title: Intra-tumor delivery of zoledronate mitigates metastasis-induced osteolysis superior to systemic administration.
abstract: Bisphosphonates (BPs) have recently been shown to have direct anti-tumor properties. Systemic treatment with BPs can have multiple adverse effects such as osteonecrosis of the jaw and BP induced bone fracturing and spine instability. While benefits of systemic BP treatments may outweigh risks, local treatment with BPs has been explored as an alternate strategy to reduce unwarranted risk. In the present study, we examined whether local delivery of BPs inhibits tumor-induced osteolysis and tumor growth more effectively than systemic treatment in an animal model of tumor-induced bone disease. Following establishment of an intra-tibial model of bone metastases in athymic mice, the experimental group was treated by local administration of zoledronate into the tibial lesion. A comparison of the effect of local versus systemic delivery of zoledronate on the formation of tumor-induced osteolysis was also carried out. A significant increase in mean bone volume/tissue volume % (BV/TV) of the locally treated group (12.30±2.80%) compared to the control group (7.13±1.22%) (P<0.001). Additionally, there was a significant increase in the BV/TV (10.90±1.25%) in the locally treated group compared to the systemically treated group (7.53±0.75%) (P=0.005). These preliminary results suggest that local delivery of BPs outperforms both systemic and control treatments to inhibit tumor-induced osteolysis.
authors.affiliation: Division of Orthopaedic Surgery, Department of Surgery, McGill University, Montreal, Québec, Canada; Department of Orthopaedic Surgery, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Anas
authors.initials: A
authors.lastname: Nooh
authors.affiliation: Division of Orthopaedic Surgery, Department of Surgery, McGill University, Montreal, Québec, Canada; Faculty of Dentistry, McGill University, 3640, Rue University, Montreal, Québec, Canada H3A 0C7.
authors.forename: Yu Ling
authors.initials: YL
authors.lastname: Zhang
authors.affiliation: Faculty of Dentistry, McGill University, 3640, Rue University, Montreal, Québec, Canada H3A 0C7.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sato
authors.affiliation: Division of Orthopaedic Surgery, Department of Surgery, McGill University, Montreal, Québec, Canada.
authors.forename: Derek H
authors.initials: DH
authors.lastname: Rosenzweig
authors.affiliation: Goodman Cancer Research Centre, McGill University, Montréal, Québec, Canada; Department of Medicine, McGill University, Montréal, Québec, Canada.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Tabariès
authors.affiliation: Goodman Cancer Research Centre, McGill University, Montréal, Québec, Canada; Department of Medicine, McGill University, Montréal, Québec, Canada; Department of Biochemistry, McGill University, Montréal, Québec, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Siegel
authors.affiliation: Division of Orthopaedic Surgery, Department of Surgery, McGill University, Montreal, Québec, Canada; Faculty of Dentistry, McGill University, 3640, Rue University, Montreal, Québec, Canada H3A 0C7.
authors.forename: Jake E
authors.initials: JE
authors.lastname: Barralet
authors.affiliation: Division of Orthopaedic Surgery, Department of Surgery, McGill University, Montreal, Québec, Canada.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Weber
keywords: Bisphosphonates; Bone metastases; Cancer pain; Local treatment; Osteolysis; Xenograft