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Bisphosphonate therapy for osteogenesis imperfecta.
Cochrane Database Syst Rev. 2016 Oct 19; 10(10):CD005088.CD

Abstract

BACKGROUND

Osteogenesis imperfecta is caused by a genetic defect resulting in an abnormal type I collagen bone matrix which typically results in multiple fractures with little or no trauma. Bisphosphonates are used in an attempt to increase bone mineral density and reduce these fractures in people with osteogenesis imperfecta. This is an update of a previously published Cochrane Review.

OBJECTIVES

To assess the effectiveness and safety of bisphosphonates in increasing bone mineral density, reducing fractures and improving clinical function in people with osteogenesis imperfecta.

SEARCH METHODS

We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Inborn Errors of Metabolism Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of journals and conference proceedings. We additionally searched PubMed and major conference proceedings.Date of the most recent search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Register: 28 April 2016.

SELECTION CRITERIA

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

DATA COLLECTION AND ANALYSIS

Two authors independently extracted data and assessed the risk of bias of the included trials.

MAIN RESULTS

Fourteen trials (819 participants) were included. Overall, the trials were mainly at a low risk of bias, although selective reporting was an issue in several of the trials. Data for oral bisphosphonates versus placebo could not be aggregated; a statistically significant difference favouring oral bisphosphonates in fracture risk reduction and number of fractures was noted in two trials. No differences were reported in the remaining three trials which commented on fracture incidence. Five trials reported data for spine bone mineral density; all found statistically significant increased lumbar spine density z scores for at least one time point studied. For intravenous bisphosphonates versus placebo, aggregated data from two trials showed no statistically significant difference for the number of participants with at least one fracture, risk ratio 0.56 (95% confidence interval 0.30 to 1.06). In the remaining trial no statistically significant difference was noted in fracture incidence. For spine bone mineral density, no statistically significant difference was noted in the aggregated data from two trials, mean difference 9.96 (95% confidence interval -2.51 to 22.43). In the remaining trial a statistically significant difference in mean per cent change in spine bone mineral density z score favoured intravenous bisphosphonates at six and 12 months. Data describing growth, bone pain, and functional outcomes after oral or intravenous bisphosphonate therapy, or both, as compared to placebo were incomplete among all studies, but do not show consistent improvements in these outcomes. Two studies compared different doses of bisphosphonates. No differences were found between doses when bone mineral density, fractures, and height or length z score were assessed. One trial compared oral versus intravenous bisphosphonates and found no differences in primary outcomes. Two studies compared the intravenous bisphosphonates zoledronic acid and pamidronate. There were no significant differences in primary outcome. However, the studies were at odds as to the relative benefit of zoledronic acid over pamidronate for lumbosacral bone mineral density at 12 months.

AUTHORS' CONCLUSIONS

Bisphophonates are commonly prescribed to individuals with osteogenesis imperfecta. Current evidence, albeit limited, demonstrates oral or intravenous bisphosphonates increase bone mineral density in children and adults with this condition. These were not shown to be different in their ability to increase bone mineral density. It is unclear whether oral or intravenous bisphosphonate treatment consistently decreases fractures, though multiple studies report this independently and no studies report an increased fracture rate with treatment. The studies included here do not show bisphosphonates conclusively improve clinical status (reduce pain; improve growth and functional mobility) in people with osteogenesis imperfecta. Given their current widespread and expected continued use, the optimal method, duration of therapy and long-term safety of bisphosphonate therapy require further investigation. In addition, attention should be given to long-term fracture reduction and improvement in quality of life indicators.

Links

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Authors+Show Affiliations

Dwan K
Cochrane Central Executive, St Albans House, 57-59 Haymarket, London, England, UK, SW1Y 4QX.
Phillipi CA
No affiliation info available
Steiner RD
No affiliation info available
Basel D
No affiliation info available

MeSH

Administration, OralBone DensityBone Density Conservation AgentsDiphosphonatesFractures, BoneHumansInjections, IntravenousOsteogenesis ImperfectaRandomized Controlled Trials as Topic

