Fosamax, a new drug from Merck available in the U.S.A., not only prevents bone loss in osteoporosis but can also increase bone mass. This is good news for the more than one in three women over the age of 50 years who suffer osteoporotic fractures. An editorial in the New England Journal of Medicine comments that drugs such as Fosamax "should have a major effect on a disease [osteoporosis] that may reach epidemic proportions during the next several decades."
Significant effects on bone mass Fosamax (alendronate sodium) was approved in September 1995 by the U.S. Food and Drug Administration for prescription in 10-mg o.d. doses for postmenopausal women with osteoporosis. Approval was based in part on two three-year trials involving 994 postmenopausal women in 16 countries. These trials showed that, after three years, subjects taking Fosamax had the following advantages over those on placebo:
* Lumbar spine bone mineral density (the primary endpoint) was approximately 10% greater than in the placebo arm.
* Bone mineral density at the hip (a secondary endpoint) increased 7.2% over that in patients taking placebos.
* Total body bone mineral density (another secondary endpoint) significantly increased. This suggests that gains in bone mineral density at the spine and the hip were not due to loss of bone mineral density elsewhere in the skeleton.
Reduced incidence of fractures The two studies were not designed to detect the effect of Fosamax on the incidence of fracture; however, fracture-related endpoints were assessed in a predefined analysis of supporting parameters (including stature, spinal fracture, and spinal deformity) from data pooled across all doses in the studies. The data do not permit assessment of the effects of individual dosages on fracture incidence, but the investigators did say that "increases in the bone mineral density of the spine, hip, and total body in women with postmenopausal osteoporosis were associated with reductions in the incidence of vertebral fractures, vertebral deformities, and loss of height, as well as a trend toward a reduction in the incidence of fractures at nonvertebral sites."
Treatment with Fosamax reduced the proportion of women who suffered new spinal fractures by 48% over those taking placebos. It also led to a 63% reduction in the total number of new spinal fractures.
Over the course of the trials, women taking Fosamax lost an average of 3 mm in height. Women on placebo lost 4.6 mm on average. Thus treatment produced a 35% reduction in overall height loss.
Good tolerability
In the trials, Fosamax proved to be well tolerated. Subjects reported occasional mild side effects that generally did not cause them to stop treatment. Adverse experiences caused 6% of subjects taking placebo (24 of 397) to discontinue treatment, but they caused only 4.1% of those taking Fosamax 10 mg (8 of 196) to drop out of the trials.
The most common drug-related side effects were abdominal and musculoskeletal pain. Gastrointestinal problems such as nausea, gastroesophageal reflux, and esophagitis were less frequently reported.
No dosage adjustment necessary
Fosamax is currently available in the U.S. in 10-mg tablets to be taken once a day. It is contraindicated for patients with low levels of calcium in their blood or who are pregnant or nursing. It should be used with caution by patients with active problems of the upper gastrointestinal tract.
Fosamax is also contraindicated for patients with severe renal disease, but those with mild-to-moderate renal insufficiency (e.g., creatinine clearance 35-60 mL/min.) can take it with no dosage adjustment. In addition, no dosage adjustment is necessary for patients with hepatic insufficiency or for the elderly.
The safety of long-term treatment (i.e., more than four years) is now under study.
