35.2 (95% CI: 34.5-35.8). Individuals who received ESI had a greater hazard of fracture at typical osteoporotic sites, HR 1.39 (95% CI 1.33-1.46) by EDS and 1.32 (1.12-1.54) by HDPS, and a greater hazard of vertebral fracture, 1.54 (1.45-1.64) by EDS and 1.69 (1.38-2.07) by HDPS. Patients who received greater cumulative ESI doses (≥3 in 1 yr) had a higher risk of fractures within the first 6 mo of follow-up. ESI exposure in older individuals is associated with an increased risk of fracture, suggesting there may be lasting detrimental skeletal effects of ESI. Further research into strategies to reduce fracture risk in this population is warranted.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"176-183"},"PeriodicalIF":5.1,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337962","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}
引用次数: 0
Retinoid-impregnated nanoparticles enable control of bone growth by site-specific modulation of endochondral ossification in mice.
IF 5.1 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-30 DOI: 10.1093/jbmr/zjaf018
Masatake Matsuoka, Kenta Uchibe, Ningfeng Tang, Hongying Tian, Akiko Suzuki, Takeshi Oichi, Yu Usami, Ivan Alferiev, Satoru Otsuru, Joshua M Abzug, John E Herzenberg, Maurizio Pacifici, Motomi Enomoto-Iwamoto, Michael Chorny, Masahiro Iwamoto

Growth-plate (GP) injures in limbs and other sites can impair GP function and cause deceleration of bone growth, leading to progressive bone lengthening imbalance, deformities and/or physical discomfort, decreased motion and pain. At present, surgical interventions are the only means available to correct these conditions by suppressing the GP activity in the unaffected limb and/or other bones in the ipsilateral region. Here, we aimed to develop a pharmacologic treatment of GP growth imbalance that involves local application of nanoparticles-based controlled release of a selective retinoic acid nuclear receptor gamma (RARγ) agonist drug. When RARγ agonist-loaded nanoparticles were implanted near the medial and lateral sides of proximal tibial growth plate in juvenile C57BL/6j mice, the GP underwent involution and closure. Overall tibia length was shortened compared to the contralateral element implanted with drug-free control nanoparticles. Importantly, when the RARγ agonist nanoparticles were implanted on the lateral side only, the adjacent epiphysis tilted toward the lateral site, leading to apical angulation of the tibia. In contrast to the local selectivity of these responses, systemic administration of RARγ agonists led to GP closure at many sites, inhibiting skeletal growth over time. Agonists for RARα and RARβ elicited no obvious responses over parallel regimens. Our findings provide novel evidence that RARγ agonist-loaded nanoparticles can control activity, function and directionality of a targeted GP, offering a potential and clinically-relevant alternative or supplementation to surgical correction of limb length discrepancy and angular deformities.

