The dysfunctional Impacts of Diabetic Nephropathy Associated With Bone Metabolic Disorder

Abstract

Background: Diabetic nephropathy is one of diabetic complication approximately affecting 40% of diabetic patients that leads significantly to morbidity and mortality. impaired kidney function in patients with diabetic nephropathy disrupts mineral metabolism leading to imbalance of hormones and altered in bone remodeling processes. Osteopenia and osteoporosis are bone diseases in which bone mineral density loss has occurred at a significant level. This aimed to show the association between diabetic nephropathy and disorder of bone metabolism with an emphasis on osteopenia and osteoporosis. Patients and Methods: A case-control study was proceeding on 55 volunteers including 25 DN patients and 30 healthy controls, aged 41–81 years. all participants were diagnosed with diabetic nephropathy by the physicians at Al-Zahraa Teaching Hospital and some private clinics in Wasit province, Iraq. Bone mineral density (BMD) was detected using dual energy X- ray absorptiometry (DEXA). Serum level of RANKL, sclerostin, FGF23 and PTH were estimated using ELISA assay according to the procedure provided by the manufacturer's instructions, Biont Co., Germany. Also, serum levels of phosphate, calcium and vitamin D were determined automatically using automated Roche cobas c111 immunoassay platform. Multi-statistical testses were used in this study (Independent sample t-test, one way (ANOVA), Kruskal-Wallis and Chi-square at significant level (P≤0.05). Results: The serum RANKL, sclerostin, FGF23 and PTH levels showed a higher significant (P > 0.05) with significantly reduced of serum Vit. D3 levels in DN patients with osteoporosis left femur than normal left femur and osteopenia left femur. While, serum levels of Ca⁺² and Pi observed a non-significant difference (P ≥ 0.05) in both DN patients (normal left femur, patients with osteopenia left femur and osteoporosis left femur) and also, in healthy groups with osteopenia left compare to patients with normal left femur. Conclusion: This study confirms that DN induced disrupts in phosphate and vitamin D homeostasis that leading to elevate FGF23 and PTH, which drive bone resorption via RANKL and sclerostin pathways. These findings may underscore the multifactorial pathogenesis of DN-related osteoporosis  and osteopenia as a renal dysfunction to reinforce its role as a risk factor to accelerate bone loss through dysregulated mineral metabolism and osteoclast activation