Commentary

The risk for a future osteoporotic fracture is independently increased by low BMD and a history of such fractures.¹ In the study by Orwoll et al, although 7% of the placebo group sustained a new vertebral fracture within 2 years, the alendronate group enjoyed almost universal protection from this complication despite a substantial deficit of bone and a 50% prevalence of vertebral fractures before treatment. This result is impressive and clinically significant. A larger and longer study would probably show that alendronate also prevents fractures at the hip and other non-vertebral sites in men at greatest risk, as it does in women.²

Although osteoporotic fractures are less common in men than in women, they are an important cause of death and disability. Whereas almost all women with osteoporosis are postmenopausal, most men with the disease are eugonadal and therefore lose bone for reasons unrelated to testosterone and estradiol. To address the possibility that variable pathogenesis might lead to variable therapeutic outcomes, Orwoll et al stratified patients according to free testosterone levels before assigning treatment. The results conclusively show that gonadal status did not influence the effect of alendronate on BMD. Although this important finding means that the drug is broadly applicable to men with osteoporosis, it also provokes new questions: do bisphosphonate and hormone replacement therapies affect the skeleton equally in hypogonadal men? Would the 2 measures increase BMD more in combination than individually as they do in postmenopausal women?³

Clinicians rarely have the opportunity to prescribe a definitively studied remedy that consistently, significantly, and safely alters the course of a common and morbid condition. The work of Orwoll et al shows that alendronate does precisely that in men with osteoporosis.