Multicentric carpotarsal osteolysis syndrome (MCTO) with generalized high bone turnover and high serum RANKL: Response to denosumab
Ravit Regev,
Etienne B. Sochett,
Yesmino Elia,
Ronald M. Laxer,
Damien Noone,
Kristi Whitney-Mahoney,
Kornelia Filipowski,
Amer Shamas,
Reza Vali
Affiliations
Ravit Regev
Division of Endocrinology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Diagnostic Imaging, The Hospital for Sick Children, Toronto, ON, Canada; University of Toronto, Toronto, ON, Canada
Etienne B. Sochett
Division of Endocrinology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Diagnostic Imaging, The Hospital for Sick Children, Toronto, ON, Canada; University of Toronto, Toronto, ON, Canada; Corresponding author at: Division of Endocrinology, Department of Paediatrics, The Hospital for Sick Children, 555 University Ave. RM.5114A, M5G 1X8 Toronto, ON, Canada.
Yesmino Elia
Division of Endocrinology, The Hospital for Sick Children, Toronto, ON, Canada
Ronald M. Laxer
Division of Rheumatology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Diagnostic Imaging, The Hospital for Sick Children, Toronto, ON, Canada; University of Toronto, Toronto, ON, Canada
Damien Noone
Division of Nephrology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Diagnostic Imaging, The Hospital for Sick Children, Toronto, ON, Canada; University of Toronto, Toronto, ON, Canada
Kristi Whitney-Mahoney
Division of Rheumatology, The Hospital for Sick Children, Toronto, ON, Canada
Kornelia Filipowski
Division of Endocrinology, The Hospital for Sick Children, Toronto, ON, Canada
Amer Shamas
Department of Paediatrics, The Hospital for Sick Children, Toronto, ON, Canada; Department of Diagnostic Imaging, The Hospital for Sick Children, Toronto, ON, Canada; University of Toronto, Toronto, ON, Canada
Reza Vali
Department of Paediatrics, The Hospital for Sick Children, Toronto, ON, Canada; Department of Diagnostic Imaging, The Hospital for Sick Children, Toronto, ON, Canada; University of Toronto, Toronto, ON, Canada
MCTO is a rare disorder, caused by mutations in the MafB gene, a negative regulator of receptor activator of nuclear factor-кB ligand (RANKL). Manifestations include carpal and tarsal osteolysis and renal failure. Pathophysiology is poorly understood, and no effective treatment is available.In this case report we describe a patient with MCTO (MafB, mutation c.206C>T, p.Ser69Leu), diagnosed at the age of 5 years. At 7 years, skeletal survey showed diffuse osteopenia. BMD was mildly reduced, and bone turnover markers increased. He was treated with denosumab, a human monoclonal RANKL inhibitor for two years. Each injection was followed by a marked reduction in C-telopeptide (CTX). Following denosumab his BMD and bone symptoms improved and the osteolysis stabilized. At the age of 13 years, osteoporosis was diagnosed using high resolution peripheral quantitative computed tomography (HRpQCT) and serum RANKL was found to be markedly increased.This initial experience suggests that the associated osteoporosis may be ameliorated by denosumab, although further study will be needed to understand the appropriate dose, frequency, and the extent of efficacy. Monitoring of CTX and bone specific alkaline phosphatase will be especially useful in this regard. Further study in other MCTO patients is also needed to determine whether high bone turnover is specific to this mutation or more common than previously appreciated. We propose a model in which osteolysis in this condition is strongly associated with the systemic osteoporosis.
