[Osteolytic metastases of breast cancer and biphosphonates]

Three-quarters of breast carcinomas at an advanced stage display metastases, usually of the osteolytic type. Osteolysis results from a predominant increase of osteoclastic activity stimulated by humoral or local factors secreted by cancerous cells. Bisphosphonates interfere with osteoclasts and therefore can reduce the osteolysis. These compounds act through three main mechanisms: physico-chemical inhibition of bone crystal, cytostatic effect on osteoclasts, and in the case of pamidronate, direct or indirect action on the mononucleate precursors of osteoclasts. Three bisphosphonates are now available: etidronate, clodronate and pamidronate. Ten published studies report on their use in breast carcinoma with osteolytic metastases, and without hypercalceamia. Four studies concern clodronate in 54 patients, and six studies concern pamidronate in 128 patients. Intravenous pamidronate seems to be the more effective of the two, with densification of the lytic areas in 25% of the cases. All studies mention a decrease of pain, risk of fracture, hypercalcaemia and new metastatic locations. Side-effects are minimal. Controlled studies are needed to confirm the position of bisphosphonates in the management of malignant osteolysis.