Secondary Osteoporosis: The Potential Relevance of Leptin and Low Body Weight

• Osteoporosis
• Leptin
• Body weight
• Bone density
• Weight loss

The diagnosis and treatment of osteoporosis have advanced greatly in the past 20 years. We now have effective (albeit imperfect) drugs, such as bisphosphonates, estrogen, and selective estrogen-receptor modulators, that substantially reduce fracture rates. Selective estrogen-receptor modulators may provide other benefits, such as alleviation of breast cancer risk. Because the techniques for assessment of bone mass and subsequent prediction of risk for fracture have improved, it is easier to make treatment decisions and to diagnose osteoporosis before fractures occur. This improvement in management is likely to continue during the next decade. By then, anabolic agents will be available to stimulate bone formation, and new diagnostic markers will allow clinicians to monitor treatment more effectively.

However, our knowledge of the pathophysiology of osteoporosis has not developed at the same rate. Despite better understanding of cell–cell interactions and identification of critical, locally active hormones in the bone microenvironment that influence bone remodeling (1), we still understand little of the essential disruption in the bone remodeling process that is responsible for the bone deficiency clinically recognized as osteoporosis. Since our knowledge of pathophysiology is limited, we currently classify cases of osteoporosis as “primary” or “secondary” on the basis of largely unexplained clinical associations. These classifications are of particular relevance to the underlying forms of bone loss described in two reports in this issue, which discuss the association of osteopenia and osteoporosis with other recognizable entities (so-called “secondary osteoporosis”). Grinspoon and colleagues (2) conducted a survey of bone mineral density at different bone sites in a large number of women with anorexia nervosa, and Bernstein and coworkers (3) showed that risk for fracture in patients with inflammatory bowel disease was increased …