LOS ANGELES, California—Patients receiving once-weekly risedronate (Actonel®, Proctor & Gamble/sanofi-aventis) have lower rates of hip and nonvertebral fractures during their first year of therapy than their counterparts who receive once-weekly alendronate (Fosamax®, Merck & Co, Inc), according to a head-to-head observational trial in Osteoporosis International.¹ The differences in fracture reduction could be related to the structure, potency, or binding properties of these agents.

"It appears patients receiving risedronate are better protected from hip and nonvertebral fractures during their first year of therapy than patients receiving alendronate," conclude researchers led by Stuart L. Silverman, MD, FACP, FACR, with the Cedars-Sinai Medical Center and David Geffen School of Medicine at the University of California Los Angeles.

Battle of the bisphosphonates

The RisedronatE and ALendronate (REAL) cohort study used records of health service utilization from July 2002 through September 2004. The researchers compared fracture rates among 12,215 women aged 65 and over receiving risedronate with fracture rates among 21,615 woman taking alendronate.

In sum, there were 507 nonvertebral fractures and 109 hip fractures. At the end of the first year, the incidence of nonvertebral fractures in the risedronate cohort was 18% lower than in the alendronate cohort, and the incidence of hip fractures in the risedronate cohort was 43% lower than in the alendronate cohort, the study showed.

By 1 year, 2% of women taking risedronate developed nonspinal fractures, compared with 2.3% of their counterparts taking alendronate. Moreover, 0.4% of women taking risedronate sustained a hip fracture, compared with 0.6% of women taking alendronate.

The differences between the two groups were seen at both 6 and 12 months after the therapy was initiated. The baseline fracture risks between the two cohorts were likely similar as evidenced by their "near unity" in fracture incidence during the first 3 months of therapy.

Numbers are "impressive"

"This is an observational study based on health service utilization records and is not a study that controlled for risk factors; however, the numbers are quite impressive," Stephen Honig, MD, director of the osteoporosis center at New York University Hospital for Joint Diseases, in New York City told CIAOMed. "There was no placebo group because it was not that type of study, so we do not know what the background incidence of fractures for this population was. There was no bone density data either, but one could assume that the indications for treatment were the same for both drugs."
Perhaps the structure of the drugs is responsible for the differences in fracture rates, Dr. Honig noted. "Risedronate has a ring structure to its R2 group, and this makes it a more potent inhibitor of the mevalonate pathway than alendronate, which has an alkyl chain as its R2 group; [therefore] alendronate binds to bone more avidly than does risedronate." He concluded, "risedronate may have better nonvertebral fracture inhibition than alendronate and may be more effective as early as 6 months after starting it."

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Reference

1. Silverman SL, Watts NB, Delmas PD, et al. Effectiveness of bisphosphonates on nonvertebral and hip fractures in the first year of therapy: The risedronate and alendronate (REAL) cohort study. Osteoporos Int. 2007;18:25-34.