常染色体显性骨质疏松症患者骨折与骨密度高度相关,与骨转换标志物呈负相关。

IF 5.9 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Michael J Econs, Stuart J Warden, Ziyue Liu, Paul Niziolek, Corinne Parks-Schenck, Netsanet Gebregziabher, Rita Gerard-O'Riley, Marian Hart, Lynda E Polgreen, Erik A Imel
{"title":"常染色体显性骨质疏松症患者骨折与骨密度高度相关,与骨转换标志物呈负相关。","authors":"Michael J Econs, Stuart J Warden, Ziyue Liu, Paul Niziolek, Corinne Parks-Schenck, Netsanet Gebregziabher, Rita Gerard-O'Riley, Marian Hart, Lynda E Polgreen, Erik A Imel","doi":"10.1093/jbmr/zjaf123","DOIUrl":null,"url":null,"abstract":"<p><p>Autosomal Dominant Osteopetrosis (ADO) is a rare, osteosclerotic disorder usually caused by missense variants in the CLCN7 gene, resulting in impaired osteoclastic bone resorption. Penetrance is incomplete and disease severity varies widely, even among relatives within the same family. Although ADO can cause visual loss, osteonecrosis, osteomyelitis, and bone marrow failure, the most common complication of ADO is fracture. We are conducting a natural history study to characterize disease progression and determinants of disease severity. We hypothesized that baseline bone mineral density and bone turnover markers would correlate with self-reported fracture history. We report cross-sectional analysis of baseline data from the natural history study in 54 individuals (42 adults, 12 children). In adults, Z scores for both volumetric (r = 0.87, p < .001) and areal bone mineral density (aBMD) of the lumbar spine, and Z scores for femoral neck, and total hip aBMD (r = 0.77 to 0.78; p < .001) were correlated with lifetime fracture number. Tartrate resistant acid phosphatase, a marker of osteoclast number, correlated positively with fracture (r = 0.52, p = .004) consistent with an adaptive response of higher numbers of osteoclasts among more severely affected individuals. However, fracture number correlated inversely with the bone resorption markers serum C-telopeptide (r = -0.60, p < .001) and urine N-telopeptide/creatinine ratio (r = -0.35, p = .047), suggesting that ADO subjects who have the most reduced osteoclast activity have a greater tendency to fracture. Correlation coefficients between fractures, BMD and bone turnover markers were similar when limited to the 37 adults with disease causing CLCN7 variants. There were no statistically significant differences between subjects with the most common CLCN7 variant (G215R), the most common variant in our cohort, compared to other CLCN7 variants with respect to fracture, bone density measures or biochemical markers of bone turnover. These data demonstrate that bone density and biochemical bone turnover markers are indicators of ADO severity as defined by fracture number.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.9000,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Fractures are Highly Correlated with Bone Density and Inversely Correlated with Bone Turnover Markers in Autosomal Dominant Osteopetrosis.\",\"authors\":\"Michael J Econs, Stuart J Warden, Ziyue Liu, Paul Niziolek, Corinne Parks-Schenck, Netsanet Gebregziabher, Rita Gerard-O'Riley, Marian Hart, Lynda E Polgreen, Erik A Imel\",\"doi\":\"10.1093/jbmr/zjaf123\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Autosomal Dominant Osteopetrosis (ADO) is a rare, osteosclerotic disorder usually caused by missense variants in the CLCN7 gene, resulting in impaired osteoclastic bone resorption. Penetrance is incomplete and disease severity varies widely, even among relatives within the same family. Although ADO can cause visual loss, osteonecrosis, osteomyelitis, and bone marrow failure, the most common complication of ADO is fracture. We are conducting a natural history study to characterize disease progression and determinants of disease severity. We hypothesized that baseline bone mineral density and bone turnover markers would correlate with self-reported fracture history. We report cross-sectional analysis of baseline data from the natural history study in 54 individuals (42 adults, 12 children). In adults, Z scores for both volumetric (r = 0.87, p < .001) and areal bone mineral density (aBMD) of the lumbar spine, and Z scores for femoral neck, and total hip aBMD (r = 0.77 to 0.78; p < .001) were correlated with lifetime fracture number. Tartrate resistant acid phosphatase, a marker of osteoclast number, correlated positively with fracture (r = 0.52, p = .004) consistent with an adaptive response of higher numbers of osteoclasts among more severely affected individuals. However, fracture number correlated inversely with the bone resorption markers serum C-telopeptide (r = -0.60, p < .001) and urine N-telopeptide/creatinine ratio (r = -0.35, p = .047), suggesting that ADO subjects who have the most reduced osteoclast activity have a greater tendency to fracture. Correlation coefficients between fractures, BMD and bone turnover markers were similar when limited to the 37 adults with disease causing CLCN7 variants. There were no statistically significant differences between subjects with the most common CLCN7 variant (G215R), the most common variant in our cohort, compared to other CLCN7 variants with respect to fracture, bone density measures or biochemical markers of bone turnover. These data demonstrate that bone density and biochemical bone turnover markers are indicators of ADO severity as defined by fracture number.</p>\",\"PeriodicalId\":185,\"journal\":{\"name\":\"Journal of Bone and Mineral Research\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":5.9000,\"publicationDate\":\"2025-09-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Bone and Mineral Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/jbmr/zjaf123\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Bone and Mineral Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/jbmr/zjaf123","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0

