Effects of Risedronate and Low-Dose Transdermal Testosterone on Bone Mineral Density in Women With Anorexia Nervosa: A Randomized, Placebo-Controlled Study

Chronic starvation in women with anorexia nervosa is associated with serious medical complications, including severe bone loss in nearly 50% of affected adult women. Bone loss in women with anorexia nervosa affects the spine preferentially, with both increased bone resorption and decreased formation. Estrogen/progestin therapy is ineffective in preventing or reversing bone loss in this population; there are no effective approved therapies for low bone mass in these women. A large number of studies have demonstrated that oral bisphosphonates are highly effective antiresorptive therapy, resulting in significant increases in bone mineral density (BMD) and reductions in risk of fractures in postmenopausal women. Whether bisphosphonates would be effective to prevent or reverse the bone loss associated with severe malnutrition in women with anorexia nervosa is unclear. No randomized, placebo-controlled studies investigating the use of oral bisphosphonates in adults with this disease have been published.This double-blind, randomized, placebo-controlled trial was designed to determine whether 12 months of treatment with the bisphosphonate, risedronate, alone or combined with low-dose transdermal testosterone would increase BMD in ambulatory women with anorexia nervosa. The study subjects were 77 women with the disorder who had been recruited or referred to a clinical research center. Women in 4 groups were randomized to receive 1 year of treatment with either risedronate 35-mg weekly plus a placebo patch (group 1), testosterone 150-pg daily patch plus a weekly placebo pill (group 2), risedronate 35-mg weekly plus testosterone 150-pg daily (group 3), or double placebo (group 4). The primary study end point (BMD at the spine) and secondary measures (BMD at the hip and radius, and body composition) were measured by dual-energy x-ray absorptiometry.In women with anorexia nervosa, risedronate increased posteroanterior spine BMD 3.2% (P < 0.0001), lateral spine BMD 3.8% (P = 0.0002), and hip BMD 1.9% (P = 0.013) compared with placebo. Testosterone administration had no significant effect on BMD at any site but increased lean body mass 1.9% compared with placebo (P = 0.037). Side-effects in all 4 groups were minimal and comparable.These findings demonstrate that a 1-year course of the bisphosphonate, risedronate, has a positive effect on spinal BMD, the main site of bone loss in females with anorexia nervosa. The data also show that low-dose testosterone does not improve