Drug-induced osteopetrosis

Michael P. Whyte, William H. McAlister, Vandana Dhiman, Nirmal Raj Gopinathan, Sanjay K. Bhadada

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Osteopetrosis (OPT) denotes the consequences from failure of osteoclasts to resorb bone and chondroclasts to remove calcified physeal cartilage throughout growth. Resulting impairment of skeletal modeling, remodeling, and growth compromises widening of medullary spaces, formation of the skull, and expansion of cranial foramina. Thus, myelophthisic anemia, raised intracranial pressure, and cranial nerve palsies complicate OPT when severe. Osteopetrotic bones fracture due to misshaping, failure of remodeling to weave the collagenous matrix of cortical osteons and trabeculae, persistence of mineralized growth plate cartilage, “hardening” of hydroxyapatite crystals, and delayed healing of skeletal microcracks. Teeth may fail to erupt. Now it is widely appreciated that OPT is caused by germline loss-of-function mutation(s) usually of genes involved in osteoclast function, but especially rarely of genes necessary for osteoclast formation. Additionally, however, in 2003 we published a case report demonstrating that prolonged excessive dosing during childhood of the antiresorptive aminobisphosphonate pamidronate can sufficiently block osteoclast and chondroclast activity to recapitulate the skeletal features of OPT. Herein, we include further evidence of drug-induced OPT by illustrating osteopetrotic skeletal changes from repeated administration of high doses of the aminobisphosphonate zoledronic acid (zoledronate) given to children with osteogenesis imperfecta.

Original languageEnglish
Article number116788
StatePublished - Aug 2023


  • Bisphosphonates
  • Bone modeling
  • Bone remodeling
  • Brittle bone disease
  • Denosumab
  • Endochondral bone formation
  • Erlenmeyer flask deformity
  • Fractures
  • Hyperostosis
  • Metabolic bone disease
  • Osteoclast
  • Osteogenesis imperfecta
  • Osteopetrosis
  • Osteosclerosis
  • Pamidronate
  • Zoledronate
  • Zoledronic acid


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