Skeletal Diseases and Mineral Homeostasis Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Department of Endocrinology, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile.
J Bone Miner Res. 2019 Apr;34(4):653-660. doi: 10.1002/jbmr.3649. Epub 2019 Jan 15.
Fibrous dysplasia (FD) is a mosaic disease in which bone is replaced with fibro-osseous tissue. Lesions expand during childhood, reaching final burden by age 15 years. In vitro data suggest that disease activity decreases in adulthood; however, there is no clinical data to support this concept. Bone turnover markers (BTMs) have been used as markers of disease activity in FD; however, the natural history of BTM changes, the effects of antiresorptive treatment, and their association to clinical outcomes have not been described. The goals of this study are to describe 1) the natural history of FD disease activity and its association with pain; 2) the impact of bisphosphonates on the natural history of BTMs; and 3) the effect of bisphosphonates on progression of FD burden during childhood. Disease burden scores and alkaline phosphatase, osteocalcin, NTx, FGF23, and RANKL levels from 178 subjects in an FD/MAS natural history study were reviewed, including 73 subjects treated with bisphosphonates. BTMs, RANKL, and FGF23 demonstrated a sustained reduction with age. Bisphosphonate treatment did not significantly impact this age-dependent decrease in BTMs. Pain was more prevalent and severe in adults compared with children and was not associated with BTMs. In children, the progression of disease burden was not affected by bisphosphonates. In conclusion, FD is associated with an age-dependent decline in bone turnover and other markers of disease activity. Pain, in contrast, is more frequent and severe in adults with FD and is not related to bone turnover. Bisphosphonate treatment does not significantly impact the age-dependent decrease in bone turnover, nor does it prevent the progression of FD disease burden in children. These findings, in association with the established adverse effects of antiresorptives, should be considered when evaluating use and response to bisphosphonates in patients being treated for FD and in any study using BTMs as surrogate endpoints. © 2019 American Society for Bone and Mineral Research.
纤维结构不良（FD）是一种镶嵌性疾病，其中骨骼被纤维骨性组织所取代。病变在儿童期扩大，到 15 岁时达到最终负担。体外数据表明，疾病活动性在成年后降低；然而，没有临床数据支持这一概念。骨转换标志物（BTMs）已被用作 FD 疾病活动性的标志物；然而，BTM 变化的自然史、抗吸收治疗的效果及其与临床结果的关系尚未描述。本研究的目的是描述 1）FD 疾病活动的自然史及其与疼痛的关系；2）双膦酸盐对 BTMs 自然史的影响；3）双膦酸盐对儿童期 FD 负担进展的影响。回顾了 178 例 FD/MAS 自然史研究中的 178 例患者的疾病负担评分和碱性磷酸酶、骨钙素、NTx、FGF23 和 RANKL 水平，其中 73 例患者接受了双膦酸盐治疗。BTMs、RANKL 和 FGF23 随年龄的增长而持续降低。双膦酸盐治疗并没有显著影响 BTMs 的这种年龄依赖性下降。与儿童相比，成人疼痛更为普遍和严重，与 BTMs 无关。在儿童中，疾病负担的进展不受双膦酸盐的影响。总之，FD 与骨转换和其他疾病活动标志物的年龄依赖性下降有关。相比之下，FD 成人的疼痛更为频繁和严重，与骨转换无关。双膦酸盐治疗并没有显著影响骨转换的年龄依赖性下降，也没有防止儿童 FD 疾病负担的进展。这些发现，加上抗吸收药物的既定不良反应，在评估用于治疗 FD 的患者的双膦酸盐的使用和反应时，以及在任何使用 BTMs 作为替代终点的研究中，都应予以考虑。
