Background: The Wnt/β-catenin signaling pathway plays a crucial role in bone development and metabolism. The low-density lipoprotein receptor-related protein 5 (LRP5), an important receptor in the Wnt signaling pathway, promotes the osteogenesis of osteoblasts and curbs bone resorption by osteoclasts.
Objectives: To determine the expression of LRP5 polymorphisms (rs556442 and rs638051) and their relationship with bone mineral density (BMD) and bone metabolism markers in postmenopausal patients with type 2 diabetes mellitus (T2DM) in Xinjiang, China.
Material and methods: According to dual-energy X-ray (DEXA) and oral glucose tolerance test (OGTT) results, 226 postmenopausal women from Xinjiang were divided into the following groups: normal glucose tolerance (NGT) + normal bone mass group (group A), NGT + abnormal bone mass group (group B), T2DM + normal bone mass group (group C), and T2DM + abnormal bone mass group (group D).
Results: Femoral neck BMD was lower in group B women with the AG/GG genotype (mutant type) compared to women with the AA genotype (wild-type) at rs556442. Alkaline phosphatase (ALP) levels were lower in group D women with the AG/GG genotype (mutant type) compared to women with the AA genotype (wild-type) at rs556442 and rs638051. The factors influencing BMD (lumbar spine vertebrae 1-4 (L1-L4)) were triglyceride (TG) levels, body mass index (BMI), menopausal transition age, and age for rs556442 patients, and TG levels and menopausal transition age for rs638051 patients in group D. The factors affecting BMD (hip) were TG levels, BMI and age for rs556442 patients, and TG levels and age for rs638051 patients.
Conclusions: The LRP5 gene mutations are linked to bone metabolism disorders in postmenopausal women with T2DM and abnormal bone mass. High BMI and TG were positively associated with BMD, while increased age and menopausal transition age were negatively associated with BMD.
Keywords: LRP5 polymorphism; bone metabolism; postmenopausal women; type 2 diabetes.