Erythropoietin augments bone formation in a rabbit posterolateral spinal fusion model

Abstract

We tested the hypothesis that erythropoietin (EPO) enhances bone formation after posterolateral spinal fusion (PLF) in a rabbit model. Thirty-four adult rabbits underwent posterolateral intertransverse arthrodesis at the L5-L6 level using 2.0 g autograft per side. The animals were randomly divided into two groups receiving subcutaneous daily injections of either EPO or saline for 20 days. Treatment commenced 2 days preoperatively. Hemoglobin was monitored at baseline and 2, 4, and 6 weeks after fusion surgery. After euthanasia 6 weeks postoperatively, manual palpation, radiographic, and histomorphometric examinations were performed. Bone volume of the fusion mass was estimated by CT after 6 weeks. EPO increased bone fusion volume to 3.85 ccm (3.66-4.05) compared with 3.26 ccm (2.97-3.55) in the control group (p < 0.01). EPO treatment improved vascularization of the fusion mass and increased hemoglobin levels (p < 0.01). Fusion rate tended to be higher in the EPO group based on manual palpation, CT, and radiographic examinations. For the first time EPO has shown to augment bone formation after autograft PLF in a rabbit model. Increased vascularization provides a partial explanation for the efficacy of EPO as a bone autograft enhancer.

The effect of erythropoietin on bone

“…However, computed tomography (CT) and other analyses should be employed to Methodological considerations study other outcome measures (Riordan et al 2013). The primary outcome measure of Paper 1 was bone volume assessed with CT (Rölfing et al 2012).…”

“…The aim of Paper 1 was to test the efficacy of low-dose, continuous EPO as an autograft enhancer (Rölfing et al 2012). Based upon the results achieved by Holstein et al, we hypothesized that EPO facilitates angiogenesis and that this leads to improved bone formation and consequently an increase in the spinal fusion rate.…”

“…EPO also stimulates multiple additional cell-based mechanisms, i.e. osteoblasts as well as hematopoietic and vascular progenitor cells (Shiozawa et al 2010;Guo et al 2012;McGee et al 2012;Rölfing et al 2012). As describe above, the applied continuous dose is the biggest challenge for in vivo trials.…”

Erythropoietin: New Directions for the Nervous System

“…EPO can protect neurons from oxidative stress [55–59], spinal cord ischemia [60], retinal disease [36,46,61,62], stroke [49,63], and demyelinating disease [64]. EPO also can promote bone formation in spinal fusion models [65], modulate vascular dilatation [66], may reduce cerebral aneurysm formation [67] and prevent endothelial cell injury [25–76], protect non-neuronal cells [37,77–80], block disability during infection [28,29,46,81], limit β-amyloid (Aβ) degeneration [26,79,82,83], and may foster memory function [26]. In related systems that directly affect central nervous system function such as the cardiac system, EPO can prevent cardiac injury during chemotherapy [84], improve cardiac contractile function [85], limit cardiac failure through the reduction of inflammation, fibrosis, and oxidative stress [86], and reduce nitrosative stress [87].…”

Osteoblasts: a Novel Source of Erythropoietin

“…Studies investigating the effects of EPO on bone are not limited to mice. In a rabbit spinal fusion model, daily subcutaneous injection of 250 IU/kg EPO beta for 20 days was sufficient to increase bone formation after 6 weeks [38]. Additionally, EPO treatment increased bone healing in porcine osteochondral and cranial defect models [39, 40].…”