Metabolic milieu associates with impaired skeletal characteristics in obesity

<div><p>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.</p></div

Difference in bone outcomes with SEM between HIGH and LOW median groups after adjustment in males and females.

<p>Difference in bone outcomes with SEM between HIGH and LOW median groups after adjustment in males and females.</p

Partial correlations between endocrine factors / obesity estimates and BTMs after controlling for age and height separately in males (n = 57) and females (n = 63).

<p>Partial correlations between endocrine factors / obesity estimates and BTMs after controlling for age and height separately in males (n = 57) and females (n = 63).</p

Partial correlation between estimates of obesity/ endocrine factors and bone outcomes in age and BMI adjusted model separately for males and females.

<p>Partial correlation between estimates of obesity/ endocrine factors and bone outcomes in age and BMI adjusted model separately for males and females.</p

Biomarkers related to smoking and gender of MI patients and non-MI subjects.

<p>Significance of the differences calculated with Mann-Whitney´s U test.</p><p>Biomarkers related to smoking and gender of MI patients and non-MI subjects.</p

Biomarkers related to smoking and gender of MI patients and non-MI subjects.

<p>Significance of the differences calculated with Mann-Whitney´s U test.</p><p>Biomarkers related to smoking and gender of MI patients and non-MI subjects.</p

Median and interquartile range (IQR) of pro- and active forms of MMP-8 between MI patients and non-MI subjects.

<p>au = arbitrary unit.</p><p>Median and interquartile range (IQR) of pro- and active forms of MMP-8 between MI patients and non-MI subjects.</p

Characteristics of the study population.

<p>ACEI = angiotensin-converting enzyme inhibitors, IQR = Interquartile range, BOP = bleeding on probing, PPD = probing pocket depth. Significance of the differences calculated with Students t-test (age), Chi 2 or Mann-Whitney´s U test.</p><p>Characteristics of the study population.</p

The mean levels of MMP-8, -9, MPO, TIMP-1 and the ratios of MMP-8 and -9/TIMP-1 in stimulated saliva from MI and non-MI subjects.

<p><i>p</i>1 indicates significance of the differences after a bivariate comparison. <i>p</i>2 indicates the significance after compensation for differences in smoking, BOP, PPD 4–5 mm and PPD ≥ 6 mm.</p><p>The mean levels of MMP-8, -9, MPO, TIMP-1 and the ratios of MMP-8 and -9/TIMP-1 in stimulated saliva from MI and non-MI subjects.</p

Temporal development of plasma levels of MMP-9 (ng/ml) in burn patients.

<p>Blue bars represent TBSA<20% patients and green bars TBSA>20% patients. The gray bar represents values from six healthy controls. Samples are grouped in time intervals, calculated from the time of injury. A Kruskall-Wallis test was performed for each time group, except time group 12 (1 patient). After using the Bonferroni correction for multiple comparisons, significance was set at <i>P</i><0.003. No significant differences were found at any time-point.</p