title: Normal bone density and trabecular bone score, but high serum sclerostin in congenital generalized lipodystrophy.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
authors.affiliation: 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.
authors.forename: Josivan Gomes
authors.initials: JG
authors.lastname: Lima
authors.affiliation: Department of Clinical Medicine, Health Science Center, Hospital Universitário Onofre Lopes (HUOL), Natal, RN, Brazil.
authors.forename: Lucia Helena C
authors.initials: LHC
authors.lastname: Nobrega
authors.affiliation: Department of Clinical Medicine, Health Science Center, Hospital Universitário Onofre Lopes (HUOL), Natal, RN, Brazil.
authors.forename: Natalia Nobrega
authors.initials: NN
authors.lastname: Lima
authors.affiliation: Department of Clinical Medicine, Health Science Center, Hospital Universitário Onofre Lopes (HUOL), Natal, RN, Brazil.
authors.forename: Marcel Catão Ferreira
authors.initials: MCF
authors.lastname: Dos Santos
authors.affiliation: Department of Clinical Medicine, Health Science Center, Hospital Universitário Onofre Lopes (HUOL), Natal, RN, Brazil.
authors.forename: Maria de Fatima P
authors.initials: MFP
authors.lastname: Baracho
authors.affiliation: Medimaps, Hôpital Xavier Arnozan, Pessac, France.
authors.forename: Renaud
authors.initials: R
authors.lastname: Winzenrieth
authors.affiliation: Division of Endocrinology and Diabetes, University of Pernambuco Medical School, Recife, PE, Brazil.
authors.forename: Francisco
authors.initials: F
authors.lastname: Bandeira
authors.affiliation: Department of Biochemistry, Biosciences Center, Natal, RN, Brazil; Institute of Tropical Medicine of Rio Grande do Norte, Natal, RN, Brazil.
authors.forename: Carolina de O
authors.initials: CO
authors.lastname: Mendes-Aguiar
authors.affiliation: Department of Biochemistry, Biosciences Center, Natal, RN, Brazil; Institute of Tropical Medicine of Rio Grande do Norte, Natal, RN, Brazil.
authors.forename: Francisco Paulo Freire
authors.initials: FPF
authors.lastname: Neto
authors.affiliation: Department of Biochemistry, Biosciences Center, Natal, RN, Brazil; Institute of Tropical Medicine of Rio Grande do Norte, Natal, RN, Brazil.
authors.forename: Leonardo Capistrano
authors.initials: LC
authors.lastname: Ferreira
authors.affiliation: Maine Medical Center Research Institute, Scarborough, USA.
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Rosen
authors.affiliation: 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.
authors.forename: Selma Maria B
authors.initials: SMB
authors.lastname: Jeronimo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D015519:Bone Density / Q000502:physiology*; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D000071556:Cancellous Bone / Q000378:metabolism*; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D005819:Genetic Markers; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood*; D006984:Hypertrophy / Q000097:blood; D007328:Insulin / Q000097:blood*; D020738:Leptin / Q000097:blood; D052497:Lipodystrophy, Congenital Generalized / Q000097:blood*; D008297:Male; D009135:Muscular Diseases / Q000097:blood; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; D007328:Insulin; D020738:Leptin; C422903:SOST protein, human
keywords: Bone; Diabetes; Lipodystrophy; Sclerostin