Suppressible RANK-Ligand Levels in a Patient with Trichorhinophalangeal Syndrome Type II on Denosumab Therapy

Abstract

Trichorhinophalangeal Syndrome Type II (TRPS2) is a rare contiguous gene syndrome caused by deletion of TRPS1 and EXT1 genes, characterized by facial, hair and skeletal abnormalities. The prevalence of osteoporosis in TRPS, especially in TRPS2, is not well known. OPG gene, which is located between TRPS1and EXT1 genes, blocks the Receptor Activator of Nuclear Factor-κB Ligand (RANKL), preventing osteoclast formation. Thus, we hypothesize that patients with loss of the Osteoprotegerin (OPG) gene will have osteoporosis in the setting of unopposed RANKL. Denosumab, a human monoclonal antibody against RANKL, may be beneficial in decreasing osteoclast differentiation and bone degradation. We describe now a 25-year-old woman with TRPS2 with osteoporosis and multiple osteochondromas. Gene testing revealed a large deletion on the long arm of chromosome 8, including TRPS1, OPG and EXT1 genes. Her osteoporosis was refractory to bisphosphonate therapy; however, after Denosumab administration her bone RANKL levels decreased with marked clinical improvement. She had no adverse effects and no additional fractures after 2 years of therapy. Denosumab may be an effective treatment option in TRPS2-associated osteoporosis.