Bisphosponates are the only medications currently available that have been demonstrated in large randomized trials to reduce the risk of hip fracture. Unfortunately, bisphosphonates have low oral bioavailability and can cause esophageal inflammation or ulceration, restricting maximal dosage. These characteristics necessitate frequent administration on an empty stomach, which may limit patient compliance.
Thus, it was with great excitement that researchers released the results of a one-year, randomized, double-blind, placebo-controlled trial on five different regimens of zoledronic acid, a potent bisphosphonate. Participants received placebo or intravenous zoledronate in doses of 0.25 mg, 0.5 mg or 1 mg, at three-month intervals. In addition, one group received a total annual dose of 4 mg as a single dose, and another received two doses of 2 mg each, six months apart. The primary endpoint of the study was lumbar-spine bone mineral density.
Interestingly, all five drug treatment schedules had about the same results, and all were better than placebo. Bone mineral density in the spine was 4.3 to 5.1% higher in all treatment groups than in the placebo group (p<0.001) and values for the femoral neck were 3.1 to 3.5% higher than placebo (p<0.001). In addition, biochemical markers of bone resorption were significantly suppressed throughout the study in all zoledronic acid groups, despite the fact that by 24 hours after administration, drug levels were less than 1% of the post-administration peak and 40% of the dose has been excreted in the urine.
The drug was generally well tolerated, and rate of retention of subjects was high. However, studies that demonstrate an effect on the rate of fractures are needed before any recommendations can be made.
Over a million people in Canada are affected by Osteoporosis, a syndrome that leaves them at higher risk of fracture, disability and even premature death.
Source
- Reid IR, Brown JP, Burckhardt P et al. Intravenous zoledronic acid in postmenopausal women with low bone mineral density. NEJM. 2002;346:653-61.
