THE EFFECT OF CHRONIC LEAD INTOXICATION ON BONE TISSUE METABOLISM AND OSTEOREPARATION: EXPERIMENTAL RATIONALE FOR COMBINED CORRECTIVE THERAPY

Background. Lead is one of the most osteotropic toxicants: up to 90% of the total body burden is deposited within the bone mineral matrix, where it competitively substitutes for Ca2+ in the hydroxyapatite lattice, suppresses osteoblast differentiation and enhances osteoclastogenesis. A pathogenetically grounded correction scheme for lead-induced bone metabolic disturbances, and its relationship to reparative osteogenesis, remain insufficiently stud­ied. Aim — to experimentally assess biochemical bone metabolism markers and reparative osteogenesis under chronic lead intoxication, and to evaluate the efficacy of combined corrective therapy (vitamin D3 + calcium citrate + succinic acid). Materials and methods. Forty-five rats were allocated to three groups (control, Pb-intoxication, Pb-intoxication + correction). Chronic intoxication was induced by lead acetate administered ad libitum via drinking water for 8 weeks; at week 4 a monocortical femoral defect was created in all animals. Serum biochemical markers and cortical bone lead content (ICP-OES) were assessed. Results. The Pb group showed significantly reduced osteoblastic activity (alkaline phosphatase −39%, osteocalcin −54%), hypocalcemia (−25%) and marked bone lead accumulation (244.1±21.0 µg/g). Corrective therapy reduced bone lead deposition by 62% and produced statistically significant partial recovery of the studied biochemical parameters. Conclusion. Chronic lead intoxication produces a complex osteotoxic syndrome with disturbed biochemical markers of reparative osteogenesis; the proposed corrective regi­men is pathogenetically justified and may serve as a basis for further clinical development of osteoprotective proto­cols.