Abstract
Purpose
Maintenance of vertebral mechanical stability is of paramount importance to prevent pathologic fractures and resultant neurologic compromise in individuals with spinal metastases. Current non-surgical treatments for vertebral metastases (i.e. chemotherapy, bisphophonates (BP) and radiation) yield variable responses in the tumour and surrounding bone. Photodynamic therapy (PDT) is a novel, minimally-invasive technology that utilizes a drug activated by light at a specific non-thermal wavelength to locally destroy tumour cells. Previously, we observed that PDT can ablate cancer cells within bone and yield short-term (1-week) improvements in vertebral architecture and biomechanical strength, particularly when combined with BP therapy. This study aims to evaluate the effects of PDT in vertebral bone over a longer (6-week) time period, alone and combined with previous BP treatment, to determine if improvements in skeletal architecture and strength are maintained.
Method
Fourty healthy rnu/rnu rats were randomly assigned to four treatment groups: (i) untreated control, (ii) BP only, (iii) PDT only and (iv) PDT following BP. BP treatments were administered on day 0 via subcutaneous injection of zoledronic acid. PDT was administered on day 7 via an intravenous injection of BPD-MA photosensitizer. A flat-cut optical fiber was inserted percutaneously adjacent to lumbar vertebra L2. After a 15-minute drug-light interval, 75J of light energy was delivered from a 690nm laser. Six weeks later, animals were euthanized. Structural properties of excised L2 vertebral bodies were quantified through semi-automated analysis of micro-CT images. In of the specimens, mechanical properties were evaluated by loading the L2 vertebral body to failure in axial compression. The remaining L2 vertebrae were analyzed for morphology, osteoid formation and osteoclast activity using histological methods.
Results
Combined PDT+BP treatment yielded the largest increases in bone volume fraction (31%), trabecular thickness (45%) and vBMD (37%) and decreases in trabecular number (14%) and separation (26%) compared to untreated controls (n=10, all p<0.05). The cortical shell mass fraction was significantly lower than that of controls (24%) indicating increases in bone structure were primarily due to trabecular changes. Mechanically, PDT+BP treatment demonstrated a trend towards an increase in ultimate force compared to controls (n=5, p=0.176). BP-only and PDT-only treatments demonstrated similar trends to the combined treatment, but with a lower magnitude of effect. Qualitatively, histological analysis suggested more osteoid formation in groups receiving PDT, and a higher proportion of bone in BP-treated groups.
Conclusion
PDT has a sustained positive effect on the mechanical and structural integrity of bone, particularly in combination with BP treatment. By ablating tumour tissue and strengthening bone, combined PDT+BP treatment presents as an attractive adjuvant minimally-invasive therapy for spinal metastasis.
