DENTON, Tex. – Data from a 2-year trial comparing the once-weekly bisphosphonates alendronate (Fosamax®) and risedronate (Actonel®) show that alendronate produced greater increases in bone mineral density (BMD), was more effective at reducing bone turnover, and significantly reduced the number of patients at risk for significant bone loss, researchers from the FOSAMAX ACTONEL Comparison Trial (FACT) report in the Journal of Clinical Endocrinology and Metabolism.¹

Lead author Sydney Bonnick, MD, of the Clinical Research Center of North Texas in Denton, Texas, writes, "Patients receiving once-weekly alendronate 70 mg had greater gains in BMD, were more likely to maintain or gain BMD, and had greater reductions in bone turnover markers than patients receiving once-weekly risedronate 35 mg after 24 months, with no differences in upper gastrointestinal tolerability."

The study, which was funded by Merck & Co, was a 1-year extension of the FACT trial and included 833 postmenopausal women with low BMD who continued their original treatment assignment to either alendronate or risedronate for a second year of treatment following completion of the original FACT trial. The primary endpoints were changes in BMD at the hip trochanter, total hip, femoral neck, and lumbar spine, and changes in markers of bone turnover at 24 months.

The 24-month assessment found that increases from baseline BMD "were significantly (P <.001) greater in alendronate patients than in risedronate patients at all sites measured: the trochanter, total hip, femoral neck, and lumbar spine." The treatment difference favoring alendronate at each of these sites increased with time.

The treatment differences were:

• 2.1% at the trochanter

• 1.7% at the total hip

• 1.9% at the femoral neck

• 1.8% at the lumbar spine

"Alendronate-treated patients were 1.4 to 1.7 times more likely than risedronate-treated patients to show a gain of 3% or more in BMD," Dr. Bonnick reports. Conversely, risedronate-treated patients were two to four times more likely to show a BMD decrease of 3% or more, depending on the site.

These differences appear to reflect variations in the underlying processes of bone resorption and formation. The investigators assessed bone turnover using urinary N-telopeptide of typed 1 human collagen (NTX) corrected for creatinine and serum C-telopeptide (CTX) as markers of bone resorption. They measured bone-specific alkaline phosphatase (BSAP) and serum N-terminal propeptide of type 1 procollagen (P1NP) as markers of bone formation.

"The differences [in bone turnover markers] between the two treatment groups were significant by as early as 3 months and were maintained at 24 months (P <.001)," the authors write.

Fractures were not an efficacy endpoint and were not radiographically confirmed but were reported by investigators as adverse events. Over the 2-year period there were 37 fractures in 34 alendronate-treated patients and 42 fractures in 34 risedronate-treated patients (P = NS).

"The most important points for clinicians are the major findings: over 2 years there were greater gains in BMD at all four skeletal sites and greater suppression in bone turnover using all four markers with alendronate compared to risedronate, with equal safety and tolerability. In addition, while a small percentage of women in both groups lost BMD, a statistically greater percentage of women lost BMD taking risedronate compared to alendronate," Dr. Bonnick told CIAOMed. "This latter point is important because studies of both drugs individually have shown that spine fracture risk reduction is significantly greater if you gain BMD while taking alendronate or risedronate than if you lose it."

Reference

1. Bonnick S, Saag KG, Kiel DP, et al. Comparison of weekly treatment of postmenopausal osteoporosis with alendronate versus risedronate over two years. J Clin Endocrin Metab. 24 April 2006; [Epub ahead of print]. doi:10.210/jc.2005-2602.