Fixation of metallic implants to bone through osseointegration is important in orthopedics and dentistry. Model systems for studying this phenomenon would benefit from a non-destructive imaging modality so that mechanical and morphological endpoints can more readily be examined in the same specimens. The purpose of this study was to assess the utility of an automated micro computed tomography (μCT) program for predicting bone-implant contact (BIC) and mechanical fixation strength in a rat model. Femurs in which 1.5 mm diameter titanium implants had been in place for four weeks were either embedded in polymethylmethacrylate (PMMA) for preparation of 1 mm thick cross-sectional slabs (16 femurs: 32 slabs) or were used for mechanical implant pull-out testing (n = 18 femurs). All samples were scanned by μCT at 70 kVp with 16 μm voxels and assessed by the manufacturer's software for assessing “osseointegration volume per total volume” (OV/TV). OV/TV measures bone volume per total volume (BV/TV) in a 3-voxel thick ring that by default excludes the 3 voxels immediately adjacent to the implant in order to avoid metal-induced artifacts. The plastic-embedded samples were also analyzed by backscatter scanning electron microscopy (bSEM) to provide a direct comparison of OV/TV with a well-accepted technique for BIC. In μCT images in which the implant was directly embedded within PMMA, there was a zone of elevated attenuation (> 50% of the attenuation value used to segment bone from marrow) which extended 48 μm away from the implant surface. Comparison of the bSEM and μCT images showed high correlations for BV/TV measurements in areas not affected by metal-induced artifacts. In addition for bSEM images, we found that there were high correlations between peri-implant BV/TV within 12 μm of the implant surface and BIC (correlation coefficients ≥ 0.8, p < 0.05). OV/TV as measured on μCT images was not significantly correlated with BIC as measured on the corresponding bSEM images. However, OV/TV was significantly, but weakly, correlated with implant pull-out strength (r=0.401, p=0.049) and energy to failure (r=0.435, p=0.035). Thus, the need for the 48 μm thick exclusion zone in the OV/TV program to avoid metal-induced artifacts with the scanner used in this study means that it is not possible to make bone measurements sufficiently close to the implant surface to obtain an accurate assessment of BIC. Current generation laboratory-based μCT scanners typically have voxel sizes of 6–8 μm or larger which will still not overcome this limitation. Thus, peri-implant bone measurements at these resolutions should only be used as a guide to predict implant fixation and should not be over-interpreted as a measurement of BIC. Newer generation laboratory-based μCT scanners have several improvements including better spatial resolution and x-ray sources and appear to have less severe metal-induced artifacts, but will need appropriate validation as they become available to researchers. Regardless of the μCT scanner being used, we recommend that de...

Particle-induced osteolysis is caused by an imbalance in bone resorption and formation, often leading to loss of implant fixation. Bone remodeling biomarkers may be useful for identification of osteolysis and studying pathogenesis, but interpretation of biomarker data could be confounded if local osteolysis engenders systemic bone remodeling. Our goal was to determine if remote bone remodeling contributes to biomarker levels. Serum concentrations of eight biomarkers and bone remodeling rates at local (femur), contiguous (tibia), and remote (humerus and lumbar vertebra) sites were evaluated in a rat model of particle-induced osteolysis. Serum CTX-1, cathepsin K, PINP, and OPG were elevated and osteocalcin was suppressed in the osteolytic group, but RANKL, TRAP 5b, and sclerostin were not affected at the termination of the study at 12 weeks. The one marker tested longitudinally (CTX-1) was elevated by 3 weeks. We found increased bone resorption and decreased bone formation locally, subtle differences in contiguous sites, but no differences remotely at 12 weeks. Thus, the skeletal response to local particle challenge was not systemic, implying that the observed differences in serum biomarker levels reflect differences in local remodeling. ß