title: Effect of subcutaneous leptin replacement therapy on bone metabolism in patients with generalized lipodystrophy.
abstract: The adipocyte-derived hormone leptin, which plays an important role in energy homeostasis, has been suggested to have an influence on bone development and remodeling. However, it is not clear from animal studies whether leptin is a stimulator or an inhibitor of bone growth. Cross-sectional studies in humans suggest that serum leptin levels are positively associated with bone mineral density (BMD), but these observations are not consistent, and whether this relationship is independent of obesity remains unclear. We therefore examined the effect of sc leptin administration on BMD and markers of bone turnover in two women, one with congenital generalized lipodystrophy and the other with acquired generalized lipodystrophy. Both patients had regular menstrual cycles. At baseline, the BMD for both patients, measured at the lumbar spine and total hip, was within 1 SD of the peak bone mass. There was no significant change in BMD in both patients after 16-18 months of leptin therapy. Similarly, concentrations of serum osteocalcin and bone-specific alkaline phosphatase or urinary excretion of deoxypyridinoline and N-telopeptides remained unchanged after 6-8 months of leptin therapy, suggesting no effects of leptin on osteoblastic or osteoclastic activity. Our preliminary data suggest that sc leptin replacement in hypoleptinemic patients with generalized lipodystrophy has no effect on the mature adult skeleton.
authors.affiliation: Division of Nutrition and Metabolic Diseases, Center for Human Nutrition, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
authors.forename: Vinaya
authors.initials: V
authors.lastname: Simha
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Zerwekh
authors.forename: Khashayar
authors.initials: K
authors.lastname: Sakhaee
authors.forename: Abhimanyu
authors.initials: A
authors.lastname: Garg
mesh_terms: D015502:Absorptiometry, Photon; D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D000596:Amino Acids / Q000652:urine; D015519:Bone Density; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism*; D003094:Collagen / Q000652:urine; D024042:Collagen Type I; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020738:Leptin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D008060:Lipodystrophy / Q000188:drug therapy*; D010006:Osteoblasts / Q000187:drug effects; D015675:Osteocalcin / Q000097:blood; D010010:Osteoclasts / Q000187:drug effects; D010455:Peptides / Q000652:urine; D014556:Urine
chemical_list: D000596:Amino Acids; D024042:Collagen Type I; D020738:Leptin; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; C122136:recombinant methionyl human leptin; D015675:Osteocalcin; C036020:deoxypyridinoline; D003094:Collagen; D000469:Alkaline Phosphatase