Zoledronic acid decreased osteolysis but not bone metastasis in a nude mouse model of canine prostate cancer with mixed bone lesions.
BACKGROUND
Bone metastasis is the most common cause of morbidity and mortality in patients with advanced prostate cancer and is manifested primarily as mixed osteoblastic and osteolytic lesions. However, the mechanisms responsible for bone metastases in prostate cancer are not clearly understood, in part due to the lack of relevant in vivo models that mimic the clinical presentation of the disease in humans. We previously established a nude mouse model with mixed bone metastases using intracardiac injection of canine prostate cancer cells (Ace-1). In this study, we hypothesized that tumor-induced osteolysis promoted the incidence of bone metastases and osteoblastic activity.


METHODS
We studied the effect of inhibition of osteolysis with zoledronic acid (ZA) on the prevention and progression of Ace-1 bone metastases in nude mice using prophylactic and delayed treatment protocols. Bioluminescent imaging, radiography, and histopathological evaluation were performed to monitor the effect of ZA on the incidence, progression and nature of bone metastases.


RESULTS
Unexpectedly, there was no significant difference in tumor burden and the incidence of metastasis between control and treatment groups as detected by bioluminescent imaging and bone histomorphometry. However, radiographic and histopathological analysis showed a significant treatment-related decrease in osteolysis, but no effect on tumor-induced trabecular bone thickness in both treatment groups compared to controls.


CONCLUSIONS
Our results demonstrated that the incidence of prostate cancer bone metastases in vivo was not reduced by zoledronic acid even though zoledronic acid inhibited bone resorption and bone loss associated with the mixed osteoblastic/osteolytic bone metastases in the Ace-1 model.
Thudi
Nanda K
NK
Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio 43210, USA.
Martin
Chelsea K
CK
Nadella
Murali V P
MV
Fernandez
Soledad A
SA
Werbeck
Jillian L
JL
Pinzone
Joseph J
JJ
Rosol
Thomas J
TJ
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000453:epidemiology / Q000556:secondary; D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000556:secondary; D002461:Cell Line, Transformed; D004164:Diphosphonates / Q000494:pharmacology*; D004195:Disease Models, Animal; D004285:Dogs; D007093:Imidazoles / Q000494:pharmacology*; D015994:Incidence; D008164:Luminescent Proteins; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology; D010014:Osteolysis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000453:epidemiology; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000473:pathology*; D011859:Radiography; D000077211:Zoledronic Acid
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D008164:Luminescent Proteins; D000077211:Zoledronic Acid