Yonsei Med J.  2015 Nov;56(6):1643-1650. 10.3349/ymj.2015.56.6.1643.

Comparative Effects of Ibandronate and Paclitaxel on Immunocompetent Bone Metastasis Model

• Chung YS
• Kang HC
• Lee T

• KMID: 2345895
• DOI: http://doi.org/10.3349/ymj.2015.56.6.1643

Abstract

PURPOSE
Bone 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 METHODS
Seventy 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.
RESULTS
Morphological 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 (F(x)) and stiffness (S) of the bone on the 30th day postsurgery. Dpd concentrations were significantly lower in the IBAN group, indicating successful inhibition of bone resorption and destruction.
CONCLUSION
Ibandronate 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.

Keyword

Tumor-induced osteolysis; immunocompetent rodent model; micro-CT; biomechanical properties

MeSH Terms

Amino Acids
Animals
Biomechanical Phenomena/*drug effects/physiology
Bone Density/drug effects/physiology
Bone Neoplasms/*drug therapy
Bone Resorption/*chemically induced
Diphosphonates/*pharmacology
Immunocompetence
Male
*Neoplasm Metastasis
*Osteolysis
Paclitaxel/*pharmacology
Rats
Rats, Sprague-Dawley
Amino Acids
Diphosphonates
Paclitaxel

Figure

• 

  Fig. 1 X-ray showing (A) sham operated left femur of SHAM group and (B) osteolytic lesions (white arrows) in left femur of CANC group.26

• 

  Fig. 2 (A) Sprague-Dawley rat femur showing the VOI for micro-CT scanning. (B) Micro-CT image of the distal femurs of SHAM, IBAN, PAC, and CANC groups at 30 days. VOI, volume of interest; ML, medial lateral; PD, proximal distal.

• 

  Fig. 3 Changes in morphological parameters of 4 different groups (SHAM, IBAN, PAC, and CANC) at 0, 10, 20, and 30 days using micro-CT. (A) Bone volume ratio, bone volume fraction (BV/TV). (B) Trabecular number (Tb.N). (C) Trabecular separation (Tb.Sp). (D) Trabecular thickness (Tb.Th). *Significance (p<0.05) with respect to CANC group by one way ANOVA with Bonferroni corrections.

• 

  Fig. 4 Changes in (A) failure load (Fx) and (B) stiffness (S) of 4 different groups (SHAM, IBAN, PAC, and CANC) at 0, 10, 20, and 30 days. *Significance (p<0.05) with respect to CANC group by one way ANOVA with Bonferroni corrections.

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