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.
Highlights
Chronic inflammatory diseases and chronic inflammation are associated with bone loss and fragility fractures [1,2]
We examined the associations of leptin, hs- CRP and insulin resistance with bone turnover markers (BTMs) and bone characteristics in 55 young obese adults and 65 non-obese controls
Concentrations of Matrix metalloproteinase 8 (MMP-8) and tissue inhibitors of metalloproteinase 1 (TIMP-1), or their molar ratio did not differ between the groups
Summary
Chronic inflammatory diseases and chronic inflammation are associated with bone loss and fragility fractures [1,2]. Obese subjects have chronic lowgrade systemic inflammation, which contribution to bone health has remained unclear. High-sensitivity C-reactive protein (hs-CRP) is widely used as a marker of systemic lowgrade inflammation. The association between hs-CRP and bone mineral density (BMD) or fracture risk has been at the scope of several studies [4,5,6]. Recent findings from the Tromsø Study indicate that elevated hs-CPR concentrations associate with higher BMI and age, lower physical activity (PA), and male gender [2]. Chronic exposure to low-grade systemic inflammation from early age, as noted in childhood obesity, predisposes to cardiovascular morbidity [7,8]. Lucas et al [11] demonstrated that high hs-CRP concentrations in overweight girls led to decreased BMD by 17 years of age
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