摘要

常染色体显性骨质疏松症(ADO)是一种罕见的骨质硬化性疾病,通常由CLCN7基因的错义变异引起,导致破骨细胞骨吸收受损。外显率不完全,疾病严重程度差异很大,即使在同一家庭的亲属之间也是如此。虽然ADO可引起视力丧失、骨坏死、骨髓炎和骨髓衰竭,但ADO最常见的并发症是骨折。我们正在进行一项自然历史研究,以确定疾病进展和疾病严重程度的决定因素。我们假设基线骨密度和骨转换标志物与自我报告的骨折史相关。我们报告了54个个体(42个成人,12个儿童)的自然历史研究基线数据的横断面分析。在成人中,两项指标的Z分数(r = 0.87, p
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Fractures are Highly Correlated with Bone Density and Inversely Correlated with Bone Turnover Markers in Autosomal Dominant Osteopetrosis.

Autosomal Dominant Osteopetrosis (ADO) is a rare, osteosclerotic disorder usually caused by missense variants in the CLCN7 gene, resulting in impaired osteoclastic bone resorption. Penetrance is incomplete and disease severity varies widely, even among relatives within the same family. Although ADO can cause visual loss, osteonecrosis, osteomyelitis, and bone marrow failure, the most common complication of ADO is fracture. We are conducting a natural history study to characterize disease progression and determinants of disease severity. We hypothesized that baseline bone mineral density and bone turnover markers would correlate with self-reported fracture history. We report cross-sectional analysis of baseline data from the natural history study in 54 individuals (42 adults, 12 children). In adults, Z scores for both volumetric (r = 0.87, p < .001) and areal bone mineral density (aBMD) of the lumbar spine, and Z scores for femoral neck, and total hip aBMD (r = 0.77 to 0.78; p < .001) were correlated with lifetime fracture number. Tartrate resistant acid phosphatase, a marker of osteoclast number, correlated positively with fracture (r = 0.52, p = .004) consistent with an adaptive response of higher numbers of osteoclasts among more severely affected individuals. However, fracture number correlated inversely with the bone resorption markers serum C-telopeptide (r = -0.60, p < .001) and urine N-telopeptide/creatinine ratio (r = -0.35, p = .047), suggesting that ADO subjects who have the most reduced osteoclast activity have a greater tendency to fracture. Correlation coefficients between fractures, BMD and bone turnover markers were similar when limited to the 37 adults with disease causing CLCN7 variants. There were no statistically significant differences between subjects with the most common CLCN7 variant (G215R), the most common variant in our cohort, compared to other CLCN7 variants with respect to fracture, bone density measures or biochemical markers of bone turnover. These data demonstrate that bone density and biochemical bone turnover markers are indicators of ADO severity as defined by fracture number.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Journal of Bone and Mineral Research
Journal of Bone and Mineral Research 医学-内分泌学与代谢
CiteScore
11.30
自引率
6.50%
发文量
257
审稿时长
2 months
期刊介绍: The Journal of Bone and Mineral Research (JBMR) publishes highly impactful original manuscripts, reviews, and special articles on basic, translational and clinical investigations relevant to the musculoskeletal system and mineral metabolism. Specifically, the journal is interested in original research on the biology and physiology of skeletal tissues, interdisciplinary research spanning the musculoskeletal and other systems, including but not limited to immunology, hematology, energy metabolism, cancer biology, and neurology, and systems biology topics using large scale “-omics” approaches. The journal welcomes clinical research on the pathophysiology, treatment and prevention of osteoporosis and fractures, as well as sarcopenia, disorders of bone and mineral metabolism, and rare or genetically determined bone diseases.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
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
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
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 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信