Concurrent administration of zoledronic acid and irradiation leads to improved bone density, biomechanical strength, and microarchitecture in a mouse model of tumor-induced osteolysis.
OBJECTIVE
Bone metastases are typically treated with bisphosphonates as adjuncts to radiation therapy. The goal of this study was to determine whether radiotherapy combined with a bisphosphonate could restore bone density, microarchitecture, and biomechanical strength of a tumor-burdened bone to normal.


METHODS
Breast cancer cells were injected into the right femur of 30 female nude mice. Mice were divided into three treatment groups (0 Gy, 20 Gy, and 20 Gy + ZA). Left limbs served as non-operated normal bones. Tumor-bearing femora were irradiated 3 weeks later. ZA (100 microg/kg SC) was administered once weekly for 6 weeks. Mice were euthanized at 9 weeks or earlier if severe lameness or pathology occurred.


RESULTS
Mice treated with 20 Gy/ZA exhibited higher bone density, bone volume, fractional trabecular bone volume, and biomechanical strength compared to mice treated with 20 Gy only (P < 0.05). Statistical analysis revealed that mice treated with 20 Gy/ZA were not significantly different from normal bones with respect to bone density and strength. Micro-CT reconstructions showed improved microarchitecture in the 20 Gy/ZA group compared to 20 Gy.


CONCLUSIONS
Treatment of an osteolytic bone with radiation therapy plus zoledronic acid restores normal bone qualities with respect to bone density, microarchitecture, and biomechanical strength.
Arrington
Sarah A
SA
Department of Orthopedic Surgery, SUNY Upstate Medical University, Syracuse, New York 13210, USA.
Damron
Timothy A
TA
Mann
Kenneth A
KA
Allen
Matthew J
MJ
D000818:Animals; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D002277:Carcinoma / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D017024:Chemotherapy, Adjuvant; D004164:Diphosphonates / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005260:Female; D005266:Femoral Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D007093:Imidazoles / Q000008:administration & dosage*; D051379:Mice; D010014:Osteolysis / Q000209:etiology / Q000517:prevention & control*; D013718:Tensile Strength; D047368:Tumor Burden; D000077211:Zoledronic Acid
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid