A meta-analysis characterizing the dose-response relationships for three oral nitrogen-containing bisphosphonates in...

A meta-analysis of spine BMD dose-response relationships for alendronate, risedronate, and ibandronate was performed. Data from all three oral bisphosphonates conform to a log-linear relationship between dose and change in spine BMD relative to placebo at 1 year, with an incremental gain of about 1 % for each doubling of dose.

Animal data suggesting differences in potency and differences in approved oral dosage strengths for alendronate, risedronate, and ibandronate in the treatment of osteoporosis raise questions about their dose-response relationships and relative potencies in humans.

A meta-analysis of dose-response relationships for spine BMD increases for these three bisphosphonates was performed using data from 21 placebo-controlled trials that collectively included over 13,000 patients on active treatment and over 8,000 on placebo.

For alendronate over the range of 1 to 20 mg/day, there was a strong log-linear relationship between dose and the increase in spine BMD relative to placebo at 1 year (R (2) = 0.994 using sample-weighted means). For each doubling in alendronate dose, there was an incremental gain of about 1 % in spine BMD. On the same scale, risedronate and ibandronate are approximately equipotent to alendronate on a weight-for-weight basis. The increases in BMD efficacy with each doubling of dose are parallel for all three nitrogen-containing bisphosphonates (NCBPs).

All three NCBPs are approximately equipotent and exhibit a log-linear relationship between dose and the increase in spine BMD. Differences in efficacy between the available oral bisphosphonate regimens appear to be a function of dose rather than inherent differences in therapeutic potential.