{"title":"Retinoid-impregnated nanoparticles enable control of bone growth by site-specific modulation of endochondral ossification in mice.","authors":"Masatake Matsuoka, Kenta Uchibe, Ningfeng Tang, Hongying Tian, Akiko Suzuki, Takeshi Oichi, Yu Usami, Ivan Alferiev, Satoru Otsuru, Joshua M Abzug, John E Herzenberg, Maurizio Pacifici, Motomi Enomoto-Iwamoto, Michael Chorny, Masahiro Iwamoto","doi":"10.1093/jbmr/zjaf018","DOIUrl":"10.1093/jbmr/zjaf018","url":null,"abstract":"<p><p>Growth-plate (GP) injures in limbs and other sites can impair GP function and cause deceleration of bone growth, leading to progressive bone lengthening imbalance, deformities and/or physical discomfort, decreased motion and pain. At present, surgical interventions are the only means available to correct these conditions by suppressing the GP activity in the unaffected limb and/or other bones in the ipsilateral region. Here, we aimed to develop a pharmacologic treatment of GP growth imbalance that involves local application of nanoparticles-based controlled release of a selective retinoic acid nuclear receptor gamma (RARγ) agonist drug. When RARγ agonist-loaded nanoparticles were implanted near the medial and lateral sides of proximal tibial growth plate in juvenile C57BL/6j mice, the GP underwent involution and closure. Overall tibia length was shortened compared to the contralateral element implanted with drug-free control nanoparticles. Importantly, when the RARγ agonist nanoparticles were implanted on the lateral side only, the adjacent epiphysis tilted toward the lateral site, leading to apical angulation of the tibia. In contrast to the local selectivity of these responses, systemic administration of RARγ agonists led to GP closure at many sites, inhibiting skeletal growth over time. Agonists for RARα and RARβ elicited no obvious responses over parallel regimens. Our findings provide novel evidence that RARγ agonist-loaded nanoparticles can control activity, function and directionality of a targeted GP, offering a potential and clinically-relevant alternative or supplementation to surgical correction of limb length discrepancy and angular deformities.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062395","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}
引用次数: 0
Biases in the performance of FRAX without BMD in predicting fracture risk in a multiethnic population with diabetes: the Diabetes & Aging Study.
IF 5.1 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-29 DOI: 10.1093/jbmr/zjaf012
Rajesh K Jain, Jennifer Y Liu, Richard W Grant, Shanzay Haider, Elbert S Huang, Neda Laiteerapong, Kasia J Lipska, Joan C Lo, Howard H Moffet, Melissa M Parker, Andrew J Karter

Fracture risk calculators, such as the Fracture Risk Assessment Tool (FRAX), calculate the risk of major osteoporotic (MOF) and hip fracture, but do not account for the excess risk of fracture in people with diabetes. We examined the predictive performance of FRAX without BMD in ethnically diverse, older patients with diabetes. Patients included were between ages 65-89 from the Kaiser Permanente Northern California Diabetes Registry and not already taking osteoporosis medications. Race and ethnicity were self-identified. We calculated FRAX without BMD based on baseline characteristics and assessed how well FRAX predicted MOF and hip fracture over follow-up. Predictive performance was based on measures of discrimination (area under the receiver operator curve, AUC) and calibration (observed-to-predicted ratio, O/P). We identified 96 914 patients (47.0% female), of whom 5383 (5.6%) and 1767 (1.8%) had MOF and hip fracture, respectively, over a mean follow-up of 4.3 years. The AUC for MOF and hip fracture were 0.72 and 0.77, respectively. FRAX mildly underestimated MOF and hip fracture rates (O/P 1.2 for both) overall. Discrimination was similar by race and ethnicity and diabetes duration but was worse in those over age 75 (AUC < 0.7). In some groups, there were substantial calibration errors, such as Hispanic women (O/P: 1.8 and 1.5), Black men (O/P: 1.5 and 1.8), those with duration of diabetes ≥20 years (O/P: 1.6 and 1.5), and those over the age of 80 (O/P: 1.4 and 1.2) for MOF and hip fracture, respectively. While the discriminatory performance of FRAX without BMD was good overall in patients with diabetes, it underestimated risk in Hispanic women, Black men, those with long duration of diabetes, and in the oldest patients with diabetes. These algorithmic biases suggest that diabetes-specific tools may be needed to stratify fracture risk in patients with diabetes.

