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Published on: December 3, 2016
Effects of denosumab treatment and discontinuation on human growth plates
Howard D Wang1, Alison M Boyce, Jeffrey Y Tsai
1Skeletal 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.
Context:
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.
Objective:
The objective of the study was to investigate the effects of denosumab treatment on skeletal growth and histology.
Design:
This was an observational case report with radiological and histopathological analyses.
Setting:
The study was conducted at a clinical research center.
Patients:
A 9-year-old boy with fibrous dysplasia treated with a 7-month course of denosumab participated in the study.
Intervention:
Histological analyses were performed and compared on growth plates from limbs that had been amputated before and 17 months after denosumab treatment.
Main Outcome Measures:
Skeletal radiographs and bone histopathology from before and after treatment were measured.
Results:
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.
Conclusions:
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.
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