Consensus Guidelines on the Medical Management of Osteopetrosis

Presentation Number: MON 358
Date of Presentation: April 3rd, 2017

Calvin Chih-Chia Wu*1, Michael John Econs2, Linda A DiMeglio3, Karl Insogna4, Michael A. Levine5, Paul Orchard6, Anna Petryk7, Eric T Rush8, Dolores M. Shoback9, Leanne Marie Ward10 and Lynda Elizabeth Polgreen11
1Harbor-UCLA Medical Center, Torrance, CA, 2Indiana Univ Med Ctr, Indianapolis, IN, 3Indiana Univ Sch of Med, Indianapolis, IN, 4Yale University, New Haven, CT, 5The Children's Hospital of Philadelphia, Philadelphia, PA, 6University of Minnesota, 7University of Minnesota, Minneapolis, MN, 8University of Nebraska Medical Center, Omaha, NE, 9UCSF/VA Med Ctr, San Francisco, CA, 10University of Ottawa, Ottawa, ON, Canada, 11Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA


Background: Osteopetrosis is a rare metabolic bone disease characterized by impaired osteoclast activity resulting in generalized high bone mineral density. Existing guidelines for the management of osteopetrosis (Schulz et al. and the ESID and EBMT 2015) focus on the severe infantile “malignant” form, which has a different clinical course and treatment compared to the milder forms of the disease. There are currently no published guidelines on the management of patients with these milder forms of osteopetrosis. Therefore, the objective of the first phase of this project was to develop expert consensus guidelines that would address the medical management of the milder forms of osteopetrosis.

Methods: A modified Delphi method was used to build consensus. This involved anonymous online surveys sent by email to participants of the Osteopetrosis Working Group. After the first survey was completed, areas of agreement and conflict were identified and used in developing a follow up survey.

Results: To date, there were 8 respondents who have followed a median of 6 patients (range 1-15) of all ages. There is a consensus that 1) a skeletal survey is the minimum needed to diagnose osteopetrosis, 2) genetic testing is important for identifying forms of osteopetrosis with unique complications but not necessary for diagnosis, 3) a team of specialists including Genetics, Endocrinology, Ophthalmology, Orthopedics, Neurosurgery and often Hematology, Infectious Disease, and Neurology, is required, 4) although calcitriol may be needed to treat hypocalcemia, high dose calcitriol to treat osteopetrosis is not recommended, and 5) treatment with interferon gamma-1b is considered experimental for the milder forms of osteopetrosis. Consensus is still needed on the baseline studies that should be obtained after the diagnosis has been made; approaches to the initiation, dosing, and monitoring of calcitriol and calcium; and studies for monitoring treatments and disease progression.

Conclusions: This first phase survey resulted in consensus in broad areas related to the diagnosis and treatment of non-malignant forms of osteopetrosis. Additional surveys will be performed to finalize consensus on specific medical therapies and monitoring of treatment, and the quality/strength of each recommendation will be determined. We anticipate that the completion and publication of these guidelines will improve the care of patients with this rare disease through standardizing treatment amongst physicians.


Disclosure: CCCW: Investigator, Horizon Pharma. MJE: Investigator, Horizon Pharma. PO: Investigator, Horizon Pharma. LEP: Investigator, Horizon Pharma. Nothing to Disclose: LAD, KI, MAL, AP, ETR, DMS, LMW