Lower bone mass in prepubertal overweight children with prediabetes

Abstract

Childhood studies of the fat-bone relationship are conflicting, possibly reflecting the influence of metabolic abnormalities in some but not all obese children. Bone mass was compared between prepubertal overweight children with (n=41) and without (n=99) pre-diabetes. Associations of bone mass with measures of total and central adiposity, glucose intolerance, insulin sensitivity, lipid profile, systemic inflammation, and osteocalcin were also determined. In 140 overweight children aged 7–11 y, an oral glucose tolerance test was used to identify those with pre-diabetes and for determination of glucose, 2-h glucose, glucose AUC, insulin, 2-hr insulin, and insulin AUC. Blood samples were also assessed for lipids, C-reactive protein, and osteocalcin. Total body bone mineral content (BMC), fat-free soft tissue mass (FFST), and fat mass (FM) were measured by DXA. Visceral adipose tissue (VAT) and subcutaneous abdominal adipose tissue (SAAT) were assessed using MRI. Total body BMC was 4% lower in overweight children with pre-diabetes than those without pre-diabetes, after controlling for sex, race, height, and weight (P=0.03). In the total sample, FM was positively related with BMC (β=0.16, P=0.01), after adjusting for sex, race, height, and FFST. However, VAT (β=−0.13, P=0.03) and SAAT (β=−0.34, P=0.02) were inversely associated with BMC, after controlling for sex, race, height, FFST, FM, and SAAT or VAT. No significant associations were found between BMC and the biochemical measurements. Prepubertal overweight children with pre-diabetes may be at risk for poor skeletal development. In addition, it appears that greater levels of central, rather than total, adiposity may be deleterious for developing bone.

The role of osteocalcin in the endocrine cross-talk between bone remodelling and energy metabolism

“…The view that osteocalcin is only a marker of bone formation should also be revisited since, at least in some cases, variations in its serum levels might reflect a transient metabolic adaptation rather than a primary effect on bone formation. In line with this notion, there was a negative association of osteocalcin levels with impaired fasting glucose and impaired glucose tolerance in overweight children but not with bone mineral content [48]. More generally, analysis of the effects of some glucose-lowering agents on the production or activation of osteocalcin may provide novel insights on their mechanism of action.…”

“…Yet, it was recently shown that ucOC levels are correlated with several metabolic variables. Indeed, higher levels of ucOC are associated with higher insulin secretion, as measured by HOMA-%B, and higher levels of high-molecular-weight adiponectin in healthy children, while lower concentrations of ucOC are associated with impaired fasting glucose and impaired glucose tolerance in children [47,48]. It has also been reported that, in adult men, serum ucOC is associated with enhanced beta cell function and negatively correlated with fat mass, fasting plasma glucose and HbA 1c [30,49].…”

Influence of visceral and subcutaneous fat in bone mineral density of obese adolescents

“…It is known that insulin induces osteoblast proliferation and collagen production; however, its action is not fully elucidated in patients with signs of insulin resistance (9,(26)(27)(28)(29).…”

Association between serum osteocalcin, adiposity and metabolic risk in obese children and adolescents

“…Data concerning serum osteocalcin in children is limited and results are often controversial [21][22][23][24]. Serum osteocalcin levels have been found to be lower in obese than in non-obese children [22] and correlated inversely with both BMI and body fat [23,25].…”