Effects Of Obesity On Bone Microstructure And Bone Metabolism

Objective: To observe the influence of obesity on bone microstructure, bone marrow adipocyte,bone metablism.Methods:1.5-6 week male Wistar rats were divided into high fat diet group(100 rats) and normal diet group(100 rats), using the high fat diet induced obese rats model, the rats were fed for 14 weeks.2.Detecting glucose, serum free fatty acid, triglyceride, total cholesterol, low density lipoprotein, high density lipoprotein level.3.Micro CT analysis the number of femoral bone, trabecular bone, bone mineral density and bone volume.4.Detecting the numberof adipocyte by HE staining.5.ELISA analysis the expression level of serum APN, TNF- alpha, RANK RANKL of two groups of rats.6.Correlation analysis of serum lipid, metabolic factors, bone metabolism, bone mechanical parameter factor.Results:1.The weight of obese group rats(284±26.00)g and control group rats(230±17.01)g began to appear significant from 4 weeks to 10 week(P<0.01) and keep increased in 4-10 weeks,does’ t increase in10-14 weeks but still have a significant different(P<0.01).2.The blood lipid test shows that two groups of rats blood glucose in 8-10 weeks difference was statistically significant(P < 0.05); Triglycerides in 4 to 8 weeks difference was statistically significant(P < 0.05), total cholesterol in 4 to 8 weeks difference was statistically significant(P < 0.05); Total cholesterol in 4, 6 weeks difference was statistically significant(P < 0.05), low density lipoprotein in 4, 6 weeks difference was statistically significant(P <0.05).3.Mirco CT results show obesity rat bone mineral density(0.849±0.168)g/cm3 begin to significantly different to normal rats0.883±0.056)g/cm3 from the 6 weeks(P<0.05), trabecular thickness(0.110±0.005)mmwere higher than that of normal rats(0.107±0.013)mm before 6weeks, after6 weeks(0.110±0.004)mm began to lower than the normal rats(0.130±0.017)mm(P<0.05), trabecular Number(4.01±0.11)/mm begin to significantly lower than normal rats(4.21±0.21)/mm(P<0.05)from the 6 weeks(P < 0.05), relative bone volume(47.100±0.430)% began significantly lower than normal rats(47.810±0.106)% from the 4weeks(P<0.05).4. Before 6 week obesity rats on a high-fat diet fat cells number gradually reduced in the marrow cavity(0 weeks 93.66 ± 2.87 to 3.00 ± 0.89) for 4 weeks, after 6 weeks bone marrowfat cells began to increase in 16.66 ± 1.36 to 10 weeks(6 weeks to 35.33 ± 1.36), and always less than normal rats.5.ELISA results showed that obese rats serum adiponectin expression levels(1.12±0.08)ng/m Lappear significantly different with normal group(1.33±0.08)ng/m L from the sixth week(P<0.05), obese rats serum TNF-α expression levels(107.53±22.87)pg/m L appear significantly different with normal group(81.78±12.61)pg/m Lfrom the sixth week(P<0.05),obese rats serum LPT expression levels(0.37±0.15)ng/m L appear significantly different with normal group(0.44±0.29)ng/m L from the sixth week(P<0.05),and RANK(55.15±13.29)pg/m L appears significant with normal group(34.52±9.71)pg/m L from the eighth week(P<0.05), RANKL(201.73±59.57)pg/m L appears significant with normal group(78.26±36.11)pg/m L from the eighth week(P<0.05)6.Statistics show TBMD are significant positive correlation with LEP(r=0.464, P=0.006),APN(r=0.049, P=0.006), negative with LDL(r=-0.441, P=0.009); TB. N are significant positive correlation with LDL(r=0.420, P=0.015), HDL(r=0.417, P=0.016), LPT(r=0.528,P=0.002); TB. Th are significant positive correlation with TG(r=0.962, P=0.000),LDL(r=0.613, P=0.000),FFA(r=0.715, P=0.000), negative with APN(r=-0.419, P=0.001);RANKL were significantly positively correlated with TG(r=0.321, P=0.016), FFA(r=0.270,P=0.044), TNF alpha(r=0.412, P=0.002); Rank showed a significant positive correlation and TG(0.326r=, P=0.014), FFA(r=0.270, P=0.044), TNF alpha(r=0.392, P=0.003), LPT(r=0.271,P=0.044).Conclusion:1. Obesity has two-way influence on bone metabolism, The first four weeks of high fat diet promote bone formation, with obesity aggravate, have inhibitory effect on bone formation.2. The first four weeks of high fat diet can cause rat bone marrow cavity fat cells decrease,continuous obesity can cause rat bone marrow cavity fat cells increase.3. Adipocyte factor,TNF alpha affecting bone metabolism may via the key factor RANK,RANKL,lead to bone metabolic abnormalities.