{"title":"Biases in the performance of FRAX without BMD in predicting fracture risk in a multiethnic population with diabetes: the Diabetes & Aging Study.","authors":"Rajesh K Jain, Jennifer Y Liu, Richard W Grant, Shanzay Haider, Elbert S Huang, Neda Laiteerapong, Kasia J Lipska, Joan C Lo, Howard H Moffet, Melissa M Parker, Andrew J Karter","doi":"10.1093/jbmr/zjaf012","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf012","url":null,"abstract":"<p><p>Fracture risk calculators, such as the Fracture Risk Assessment Tool (FRAX), calculate the risk of major osteoporotic (MOF) and hip fracture, but do not account for the excess risk of fracture in people with diabetes. We examined the predictive performance of FRAX without BMD in ethnically diverse, older patients with diabetes. Patients included were between ages 65-89 from the Kaiser Permanente Northern California Diabetes Registry and not already taking osteoporosis medications. Race and ethnicity were self-identified. We calculated FRAX without BMD based on baseline characteristics and assessed how well FRAX predicted MOF and hip fracture over follow-up. Predictive performance was based on measures of discrimination (area under the receiver operator curve, AUC) and calibration (observed-to-predicted ratio, O/P). We identified 96 914 patients (47.0% female), of whom 5383 (5.6%) and 1767 (1.8%) had MOF and hip fracture, respectively, over a mean follow-up of 4.3 years. The AUC for MOF and hip fracture were 0.72 and 0.77, respectively. FRAX mildly underestimated MOF and hip fracture rates (O/P 1.2 for both) overall. Discrimination was similar by race and ethnicity and diabetes duration but was worse in those over age 75 (AUC < 0.7). In some groups, there were substantial calibration errors, such as Hispanic women (O/P: 1.8 and 1.5), Black men (O/P: 1.5 and 1.8), those with duration of diabetes ≥20 years (O/P: 1.6 and 1.5), and those over the age of 80 (O/P: 1.4 and 1.2) for MOF and hip fracture, respectively. While the discriminatory performance of FRAX without BMD was good overall in patients with diabetes, it underestimated risk in Hispanic women, Black men, those with long duration of diabetes, and in the oldest patients with diabetes. These algorithmic biases suggest that diabetes-specific tools may be needed to stratify fracture risk in patients with diabetes.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057450","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}
引用次数: 0
Prediction of hip fracture by high-resolution peripheral quantitative computed tomography in older Swedish women.
IF 5.1 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-27 DOI: 10.1093/jbmr/zjaf020
Raju Jaiswal, Aldina Pivodic, Michail Zoulakis, Kristian F Axelsson, Henrik Litsne, Lisa Johansson, Mattias Lorentzon

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.

{"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}
引用次数: 0
Probability of Achieving Bone Mineral Density Treatment Goals with Denosumab Treatment in Postmenopausal Women with Osteoporosis.
IF 5.1 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-25 DOI: 10.1093/jbmr/zjaf014
Felicia Cosman, Zhenxun Wang, Xiaodong Li, Steven R Cummings

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.

{"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}
引用次数: 0
Trabecular bone deficits predominate in the appendicular skeleton of midlife women living with HIV: findings from a cross-sectional study in Zimbabwe.
IF 5.1 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-25 DOI: 10.1093/jbmr/zjaf021
Mícheál Ó Breasail, Tafadzwa Madanhire, Cynthia Kahari, Peter R Ebeling, Victoria Simms, Lisa K Micklesfield, Rashida A Ferrand, Celia L Gregson, Kate A Ward

HIV-related mortality has fallen due to scale-up of antiretroviral therapy (ART), so more women living with HIV (WLH) now live to reach menopause. Menopausal estrogen loss causes bone loss, as do HIV and certain ART regimens. However, quantitative bone data from WLH are few in Africa. A cross-sectional study of women aged 40-60 years (49% WLH) was conducted in Harare, Zimbabwe. Menopause status, fracture history, HIV status and treatment, and anthropometry were collected, and radial/tibial peripheral Quantitative Computed Tomography (pQCT) scans performed. pQCT outcomes were: distal radius and tibia trabecular volumetric bone mineral density (vBMD), total area, and compressive bone strength (BSIc); proximal radius and tibia cortical vBMD, bone mineral content (BMC), cortical thickness, bone area, and stress-strain index (SSI). Linear regression determined differences by HIV status, minimally adjusted for age and menopause status, and further adjusted for height and fat mass. Relationships between pQCT parameters and major osteoporotic fracture history were explored using univariate logistic regression. In WLH, linear regression assessed associations between HIV and ART durations on pQCT measures. 384 women mean(SD) age 49.7(5.8) years had pQCT data. WLH had lower absolute pQCT measures at all sites. Overall, HIV-related deficits were robust to adjustment for age, menopause status, height, and fat mass: WLH had lower trabecular vBMD (radius -7.3 [-12.5; -2.0]%, tibia -5.4 [-9.1; -1.7]%), and cortical vBMD (radius -3.5 [-5.9; -1.1]%, tibia -1.1[-1.6; -0.5]%). Strength estimates were lower in WLH and of similar magnitude at the radius and tibia. Longer HIV duration was associated with lower radius bone area, BMC, estimates of bone strength, independent of ART duration. Trabecular deficits predominate in WLH, though with age cortical compartment bone loss may increase in importance. This is particularly concerning as these differences were observed at the radius, a common site of postmenopausal osteoporotic fracture.

