| BackgroundOsteoporosis has been a major public health problem. However, in type 2 diabetic population, bone mineral density (BMD)/T value and fracture assessment tool (FRAX), which has been considered as general methods to screen for patients with high risks of osteoporotic fractures, may underestimate the fracture risks in these patients. Moreover, more and more evidence has shown that type 2 diabetic patients have higher fracture risks than non-diabetic patients. Thus, for type 2 diabetic patients, we should find additional markers to predict fracture risks, by exploring the underlying mechanisms that may explain the increased fracture risks in type 2 diabetic patients. On the other hand, we should note that there is a lack of studies investigating the associations of type 2 diabetes and osteoporotic fracture and bone turnover in Chinese population, not to mention the prospective studies. Therefore, by our prospective study, we hope to find the influence of type 2 diabetes on osteoporotic fractures in Chinese population and explore the possible underlying mechanisms.Objective1. Comparing the baseline characteristics, especially the serum levels of bone turnover markers and BMDs, between type 2 diabetic subjects and non-diabetic subjects.2. Analyzing the correlations of fasting plasma glucose and duration of diabetes with bone turnover markers and BMDs.3. Investigating the 5-year incident osteoporotic fracture risks in type 2 diabetic patients.4. Analyzing all the results aforementioned in population with different BMI status.Subjects and methods1. Subjects:1100 postmenopausal women participated in our PK-VF follow-up study. After excluding 240 subjects according to the exclusion criteria, we finally included 860 subjects in our prospective study.2. Methods: 1) We adopted clinical data by questionnaires. Clinical data adopted included age, years since menopause, height, weight, histories of diabetes and fractures, etc.2) Fasting blood sample was collected for each subjects. Serum levels of C-terminal telopeptide of type I collagen (β-CTX), N-terminal prepeptide of type I procollagen (P1NP),25-hydroxyvitamin D (25[OH]D), alanine aminotransferase (ALT), alkaline phosphatase (ALP), calcium, phosphates and creatinine, as well as plasma glucose were measured.3) Bone mineral densities at lumbar spine (L2-4) and femoral neck were measured by dual-energy x-ray absorptiometry (DXA) for each subject.4) All the statistical analyses were performed by SPSS. Pearson chi-square test was used to compare the differences of categorical variables between groups, while unpaired t test and Mann-whitey test were used to compare the continuous variables. General linear model analysis of variance was conducted to compare the differences of bone turnover markers and bone mineral densities between groups, adjusting for age and years since menopause. Spearman correlation analysis and partial correlation analysis were adopted to investigate the correlations of plasma glucose or duration of diabetes with bone turnover markers and bone mineral densities. Cox regression analysis was performed to analyze the fracture risks in type 2 diabetic subjects and non-diabetic subjects.Results1. Comparing to non-diabetic subjects, type 2 diabetic subjects had significantly lower levels of bone turnover markers (P< 0.001), while a significantly higher (P<0.05) or indifferent BMDs (P>0.05).2. Level of plasma glucose was significantly negatively correlated with levels of bone turnover markers (P< 0.001), while significantly positively correlated with BMDs (P <0.02).3. Independent of age, years since menopause and BMD of femoral neck, type 2 diabetic subjects had higher fracture risks (HR=2.561), especially the non-major osteoporotic fracture risks (HR=3.613), than the non-diabetic subjects (P<0.05).4. The association of type 2 diabetes with high fracture risks were more significant in population with BMI<30kg/m2 (total incident osteoporotic fracture:HR=2.864; non-major osteoporotic fracrure:HR=3.431);5. The correlation between low bone turnover and high fracture risk was not statistically significant (P>0.05).ConclusionsType 2 diabetic subjects had higher fracture risks than non-diabetic subjects, indicating that type 2 diabetes was a risk factor for osteoporotic fracture. On the other hand, BMDs of type 2 diabetic subjects were comparable to non-diabetic patients, suggesting that BMD was not an appropriate index to screen for patients with high fracture risks in type 2 diabetic population. Instead, bone turnover marker might be a useful fracture-screening marker, since the bone turnover was significantly suppressed in type 2 diabetic subjects. However, no association of low bone turnover and high fracture risks indicates that additional mechanisms may influence the fracture risks in type 2 diabetic subjects. Recent studies have proposed that advanced glycation end-products (AGEs), insulin-like growth factor-1 (IGF-1) and change of adipose composition in bone marrow may have roles in the underlying mechanisms of type 2 diabetes increasing the fracture risks. |
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