Normal bone density and trabecular bone score, but high serum sclerostin in congenital generalized lipodystrophy

Context: Berardinelli-Seip Congenital Lipodystrophy (BSCL) is a rare autosomal recessive syndrome characterized by a difficulty in storing lipids in adipocytes, low body fat mass, hypoleptinemia, and hyperinsulinemia. Sclerostin is a product of SOST gene that blocks the Wnt/beta-catenin pathway, decreasing bone formation and enhancing adipogenesis. There are no data about sclerostin in people with BSCL. Objective: We aimed to evaluate serum sclerostin, bone mineral density (BMD), and L1-L4Trabecular Bone Score (TBS) in BSCL patients, generating new knowledge about potential mechanisms involved in the bone alterations of these patients. Design, setting, and patients: In this cross-sectional study, we included 11 diabetic patients with BSCL (age 24.7 8.1 years; 6 females). Sclerostin, leptin, L1-L4 TBS, BMD were measured. Potential pathophysiological mechanisms have been suggested. Results: Mean serum sclerostin was elevated (44.7 +/- 13.4 pmol/L) and was higher in men than women (55.3 +/- 9.0 vs. 35.1 +/- 8.4 pmol/L, p = 0.004). Median of serum leptin was low [0.9 ng/mL (0.5-1.9)]. Seven out of 11 patients had normal BMD, while four patients had high bone mass (defined as Z-score > + 2.5SD). Patients on insulin had lower sclerostin (37.3 +/- 9.2 vs. 52.6 +/- 13.4 pmol/L, p = 0.05). The mean TBS was 1.402 +/- 0.106, and it was higher than 1300 in nine patients. Conclusions: Patients with lipoatrophic diabetes (BSCL) have high serum concentrations of sclerostin, normal or high BMD, and reasonable trabecular bone mass measured by TBS. This is the first report of high sclerostin and good bone microarchitecture (TBS) in BSCL patients. (C) 2017 Elsevier Inc. All rights reserved.