Effects of Risedronate and Low-Dose Testosterone Replacement Skin Patch on Bone Density in Anorexia Nervosa

Dr. David Herzog was the first Endowed Professor of Psychiatry in the Field of Eating Disorders at Harvard Medical School.  For over 25 years, he has collaborated with the Neuroendocrine Unit at Massachusetts General Hospital to learn more about the biology of anorexia nervosa and interventions that affect the course of the illness.  Several studies test treatments for complications such as severe bone loss, which occurs in nearly half of adult women with anorexia nervosa, increasing their risk for fractures and permanent disability.

Bone loss in adults with anorexia nervosa is characterized by both increased bone resorption (breakdown) and decreased formation. Risedronate is a biphosphonate, a class of drugs that slows bone resorption and has been shown to be effective in the treatment of osteoporosis in postmenopausal women.

Although some people think of testosterone as existing only in men, small amounts of this hormone are also produced by women, mostly in the ovaries. One of testosterone’s roles is to stimulate bone formation. Testosterone levels are low in women with anorexia nervosa (as compared to normal controls) and this deficiency is associated with abnormal bone density.

Dr. Herzog and his team in the Neuroendocrine Unit conducted a one-year study to determine whether therapy with risedronate alone or in combination with a low-dose testosterone replacement skin patch would increase bone density in women with anorexia nervosa.  77 ambulatory women with anorexia nervosa were randomly assigned to receive one of four treatments: 1) risedronate 35 mg. weekly plus a placebo (inert) patch, 2) a daily low-dose testosterone replacement skin patch plus a weekly placebo pill, 3) risedronate 35 mg. weekly plus the daily testosterone patch, or 4) double placebo. All participants had dual energy x-ray absorptiometry (DXA) to measure their bone density and blood tests to determine their hormone levels.

The study demonstrated that risedronate administration increased spinal bone density, the primary site of bone loss in women with anorexia nervosa.  Low-dose testosterone did not change bone density but increased lean body mass.  This is an important finding given the lack of effectiveness of other agents, including estrogen, to prevent or reverse bone loss in adults with anorexia nervosa.  Additional studies are needed to optimize treatment for the severe bone loss experienced in this population at increased risk for fracture.