title: Reduced bone mineral density in glycogen storage disease type III: evidence for a possible connection between metabolic imbalance and bone homeostasis.
abstract: BACKGROUND
  Glycogen storage disease type III (GSDIII) is an inborn error of carbohydrate metabolism caused by deficient activity of glycogen debranching enzyme (GDE). It is characterized by liver, cardiac muscle and skeletal muscle involvement. The presence of systemic complications such as growth retardation, ovarian polycystosis, diabetes mellitus and osteopenia/osteoporosis has been reported. The pathogenesis of osteopenia/osteoporosis is still unclear.
  
  
  OBJECTIVE
  The aim of the current study was to evaluate the bone mineral density (BMD) in GSDIII patients and the role of metabolic and endocrine factors and physical activity on bone status.
  
  
  METHODS
  Nine GSDIII patients were enrolled (age 2-20years) and compared to eighteen age and sex matched controls. BMD was evaluated by Dual-emission-X-ray absorptiometry (DXA) and Quantitative ultrasound (QUS). Clinical and biochemical parameters of endocrine system function and bone metabolism were analyzed. Serum levels of the metabolic control markers were evaluated. Physical activity was evaluated by administering the International Physical Activity Questionnaire (IPAQ).
  
  
  RESULTS
  GSDIII patients showed reduced BMD detected at both DXA and QUS, decreased serum levels of IGF-1, free IGF-1, insulin, calcitonin, osteocalcin (OC) and increased serum levels of C-terminal cross-linking telopeptide of type I collagen (CTX). IGF-1 serum levels inversely correlated with AST and ALT serum levels. DXA Z-score inversely correlated with cholesterol and triglycerides serum levels and directly correlated with IGF-1/IGFBP3 molar ratio. No difference in physical activity was observed between GSDIII patients and controls.
  
  
  CONCLUSIONS
  Our data confirm the presence of reduced BMD in GSDIII. On the basis of the results, we hypothesized that metabolic imbalance could be the key factor leading to osteopenia, acting through different mechanisms: chronic hyperlipidemia, reduced IGF-1, Insulin and OC serum levels. Thus, the mechanism of osteopenia/osteoporosis in GSDIII is probably multifactorial and we speculate on the factors involved in its pathogenesis.
authors.affiliation: Department of Translational Medical Sciences, Section of Pediatrics, Federico II University, Naples, Italy. Electronic address: daniela.melis@unina.it.
authors.forename: Daniela
authors.initials: D
authors.lastname: Melis
authors.affiliation: Department of Translational Medical Sciences, Section of Pediatrics, Federico II University, Naples, Italy. Electronic address: ale.ro_ar@libero.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rossi
authors.affiliation: Department of Medicine and Surgery, Section of Endocrinology, Federico II University, Naples, Italy. Electronic address: rosario.pivonello@unina.it.
authors.forename: Rosario
authors.initials: R
authors.lastname: Pivonello
authors.affiliation: Department of Medicine and Surgery, Section of Rheumatology, Federico II University, Naples, Italy. Electronic address: delpuente@unina.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Del Puente
authors.affiliation: Department of Medicine and Surgery, Section of Endocrinology, Federico II University, Naples, Italy. Electronic address: cpivonello@gmail.com.
authors.forename: Claudia
authors.initials: C
authors.lastname: Pivonello
authors.affiliation: Clinical Pathology Laboratory, Istituto Giannina Gaslini, Genoa, Italy. Electronic address: giuliana.cangemi@gmail.com.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Cangemi
authors.affiliation: Department of Medicine and Surgery, Section of Endocrinology, Federico II University, Naples, Italy. Electronic address: negrimariarosaria@yahoo.it.
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Negri
authors.affiliation: Department of Medicine and Surgery, Section of Endocrinology, Federico II University, Naples, Italy. Electronic address: colao@unina.it.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Colao
authors.affiliation: Department of Translational Medical Sciences, Section of Pediatrics, Federico II University, Naples, Italy. Electronic address: andria@unina.it.
authors.forename: Generoso
authors.initials: G
authors.lastname: Andria
authors.affiliation: Department of Translational Medical Sciences, Section of Pediatrics, Federico II University, Naples, Italy. Electronic address: parenti@unina.it.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Parenti
mesh_terms: D015502:Absorptiometry, Photon; D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D015519:Bone Density; D001842:Bone and Bones / Q000378:metabolism*; D002116:Calcitonin / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002784:Cholesterol / Q000097:blood; D015444:Exercise; D005260:Female; D006010:Glycogen Storage Disease Type III / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology*; D006706:Homeostasis; D006728:Hormones / Q000097:blood; D006801:Humans; D008297:Male
chemical_list: D015415:Biomarkers; D006728:Hormones; D002116:Calcitonin; D002784:Cholesterol
keywords: Bone mineral density; GSDIII; Hyperlipidemia; IGF-1; Insulin; Osteocalcin