Daniela Melis1, Alessandro Rossi2, Rosario Pivonello3, Antonio Del Puente4, Claudia Pivonello5, Giuliana Cangemi6, Mariarosaria Negri7, Annamaria Colao8, Generoso Andria9, Giancarlo Parenti10. 1. Department of Translational Medical Sciences, Section of Pediatrics, Federico II University, Naples, Italy. Electronic address: daniela.melis@unina.it. 2. Department of Translational Medical Sciences, Section of Pediatrics, Federico II University, Naples, Italy. Electronic address: ale.ro_ar@libero.it. 3. Department of Medicine and Surgery, Section of Endocrinology, Federico II University, Naples, Italy. Electronic address: rosario.pivonello@unina.it. 4. Department of Medicine and Surgery, Section of Rheumatology, Federico II University, Naples, Italy. Electronic address: delpuente@unina.it. 5. Department of Medicine and Surgery, Section of Endocrinology, Federico II University, Naples, Italy. Electronic address: cpivonello@gmail.com. 6. Clinical Pathology Laboratory, Istituto Giannina Gaslini, Genoa, Italy. Electronic address: giuliana.cangemi@gmail.com. 7. Department of Medicine and Surgery, Section of Endocrinology, Federico II University, Naples, Italy. Electronic address: negrimariarosaria@yahoo.it. 8. Department of Medicine and Surgery, Section of Endocrinology, Federico II University, Naples, Italy. Electronic address: colao@unina.it. 9. Department of Translational Medical Sciences, Section of Pediatrics, Federico II University, Naples, Italy. Electronic address: andria@unina.it. 10. Department of Translational Medical Sciences, Section of Pediatrics, Federico II University, Naples, Italy. Electronic address: parenti@unina.it.
Abstract
INTRODUCTION: 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. OBJECTIVES: 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. DISCUSSION: 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.
INTRODUCTION: 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. OBJECTIVES: 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. DISCUSSION: 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: I Rodríguez-Gómez; A Santalla; J Díez-Bermejo; D Munguía-Izquierdo; L M Alegre; G Nogales-Gadea; J Arenas; M A Martín; A Lucía; I Ara Journal: J Inherit Metab Dis Date: 2018-03-28 Impact factor: 4.982
Authors: Alberto Molares-Vila; Alberte Corbalán-Rivas; Miguel Carnero-Gregorio; José Luís González-Cespón; Carmen Rodríguez-Cerdeira Journal: Int J Mol Sci Date: 2021-04-22 Impact factor: 5.923
Authors: Ghada Hijazi; Anna Paschall; Sarah P Young; Brian Smith; Laura E Case; Tracy Boggs; Sathya Amarasekara; Stephanie L Austin; Surekha Pendyal; Areeg El-Gharbawy; Kristen L Deak; Andrew J Muir; Priya S Kishnani Journal: Mol Genet Metab Rep Date: 2021-11-11