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Ceramic composite with gentamicin decreases persistent infection and increases bone formation in a rat model of debrided osteomyelitis.

ABSTRACT: Introduction: Current methods of managing osteomyelitic voids after debridement are inadequate and result in significant morbidity to patients. Synthetic ceramic void fillers are appropriate for non-infected bone defects but serve as a nidus of re-infection in osteomyelitis after debridement. CERAMENT G (CG) is an injectable ceramic bone void filler which contains gentamicin and is currently being evaluated for use in osteomyelitic environments after debridement due to its theoretical ability to serve as a scaffold for healing while eliminating residual bacteria after debridement through the elution of antibiotics. The goal of this study was to evaluate (1) the rate of persistent infection and (2) new bone growth of a debrided osteomyelitic defect in a rat model which has been treated with either gentamicin-impregnated ceramic cement (CERAMENT G) or the same void filler without antibiotics (CERAMENT, CBVF). Methods: Osteomyelitis was generated in the proximal tibia of Sprague Dawley rats, subsequently debrided, and the defect filled with either (1) CG ( n=20 ), (2) CBVF ( n=20 ), or (3) nothing ( n=20 ). Each group was euthanized after 6 weeks. Infection was detected through bacterial culture and histology. Bone growth was quantified using microCT. Results: Infection was not detected in defects treated with CG as compared with 35 % of defects ( 7/20 ) treated with CBVF and 50 % ( 10/20 ) of empty defects ( p=0.001 ). Bone volume in the defect of CG-treated rats was greater than the CBVF (0.21 vs. 0.17, p=0.021 ) and empty groups (0.21 vs. 0.11, p<0.001 ) at 6 weeks after implantation. Conclusions: Ceramic void filler with gentamicin (CERAMENT G) decreased the rate of persistent infection and increased new bone growth as compared to the same void filler without antibiotics (CERAMENT) and an empty defect in a rat model of debrided osteomyelitis.

SUBMITTER: Dvorzhinskiy A

PROVIDER: S-EPMC8320378 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Activating mutations of calcium-sensing receptor (CaSR) cause autosomal dominant hypocalcemia type 1 (ADH1). Patients with ADH1 exhibit similar features to patients with hypoparathyroidism, including reduced serum parathyroid hormone (PTH) and Ca with low bone turnover. Although persistent suppression of bone turnover may increase bone fragility, bone strength in ADH1 patients has been unclear. We created knock-in mice harboring the A843E activating mutation of CaSR, mimicking severe features of ADH1 patients. The severe form of ADH1 model mice showed smaller body and bone size with lower bone mineral density (BMD) and cortical area of the femur compared with age-matched wild-type (WT) mice. Bone strength in the femur was lower in ADH1 mice even after correction by bone geometry and/or BMD. Microcracks were markedly increased in ADH1 mice, but were rarely detected in WT mice. There was a negative correlation between bone strength corrected by bone geometry and/or BMD and microcrack number or density in ADH1 and WT mice. Among ADH1 mice, negative correlation was still observed between bone strength and microcrack number or density. Microcracks increased with age in ADH1 mice, and were negatively correlated with bone strength. Treatment with PTH(1-34) or a calcilytic, JTT-305, increased bone turnover, reduced microcracks, and increased bone strength to similar levels to those in WT mice. The increase in microcracks was associated with a reduction in bone strength in ADH1 mice, and aging aggravates these changes. These results demonstrate that activating mutation of CaSR causes reduction in PTH secretion with suppressed bone turnover, that reduced bone turnover is associated with an age-dependent increase in microcracks with a reduction in bone strength, and that both PTH(1-34) and calcilytic ameliorate all these changes in bone turnover and strength. It is suggested that fracture susceptibility may be increased in severe types of ADH1 patients especially in the elderly. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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Ceramic composite with gentamicin decreases persistent infection and increases bone formation in a rat model of debrided osteomyelitis.

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