Ibandronate treatment decreases the effects of tumor-associated lesions on bone density and strength in the rat

Abstract

Bisphosphonate treatment is beneficial against symptoms of metastatic bone disease, although less is known about the effect of preventative treatment schedules. We investigated the effect of various treatment regimens of the bisphosphonate, ibandronate (IB), on the preservation of bone quality in a rat model of tumor-induced osteolysis. Osteolytic Walker 256 (W256) carcinosarcoma cells were implanted into the left femur of female Sprague-Dawley rats, resulting in a 10% reduction in bone mineral density (BMD), a 16% reduction in bone density (BD), and a 26% reduction in failure load compared with the right femur 28 days after implantation. IB was administered subcutaneously in five different treatment schedules: (1) IB PRE-POST received IB for 26 days, prior to implantation of W256 cells in the medullary canal of the femur, and for 28 additional days after surgery; (2) IB PRE-POST SHAM received the same IB administration, but with a sham operation; (3) IB PRE received IB injections before W256 cell insertion only; (4) IB PRE-0 received IB injections for 26 days and was then killed to serve as a time zero control; and (5) IB POST received sham injection with saline before W256 cell insertion, and then received IB injections for 28 days until killing. Controls (TUMOR ONLY) received sham injections with saline prior to W256 cell insertion, and then for 28 additional days until killing. We used dual-energy X-ray absorptiometry (DXA) to measure distal femur BMD and bone mineral content (BMC), peripheral quantitative computed tomography (pQCT) to measure distal femur BD, and torsion testing to obtain torsional failure load. Combined preventative and interventional IB treatment best preserved bone mass and strength, although all treatment schedules resulted in significant improvement compared with untreated controls (TUMOR ONLY). The possibility of reducing or even preventing skeletal morbidity in cancer patients with a high risk of developing metastatic spreading to bone is exciting, and warrants further exploration.