In a head-to-head comparison of 2 bisphosphonate agents, alendronate resulted in significantly greater increases in bone mineral density (BMD) in osteoporosis patients than did risedronate. Alendronate also reduced markers of bone turnover to a significantly greater degree as compared to risedronate. The findings came from the Fosamax Actonel Comparison Trial (FACT), the first direct comparison of weekly-dosed formulations of the 2 bisphosphonate drugs.

The trial studied 1053 postmenopausal women with low BMD, defined by 2 or more standard deviations below the mean BMD for a reference population of young, healthy women. Participants, community-dwelling, ambulatory women who had been postmenopausal for at least 6 months, were randomized to alendronate 70 mg qw or risedronate 35 mg qw and followed for 12 months. The primary endpoint was the percent change from baseline to 12 months in hip trochanter BMD.

"The results show that alendronate does a better job than risedronate of improving bone mineral density," said Clifford Rosen, MD, of the Maine Center of Osteoporosis Research and Education and St. Joseph Hospital in Bangor, Maine, at the 26th annual meeting of the American Society of Bone Mineral Research in Seattle. "Alendronate also was more powerful in terms of reducing markers of bone turnover."

Although the study was not statistically powered to assess fracture rates, Dr. Rosen noted that "bone mineral density is the best surrogate marker we have for fracture risk."

After 12 months of follow up, hip trochanter BMD had increased 3.4% in the alendronate group and 2.1% in the risedronate group. The between-group difference was highly significant at 6 and 12 months (P <0.001). All other BMD measurements demonstrated significant advantages of alendronate.

Bone turnover markers decreased substantially from baseline in both groups of patients; however, with alendronate use, reductions were significantly greater and were evident within 3 months of follow-up (P <0.001). Urinary N-telopeptide of type-I collagen decreased by 53% with alendronate vs 40% with risedronate; serum C-telopeptide of type-I collagen decreased by 74% vs 55%; serum bone specific alkaline phosphatase decreased by 41% vs 28%; and serum procollagen-N-terminal peptide decreased by 64% and 48%.

Tolerability was comparable with no significant differences found between the 2 therapies. Also, the proportion of trial participants reporting any adverse event or serious adverse events did not differ between the 2 treatment groups. Specifically, upper gastrointestinal adverse events were reported by 22.5% of alendronate patients and 20.5% of the risedronate group. Discontinuation rates due to adverse events were 6.4% with alendronate and 6.5% with risedronate. Discontinuation due to upper gastrointestinal events occurred in 2.5% of the alendronate group and 3.0% of the risedronate patients.

"The tolerability data are one of the most interesting aspects of the study," said Dr. Rosen. "I think these results should put to rest the idea that one drug is better than another because it is more tolerable from a gastrointestinal perspective."

References:

Rosen C, Hochberg M, Bonnick S, et al. Alendronate produces greater gains in BMD and greater reduction in markers of bone turnover than risedronate with similar tolerability. J Bone Miner Metab. 2004;19(suppl 1):S94. Abstract F412.