Early changes in serum osteocalcin and body weight are predictive of implant fixation in a rat model of implant loosening

Abstract

Biomarkers are of interest to identify patients at risk for peri‐implant osteolysis and aseptic loosening. We used a rat model of particle‐induced peri‐implant osteolysis to investigate if early changes in biomarkers were associated with subsequent implant fixation strength. Implants were placed in rat femora, which were then challenged with intra‐articular knee injections of either clean polyethylene, lipopolysaccharide‐doped polyethylene, or cobalt‐chromium alloy particles, with particle‐free vehicle serving as control (n ≥ 8 per group). Rats were weighed weekly, blood was collected at weeks 0, 3, 5, and 6, and locomotor behavior was assessed 4 days before study conclusion. Rats were euthanized 6 weeks post surgery. Week 6 serum was analyzed for five bone remodeling markers, while longitudinal serum was assessed for osteocalcin. Bone‐implant contact, peri‐implant trabecular architecture, and implant fixation strength were measured. Rats challenged with cobalt‐chromium particles had a significant reduction in implant fixation strength compared with the vehicle‐control group (P = .034). This group also had elevated serum osteocalcin (P = .005), depressed weight gain (P = .001) and less frequent rearing behavior (P = .029). Regardless of group, change in serum osteocalcin at week 3 (r = −.368; P = .046), change in weight at week 2 (r = .586; P < .001), as well as weight change at all other time intervals were associated with fixation strength. The finding that early alterations in serum osteocalcin and body weight were predictive of subsequent implant fixation strength supports continued investigation of biomarkers for early detection of peri‐implant osteolysis and implant loosening. Further, change in biomarker levels was found to be more indicative of implant fixation status than any single measurement.

The gut microbiota may be a novel pathogenic mechanism in loosening of orthopedic implants in rats

“…Specifically, in this experiment peri‐implant bone volume (BV/TV) varied among the experimental groups (1‐way ANOVA: P = .001) with significant decreases in both the CoCr (Bonferroni: P < .001) and LPS‐PE (Bonferroni: P < .001) groups compared to naïve rats 57 . CoCr (Bonferroni: P < .001) and LPS‐PE‐treated (Bonferroni: P = .001) rats also had significantly lower BV/TV than rats treated with clean‐PE 57 . The loss of peri‐implant BV/TV was accompanied by depressed implant fixation strength, a preclinical surrogate of implant loosening (1‐way ANOVA: P = .002), with decreased fixation strength with CoCr treatment compared to vehicle‐treated (Bonferroni: P = .007) and clean PE group (Bonferroni: P = .002) with a trend in the same direction compared to the LPS‐PE group (Bonferroni: P = .051).…”

“…Specifically, in this experiment peri-implant bone volume (BV/TV) varied among the experimental groups (1-way ANOVA: P = .001) with significant decreases in both the CoCr (Bonferroni: P < .001) and LPS-PE (Bonferroni: P < .001) groups compared to naïve rats. 57 CoCr (Bonferroni: P < .001) and LPS-PE-treated (Bonferroni: P = .001) rats also had significantly lower BV/TV than rats treated with clean-PE. 57 The loss of F I G U R E 3 Mason's Trichrome Staining of Knee Joints.…”

“…57 CoCr (Bonferroni: P < .001) and LPS-PE-treated (Bonferroni: P = .001) rats also had significantly lower BV/TV than rats treated with clean-PE. 57 The loss of F I G U R E 3 Mason's Trichrome Staining of Knee Joints. A-2x stitched images of sagittal sections.…”

“…Some data for Experiment 1 were recently reported 57 . For experiment 1, 35 of 43 Sprague Dawley (SD) rats (380‐400 g, Envigo) underwent bilateral implant surgery to place titanium (Ti) rods (15 mm × 1.5 mm) in the femoral intramedullary canal 39 (Table 1).…”

“…The BV/TV and Fixation Strength data for Experiment 1 were reported for some groups previously. 57 and vacuolation, depending upon treatment (chi-square: P = .013, Table 2). Specifically, 4 out of 4 CoCr-treated rats and 3 out of 4 LPS-PE-treated rats had inflammation present in the peri-portal region.…”