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/β-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-L4 Trabecular 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±8.1years; 6 females). Sclerostin, leptin, L1-L4 TBS, BMD were measured. Potential pathophysiological mechanisms have been suggested. RESULTS: Mean serum sclerostin was elevated (44.7±13.4pmol/L) and was higher in men than women (55.3±9.0 vs. 35.1±8.4pmol/L, p=0.004). Median of serum leptin was low [0.9ng/mL (0.5-1.9)]. Seven out of 11 patients had normal BMD, while four patients had high bone mass (defined as Z-score\u3e+2.5SD). Patients on insulin had lower sclerostin (37.3±9.2 vs. 52.6±13.4pmol/L, p=0.05). The mean TBS was 1.402±0.106, and it was higher than 1.300 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

Causes of death in patients with Berardinelli-Seip congenital generalized lipodystrophy - Fig 3

<p>(A) Causes of death (n) stratified according to the age group of patients. (B) Patients’ mean age according to the cause of death.</p

Main causes of death in Berardinelli-Seip Congenital Lipodystrophy patients.

<p>Results divided by gender: female (B), and male (C).</p

Age at death (years-old) of Berardinelli-Seip Congenital Lipodystrophy patients according to the year of death.

<p>Age at death (years-old) of Berardinelli-Seip Congenital Lipodystrophy patients according to the year of death.</p

Causes of death and individual clinical features of patients with Berardinelli-Seip Congenital Lipodystrophy.

<p>Causes of death and individual clinical features of patients with Berardinelli-Seip Congenital Lipodystrophy.</p