{"title":"Trabecular bone deficits predominate in the appendicular skeleton of midlife women living with HIV: findings from a cross-sectional study in Zimbabwe.","authors":"Mícheál Ó Breasail, Tafadzwa Madanhire, Cynthia Kahari, Peter R Ebeling, Victoria Simms, Lisa K Micklesfield, Rashida A Ferrand, Celia L Gregson, Kate A Ward","doi":"10.1093/jbmr/zjaf021","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf021","url":null,"abstract":"<p><p>HIV-related mortality has fallen due to scale-up of antiretroviral therapy (ART), so more women living with HIV (WLH) now live to reach menopause. Menopausal estrogen loss causes bone loss, as do HIV and certain ART regimens. However, quantitative bone data from WLH are few in Africa. A cross-sectional study of women aged 40-60 years (49% WLH) was conducted in Harare, Zimbabwe. Menopause status, fracture history, HIV status and treatment, and anthropometry were collected, and radial/tibial peripheral Quantitative Computed Tomography (pQCT) scans performed. pQCT outcomes were: distal radius and tibia trabecular volumetric bone mineral density (vBMD), total area, and compressive bone strength (BSIc); proximal radius and tibia cortical vBMD, bone mineral content (BMC), cortical thickness, bone area, and stress-strain index (SSI). Linear regression determined differences by HIV status, minimally adjusted for age and menopause status, and further adjusted for height and fat mass. Relationships between pQCT parameters and major osteoporotic fracture history were explored using univariate logistic regression. In WLH, linear regression assessed associations between HIV and ART durations on pQCT measures. 384 women mean(SD) age 49.7(5.8) years had pQCT data. WLH had lower absolute pQCT measures at all sites. Overall, HIV-related deficits were robust to adjustment for age, menopause status, height, and fat mass: WLH had lower trabecular vBMD (radius -7.3 [-12.5; -2.0]%, tibia -5.4 [-9.1; -1.7]%), and cortical vBMD (radius -3.5 [-5.9; -1.1]%, tibia -1.1[-1.6; -0.5]%). Strength estimates were lower in WLH and of similar magnitude at the radius and tibia. Longer HIV duration was associated with lower radius bone area, BMC, estimates of bone strength, independent of ART duration. Trabecular deficits predominate in WLH, though with age cortical compartment bone loss may increase in importance. This is particularly concerning as these differences were observed at the radius, a common site of postmenopausal osteoporotic fracture.</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":"143035478","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}
引用次数: 0
Comparative cardiovascular safety of romosozumab versus bisphosphonates in Japanese patients with osteoporosis: a new-user, active comparator design with instrumental variable analyses. 比较romosozumab与双膦酸盐在日本骨质疏松症患者的心血管安全性:一种新的用户,具有工具变量分析的主动比较设计
IF 5.1 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-17 DOI: 10.1093/jbmr/zjaf010
Ryoji Tominaga, Tatsuyoshi Ikenoue, Ryosuke Ishii, Kakuya Niihata, Tetsuro Aita, Tadahisa Okuda, Sayaka Shimizu, Masataka Taguri, Noriaki Kurita

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.

