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Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_17 | Pages 85 - 85
1 Dec 2018
Ferguson J Diefenbeck M McNally M
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Aim

Antibiotic-loaded biomaterials are often used in dead space management after excision of infected bone. This study assessed the chronological progression of new bone formation in infected defects, filled only with an absorbable, osteoconductive bone void filler with Gentamicin (1).

Method

163 patients were treated for osteomyelitis or infected fractures with a single-stage excision, implantation of antibiotic carrier, stabilisation and wound closure. All had Cierny & Mader Type III (n=128) or Type IV (n=35) infection. No bone grafting was performed in any patient.

Patients were followed up for a minimum of 12 months (mean 21.4 months; 12–56). Bone void filling was assessed on serial digitised, standardized radiographs taken immediately after surgery, at 6 weeks, 3, 6 and 12 months and then yearly. Data on defect size, location, degree of void filling, quality of the bone-biomaterial interface and material leakage were collected.

Bone formation was calculated at final follow-up, as a percentage of initial defect volume, by determining the bone area on AP and lateral radiographs to the nearest 5%.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_16 | Pages 96 - 96
1 Nov 2018
Perdikouri C Lidén E Diefenbeck M
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Nitrogen-containing bisphosphonates such as Zoledronic Acid (ZA) are used clinically for the treatment of skeletal diseases related with increased bone resorption. The gold standard is to administrate the drug through a systemic pathway, however this is often associated with high dosages, risk of side-effects, reduced site-specific drug delivery and hence, limited drug-effectiveness. A controlled local drug delivery, via a biomimetic bone graft, could be beneficial by direct and time-regulated application of significantly lower drug dosage at the site of interest. Thus, higher efficacy and reduced side-effects could be expected. In this experimental in vivo study, we examined the effect of ZA when used together with a Calcium Sulphate/Hydroxyapatite biomaterial in a femoral condyle bone defect in rats and compared local to systemic administration. The following groups were used: group1: empty defect (no biomaterial & no treatment), group2: biomaterial alone, group3: biomaterial + systemic ZA (0.1mg ZA/kg – single subcutaneous injection), group4–6: biomaterial conjugated with ZA at different concentrations, (0.07 to 0.70 mg ZA/mL of paste, corresponding to 0.0024 to 0.024 mg ZA/kg). The animals were sacrificed at 6 weeks and toxicological examination was performed. Bone regeneration was evaluated using qualitative and quantitative micro-CT analysis and Histomorphometry. The results showed a significant difference between the groups, suggesting that ZA has an overall effect on bone healing. The most pronounced effect was seen with the local application of approximately 10 times less ZA-dosage when compared to systemic use (p<0.001). This study demonstrates the importance of local ZA administration in bone regeneration.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_22 | Pages 98 - 98
1 Dec 2017
Diefenbeck M Bischoff S Lidén E Poh P van Griensven M Hettwer W
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Aim

A gentamicin-eluting biocomposite consisting of hydroxyapatite (HA) and calcium sulphate (CaS)*1 can provide effective dead space management and bone formation in chronic osteomyelitis. However, radiographic follow-up after implantation of this biomaterial has shown imaging features previously not described with other comparable bone graft substitutes. Last year we presented preliminary results with a follow-up of 6 months. Now we present the radiographic, µCT and histological one-year follow-up of the critical-size bone defect model in sheep. The aim of this study was to simulate the clinical situation in a large animal model to correlate different imaging techniques used in the clinic (Radiography, CT and MRI scans) with histological finding.

Methods

Standardised bone defects were created in ten Merino-wool sheep (age two to four years). Large drill holes (diameter 2.5cm, depth 2cm, volume approx. 10ml) were placed in the medial femoral condyles of both hind legs and filled with gentamicin-eluting biocomposite. Initially surgery was carried out on the right hind leg.

Three months later, an identical intervention was performed on the contralateral side. Animals were sacrificed at three and six weeks and 4.5, six and twelve months. Radiographs and MRI scans were taken immediately after sacrifice. Filled bone voids were harvested en-block and analysed using µCT, and histology.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_23 | Pages 83 - 83
1 Dec 2016
McNally M Ferguson J Diefenbeck M Lau A Stubbs D Scarborough M Ramsden A Atkins B
Full Access

Aim

Eradication of infection in chronic osteomyelitis requires effective dead space management after debridement. Residual bacteria in biofilm may be resistant to normal levels of systemic antibiotic penetrating bone and will contribute to recurrence of osteomyelitis. This study evaluated a new antibiotic-loaded biocomposite in the eradication of chronic infection from bone defects.

