title: The impact of metastasis on the mineral phase of vertebral bone tissue.
abstract: The negative impact of metastases on the mechanical performance of vertebral bone is often attributed to reduced bone density and/or compromised architecture. However limited characterization has been done on the impact of metastasis on the mineralization of bone tissue and resulting changes in material behaviour. This study aimed to evaluate the impact of metastasis on micro and nano scale characteristics of the mineral phase of bone, specifically mineral crystal growth, homogeneity of mineralization and changes in intrinsic material properties. Female athymic rats were inoculated with HeLa or Ace-1 cancer cells lines producing osteolytic or mixed (osteolytic & osteoblastic) metastases respectively (N=17 per group). A maximum of 21 days was allowed between inoculation and sacrifice of inoculated rats and healthy age-matched uninoculated controls (N=11). X-ray diffraction was used to assess average crystal size in crushed L1-L3 vertebrae; backscatter electron microscopy and nanoindentation were utilized to evaluate modifications in bone mineral density distribution and material behaviour (tissue hardness and modulus) in sagittal-sectioned, embedded and polished L5 vertebrae. HeLa inoculated samples showed reduced mineral crystal width compared to healthy controls. While both types of metastatic involvement reduced tissue mineral content, pathological osteoblastic bone, specific to Ace-1 inoculated samples, significantly decreased tissue mineral homogeneity, whereas osteolytic bone from HeLa samples saw a slight increase in homogeneity. The modulus and hardness of pathological osteoblastic bone was diminished compared to all other bone. Elucidating changes in material behaviour and mineralization of bone tissue is key to defining bone quality in the presence of metastatic involvement.
authors.affiliation: Institution of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada; Orthopaedics Biomechanics Laboratory, Sunnybrook Research Institute, Toronto, ON, Canada.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Burke
authors.affiliation: Orthopaedics Biomechanics Laboratory, Sunnybrook Research Institute, Toronto, ON, Canada.
authors.forename: Ayelet
authors.initials: A
authors.lastname: Atkins
authors.affiliation: Evaluative Clinical Sciences, Hurvitz Brain Science Program, Sunnybrook Research Institute, Toronto, ON, Canada.
authors.forename: Alex
authors.initials: A
authors.lastname: Kiss
authors.affiliation: Department of Surgery, University of Toronto, Toronto, ON, Canada; Techna, University Health Network, Toronto, ON, Canada.
authors.forename: Margarete
authors.initials: M
authors.lastname: Akens
authors.affiliation: Department of Surgery, University of Toronto, Toronto, ON, Canada; Physical Sciences, Holland Musculoskeletal Research Program, Sunnybrook Research Institute, Canada.
authors.forename: Albert
authors.initials: A
authors.lastname: Yee
authors.affiliation: Institution of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada; Orthopaedics Biomechanics Laboratory, Sunnybrook Research Institute, Toronto, ON, Canada; Department of Surgery, University of Toronto, Toronto, ON, Canada. Electronic address: cari.whyne@sunnybrook.ca.
authors.forename: Cari
authors.initials: C
authors.lastname: Whyne
mesh_terms: D000818:Animals; D015519:Bone Density; D001842:Bone and Bones / Q000473:pathology*; D002113:Calcification, Physiologic; D005260:Female; D006367:HeLa Cells; D006801:Humans; D009362:Neoplasm Metastasis / Q000473:pathology*; D051381:Rats; D013131:Spine / Q000473:pathology; D014961:X-Ray Diffraction
keywords: Backscatter electron microscopy; Metastasis; Mineralization; Nanoindentation; Vertebral bone quality; X-ray diffraction