By 50 years of age, a postmenopausal white woman has at least a 40 percent chance of having an osteoporotic fracture during the remainder of her life. In each age group, the fracture risk for osteoporotic women is four times that of women without osteoporosis. Rigid dosing requirements have been implicated in the relatively low participation in therapies to prevent osteoporosis, even among high-risk women. Bisphosphonate therapy has a complex regimen that can be inconvenient for many women. Patients must take the tablet while fasting and then remain upright and avoid food or other medication for at least 30 minutes to minimize esophageal irritation. Luckey and colleagues studied the efficacy and safety of alendronate in a once-weekly dosage of 35 mg.

Healthy postmenopausal women 40 to 70 years of age with no evidence of osteoporosis on bone density scans and radiography were recruited at 43 centers in seven countries. Exclusion criteria were the presence of upper gastrointestinal bleeding or significant disease, including ulceration and uncontrolled dyspepsia; renal, hepatic, cardiac, or bone disease; and the use of estrogens, steroids, or anti-osteoporotic medications. After baseline screening, 362 women were randomized to receive alendronate in a dosage of 35 mg weekly plus placebo tablets on other days. The remaining 361 women took alendronate in a dosage of 5 mg daily. All participants received the same instructions for taking medications, and all received 500 mg of calcium plus 250 mg of vitamin D daily.

Participants were followed at one, three, six, and 12 months by clinical interview and examination, plus laboratory assessment, including markers of bone turnover. Bone mineral density in the lumbar spine and hip was assessed at baseline and at the end of the study. Any clinical report suggesting fracture was radiologically investigated. All radiographs and bone scans were interpreted by staff who were unaware of treatment allocation.

The two groups were comparable at the beginning of the study. Women in both groups showed significant gains in bone density during treatment (see accompanying table), with no significant differences. The groups also were similar in biochemical markers of bone turnover. No serious adverse effects were reported, but about 25 percent of women in each group had gastrointestinal events. The rates of discontinuation from adverse effects were 9.4 percent in women on daily therapy and 5.2 percent in those on weekly treatment. No vertebral fractures or cases of esophagitis occurred during the study.

The authors conclude that alendronate in a dosage of 35 mg once per week provides comparable efficacy to daily treatment with 5 mg for osteoporosis. The weekly treatment was well tolerated and associated with somewhat fewer adverse effects and greater convenience.