Kidney and mineral-bone disorders In clinical practice

On March 15, the Faculty of Medical Sciences at the University of Kragujevac will mark World Kidney Day as part of continuing medical education. Through lectures delivered by eminent nephrology professors, the event will address clinical problem-solving on the topic “Kidney and Mineral-Bone Disorders in Clinical Practice.”

The target audience for this educational program includes physicians, pharmacists, biochemists, nurses, and healthcare technicians.

Chronic kidney disease (CKD) is a major global health problem. Disorders of mineral and bone metabolism (CKD-MBD) are common and significant complications of CKD. This systemic disorder involves:

Biochemical abnormalities (serum concentrations of calcium, phosphate, calcidiol, calcitriol, fibroblast growth factor 23, soluble Klotho protein, and parathyroid hormone);
Bone metabolism disorders (high and low bone turnover disorders: secondary hyperparathyroidism, adynamic bone disease, osteoporosis); and
Cardiovascular calcification (vascular calcification, valvular calcification, calciphylaxis).
The main clinical complications of CKD-MBD include reduced bone mineral density and an increased risk of fractures, as well as cardiovascular calcification (atherosclerotic vascular calcification such as coronary artery disease; medial calcification, including arterial stiffness, arterial hypertension, and heart failure with preserved ejection fraction; valvular calcification, such as aortic stenosis and mitral stenosis; and calciphylaxis).

In patients with advanced stages of CKD (CKD G3-G5D), assessment of bone mineral density (BMD) using the DXA method is indicated to diagnose osteoporosis, assess fracture risk, and guide treatment decisions. In addition to assessing BMD, it is crucial to determine whether the patient has high-turnover bone disease (serum intact parathyroid hormone [iPTH] >600 pg/mL and total or bone-specific alkaline phosphatase levels above the reference range median) or low-turnover bone disease, such as adynamic bone disease (serum iPTH <150 pg/mL and total or bone-specific alkaline phosphatase below the lower normal limit).

For patients with osteoporosis and high bone turnover, antiresorptive drugs such as bisphosphonates and denosumab (a human monoclonal antibody, anti-RANKL antibody) are used. Bisphosphonates inhibit osteoclast activity and bone resorption. They are administered to patients with osteoporosis, low bone mineral density, high bone turnover, and an estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m². Major adverse effects of bisphosphonates include acute kidney injury, focal segmental glomerulosclerosis, and a high potential for developing adynamic bone disease.

Denosumab, a human monoclonal antibody against RANKL (anti-RANKL antibody), inhibits RANKL binding to the RANK receptor on osteoclast precursors, reducing osteoclastogenesis, differentiation, and activation, and subsequently decreasing bone resorption. It improves bone mineral density in the spine and femoral neck and reduces fracture risk. The main adverse effect of denosumab is hypocalcemia, but it can be used in patients with advanced CKD/ESRD, including those on hemodialysis.

For patients with osteoporosis and low bone turnover, osteoanabolic drugs such as teriparatide and romosozumab are recommended. Teriparatide is a recombinant human parathyroid hormone that stimulates osteoblast activity and bone formation (osteoanabolic effect). It is used in patients with osteoporosis, low bone mineral density, low bone turnover, and high fracture risk, with an eGFR >30 mL/min/1.73 m². It is not used in patients with secondary hyperparathyroidism, and its main adverse effect is hypercalcemia.

Romosozumab is a human monoclonal antibody against sclerostin (anti-sclerostin antibody). Sclerostin is a key endogenous inhibitor of the Wnt/β-catenin intracellular signaling pathway, which stimulates osteoblastogenesis. By binding to sclerostin, romosozumab prevents the inhibition of Wnt/β-catenin signaling in osteoblasts, promoting stable osteoblastogenesis, differentiation, activation, and bone formation, increasing bone mineral density and reducing fracture risk. It is used in patients with osteoporosis, low bone mineral density, low bone turnover, and the absence of vascular calcification, with an eGFR >30 mL/min/1.73 m².

In patients on dialysis (hemodialysis, peritoneal dialysis), individualized dialysis prescription and preservation of residual renal function play a key role in optimal CKD-MBD management. Addressing clinical issues enables the selection of appropriate therapeutic strategies through case-based clinical practice. Continuing medical education aims to educate and equip physicians to “identify” this specific patient population (CKD-MBD) at increased risk of bone fractures and vascular complications in everyday clinical practice.