Adiponectin and its association with bone mass accrual in childhood

Abstract

Circulating adiponectin levels are inversely related to bone mineral density (BMD) in humans and animal models. Previous studies in humans have been confined largely to adult populations, and whether adiponectin influences bone mass accrual in childhood is unclear. We examined this question using the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort by investigating relationships between circulating adiponectin levels at a mean age of 9.9 years, indices of bone mass as measured by total-body dualenergy X-ray absorptiometry (DXA) at ages 9.9 and 15.5 years, and cortical bone parameters as measured by peripheral quantitative computed tomography (pQCT) of the midtibia at age 15.5 years. A total of 4927 children were included at age 9.9 years, of whom 97% and 90% of boys and girls, respectively, were in prepuberty or early puberty, as defined by Tanner stage 1-2. A total of 2754 children were included at age 15.5 years, of whom 95% and 97% of boys and girls, respectively, were in late puberty, as defined by Tanner stage 4-5. Circulating adiponectin was found to be related to fat mass, lean mass, and, to a lesser extent, height, so analyses were adjusted for these three variables to identify possible independent effects of adiponectin on bone development. Adiponectin was inversely related to totalbody-less-head bone mineral content (BMC; À3.0%), bone area (BA; À1.8%), BMC divided by BA (BMD; À4.8%), and BMC adjusted for BA by linear regression (aBMC; À5.6%), as measured at age 9.9 years (coefficients show change per doubling in adiponectin concentration, p < .001). Consistent with these results, inverse associations also were seen between adiponectin and cortical BMC (À4.8%) and cortical bone area (À4.7%), as measured by tibial pQCT at age 15.5 years (p < .001). Further pQCT results suggested that this inverse association of adiponectin with skeletal development predominantly involved a negative association with endosteal relative to periosteal expansion, as reflected by cortical thickness (À6.0%, p < .001). We conclude that, independent of fat mass, lean mass, and height, adiponectin is associated with lower bone mass in childhood predominantly owing to an influence on relative endosteal expansion. Since these associations were observed before and after puberty, this suggests that setting of adiponectin levels in midchildhood has the potential to exert long-term effects on bone strength and fracture risk. ß

A Metabolic Screen in Adolescents Reveals an Association Between Circulating Citrate and Cortical Bone Mineral Density

“…Although positive relationships between fat mass and bone parameters could reflect a response to greater mechanical strain caused by greater weight, we previously observed fat mass to be positively related to upper limb bone mass, suggesting a role of metabolic pathways independently of body weight . In terms of metabolic pathways which might mediate positive influences of fat mass on bone accrual, we previously found that whereas fat mass is inversely related to adiponectin levels, the latter is inversely related to cortical bone size …”

“…Periosteal circumference (PC), endosteal circumference (EC) and cortical thickness (CT) were derived using a circular ring model as described in the Stratec user manual. Cortical bone was defined using a threshold above 650 mg/cm 3 and BMD C subsequently derived . Strength strain index (SSI) was calculated according to the formula published by Hasegawa and colleagues .…”

“…Ordinary least squares (OLS) linear regression was used to investigate: (i) the relationship between each metabolic measure and PC, CT, and BMD C adjusted for age and sex (ie, model 1); (ii) the effect of further adjustment for Tanner stage (model 2); (iii) the effect of further adjustment for height (model 3); and (iv) for lean mass, fat mass, and height (ie, model 4). Fat and lean mass were adjusted for, in preference to weight, to account for the distinct relationship of these two compartments with cortical bone parameters . A type‐1 error rate of α = 0.002 (0.05/22) was used to infer statistical significance for each of the three traits examined, following Bonferroni correction to account for the number of independent metabolic traits identified by PCA.…”

Body Composition and Skeletal Health: Too Heavy? Too Thin?

“…Studies have shown high, normal, or low levels in patients with AN [101–103], and one study showed an inverse association between adiponectin values and bone density parameters in adolescents with AN [104]. Adiponectin levels are inversely associated with BMD in children and adults [95, 100, 105, 106].…”

Bone Health and the Female Athlete Triad in Adolescent Athletes

“…In addition, stimulation of the Y2 receptor by PYY (a hormone secreted by the L-cells of the distal gut that suppresses hunger) is believed to be deleterious to bone, based on the Y2 receptor knock-out mouse having increased bone mass associated with increased bone formation [65, 66]. Data regarding the relationship between adiponectin (another adipose-derived peptide) and BMD in childhood, adolescence, and young adulthood have been mixed [65, 67, 68], with in vitro and animal data indicating an increase in both osteoblastic and osteoclastic activity with adiponectin [69, 70]. Finally, high cortisol levels are deleterious to bone at multiple levels, and may increase in conditions of energy deficit [71].…”