The Fracture Intervention Trial was designed to study the effects of alendronate in increasing bone density and reducing the risk of vertebral fracture in women with low bone mineral density. The trial studied two groups of women: the first group had had vertebral fractures; the second had not. In this part of the study, Cummings and associates evaluated the effectiveness of four years of treatment with alendronate in reducing the risk of clinical fractures in postmenopausal women with osteoporosis but no history of vertebral fractures.
Patients were included if their femoral neck bone mineral density was 0.68 g per cm2 or approximately two standard deviations below the mean for normal young white women. Exclusion criteria included a recent history of severe hypertension, myocardial infarction, peptic ulcer, dyspepsia, significant renal or hepatic dysfunction, or a recent history of taking estrogen, calcitonin, bisphosphonates or fluoride. However, about 10 percent of the women in this study took estrogen at some point during the study period.
Patients were randomized to receive either placebo or alendronate, with an initial dosage of 5 mg daily, increasing to 10 mg daily during the second year. Height and total body bone mineral density were measured at baseline and at the end of the study. Follow-up visits were conducted twice yearly, at which time patients reported any instance of clinical fracture confirmed by a physician and any adverse health events that may have occurred. Pathologic fractures and fractures related to trauma were not included.
A total of 4,432 women were included in this part of the study, with 2,214 in the alen-dronate group and 2,218 in the control group. Follow-up was an average of 4.2 years and, at the end of the study period, more than 80 percent of women in each group were still taking their assigned medication. Patients in the alendronate group experienced increases in bone mineral density at multiple sites and had a lower incidence of clinical fractures than patients in the control group. The risk of clinical fractures was related to patients' initial femoral neck bone mineral density, with the greatest benefit of treatment occurring in patients whose initial bone mineral density was lowest. Specifically, women whose initial femoral neck bone mineral density was at least two standard deviations below the mean had a 22 percent lower risk of clinical fracture. In patients with higher BMDs, treatment did not reduce the risk of clinical fracture. The incidence of adverse health effects was not significantly different between groups.
The authors conclude that a four-year course of alendronate decreases the risk of clinical fracture in women with previously low bone mineral density and no vertebral fractures. They note, however, that it is not clear how long the course of alendronate should be continued.
In a related editorial, Heaney discusses some of the difficulties inherent in studying the complexities of osteoporosis and fracture prevention. The most important of these may be the inability to identify, given two patients with identical bone mineral densities, which patient is more likely to sustain a fracture. Fragility appears to be governed by more than just low bone mass, but bone mass is frequently studied, since it is a parameter that can be changed with physician intervention. At present, treatment with bisphosphonates seems to be reasonable in women with a bone mineral density of more than 2.5 standard deviations below the mean, a history of any fracture after age 40, corticosteroid therapy, impending prolonged immobilization or a maternal history of hip fracture. In women at lower risk, other options include estrogen receptor modulators, hormone replacement therapy, and calcium and vitamin D. All women at risk should be encouraged to participate in weight-bearing exercise and to take at least 1,500 mg of calcium and at least 600 IU (up to 1,000 IU) of vitamin D daily.
editor's note: The National Osteoporosis Foundation has recently issued guidelines calling for osteoporosis screening in all white women over age 65 years. In addition, the foundation recommends bone mineral density testing about every two years in women taking estrogen replacement therapy. The American Academy of Family Physicians does not currently recommend screening with bone mineral density tests but does urge counseling at-risk patients about methods to maintain bone mass. Risk factors for fracture include a history of fracture after 40 years of age; a history of parental fracture after 50 years of age; advanced age; white race; female sex; dementia; frailty; cigarette smoking; weight of less than 57 kg (125 lb); estrogen deficiency; history of low calcium intake; alcoholism; history of recurrent falls; and inactivity. g.b.h.