Radiographic and Histological Analysis of a Synthetic Bone Graft Substitute Eluting Gentamicin in the Treatment of Chronic Osteomyelitis

Abstract

Introduction: Managing chronic osteomyelitis can be challenging and attention to the osseous dead-space left following resection is an important part of successful treatment. We assess radiographic bone healing following implantation of a gentamicin-eluting synthetic bone graft substitute (gBGS) used at chronic osteomyelitis (cOM) resection. We also describe histological carrier changes from biopsies in nine cases at various time points. Methods: This was a retrospective review of a prospectively collected consecutive series of 163 patients with Cierny-Mader Type III or IV cOM who underwent single-stage excision, insertion of gBGS and definitive soft-tissue closure or coverage. Bone defect filling was assessed radiographically using serial radiographs. Nine patients had subsequent surgery, not related to infection recurrence, allowing opportunistic biopsy between 19 days and two years after implantation. Results: Infection was eradicated in 95.7% with a single procedure. 138 patients had adequate radiographs for assessment with minimum one-year follow-up (mean 1.7 years, range 1.0-4.7 years). Mean void-filling at final follow-up was 73.8%. There was significantly higher void-filling in metaphyseal compared to diaphyseal voids (mean 79.0% versus 65.6%; p=0.017) and in cases with good initial interdigitation of the carrier (mean 77.3% versus 68.7%; p=0.021). Bone formation continued for more than two years in almost two-thirds of patients studied (24/38; 63.2%). Histology revealed active biomaterial remodelling. It was osteoconductive with osteoblast recruitment, leading to the formation of osteoid, then woven and lamellar bone on the substrate's surface. Immunohistochemistry demonstrated osteocyte specific markers, dentine matrix protein-1 and podoplanin within the newly formed bone. Conclusion: This antibiotic-loaded biomaterial is effective in managing dead-space in surgically treated cOM with a low infection recurrence rate (4.3%) and good mean bone void-filling (73.8%). The radiographic resolution of the bone defect is associated with bone formation, as supported by histological analysis.

Keywords: bone graft substitute; histology; osteomyelitis; outcome; radiology; treatment.

Figure 1

Flowchart demonstrating excluded cases.

Figure 2

(A) Immediate post-operative follow-up radiographs (AP and lateral view) after debridement and filling of an osteomyelitic bone defect of the distal tibia. (B) Follow-up radiographs (AP and lateral view) six weeks following surgery. Note “Halo sign” in lateral view at six weeks. (C) Images taken 12 months following surgery. There is almost complete filling of the void with new bone.

Figure 3

(A) AP radiograph 6 weeks after debridement and filling of an osteomyelitic bone void in the distal tibia. Halo sign: Radio-dense ring around the gBGS (arrows). (B) Marble sign noted at 12 weeks with remnant of the biocomposite appears in the bone void (arrow). (C) Puddle sign at 26 weeks with remnants of the biocomposite accumulating at the bottom of bone void (arrow).

Figure 4

Histology of CERAMENT®|G (A) an early biopsy showing CERAMENT®|G (see asterisk) covered by an osteoid-like matrix produced by osteoblastic cells seen lining the gBGS surface (see arrow). (B) shows focal mineralisation of the osteoid matrix and early woven bone formation around the residual gBGS (see asterisk). (C) immunohistochemistry demonstrating osteocytes in woven bone (brown staining) around the gBGS, expressing dentine matrix protein-1 (DMP-1) and podoplanin (see arrow). (D) later biopsy (at 2 years) demonstrating BSG particles (see asterick) incorporated into formed lamellar bone trabeculae (see arrow).