title: Bone mineral content in patients with congenital generalized lipodystrophy is unaffected by metreleptin replacement therapy.
abstract: BACKGROUND
  Leptin alters bone and mineral metabolism in rodents, but this has not been verified in humans. PATIENTS with congenital generalized lipodystrophy (CGL) have low leptin due to deficient adipose mass and serve as models of leptin deficiency and replacement.
  
  
  OBJECTIVE
  To study the effects of recombinant human methionyl leptin (metreleptin) on bone mineral content (BMC) and mineral metabolism.
  
  
  METHODS
  An open-label nonrandomized study at the National Institutes of Health.
  
  
  METHODS
  Thirty-one patients with CGL (ages 4.3 to 46.7 y).
  
  
  METHODS
  Metreleptin (0.06 to 0.24 mg/kg/d) for 6 months to 11 years.
  
  
  METHODS
  BMC was assessed by dual-energy x-ray absorptiometry. SD scores (SDS) for BMC were calculated based on height, race, sex, and age using population normative data. Calcium, phosphorus, PTH, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D were measured at baseline and follow-up.
  
  
  RESULTS
  At baseline, patients demonstrated significantly increased total body less head BMC (mean SDS, 1.8 ± 0.7), height (mean SDS, 1.3 ± 1.3), and lean mass index, defined as lean body mass per height squared (mean SDS, 1.5 ± 0.83), vs population normative data. No change in total body less head BMC was observed after metreleptin. Lean mass index decreased with metreleptin. Serum calcium decreased with metreleptin, but remained within normal limits. No changes were seen in phosphorus, PTH, or vitamin D.
  
  
  CONCLUSIONS
  In contrast to rodent models, CGL patients have increased BMC in the leptin-deficient state, which does not change with leptin replacement. The high BMC in these patients is partially explained by high lean mass and tall stature.
authors: Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases (J.D.C., E.C., P.G., K.I.R., R.J.B.), National Institute of Dental and Craniofacial Research (M.T.C., R.I.G.), Nuclear Medicine Department, Clinical Center (J.C.R.), National Institutes of Health, Bethesda, Maryland 20892; and Joslin Diabetes Center (A.O.L.), Brookline, Massachusetts 02215.
authors: John D
authors: JD
authors: Christensen
authors: Andreea O
authors: AO
authors: Lungu
authors: Elaine
authors: E
authors: Cochran
authors: Michael T
authors: MT
authors: Collins
authors: Rachel I
authors: RI
authors: Gafni
authors: James C
authors: JC
authors: Reynolds
authors: Kristina I
authors: KI
authors: Rother
authors: Phillip
authors: P
authors: Gorden
authors: Rebecca J
authors: RJ
authors: Brown
mesh_terms: D015502:Absorptiometry, Photon; D000293:Adolescent; D000328:Adult; D001823:Body Composition / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects*; D001846:Bone Development / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D020738:Leptin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D052497:Lipodystrophy, Congenital Generalized / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D055815:Young Adult
chemical_list: D020738:Leptin; C415771:metreleptin