Supplementary Material for: The Bone Markers Sclerostin, Osteoprotegerin, and Bone-Specific Alkaline Phosphatase Are Related to Insulin Resistance in Children and Adolescents, Independent of Their Association with Growth and Obesity

<b><i>Background/Aims:</i></b> Sclerostin, osteoprotegerin, and bone-specific alkaline phosphatase (B-ALP), which are primarily related to bone metabolism, have been linked with insulin resistance in adults. We aimed to evaluate the association of these markers with growth, obesity, and parameters of insulin resistance in lean and obese children and adolescents. <b><i>Methods:</i></b> We measured sclerostin, osteoprotegerin, and B-ALP in fasting and oral glucose tolerance test (oGTT) serum samples from 1,325 children and adolescents, and during 24-h profiles and after exercise and glucose exposure in young adults. <b><i>Results:</i></b> In addition to the positive relationship with height standard deviation scores (SDS), sclerostin (<i>r</i> = 0.035, <i>p</i> < 0.001) and B-ALP (<i>r</i> = 0.06, <i>p</i> = 0.028) increased, whereas osteoprotegerin (<i>r</i> = –0.098, <i>p</i> < 0.001) decreased with BMI SDS. Furthermore, B-ALP correlated with fasting- and oGTT-derived markers of glucose and insulin metabolism suggestive of insulin resistance. To evaluate potential confounding diurnal variation of bone markers, we performed 24-h profiles. B-ALP and osteoprotegerin had lower night-time levels. Exercise acutely and transiently increased B-ALP and osteoprotegerin levels, but glucose ingestion had no effect. <b><i>Conclusions:</i></b> Besides their association with growth, sclerostin and osteoprotegerin levels are altered in childhood obesity. Particularly B-ALP was related to insulin resistance indices. Our findings accent the link between bone, growth, and insulin resistance.