Diagnosis and Management of Osteopetrosis: Consensus Guidelines From the Osteopetrosis Working Group

J Clin Endocrinol Metab. 2017 Sep 1;102(9):3111-3123. doi: 10.1210/jc.2017-01127.


Background: Osteopetrosis encompasses a group of rare metabolic bone diseases characterized by impaired osteoclast activity or development, resulting in high bone mineral density. Existing guidelines focus on treatment of the severe infantile forms with hematopoietic cell transplantation (HCT) but do not address the management of patients with less severe forms for whom HCT is not the standard of care. Therefore, our objective was to develop expert consensus guidelines for the management of these patients.

Methods: A modified Delphi method was used to build consensus among participants of the Osteopetrosis Working Group, with responses to an anonymous online survey used to identify areas of agreement and conflict and develop a follow-up survey. The strength of recommendations and quality of evidence was graded using the Grading of Recommendations Assessment, Development and Evaluation system.

Results: Consensus was found in the areas of diagnosis, monitoring, and treatment. We recommend relying on characteristic radiographic findings to make the diagnosis and found that genetic testing adds important information by identifying mutations associated with unique disease complications. We recommend ongoing monitoring for changes in mineral metabolism and other complications, including cranial nerve impingement, anemia, leukopenia, and dental disease. We suggest that calcitriol should not be used in high doses and instead recommend symptom-based supportive therapy for disease complications because noninfantile osteopetrosis has no effective treatment.

Conclusions: Scarcity of published studies on osteopetrosis reduce the ability to develop evidence-based guidelines for the management of these patients. Expert opinion-based guidelines for this rare condition are nevertheless important to enable improved care.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcitriol / therapeutic use
  • Combined Modality Therapy
  • Consensus
  • Evidence-Based Medicine
  • Female
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Incidence
  • Male
  • Osteopetrosis / epidemiology
  • Osteopetrosis / genetics*
  • Osteopetrosis / pathology
  • Osteopetrosis / therapy*
  • Practice Guidelines as Topic*
  • Prognosis
  • Tomography, X-Ray Computed / methods
  • Treatment Outcome


  • Calcitriol