The effect of a doxorubicin, cisplatin and ifosfamide combination chemotherapy on bone turnover

Background: Use of combination adjuvant chemotherapies have improved the disease-free survival rate of tumor patients significantly. Previous experimental studies have shown that chemotherapeutic agents have negative effects on fixation of porous coated prosthesis, but the effects on normal bone turnover rate and mechanical properties have been reported to be minimal. Materials and Methods: Fourteen dogs were used to study the effect of a doxorubicin, cisplatin and ifosfamide combination in normal bone turnover. We developed a safe and clinically-relevant canine model for multidrug perioperative chemotherapy that simulates current cancer treatment. The bone specimens were analyzed using microradiography, bone histomorphometry and torsional testing. The results were compared with canines that underwent a similar surgical protocol without chemotherapy. Results: The results showed no differences in mechanical properties after 22 weeks of chemotherapy. The porosity, osteonal activity and mineral apposition rate of the cortical bone were unaffected. The results also showed no difference in porosity of perimeter in cancellous bone, but the mineral apposition rate was significantly reduced. Conclusion: The difference in mineral appostion rate of cancellous bone shows that, although the effect of temporary chemotherapy on bone may have minor effects on normal turnover and that the effect may be reversible, it causes disturbance in bone mass accumulation. This may later raise the risk for fragility fractures and osteoporosis.