Bone
metastases are severe complications of
cancers associated with increased morbidity,
pain, risk fracture, and reduced life span for patients.
Bisphosphonates emerged as a relief treatment in bone
metastases. A single dose of
zoledronic acid (78 microg/kg) was injected into six Copenhagen rats 4 days before receiving an intraosseous inoculation of metastatic anaplastic
tumor of lymph node and lung cell (MLL)
prostate cancer cells. Rat femurs were analyzed for changes by microCT and histomorphometry; trabecular volume, trabecular characteristics, osteoid parameters, osteoblastic surfaces, and osteoclast number were measured. Values were compared to a group of
SHAM animals, a group of
SHAM animals having received
zoledronic acid and animals inoculated with MLL cells. All rats were euthanized after 1 month. MLL cells induced
osteolysis in the metaphysis with extension of the
tumor to soft tissues through cortical perforations.
Zoledronic acid induced a marked
osteosclerosis in the primary spongiosa in both
SHAM and rats inoculated with MLL.
Osteosclerosis was obtained in the secondary spongiosa of MLL rats. The
bisphosphonate preserved cortical integrity in all animals, and no extension to soft tissues was observed in most animals. The number of osteoclasts was elevated, indicating that there was no apoptosis of osteoclasts but they became inactive.
Osteosclerosis was associated with increased osteoblastic surfaces. A single
zoledronic acid injection turned osteolytic
metastases into osteosclerotic and preserved cortical integrity.