Skeletal Clinical Studies Unit (H.D.W., J.Y.T., R.I.G., M.T.C.), Craniofacial and Skeletal Diseases Branch, and Oral and Pharyngeal Cancer Branch (A.A.M.), National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892; University of Maryland School of Medicine (H.D.W.), Baltimore, Maryland 21201; Department of Plastic and Reconstructive Surgery (H.D.W.), Johns Hopkins Hospital, Baltimore, Maryland 21231; Division of Endocrinology and Diabetes (A.M.B.) and Bone Health Program (A.M.B.), Division of Orthopaedics and Sports Medicine, Children's National Medical Center, Washington, DC 20010; Tufts University School of Dental Medicine (J.Y.T.), Boston, Massachusetts 02111; and University of Michigan Health Systems (F.A.F., J.Z.K.-V.), University of Michigan, Ann Arbor, Michigan 48109.
J Clin Endocrinol Metab. 2014 Mar;99(3):891-7. doi: 10.1210/jc.2013-3081. Epub 2014 Jan 1.
Denosumab is a humanized monoclonal antibody to receptor activator of nuclear factor-κB ligand used primarily for postmenopausal osteoporosis and skeletal-related events from metastatic cancer. Its safety in children has not been established.
The objective of the study was to investigate the effects of denosumab treatment on skeletal growth and histology.
This was an observational case report with radiological and histopathological analyses.
The study was conducted at a clinical research center.
A 9-year-old boy with fibrous dysplasia treated with a 7-month course of denosumab participated in the study.
Histological analyses were performed and compared on growth plates from limbs that had been amputated before and 17 months after denosumab treatment.
Skeletal radiographs and bone histopathology from before and after treatment were measured.
After initiating denosumab, sclerotic metaphyseal bands appeared on radiographs. Posttreatment radiographs revealed migration of the bands away from the growth plates, consistent with continued linear growth. Histologically, the bands were composed of horizontally arranged trabeculae containing calcified cartilage. This cartilage appeared to derive from unresorbed primary spongiosa as a result of osteoclast inhibition by denosumab, similar to what has been observed with bisphosphonates. By 17 months after treatment, active bone resorption and formation had returned, as evidenced by the presence of active osteoclasts in resorption pits and osteoid surfaces.
Further studies are needed to determine the safety of denosumab on the growing skeleton. However, in this child there was continued epiphyseal activity both during and after treatment and reversal of bone turnover suppression after treatment discontinuation, suggesting that denosumab did not have significant adverse effects on growth.
地舒单抗是一种针对核因子-κB 配体受体激活剂的人源化单克隆抗体，主要用于绝经后骨质疏松症和转移性癌症的骨骼相关事件。其在儿童中的安全性尚未确定。
本研究旨在探讨地舒单抗治疗对骨骼生长和组织学的影响。
这是一项观察性病例报告，包括放射学和组织病理学分析。
该研究在临床研究中心进行。
一名 9 岁男孩，患有纤维结构不良，接受了 7 个月的地舒单抗治疗，参与了这项研究。
对接受地舒单抗治疗前和治疗后 17 个月截肢肢体的生长板进行了组织学分析。
治疗前后的骨骼 X 线片和骨组织病理学进行了测量。
开始使用地舒单抗后，影像学上出现硬化性干骺端带。治疗后的 X 线片显示，这些带从生长板迁移，与持续线性生长一致。组织学上，这些带由水平排列的小梁组成，其中含有钙化软骨。由于地舒单抗抑制破骨细胞，这种软骨似乎来源于未被吸收的初级松质骨，与双膦酸盐的观察结果相似。治疗后 17 个月，骨吸收和形成恢复了活性，表现为破骨细胞在吸收陷窝和类骨质表面的活性。
需要进一步研究以确定地舒单抗对生长骨骼的安全性。然而，在这个孩子中，在治疗期间和治疗后都有持续的骺板活动，并且在治疗停止后骨转换抑制逆转，这表明地舒单抗对生长没有显著的不良影响。
