Introduction. The purpose of this study was to analyse the efficacy and complications associated with the use of Calcium Sulphate synthetic bone graft in a paediatric population. There are no published articles on the use in children. Materials & Methods. A retrospective review was undertaken of the notes, microbiology, and X-Rays of 17 cases (in 15 patients) of calcium sulphate use in paediatric patients. As well as patient demographic data, data collected included indication, use of additional agents (antibiotics), return to theatre, and wound complications. Major complications were also assessed for. Results. There were 17 cases, in 15 patients, in our case series where calcium sulphate synthetic bone graft was used. The average patient age was 12.0 years (range 5 years – 17 years). Indications for use included likely infection (12), possible infection (3), and 2 elective finger cases (enchondroma and osteotomy). The humerus was the most common target site (5), followed by the femur (4), tibia (3), calcaneum (2), finger (2) and metatarsal (1) also included. There were positive intra-operative microbiology samples for eleven cases (Staphylococcus aureus and Staphylococcus epidermidis). Antibiotics were used in all cases except the elective finger surgery, and choice ranged between vancomycin, gentamicin, or a combination of both. Two patients required return to theatre for management of ongoing deep infection, although one case was later deemed to be non-infective osteomyelitis. Seven patients had undergone debridements prior to the definitive one with calcium sulphate (5 without Calcium Sulphate, 2 with Calcium Sulphate). Three patients experienced wound issues in the form of discharge/leakage, all were managed with dressings and did not require return to theatre. Conclusions. Calcium Sulphate synthetic bone graft, with addition of antibiotics, is an efficacious treatment in the paediatric population and is not associated with any major complications. Wound discharge should be observed for, and patients/parents warned about this, but only as per the adult population

Degenerative disc disease (DDD) is a common cause of lower back pain. Calcification of the intervertebral disc (IVD) has been correlated with DDD, and is especially prevalent in scoliotic discs. The appearance of calcium deposits has been shown to increase with age, and its occurrence has been associated with several other disorders such as hyperparathyroidism, chondrocalcinosis, and arthritis. Trauma, vertebral fusion and infection have also been shown to increase the incidence of IVD calcification. Our data indicate that Ca. 2+. and expression of the extracellular calcium-sensing receptor (CaSR) are significantly increased in mild to severely degenerative human IVDs. In this study, we evaluated the effects of Ca. 2+. and CaSR on the degeneration and calcification of IVDs. Human donor lumbar spines of Thompson grade 2, 3 and 4 through organ donations within 24 hs after death. IVD cells, NP and AF, were isolated from tissue by sequential digestion with Pronase followed by Collagenase. Cells were expanded for 7 days under standard cell culture conditions. Immunohistochemistry was performed on IVD tissue to validate the grade and expression of CaSR. Free calcium levels were also measured and compared between grades. Immunocytochemistry, Western blotting and RT-qPCR were performed on cultured NP and AF cells to demonstrate expression of CaSR, matrix proteins aggrecan and collagen, catabolic enzymes and calcification markers. IVD cells were cultured in increasing concentrations of Ca. 2+. [1.0-5.0 mM], CaSR allosteric agonist (cincalcet, 1 uM), and IL-1b [5 ng/mL] for 7 days. Ex vivo IVD organ cultures were prepared using PrimeGrowth Disc Isolation System (Wisent Bioproducts, Montreal, Quebec). IVDs were cultured in 1.0, 2.5 mM Ca. 2+. or with cinacalcet for 21 days to determine effects on disc degeneration, calcification and biomechanics. Complex modulus and structural stiffness of disc tissues was determined using the MACH-1 mechanical testing system (Biomomentum, Laval, Quebec). Ca. 2+. dose-dependently decreased matrix protein synthesis of proteoglycan and Col II in NP and AF cells, similar to treatment with IL-1b. (n = 4). Contrarily to IL-1b, Ca. 2+. and cincalcet did not significantly increase the expression of catabolic enzymes save ADAMTS5. Similar effects were observed in whole organ cultures, as Ca. 2+. and cinacalcet decreased proteoglycan and collagen content. Although both Ca. 2+. and cinacalcet increased the expression of alkaline phosphatase (ALP), only in Ca. 2+. -treated IVDs was there evidence of calcium deposits in NP and AF tissues as determined by von Kossa staining. Biomechanical studies on Ca. 2+. and cinacalcet-treated IVDs demonstrated decreases in complex modulus (p<0.01 and p<0.001, respectively; n=5), however, only Ca. 2+. -treated IVDs was there significant increases stiffness in NP and AF tissues (p<0.001 and p<0.05, respectively; n=3). Our results suggest that changes in the local concentrations of calcium and activation of CaSR affects matrix protein synthesis, calcification and IVD biomechanics. Ca. 2+. may be a contributing factor in IVD degeneration and calcification

