Background: Osteogenesis imperfecta is a rare metabolic disorder associated with reduced
mineralization of bone and corresponds to increased fracture risk. We carried out the present
network meta-analysis comparing all the medical interventions for osteogenesis imperfecta.
Method: Electronic databases were searched for randomized controlled clinical trials evaluating the
use of drugs in patients with osteogenesis imperfecta. Percent change in BMD was the primary and
fracture risk reduction and adverse events were the secondary outcome measures. The weighted
mean difference was the pooled estimate for primary outcome and odds ratio with 95% confidence
interval for the secondary outcome measures. Direct and mixed treatment comparisons between the
interventions were carried out by inverse heterogeneity model. Sub-group analyses were carried out
on children, adults and within bisphosphonate groups. The trial sequential analysis was carried out
for the comparison of oral bisphosphonates with placebo.
Results: A total of 16 studies were included evaluating oral and intravenous bisphosphonates, teriparatide,
anti-sclerostin antibody, high dose vitamin D and recombinant growth hormone (rGH)
combined with intravenous bisphosphonates. Oral bisphosphonates and teriparatide were observed
with a statistically significant increase in BMD compared to placebo. Also, only oral bisphosphonates
were associated with significant reduction in the fracture risk but when the alpha error was
adjusted for the information accrued till date as well as when the results of a trial were excluded, no
significant difference was observed. Either low or very low quality was observed for pooled estimates
of the key comparisons.
Conclusion: Oral bisphosphonates and teriparatide significantly increase BMD but are not associated
with fracture risk reduction. Of the available interventions, oral bisphosphonates could perform
better than others in osteogenesis imperfecta. This evidence should be considered preliminary and
may change with future head-to-head clinical trials.