INFLUENCE OF ANTITUMOR CHEMOTHERAPEUTICS ON THE STRUCTURE AND PHOSPHORUS-CALCIUM METABOLISM OF INJURED LONG TUBULAR SKELETAL BONES

Tetiana V. Riabenko

doi:10.21272/eumj.2021;9(3):295-307

Abstract

The high frequency of fractures in cancer patients is due to a decrease in bone strength which is associated with bone metabolism disorders such as osteoporosis, metastatic bone disease, and pathological fractures. Anticancer chemotherapy is prescribed for long-term periods and affects bone metabolism, in particular mineralization of bony tissue. To study the structure and macronutrient composition of long tubular bones in rats under the influence of antitumor chemotherapeutics. The study involved 96 white laboratory 7 month-old male rats weighing 230 ± 10 g that were cut by a ball-shaped dental burr to obtain a 2 mm diameter perforation defect to the medullary cavity in the middle third of the femoral shaft. The animals were divided into the control (n = 24) and three experimental groups (Group I, II, and III, n = 72), which were given intraperitoneal antitumor chemotherapeutics after the cut procedure: Group I (n = 24) – doxorubicin (60 mg/m²), Group II (n = 24) – 5-fluorouracil (600 mg/m²), Group III (n = 24) – methotrexate (40 mg/m²). The therapy was repeated every 21 days throughout the experiment. On the 15th, 30th, 45th, and 60th day after the injury, the animals were sacrificed with subsequent removal of the injured long tubular bones. The samples were studied using scanning electron microscopy and X-ray energy dispersive spectroscopy. Statistical analysis of the obtained digital values was performed with the help of MX Excel XP statistical computer program using the Student's t‑test. The difference was considered significant at p ˂ 0.05. Antitumor chemotherapy slows down the formation of bone regenerate in the area of the defect and causes disorders of phosphorus-calcium metabolism in the injured bone. This is manifested by a decrease in the intensity of newly formed organic matrix mineralization in the area of the defect and a decrease in the level of calcium and phosphorus in the native bone and on its border with the regenerate. Doxorubicin and methotrexate provide the most negative impact on mineralization process among antitumor chemotherapeutic agents. The use of antitumor chemotherapeutic agents – doxorubicin, 5-fluorouracil and methotrexate – slows down the processes of reparative regeneration at all stages of recovery after injury and reduces the phosphorus-calcium metabolism of injured long tubular bones.

Highlights

The study involved 96 white laboratory 7 month-old male rats weighing 230 ± 10 g that were cut by a ballshaped dental burr to obtain a 2 mm diameter perforation defect to the medullary cavity in the middle third of the femoral shaft
The animals in experimental groups were given intraperitoneal antitumor chemotherapeutics, which are most often used in antitumor chemotherapy protocols; the therapy was repeated every 21 days of the study
Antitumor chemotherapy slows down the formation of callus in the area of the defect and causes disorders of phosphorus-calcium metabolism both in the native bone and regenerate. This is manifested by a decrease in the intensity of mineralization of the newly formed bone matrix and a slowdown in the remodeling activity of the native bone

Summary

Introduction

The study involved 96 white laboratory 7 month-old male rats weighing 230 ± 10 g that were cut by a ballshaped dental burr to obtain a 2 mm diameter perforation defect to the medullary cavity in the middle third of the femoral shaft. The animals were divided into the control (n = 24) and three experimental groups (Group I, II, and III, n = 72), which were given intraperitoneal antitumor chemotherapeutics after the cut procedure: Group I (n = 24) – doxorubicin (60 mg/m2), Group II (n = 24) – 5-fluorouracil (600 mg/m2), Group III (n = 24) – methotrexate (40 mg/m2). The therapy was repeated every 21 days throughout the experiment. On the 15th, 30th, 45th, and 60th day after the injury, the animals were sacrificed with subsequent removal of the injured long tubular bones.

Methods

Results

Conclusion