Alendronate vs Risedronate
Abstract & Commentary
Leon Speroff, MD, Professor of Obstetrics and Gynecology, Oregon Health Sciences University, Portland, is Editor for OB/Gyn Clinical Alert
Synopsis: Alendronate increased bone density and reduced biochemical markers of bone turnover slightly greater than risedronate, both given once weekly.
Source: Rosen CJ, et al. J Bone Miner Res. 2005;20:141-151.
Rosen and colleagues reported the results of a 1-year, multicenter, randomized, clinical trial comparing the once-a-week administration of alendronate and risedronate to postmenopausal women with osteoporosis (the FACT study-Fosamax Actonel Comparison Trial). The 1053 women were treated with either 70 mg alendronate or 35 mg risedronate weekly, taken with a full glass of water after fasting, and in the upright position after awakening in the morning. Alendronate increased the bone density in the hip trochanter an average of 1.3% greater than risedronate at 6 months and 1.4% greater after one year. A similar result was observed in total hip bone measurements. In the lumbar spine, a difference favoring alendronate amounted to an average difference of 0.7%. Significantly fewer alendronate patients experienced a loss of bone, an average 6.3% difference in the hip trochanter and 2.8% in the spine. These findings were supported by changes in biochemical markers of bone turnover, ie, a greater reduction in bone turnover in alendronate patients. Upper gastrointestinal adverse events occurred in 22.5% of alendronate patients and 20.1% of risedronate patients, not a significant difference.
Comment by Leon Speroff, MD
It is rare to see a head-to-head comparison of competing drugs. The financial support for this trial was not specified, but it can be deduced to be Merck & Co., because 4 coauthors work for Merck. I hope the study would have been published even if the results had been reversed.
The key issue is whether this difference actually makes a difference! Do these differences in bone density and biochemical markers translate into a meaningful clinical difference in fractures? Bone people regularly argue over the extent to which changes in bone density and biochemical markers influence the risk of fractures. For example, there is even a report that patients who lose bone density during antiresorptive therapy still have some reduction in fracture risk.1 And in this study, the differences, while statistically significant, were not large. Furthermore, do we know for sure that the 2 different doses of these bisphosphonates represent equivalent therapy? The only way to answer these questions is to perform a fracture study, but the huge numbers of participants required to provide a reliable measure make it impossible.
The most important contribution of this report may be the similar incidence of gastrointestinal side effects with the 2 drugs. Risedronate is touted by its pharmaceutical company for having fewer side effects, but the results indicate no difference, including upper gastrointestinal problems.
The bisphosphonates bind to bone and remain in place for great lengths of time. With bone remodeling, the bound drug is released and used again. Over a long length of time, continued administration is in effect producing a high-dose situation. There remains concern that long-term treatment may produce excessive suppression of turnover. For these reasons, the use of bisphosphonates for young postmenopausal women is actively discouraged. Bisphosphonates are best reserved for the treatment of older postmenopausal women at high risk of fractures. Let me say this in a different way: Hormone therapy is a preferable option for younger postmenopausal women, and it is the only antiresorptive treatment demonstrated in a clinical trial to reduce fractures in women without osteoporosis.
Reference
- Cummings SR, et al. Am J Med. 2002;112:281-289.
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