title: The benefits of photodynamic therapy on vertebral bone are maintained and enhanced by combination treatment with bisphosphonates and radiation therapy.
abstract: Photodynamic therapy (PDT) has been shown to ablate tumors within vertebral bone and yield short-term improvements in vertebral architecture and biomechanical strength, in particular when combined with bisphosphonate (BP) treatment. Longer-term outcomes of PDT combined with current treatments for skeletal metastases are essential to understand its therapeutic potential. The objective of this study is to evaluate the response of vertebrae to PDT after a longer (6-week) time period, alone and combined with previous BP or radiation treatment (RT). Sixty-three female rnu/rnu rats were randomized to six treatment groups: untreated control, BP-only, RT-only, PDT-only, combined BP + PDT and combined RT + PDT. L2 vertebrae were structurally analyzed through µCT-based analysis, axial compressive load-to-failure testing and histological analysis of morphology, osteoid formation and osteoclast activity. Combined BP + PDT treatment yielded the largest improvements in bone architecture with combined RT + PDT treatment yielding similar findings, but of a lesser magnitude. Mechanically, ultimate force and stress were correlated to stereological parameters that demonstrated a positive structural effect from combinatory treatment. Increased osteoid formation was observed in both combination therapies without any significant differences in osteoclast activity. Overall, multimodality treatment demonstrated a sustained positive effect on vertebral structural integrity, motivating PDT as a minimally-invasive adjuvant treatment for spinal metastases.
authors.affiliation: Orthopaedic Biomechanics Laboratory, Sunnybrook Research Institute, UB-55, 2075 Bayview Avenue, Toronto, Ontario, M4N 3M5, Canada.
authors.forename: Victor C K
authors.initials: VC
authors.lastname: Lo
authors.forename: Margarete K
authors.initials: MK
authors.lastname: Akens
authors.forename: Lisa
authors.initials: L
authors.lastname: Wise-Milestone
authors.forename: Albert J M
authors.initials: AJ
authors.lastname: Yee
authors.forename: Brian C
authors.initials: BC
authors.lastname: Wilson
authors.forename: Cari M
authors.initials: CM
authors.lastname: Whyne
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D003131:Combined Modality Therapy; D004164:Diphosphonates / Q000494:pharmacology*; D005260:Female; D007093:Imidazoles / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D008159:Lumbar Vertebrae / Q000187:drug effects* / Q000503:physiopathology / Q000528:radiation effects*; D008422:Materials Testing; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology; D011166:Porphyrins / Q000494:pharmacology; D011878:Radiotherapy / Q000379:methods*; D051381:Rats; D011923:Rats, Nude; D013314:Stress, Mechanical; D000077362:Verteporfin; D016474:Weight-Bearing; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin; D000077211:Zoledronic Acid
keywords: bisphosphonate; photodynamic therapy; radiation therapy; spine; vertebral metastasis