The study of association between LRP5 gene polymorphisms and bone metabolism in postmenopausal women with type 2 diabetes mellitus
Authors: Li Jun , 黎 娅 , Li Siyuan , Lu Yunqiu , Rai Partab 
Published: November 2023

Abstract
Objective:To investigate the factors affecting bone mineral density in middle-aged and elderly residents, and to analyze the relationship between polymorphisms at the LRP5 gene locus and abnormal bone mass in postmenopausal women.
Methods: Based on bone mineral density (BMD) measurements, the 844 subjects were separated into three groups, normal bone mass group (NBM; n = 304)，osteopenia group (n = 349) and osteoporosis group (OP; n = 191) . 1. Gender, age, height, blood pressure, weight, systolic blood pressure (SBP), diastolic blood pressure (DBP) and body mass index (BMI) of all subjects were measured and recorded. 2. Metabolic indices, including fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), cholesterol (TC), triglycerides (TG), creatinine (Cr), blood urea nitrogen (BUN), and uric acid (UA). 3. Bone mineral density (BMD) of L1-L4, the whole lumbar spine, and the femoral neck was measured using a dual-energy X-ray absorptiometry (DEXA). 4. LRP5 locus polymorphisms were determined by time-of-flight mass spectrometry (MALDI-TOF-MS).
Results:1. Compared to the group with normal bone mass, the proportion of female in Osteopenia and OP group increased significantly (p <0.01), and the OP group was substantially older than both the osteoporosis and normal bone mass groups (p <0.01), but BMI was lower (p <0.01). Age, ALP, Cr and BUN levels were higher in the Osteopenia and OP groups than in the group with normal bone mass, but UA levels were lower (P<0.05). In addition, serum P was significantly higher in the OP group than in the group with normal bone mass (P<0.05). 2. Compared with the osteopenia group, there was a statistically significant difference in diabetes mellitus in the osteoporosis group (χ2=10.782, P<0.01). Compared with normal bone mass, there was a statistically significant difference in menopausal difference between patients with osteopenia and osteoporosis (χ2=74.661, P<0.01). Multivariate logistic regression analysis showed that gender and whether or not to take calcium tablets were independent risk factors, (OR=6.937, P<0.05; OR=2.587, P<0.05). 3.The ROC curves for different BMD sites such as L1, L2, L3, L4, L total, femoral neck, and Ward's triangle were 0.922, 0.927, 0.917, 0.906, 0.933, 0.923, and 0.921, (p <0.01). 4. At rs3736228locus, there was no significant difference between wild-type (CC) and mutant (CT/TT) in the normal bone mass group and the abnormal bone mass group (P>0.05). At rs7125942 locus, there was statistically significant difference in the distribution of wild type (GG) and mutant (CG) groups with normal bone mass and abnormal bone mass groups (P<0.05). 5.At rs7125942 locus,Compared with wild-type (CC), mutant (CG) had lower LDL (P<0.05) in the normal bone mass group, and lower serum ALP in the bone abnormality group (P<0.05). At rs3736228 locus, the HDL of mutan-tyt type (CT/TT) was higher than that of wild-type (CC) in the normal bone mass group (P<0.05), and the serum P of mutant type (CC/TT) was lower in the bone mass group (P<0.05).6.Age and menopausal years were negatively correlated with BMD of the femoral neck and L1-4 (P<0.05), and BMI and TG were positively correlated with BMD of L1-4 (P<0.05). 7.The results of multiple linear regression analysis showed that age was an independent risk factor affecting femoral neck and L1-4 bone density (P<0.05), while BIM and TG were independent protective factors affecting BMD of L1-4 (P<0.05) .