From disease to treatment: from rare skeletal disorders to treatments for osteoporosis

Endocrine. 2016 Jun;52(3):414-26. doi: 10.1007/s12020-016-0888-7. Epub 2016 Feb 18.


During the past 15 years there has been an expansion of our knowledge of the cellular and molecular mechanisms regulating bone remodeling that identified new signaling pathways fundamental for bone renewal as well as previously unknown interactions between bone cells. Central for these developments have been studies of rare bone disorders. These findings, in turn, have led to new treatment paradigms for osteoporosis some of which are at late stages of clinical development. In this article, we review three rare skeletal disorders with case descriptions, pycnodysostosis and the craniotubular hyperostoses sclerosteosis and van Buchem disease that led to the development of cathepsin K and sclerostin inhibitors, respectively, for the treatment of osteoporosis.

Keywords: Cathepsin K; Osteoporosis; Pycnodystostosis; Sclerosteosis; Sclerostin; Van Buchem disease.

Publication types

  • Review

MeSH terms

  • Bone Diseases / etiology*
  • Bone Diseases / therapy*
  • Bone Remodeling / physiology
  • Drug Discovery* / methods
  • Humans
  • Hyperostosis / etiology
  • Hyperostosis / therapy
  • Osteochondrodysplasias / etiology
  • Osteochondrodysplasias / therapy
  • Osteoporosis / etiology
  • Osteoporosis / therapy*
  • Rare Diseases
  • Syndactyly / etiology
  • Syndactyly / therapy

Supplementary concepts

  • Sclerosteosis