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Rønne MS^1,2, Heidemann M¹, Lylloff L^3,4, Schou AJ¹, Tarp J⁵, Bugge A^5,6, Laursen JO⁷, Jørgensen NR^3,8, Husby S^1,2, Wedderkopp N^5,9, Mølgaard C^1,2,10

¹Hans Christian Andersen Children’s Hospital, Odense University Hospital, Odense C, Denmark; ²Department of Clinical Research, University of Southern Denmark, Odense C, Denmark; ³Department of Clinical Biochemistry, Rigshospitalet, Glostrup, Glostrup, Denmark; ⁴Department of Clinical Biochemistry, Hospital Unit West, Gl. Herning, Denmark; ⁵Research Unit for Exercise Epidemiology, Research in Childhood Health, Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense M, Denmark; ⁶Department of Physiotherapy and Occupational Therapy, University College Copenhagen, København N, Denmark; ⁷Emergency Department, Hospital of South Jutland, Aabenraa, Denmark; ⁸OPEN, Odense Patientdata Explorative Network, Department of Clinical Research, University of Southern Denmark, Odense C, Denmark; ⁹Department of Orthopaedics, Hospital of Southwestern Denmark, Esbjerg, Denmark; ¹⁰Department of Nutrition, Exercise and Sports, University of Copenhagen, København N, Denmark

Bone 2019;122:1–7

Background: Existing data shows that insulin may exert an osteogenic effect on bone but the relationship maybe different depending on underlying body composition. Recent studies demonstrate that osteocalcin a bone specific non-collagen protein secreted by osteoblast may influence glucose metabolism and increase insulin sensitivity. The aim of this study was to evaluate the association between insulin resistance measured by the homeostasis model of insulin resistance (HOMA-IR) and dual energy absorptiometry (DXA) bone mass in healthy children. The secondary aim was to identify if body composition, physical activity or osteocalcin may influence the association between insulin resistance and bone mass in healthy children.

Methods: Data from a 6 year longitudinal study, The Childhood Health Activity and Motor Performance School Study, Denmark (CHAMPS-study, DK) with a total of 562 healthy children (277 boys) aged between 6 and 11 years were included in this study. Subjects were included if a baseline DXA and at least one follow-up DXA together with a fasting blood sample were obtained. Fasting blood samples were analysed for glucose, insulin and osteocalcin. Physical activity was measured by accelerometers worn at least for 7 days. Maturity was defined as number of years from age at peak height velocity based on previous published equations.

Results: Mean age of subjects at baseline was 9.6 years (range 7.7–12.0 years). At baseline, 16.4% were overweight and 3.4% were obese. At follow-up, HOMA-IR was negatively associated with DXA total body less head bone mineral content (TBLH-BMC) after adjusting for maturity, sex, height and DXA bone area (p < 0.0001). A sex difference was identified, including in stratified analysis where HOMA-IR was negatively associated with DXA TBLH-BMC only in boys (ß = –31.4, p < 0.001). Additional adjustment for weight, DXA %fat, physical activity and osteocalcin showed similar associations between HOMA-IR and DXA TBLH-BMC (boys: ß –29.3, p < 0.0001; girls: ß –1.5, p = ns).

Conclusion: In a large cohort of healthy children and adolescents, measure of insulin sensitivity with HOMA-IR was inversely associated with DXA bone mineral content, following adjustment for numerous co-variates, including physical activity and osteocalcin. This relationship however was only present in boys.

Reprinted with permission from Elsevier.

Comments

In this cohort of healthy children, insulin sensitivity measured by homeostasis model of insulin resistance was inversely associated with dual energy absorptiometry bone mass. The intriguing association present only in boys needs to be explored in further studies. It is unclear whether this association or the strength of this association is different in children with normal body mass index and those who are overweight and obese, given that insulin levels and homeostasis model of insulin resistance were generally in the “normal” ranges in this study. In addition, the interaction of nutritional intake should be explored in further studies.

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