Josivan Gomes Lima1, Lucia Helena C Nobrega2, Natalia Nobrega Lima2, Marcel Catão Ferreira Dos Santos2, Maria de Fatima P Baracho2, Renaud Winzenrieth3, Francisco Bandeira4, Carolina de O Mendes-Aguiar5, Francisco Paulo Freire Neto5, Leonardo Capistrano Ferreira5, Clifford J Rosen6, Selma Maria B Jeronimo7. 1. Department of Clinical Medicine, Health Science Center, Hospital Universitário Onofre Lopes (HUOL), Natal, RN, Brazil; Health Post-Graduate Program, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil. Electronic address: josivanlima@gmail.com. 2. Department of Clinical Medicine, Health Science Center, Hospital Universitário Onofre Lopes (HUOL), Natal, RN, Brazil. 3. Medimaps, Hôpital Xavier Arnozan, Pessac, France. 4. Division of Endocrinology and Diabetes, University of Pernambuco Medical School, Recife, PE, Brazil. 5. Department of Biochemistry, Biosciences Center, Natal, RN, Brazil; Institute of Tropical Medicine of Rio Grande do Norte, Natal, RN, Brazil. 6. Maine Medical Center Research Institute, Scarborough, USA. 7. Department of Biochemistry, Biosciences Center, Natal, RN, Brazil; Institute of Tropical Medicine of Rio Grande do Norte, Natal, RN, Brazil; National Institute of Science and Technology of Tropical Diseases, Natal, RN, Brazil.
Abstract
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>+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.
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 BSCLpatients, 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 diabeticpatients 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>+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 BSCLpatients.
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