本研究分析了romosozumab(一种具有骨形成和骨吸收抑制作用的人单克隆抗体)和双膦酸盐与骨质疏松症患者心血管疾病发展的关系。采用新用户设计来解决选择偏差,并使用工具变量分析来解决指征混淆。年龄≥40岁、被诊断患有骨质疏松症或经历过脆性骨折的日本患者被送入商业行政索赔数据库涵盖的医疗机构,在romosozumab在日本商业化(2019年3月4日)后新开的romosozumab或双膦酸盐被纳入,基于180天洗脱期的验证。心血管疾病(心肌梗死或中风)是根据诊断信息、医疗程序和药物代码确定的。机构级别处方对罗莫索单抗的偏好被用作工具变量,定义为在指标日期前90天内在患者机构开处方的罗莫索单抗的比例。在纳入的59694张处方中,8808张是romosozumab, 50886张是双膦酸盐。romosozumab组的平均年龄高于双膦酸盐组(分别为80.5岁和78.2岁),且大多数患者为女性(分别为85.3岁和80.2%)。处方1年内心血管疾病的发病率为romosozumab每100人年12.3例,而双膦酸盐为11.4例(未调整的发病率比:1.08,95%可信区间:1.00-1.18)。使用两阶段残留纳入法的工具变量分析显示,1年内romosozumab与双膦酸盐相比的风险比为1.30(95%置信区间:0.88-1.90)。虽然可能不够有力,但这项研究表明,与双膦酸盐相比,在骨质疏松症患者中,没有观察到使用romosozumab增加心血管风险的明确证据。这些发现应该通过更大规模的药物流行病学研究来进一步验证,以减轻临床医生对romosozumab安全性的担忧。
{"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":"https://doi.org/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}
引用次数: 0
Time-lapse HR-pQCT reliably assesses and monitors local bone turnover in patients with chronic kidney disease. 延时HR-pQCT可靠地评估和监测慢性肾脏疾病患者的局部骨转换。
IF 5.1 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-15 DOI: 10.1093/jbmr/zjaf006
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

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.

骨转换评估和监测对于慢性肾脏疾病(CKD)相关的骨护理至关重要。由于骨转换异常高或低,CKD患者骨折风险显著增加,这需要根据患者特异性骨转换数据进行截然相反的治疗。然而,一个可靠的、可获得的、无创的骨转换评估和监测工具仍然是一个未满足的临床需求。将延时(TL)分析与高分辨率外周定量计算机断层扫描(HR-pQCT)扫描相结合,可以进行体内时空骨重塑评估。本研究旨在评估应用TL HR-pQCT评估和监测CKD患者局部骨形成和骨吸收的可行性。在第二代HR-pQCT平台上开发了定制的TL HR-pQCT流水线,并使用离体尸体幻影和活体扫描HR-pQCT图像进行了优化。使用体内纵向再现图像评估骨形成和吸收的年化最不显著变化。最后,评估了TL HR-pQCT管道在终末期肾病(ESKD;n = 9)。我们发现2个月的时间间隔足以让TL HR-pQCT管道可靠地评估和监测ESKD患者的局部骨转换。我们还证明了使用纵向基线/随访而不是短期扫描-扫描数据集表征TL HR-pQCT精度指标的重要性。TL HR-pQCT管道评估了一系列骨形成指标,这些指标与文献中报道的CKD和ESKD患者组织形态学骨形成的金标准一致。我们的研究结果强调,TL HR-pQCT有望作为一种“虚拟骨活检”,可靠地评估和监测CKD骨护理的局部骨转换。后续的工作将侧重于验证TL HR-pQCT管道与定量组织形态学测定的金标准骨活检。
{"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}
引用次数: 0
期刊
Journal of Bone and Mineral Research
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1