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Review
Systematic Review

Language

eng

PubMed ID

27760454

Citation

Dwan, Kerry, et al. "Bisphosphonate Therapy for Osteogenesis Imperfecta." The Cochrane Database of Systematic Reviews, vol. 10, no. 10, 2016, p. CD005088.
Dwan K, Phillipi CA, Steiner RD, et al. Bisphosphonate therapy for osteogenesis imperfecta. Cochrane Database Syst Rev. 2016;10(10):CD005088.
Dwan, K., Phillipi, C. A., Steiner, R. D., & Basel, D. (2016). Bisphosphonate therapy for osteogenesis imperfecta. The Cochrane Database of Systematic Reviews, 10(10), CD005088.
Dwan K, et al. Bisphosphonate Therapy for Osteogenesis Imperfecta. Cochrane Database Syst Rev. 2016 Oct 19;10(10):CD005088. PubMed PMID: 27760454.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Bisphosphonate therapy for osteogenesis imperfecta. AU - Dwan,Kerry, AU - Phillipi,Carrie A, AU - Steiner,Robert D, AU - Basel,Donald, Y1 - 2016/10/19/ PY - 2016/11/2/pubmed PY - 2016/12/15/medline PY - 2016/11/2/entrez SP - CD005088 EP - CD005088 JF - The Cochrane database of systematic reviews JO - Cochrane Database Syst Rev VL - 10 IS - 10 N2 - BACKGROUND: Osteogenesis imperfecta is caused by a genetic defect resulting in an abnormal type I collagen bone matrix which typically results in multiple fractures with little or no trauma. Bisphosphonates are used in an attempt to increase bone mineral density and reduce these fractures in people with osteogenesis imperfecta. This is an update of a previously published Cochrane Review. OBJECTIVES: To assess the effectiveness and safety of bisphosphonates in increasing bone mineral density, reducing fractures and improving clinical function in people with osteogenesis imperfecta. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Inborn Errors of Metabolism Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of journals and conference proceedings. We additionally searched PubMed and major conference proceedings.Date of the most recent search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Register: 28 April 2016. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing bisphosphonates to placebo, no treatment, or comparator interventions in all types of osteogenesis imperfecta. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed the risk of bias of the included trials. MAIN RESULTS: Fourteen trials (819 participants) were included. Overall, the trials were mainly at a low risk of bias, although selective reporting was an issue in several of the trials. Data for oral bisphosphonates versus placebo could not be aggregated; a statistically significant difference favouring oral bisphosphonates in fracture risk reduction and number of fractures was noted in two trials. No differences were reported in the remaining three trials which commented on fracture incidence. Five trials reported data for spine bone mineral density; all found statistically significant increased lumbar spine density z scores for at least one time point studied. For intravenous bisphosphonates versus placebo, aggregated data from two trials showed no statistically significant difference for the number of participants with at least one fracture, risk ratio 0.56 (95% confidence interval 0.30 to 1.06). In the remaining trial no statistically significant difference was noted in fracture incidence. For spine bone mineral density, no statistically significant difference was noted in the aggregated data from two trials, mean difference 9.96 (95% confidence interval -2.51 to 22.43). In the remaining trial a statistically significant difference in mean per cent change in spine bone mineral density z score favoured intravenous bisphosphonates at six and 12 months. Data describing growth, bone pain, and functional outcomes after oral or intravenous bisphosphonate therapy, or both, as compared to placebo were incomplete among all studies, but do not show consistent improvements in these outcomes. Two studies compared different doses of bisphosphonates. No differences were found between doses when bone mineral density, fractures, and height or length z score were assessed. One trial compared oral versus intravenous bisphosphonates and found no differences in primary outcomes. Two studies compared the intravenous bisphosphonates zoledronic acid and pamidronate. There were no significant differences in primary outcome. However, the studies were at odds as to the relative benefit of zoledronic acid over pamidronate for lumbosacral bone mineral density at 12 months. AUTHORS' CONCLUSIONS: Bisphophonates are commonly prescribed to individuals with osteogenesis imperfecta. Current evidence, albeit limited, demonstrates oral or intravenous bisphosphonates increase bone mineral density in children and adults with this condition. These were not shown to be different in their ability to increase bone mineral density. It is unclear whether oral or intravenous bisphosphonate treatment consistently decreases fractures, though multiple studies report this independently and no studies report an increased fracture rate with treatment. The studies included here do not show bisphosphonates conclusively improve clinical status (reduce pain; improve growth and functional mobility) in people with osteogenesis imperfecta. Given their current widespread and expected continued use, the optimal method, duration of therapy and long-term safety of bisphosphonate therapy require further investigation. In addition, attention should be given to long-term fracture reduction and improvement in quality of life indicators. SN - 1469-493X UR - https://www.unboundmedicine.com/medline/citation/27760454/Bisphosphonate_therapy_for_osteogenesis_imperfecta_ DB - PRIME DP - Unbound Medicine ER -