Comparative Effects of Ibandronate and Paclitaxel on Immunocompetent Bone Metastasis Model

Abstract

PurposeBone metastasis invariably increases morbidity and mortality. This study compares the effects of ibandronate and paclitaxel on bone structure and its mechanical properties and biochemical turnover in resorption markers using an immunocompetent Walker 256-Sprague-Dawley model, which was subjected to tumor-induced osteolysis.Materials and MethodsSeventy rats were divided equally into 4 groups: 1) sham group (SHAM), 2) tumor group (CANC), 3) ibandronate treated group (IBAN), and 4) paclitaxel treated group (PAC). Morphological indices [bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp)] and mechanical properties (failure load, stiffness) were evaluated after thirty days of treatment period. Bone resorption rate was analysed using serum deoxypyridinoline (Dpd) concentrations.ResultsMorphological indices showed that ibandronate (anti-resorptive drug) had a better effect in treating tumor-induced architectural changes in bone than paclitaxel (chemotherapeutic drug). The deterioration in bone architecture was reflected in the biomechanical properties of bone as studied with decreased failure load (Fx) and stiffness (S) of the bone on the 30th day post-surgery. Dpd concentrations were significantly lower in the IBAN group, indicating successful inhibition of bone resorption and destruction.ConclusionIbandronate was found to be as effective as higher doses of paclitaxel in maintaining stiffness of bone. Paclitaxel treatment did not appear to inhibit osteoclast resorption, which is contrary to earlier in-vitro literature. Emphasis should be placed on the use of immunocompetent models for examining drug efficacy since it adequately reflects bone metastasis in clinical scenarios.

Biomechanical Properties of Metastatically Involved Osteolytic Bone

“…Mechanical and material properties of healthy and metastatically involved bone have also been assessed for treatments such as bisphosphonates [122][123][124][125][126][127], chemotherapeutics [128][129][130][131], photodynamic therapy (PDT) [85,132], Rank-L inhibitors [133][134][135][136], and multimodal treatment combinations [137,138]. Bisphosphonates and Rank-L inhibitors slow down bone turnover, leading to increased bone mineralization and slower osteolytic tumour growth.…”

Walker-256 Tumor: Experimental Model, Implantation Sites and Number of Cells for Ascitic and Solid Tumor Development

“…However, it case diverse collateral effects and are not efficient in complete remission of tumor. Therefore, several studies are developed searching for new substances that can substitute the conventional method 4,5,6,7,8,9,10,11 . Thus, it is necessary to use experimental models that corresponds more to the reality of individuals affected by this disease.…”