Effect of long-term leptin replacement therapy on bone mass in a pre-menopausal woman with genetic leptin deficiency — ASN Events
  1. Schedule
  2. Poster Viewing I (odd numbers)
  3. Effect of long-term leptin replacement therapy on bone mass in a pre-menopausal woman with genetic leptin deficiency

Effect of long-term leptin replacement therapy on bone mass in a pre-menopausal woman with genetic leptin deficiency (#199)

Alexander Rodriguez 1 , Gilberto Paz-Filho 2 , Tuncay Delibasi 3 , Peter Ebeling 1 4 , Ma-Li Wong 5 , Julio Licinio 5
  1. Bone and Muscle Research Group, School of Clinical Sciences at Monash Health, Monash University, Melbourne, Victoria, Australia
  2. Department of Genome Biology, John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia
  3. Department of Internal Medicine (Kastamonu), Hacettepe University, Ankara, Turkey
  4. Melbourne Medical School-Western Campus, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia
  5. Mind and Brain Theme, South Australian Health and Medical Research Institute and Flinders, University of South Australia, Adelaide, South Australia, Australia

Background: Leptin is important for musculoskeletal development throughout life. Genetic leptin deficiency, from Leptin gene mutations, is extremely rare and culminates in multiple severe metabolic abnormalities. The effect of leptin on bone mineral density (BMD) is unclear, with heterogeneous findings in mice and humans. Here we report a case of a 33 year-old Turkish female with genetic leptin deficiency due to a missense Lep mutation (C105T), who had received seven years of r-metHuLeptin/metreleptin (synthetic leptin analogue) therapy.

Case and methodology: The patient presented with severe obesity (BMI 64.3 kg/m2), hypogonadotropic hypogonadism, and dyslipidaemia. The diagnosis of genetic leptin deficiency was made through Sanger sequencing of the Leptin gene, and measurement of serum leptin levels. She was started on metreleptin 4.2 mg/day (0.04 mg/kg), subcutaneously. Doses were titrated during follow-up, according to weight variations. Once-yearly BMD and bone mineral content (BMC) measurements performed with dual-energy x-ray absorptiometry (Hologic QDR4500).

 Results: At first consultation, total hip, femoral neck and L1-L4 spine BMDs were 0.915 g/cm2, 0.949 g/cm2 and 1.098 g/cm2 respectively. T-scores for these regions were all normal (-0.2, 0.9 and 0.5, respectively). BMCs were 15.36 g/cm, 4.75 g/cm and 16.19 g/cm, respectively. After 7 years of metreleptin therapy, the dose was reduced progressively to 2.5 mg/day, and the patient’s BMI fell to 39.3kg/m2. Total hip, femoral neck and lumbar spine BMDs were 0.966g/cm2, 0.931g/cm2 and 1.221g/cm2, respectively. T-scores remained unchanged and normal (-0.3, -0.8 and 0.3). Hip BMC increased (29.99 g/cm), femoral neck BMC decreased (3.31 g/cm) and spine BMC remained unchanged (16.67 g/cm).

Conclusions: We previously reported significant metabolic, cognitive and body composition improvements from long-term metreleptin treatment in this individual. Despite significant weight loss, BMD was maintained following leptin supplementation while femoral neck BMC decreased, suggesting little influence of leptin treatment on bone after puberty.