SAN DIEGO — Postmenopausal women with low bone density who received once-weekly alendronate 70 mg had significantly greater increases in bone mineral density and reductions in markers of bone turnover over a 2-year period, compared with those who received once-weekly risedronate 35 mg, results from a randomized, double-blind trial demonstrated.
In addition, there were no differences between the two treatment groups in terms of upper-gastrointestinal adverse events or overall safety and tolerability, Dr. Anne E. de Papp reported during a poster session at the annual meeting of the International Society for Clinical Densitometry.
“There has always been a perception that risedronate is better tolerated,” Dr. de Papp, senior medical director of clinical development for Merck & Co., said in an interview. “This is nice evidence that at least in a clinical trial setting, there is no difference [between risedronate and alendronate] in upper GI tolerability.”
However, she quickly cautioned that this head-to-head study only compared surrogate end points for bone fracture risk, not the actual rate of clinical fractures. “To do a head-to-head fracture trial between two agents that are active therapies for osteoporosis would require huge numbers of patients for many years,” she said. “I think when you're comparing two drugs that work by the same mechanism of action, it's reasonable to compare them using surrogate markers of efficacy.
“We saw greater gains in BMD and greater reductions in [markers of] bone turnover [with alendronate treatment], but the contention is, what does that mean in terms of fracture outcomes? We don't know, but … there is evidence to support that drugs causing greater gains in BMD and greater reductions in bone turnover are associated with greater fracture reduction.”
In the study, led by Dr. Sydney Bonnick of the Denton, Tex.-based Clinical Research Center of North Texas, researchers performed a 1-year extension of the original 1-year, randomized, double-blind Fosamax Actonel Comparison Trial (J. Bone Miner. Res. 2005;20:141–51).
Of the 833 patients, 419 received once-weekly risedronate 35 mg and 414 received once-weekly alendronate 70 mg. Their mean age was 64 years, and all had low bone density. This was defined as greater than or equal to 2.0 standard deviations below young normal mean bone mass in at least one of four sites: total hip, hip trochanter, femoral neck, or lumbar spine (L1-L4).
All patients underwent a DXA and lab analyses of biochemical markers at baseline and at 2 years.
Patients in the alendronate group had significantly greater increases in bone mineral density at 2 years, compared with their counterparts in the risedronate group at the following sites: hip trochanter (4.6% vs. 2.5%), total hip (3.0% vs. 1.3%), femoral neck (2.8% vs. 1.0%), and lumbar spine (5.2% vs. 3.4%).
Significantly greater reductions of serum bone-specific alkaline phosphatase and other bone markers were seen in the alendronate group, compared with the risedronate group.
Merck & Co. funded the study.
There is no difference between risedronate and alendronate in upper GI tolerability. DR. DE PAPP
