Mechanistic Insights into Osteoporosis in Patients with Lipodystrophy and Review of the Literature

Objective: To demonstrate the underlying pathogenesis of osteoporosis occurring in patients with lipodystrophy. Methods: MEDLINE was searched using the following key terms: lipodystrophy, osteoporosis, and reduced bone mineral density. Manual searching identified additional studies from the bibliographies of reports and reviews obtained in the MEDLINE search. Results: Lipodystrophy is a very rare disease characterized by pathologic alterations in the distribution of adipose tissues in association with a diverse range of metabolic derangements such as hypertriglyceridemia, insulin resistance, diabetes, and abnormal bone formation. Reduced bone mineral density has been assessed extensively in human immunodeficiency virus-infected patients with lipodystrophy, but far less is known in other lipodystrophy types. This is the first review to discuss the mechanisms of osteoporosis occurrence in various types of lipodystrophy. We herein focus on the cross-regulation of fat and bone and propose that marrow fat accumulation and reduced serum leptin and adiponectin levels may play important roles in the pathophysiologic process of osteoporosis in patients with lipodystrophy. Conclusion: Osteoporosis is an emerging threat to patients with lipodystrophy. When evaluating the clinical course of a patient with lipodystrophy, osteoporosis should also be considered. Abbreviations: BMD = bone mineral density; CGL = congenital generalized lipodystrophy; HIV = human immunodeficiency virus; MAT = marrow adipose tissue; OB-R = leptin receptor