Patients and Method

We report a prospective study of 100 patients with Cierny and Mader types III and IV chronic osteomyelitis, in 105 bones. Osteomyelitis followed open fracture or ORIF of closed fractures in 71%. Nine had concomitant septic arthritis. 80% had comorbidities (Cierny-Mader Class B hosts). Ten had infected non-unions.

All patients were treated by a multidisciplinary team with a single-stage protocol including; debridement, multiple sampling, culture-specific systemic antibiotics, stabilisation, dead space filling with Cerament G™ and immediate primary skin closure.

Stabilisation was required in 21 cases and 5 required joint fusion as part of the initial surgery. Plastic surgical skin closure was needed in 23 cases (18 free flaps).

Patients were followed up for a minimum of one year (mean 19.5 months; 12–34).


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_23 | Pages 68 - 68
1 Dec 2016
Hettwer W Bischoff S Schubert H Liden E Diefenbeck M
Full Access

Aim

A gentamicin-eluting biocomposite consisting of hydroxyapatite and calcium sulfate1 can provide effective dead space management in chronic osteomyelitis. However, radiographic follow-up after implantation of this novel material has consistently shown evidence of several unique imaging features previously not described with other comparable bone graft substitutes. Conclusive interpretation of these newly described imaging features is difficult as long term follow-up and histological correlation is not yet available. The aim of this study was to establish a large animal model, closely simulating the clinical situation in order to permit further analysis of imaging features in correlation with histological progression of bone remodelling.

Method

Standardised bone defects were created in ten Merino-wool sheep (age: two to four years). Large drill holes (diameter 2.5cm, depth 2cm, volume approx. 10ml) were placed in the medial femoral condyles of both hind legs and filled with a gentamicin antibiotic eluting bone graft substitute*. Initially surgery was carried out on the right hind leg. Three months later, an identical intervention was performed on the contralateral side. With sacrifice planned after six or twelve months, bone voids three, six, nine and twelve months post-implantation are obtained for evaluation. The study was approved by the Animal Care Committee of Thuringia, Germany.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_23 | Pages 40 - 40
1 Dec 2016
McNally M Diefenbeck M Stubbs D Athanasou N
Full Access

Aim

This study describes and correlates the radiographic and histologic changes which develop in a Gentamicin-eluting synthetic bone graft substitute* in the management of bone defects after resection of chronic osteomyelitis (COM).

Method

100 patients with COM were treated with a single stage procedure, including management of the dead space with insertion of a Gentamicin-eluting synthetic bone graft substitute*. Radiographs of 73 patients with a follow-up of at least 12 months (range 12–33 months) were available for review. Bone defects were diaphyseal in 32, metaphyseal in 34 and combined in 7 patients. In 3 patients, radiographs were not of sufficient quality to allow analysis.

Five patients had subsequent surgery, not related to recurrence of infection, which allowed biopsy of the implanted material. These biopsies were harvested between 12 days and 9 months after implantation. Tissue was fixed in formalin and stained with haematoxylin-eosin and immunohistochemically for bone matrix markers.


The Bone & Joint Journal
Vol. 98-B, Issue 9 | Pages 1289 - 1296
1 Sep 2016
McNally MA Ferguson JY Lau ACK Diefenbeck M Scarborough M Ramsden AJ Atkins BL

Aims

Chronic osteomyelitis may recur if dead space management, after excision of infected bone, is inadequate. This study describes the results of a strategy for the management of deep bone infection and evaluates a new antibiotic-loaded biocomposite in the eradication of infection from bone defects.

Patients and Methods

We report a prospective study of 100 patients with chronic osteomyelitis, in 105 bones. Osteomyelitis followed injury or surgery in 81 patients. Nine had concomitant septic arthritis. 80 patients had comorbidities (Cierny-Mader (C-M) Class B hosts). Ten had infected nonunions.

All patients were treated by a multidisciplinary team with a single-stage protocol including debridement, multiple sampling, culture-specific systemic antibiotics, stabilisation, dead space filling with the biocomposite and primary skin closure.