Metabolic milieu associates with impaired skeletal characteristics in obesity

Abstract

High leptin concentration, low-grade inflammation, and insulin resistance often coexist in obese subjects; this adverse metabolic milieu may be the main culprit for increased fracture risk and impaired bone quality seen in patients with type 2 diabetes. We examined the associations of leptin, hs (high sensitivity)- CRP and insulin resistance with bone turnover markers (BTMs) and bone characteristics in 55 young obese adults (median BMI 40 kg/m2) and 65 non-obese controls. Mean age of the subjects was 19.5 ± 2.5 years (mean ± SD). Concentrations of leptin, adiponectin, hs-CRP, MMP-8 and TIMP-1, fasting plasma glucose and insulin (to calculate HOMA), BTMs (BAP, P1NP, CTX-1, and TRAC5b) were measured. Bone characteristics were determined with pQCT at radius and tibia, and with DXA for central sites. Leptin, hs-CRP and HOMA correlated inversely with BTMs: the partial coefficients were 1.5–1.9 fold higher in males than in females. After adjusting for age, BMI, and other endocrine factors, leptin displayed an independent effect in males on radial bone mass (p = 0.019), tibial trabecular density (p = 0.025) and total hip BMD (p = 0.043), with lower densities in males with high leptin. In females, the model adjusting for age, BMI, and other endocrine factors, revealed that hs-CRP had independent effects on radial bone mass (p = 0.034) and lumbar spine BMD (p = 0.016), women with high hs-CRP having lower values. Partial correlations of adiponectin and TIMP-1 with bone characteristics were discrepant; MMP-8 showed no associations. In conclusion, in young obese adults and their controls, leptin, hs-CRP and HOMA associate inversely with BTMs and bone characteristics. Leptin appears to be the key independent effector in males, whereas hs-CRP displayed a predominant role in females.

Sex‐specific associations between insulin resistance and bone parameters in overweight and obese older adults

“…This table demonstrated that after exclusion of individuals with self‐reported diabetes or use of glucose‐lowering medications, all associations between HOMA‐IR and radial cortical vBMD became nonsignificant. Lastly, a recent study by Viljakainen et al utilizing similar methodology to our study reported that in adolescent males, HOMA‐IR was positively correlated with various bone structural parameters and to a greater degree than in adolescent women. The different associations reported in these studies may be due to a disparity in sex‐hormone concentrations between the populations, adolescents likely having a shorter exposure to an adverse metabolic state, or not having reached peak bone mass.…”

Bone mass development is sensitive to insulin resistance in adolescent boys

“…Our findings are thus in line with results from previous cross-sectional studies [5,10,11] that found similar sex differences in the association between HOMA-IR and bone mass. The participants in this study were apparently healthy children and adolescents without diabetes, and thus a higher HOMA-IR will mainly be driven by higher insulin levels as the range of glucose levels was relatively narrow.…”

“…The association between bone mass and fasting insulin or insulin resistance (as expressed by the homeostasis model assessment of insulin resistance, HOMA-IR) may be sex-specific as suggested in some cross-sectional studies [5,10,11]. Studies with longitudinal data in children are few, but Dalskov et al [12] found no association between insulin and bone mass over a time period of six months.…”

Bone health in women with a history of gestational diabetes or obesity

“…The results from these previous studies are in accordance with our results, and suggest that the beneficial effects of higher weight on bone, if any, do not compensate for the adverse effects of body fat. Possible mechanisms behind the adverse effects of body fat on bone health include obesity‐related low‐grade inflammation, which is associated with impaired bone characteristics …”

“…Possible mechanisms behind the adverse effects of body fat on bone health include obesity-related low-grade inflammation, which is associated with impaired bone characteristics. 46 The strengths of our study include a cohort of over 200 women with a history of GDM and/or obesity. The women recruited for the RADIEL study represent the heterogenic population of women at high risk for GDM, because in addition to obese women, women with normal BMI who had a history of GDM were also included.…”