Rapid skeletal turnover in a radiographic mimic of osteopetrosis

Michael P. Whyte, Katherine L. Madson, Steven Mumm, William H. McAlister, Deborah V. Novack, Jo C. Blair, Timothy R. Helliwell, Marina Stolina, Laurence J. Abernethy, Nicholas J. Shaw

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Among the high bone mass disorders, the osteopetroses reflect osteoclast failure that prevents skeletal resorption and turnover, leading to reduced bone growth and modeling and characteristic histopathological and radiographic findings. We report an 11-yearold boy with a new syndrome that radiographically mimics osteopetrosis (OPT), but features rapid skeletal turnover. He presented at age 21 months with a parasellar, osteoclast-rich giant cell granuloma. Radiographs showed a dense skull, generalized osteosclerosis and cortical thickening, medullary cavity narrowing, and diminished modeling of tubular bones. His serum alkaline phosphatase was >5000 IU/L (normal <850 IU/L). After partial resection, the granuloma re-grew but then regressed and stabilized during 3 years of uncomplicated pamidronate treatment. His hyperphosphatasemia transiently diminished, but all bone turnover markers, especially those of apposition, remained elevated. Two years after pamidronate therapy stopped, bone mineral density (BMD) Z-scores reached +9.1 and +5.8 in the lumbar spine and hip, respectively, and iliac crest histopathology confirmed rapid bone remodeling. Serum multiplex biomarker profiling was striking for low sclerostin. Mutation analysis was negative for activation of lipoprotein receptorrelated protein 4 (LRP4), LRP5, or TGFβ1, and for defective sclerostin (SOST), osteoprotegerin (OPG), RANKL, RANK, SQSTM1, or sFRP1. Microarray showed no notable copy number variation. Studies of his nonconsanguineous parents were unremarkable. The etiology and pathogenesis of this unique syndrome are unknown.

Original languageEnglish
Pages (from-to)2601-2609
Number of pages9
JournalJournal of Bone and Mineral Research
Volume29
Issue number12
DOIs
StatePublished - Dec 1 2014

Keywords

  • Biomarker profiling
  • Giant cell granuloma
  • Osteosclerosis
  • Sclerostin

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