Bisphosphonate therapy for osteogenesis imperfecta.
BACKGROUND
In osteogenesis imperfecta (OI) a genetic defect in type I collagen results in multiple fractures with little or no trauma. Bisphosphonates are used to attempt to reduce these fractures.


OBJECTIVE
To assess the effectiveness and safety of bisphosphonates in increasing bone mineral density (BMD), reducing fractures and improving clinical function in people with OI.


METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearches of journals and conference proceedings. We searched PubMed and major conference proceedings.Register last searched: August 2008.


METHODS
Randomised and quasi-randomised controlled trials comparing bisphosphonates to placebo, no treatment, or comparator interventions in all types of OI.


METHODS
Two authors independently extracted data and assessed trial quality.


RESULTS
Eight studies (403 participants) were included. Data for oral bisphosphonates versus placebo could not be aggregated. A significant difference favouring bisphosphonates in fracture risk reduction and number of fractures was noted in one trial. No differences were reported in the remaining three trials. Two trials reported data for spine BMD; one found significantly increased lumbar spine density z scores at 12 months and one reported a significant increase in lumbar spine BMD at 12, 24 and 36 months; both favouring bisphosphonates. For intravenous bisphosphonates versus placebo, aggregated data from two trials showed no significant difference for the number of participants with at least one fracture, RR 0.56 (95% CI 0.30 to 1.06). In the remaining trial no significant difference was noted in fracture incidence. For spine BMD, no significant difference was noted in the aggregated data from two trials, MD 9.96 (95%CI -2.51 to 22.43). In the remaining trial a significant difference in mean per cent change in spine BMD z score favoured intravenous bisphosphonates at 6 and 12 months. One trial compared oral versus intravenous bisphosphonates and found no differences in primary outcomes. Data describing growth, bone pain, and functional outcomes after bisphosphonate therapy were incomplete.


CONCLUSIONS
Evidence suggests oral or intravenous bisphosphonates increase BMD in children and adults with OI. These were not shown to be different in their ability to increase BMD; it is unclear whether either treatment decreases fractures. Additional studies may determine whether bisphosphonates improve clinical status (reduce fractures and pain; improve growth and functional mobility) in this population. Optimal method, duration of therapy and long-term safety of bisphosphonate therapy requires further investigation.
Pediatrics Department, Oregon Health & Science University, 707 SW Gaines Street, Portland, Oregon 97239-2901, USA. phillica@ohsu.edu
Carrie A
CA
Phillipi
Tracey
T
Remmington
Robert D
RD
Steiner
D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D004164:Diphosphonates / Q000627:therapeutic use*; D050723:Fractures, Bone / Q000517:prevention & control*; D006801:Humans; D010013:Osteogenesis Imperfecta / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic
D050071:Bone Density Conservation Agents; D004164:Diphosphonates