Does alendronate treatment prevent vertebral fractures in men with osteoporosis?

BACKGROUND: Although osteoporosis is more common in women, approximately one fourth of all hip fractures occur in men. There are no approved therapies in the United States for men with osteoporosis. The drug alendronate, a potent bisphosphonate, has been shown to increase bone mineral density and reduce the incidence of major osteoporotic fractures in women.

POPULATION STUDIED: The men were recruited at osteoporosis clinics and at community assessments of bone mineral density across 20 centers in the United States and 10 other countries. Men could qualify for the study in 2 ways: (1) bone mineral density (BMD) at the femoral neck that was 2 standard deviations (SDs) below the mean value of normal young men and BMD at the lumbar spine 1 SD below the mean in normal young men, or (2) BMD at the femoral neck 1 SD below the mean in normal young men and at least one vertebral deformity or a history of osteoporotic fracture. All men with secondary causes of osteoporosis other than low serum-free testosterone concentrations were excluded. A total of 241 men with a mean age of 63 years (range=31-87 years) were enrolled in the study.

STUDY DESIGN AND VALIDITY: In this 2-year double-blind trial the men were randomized to either alendronate 10 mg or matching placebo. Subjects who were androgen deficient or androgen replete were stratified to ensure equal distribution between the 2 treatment groups. Calcium and vitamin D supplements were provided to all of the men. BMD, height, and fractures were measured at the follow-up visits. The 2 groups were similar in age, race, testosterone levels, smoking history, consumption of alcohol, body mass index, baseline BMD scores, and vertebral fractures. Most of the men were white, which may limit generalization of these results to other racial groups. The authors did not report the method of randomization or how allocation to treatment or control groups was concealed from the patients and their physicians. Radiologists were blinded to the treatment assignment, and analysis was appropriately by intention to treat.

OUTCOMES MEASURED: The main patient-oriented outcome was the incidence of vertebral fractures between the placebo and the alendronate groups. Disease-oriented outcomes included changes in BMD (lumbar spine, femoral neck, and total body) and vertebral height.

RESULTS: The incidence of vertebral fractures was 7.1% in the placebo group and 0.8% in the alendronate group (P=.02). There were 4 painful vertebral fractures in the placebo group and 1 in the alendronate group (P=.3), but the study was too small and too short to prove this outcome. Men in the placebo group lost 2.4 mm in stature compared with a nonsignificant change of 0.6 mm in the alendronate group (P=.02). In the alendronate group, BMD increased by a mean of 7.1%±0.3% at the lumbar spine, 2.5%±0.4% at the femoral neck, and 2.0%± 0.2% for the total body (P <.001). For the placebo group, the BMD increased by a mean of 1.8%±0.5% at the lumbar spine (P <.001). No significant changes in BMD at the femoral neck or total body were found for the placebo group. At each site the alendronate group had a significantly greater increase in BMD than the placebo group. These effects were independent of baseline serum-free testosterone concentrations.