title: Glucose-loading reduces bone remodeling in women and osteoblast function in vitro.
abstract: Aging is associated with a reduction in osteoblast life span and the volume of bone formed by each basic multicellular unit. Each time bone is resorbed, less is deposited producing microstructural deterioration. Aging is also associated with insulin resistance and hyperglycemia, either of which may cause, or be the result of, a decline in undercarboxylated osteocalcin (ucOC), a protein produced by osteoblasts that increases insulin sensitivity. We examined whether glucose-loading reduces bone remodeling and ucOC in vivo and osteoblast function in vitro, and so compromises bone formation. We administered an oral glucose tolerance test (OGTT) to 18 pre and postmenopausal, nondiabetic women at rest and following exercise and measured serum levels of bone remodeling markers (BRMs) and ucOC. We also assessed whether increasing glucose concentrations with or without insulin reduced survival and activity of cultured human osteoblasts. Glucose-loading at rest and following exercise reduced BRMs in pre and postmenopausal women and reduced ucOC in postmenopausal women. Higher glucose correlated negatively, whereas insulin correlated positively, with baseline BRMs and ucOC. The increase in serum glucose following resting OGTT was associated with the reduction in bone formation markers. D-glucose (>10 mmol L(-1)) increased osteoblast apoptosis, reduced cell activity and osteocalcin expression compared with 5 mmol L(-1). Insulin had a protective effect on these parameters. Collagen expression in vitro was not affected in this time course. In conclusion, glucose exposure reduces BRMs in women and exercise failed to attenuate this suppression effect. The suppressive effect of glucose on BRMs may be due to impaired osteoblast work and longevity. Whether glucose influences material composition and microstructure remains to be determined.
authors: Clinical Exercise Science Program, Institute of Sport, Exercise and Active Living (ISEAL), Victoria University, Melbourne, Australia itamar.levinger@vu.edu.au.
authors: Itamar
authors: I
authors: Levinger
authors: Department of Endocrinology, Austin Health, University of Melbourne, Melbourne, Australia.
authors: Ego
authors: E
authors: Seeman
authors: Department of Endocrinology, Austin Health, University of Melbourne, Melbourne, Australia.
authors: George
authors: G
authors: Jerums
authors: Clinical Exercise Science Program, Institute of Sport, Exercise and Active Living (ISEAL), Victoria University, Melbourne, Australia College of Health and Biomedicine, Victoria University, Melbourne, Australia.
authors: Glenn K
authors: GK
authors: McConell
authors: Department of Physiology, Bosch Institute for Medical Research, University of Sydney, Sydney, Australia.
authors: Mark S
authors: MS
authors: Rybchyn
authors: Clinical Exercise Science Program, Institute of Sport, Exercise and Active Living (ISEAL), Victoria University, Melbourne, Australia.
authors: Samantha
authors: S
authors: Cassar
authors: PathWest QEII Medical Centre, Perth, Australia.
authors: Elizabeth
authors: E
authors: Byrnes
authors: School of Exercise & Nutrition Sciences, Deakin University, Melbourne, Australia.
authors: Steve
authors: S
authors: Selig
authors: Department of Physiology, Bosch Institute for Medical Research, University of Sydney, Sydney, Australia.
authors: Rebecca S
authors: RS
authors: Mason
authors: Department of Medicine, School of Clinical Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia.
authors: Peter R
authors: PR
authors: Ebeling
authors: Department of Physiology, Bosch Institute for Medical Research, University of Sydney, Sydney, Australia.
authors: Tara C
authors: TC
authors: Brennan-Speranza
mesh_terms: D000328:Adult; D000375:Aging / Q000502:physiology*; D001786:Blood Glucose / Q000032:analysis; D016723:Bone Remodeling / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D018592:Cross-Over Studies; D015444:Exercise / Q000502:physiology; D005260:Female; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D006801:Humans; D007118:Immunoassay; D007328:Insulin / Q000097:blood; D008875:Middle Aged; D010006:Osteoblasts / Q000187:drug effects*; D015675:Osteocalcin / Q000096:biosynthesis / Q000097:blood; D017698:Postmenopause
chemical_list: D001786:Blood Glucose; D007328:Insulin; D015675:Osteocalcin; D005947:Glucose
keywords: Bone remodeling; exercise; glycemic control; in vitro; in vivo; osteoblasts function