Osteosarcoma (OSA) is an aggressive, highly metastatic and lytic primary
bone neoplasm commonly affecting the appendicular skeleton of dogs and children. Current treatment options include
amputation of the afflicted limb, limb-sparing procedures, or palliative radiation with or without adjunct
chemotherapy.
Therapies that inhibit
bone resorption, such as the
bisphosphonates, may be an effective
palliative therapy by limiting the local progression of OSA in those patients that are not viable candidates for
amputation. We have developed a mouse model of canine skeletal OSA following intratibial inoculation of OSCA40 cells that spontaneously metastasized to the lungs. We demonstrated that
therapy with a
nitrogen-containing
bisphosphonate,
zoledronic acid (Zol), reduced OSA-induced bone lysis; however, Zol monotherapy or in combination with
amputation was not effective at inhibiting pulmonary
metastasis. While not reaching statistical significance,
amputation of the
tumor-bearing limb reduced the average incidence of lung
metastases; however, this effect was nullified when Zol was added to the treatment protocol. In untreated mice, the magnitude of proximal tibial lysis was significantly correlated with the incidence of
metastasis. The data support
amputation alone for the management of appendicular OSA rather than combining
amputation with Zol. However, in patients that are not viable candidates for
amputation, Zol may be a useful
palliative therapy for OSA by reducing the magnitude of lysis and therefore bone
pain, despite the risk of increased pulmonary
metastasis.