The Cross-over of Anticancer Agents with Osteoclast Activities

Bone loss and increased risk of fractures often result from treatment with antitumoral agents due to more or less severe reduction of bone remodeling. Although various anticancer treatments reduce or inhibit osteoclast activities, the balance of bone remodeling is usually not biased towards osteoblast activity. The activity of osteoclasts is coupled with the activity of osteoblasts. Consequently, inhibition of osteoclast activity often implies reduction of osteoblast activity as well, or vice versa. Depending on the antitumoral substance used, there are large differences in the actions of antitumoral substances on this balancing effect. The less broad the antiproliferative properties of anticancer agents are, and the more they act in a targeted way, the more they show specific effects on both osteoclasts and osteoblasts. However, osteopenia and osteoporosis common in cancer patients is not caused solely by the anticancer treatment. Metastasizing cancer cells in the bone may provoke increased osteoclastogenesis and disturb the bone remodeling balance. Moreover, cancer patients with localized squamous-cell head and neck cancer already show increased bone resorption and decreased bone mass independently of treatment, and smoking or drinking habits. And even carcinogenesis in the intestine and other sites can be prevented by antirheumatic substances that inhibit osteoclastogenesis and have an antiinflammatory action. The question thus arises as to how bone remodeling and cancer development are related. Is the anti-osteoclastic activity of antitumoral agents involved in the prevention of carcinogenesis, and part of the antitumoral activity? This review demonstrates that osteoclastogenesis and cancer may be related in a complex manner. Experimental studies suggest that anticancer agents exert their activity by inhibiting the signaling pathways commonly over-expressed in cancer cells, as well as in cells responsible for bone remodeling.