Aims. Delayed postoperative inoculation of orthopaedic implants with persistent wound drainage or bacterial seeding of a haematoma can result in periprosthetic joint infection (PJI). The aim of this in vivo study was to compare the efficacy of vancomycin powder with vancomycin-eluting calcium sulphate beads in preventing PJI due to delayed inoculation. Methods. A mouse model of PJI of the knee was used. Mice were randomized into groups with intervention at the time of surgery (postoperative day (POD) 0): a sterile control (SC; n = 6); infected control (IC; n = 15); systemic vancomycin (SV; n = 9); vancomycin powder (VP; n = 21); and vancomycin bead (VB; n = 19) groups. Delayed inoculation was introduced during an arthrotomy on POD 7 with 1 × 10. 5. colony-forming units (CFUs) of a bioluminescent strain of Staphylococcus aureus. The bacterial burden was monitored using bioluminescence in vivo. All mice were killed on POD 21. Implants and soft-tissue were harvested and sonicated for analysis of the CFUs. Results. The mean in vivo bioluminescence in the VB group was significantly lower on POD 8 and POD 10 compared with the other groups. There was a significant 1.3-log. 10. (95%) and 1.5-log. 10. (97%) reduction in mean soft-tissue CFUs in the VB group compared with the VP and IC groups (3.6 × 10. 3. vs 7.0 × 10. 4. ; p = 0.022; 3.6 × 10. 3. vs 1.0 × 10. 5. ; p = 0.007, respectively) at POD 21. There was a significant 1.6-log. 10. (98%) reduction in mean implant CFUs in the VB group compared with the IC group (1.3 × 10. 0. vs 4.7 × 10. 1. , respectively; p = 0.038). Combined soft-tissue and implant infection was prevented in 10 of 19 mice (53%) in the VB group as opposed to 5 of 21 (24%) in the VP group, 3 of 15 (20%) in the IC group, and 0% in the SV group. Conclusion. In our in vivo mouse model, antibiotic-releasing calcium sulphate beads appeared to outperform vancomycin powder alone in lowering the bacterial burden and preventing soft-tissue and implant infections. Cite this article: Bone Joint J 2024;106-B(6):632–638

Aim. Megaprosthesis have become a standard option in limb preserving surgery after bone resection in musculoskeletal tumors. Recently they have also been used in complex revision arthroplasty in cases with massive bone loss. The aim of this study was to analyze the incidence of periprosthetic joint infection (PJI) both in primary oncology cases and aseptic revision cases and analyze which are the significant risk factors for PJI with a special interest on the use of prophylactic antibiotic loaded calcium sulfate beads. Method. All patients undergoing surgery with the use of megaprosthesis in our institution between January/2012 and December/2022 were retrospectively reviewed. Data was collected from electronic medical records. We identified 108 procedures involving megaprosthesis in 90 patients with an average follow-up of 37 months. Indications were 79 primary musculoskeletal tumors and 29 aseptic complex revision arthroplasty. Results. Table 1 shows relevant clinical information. No significant risk factor was found either in uni or multivariate analysis. PJI rate was 15% (12/79) for primary musculoskeletal surgery and 31% (9/29) for complex revision surgery. The use of antibiotic loaded calcium sulfate beads did not show an advantage – 22% (9/41) with vs. 18% (12/67) without. Conclusions. In this relatively small series it was not possible to show a significal association between PJI and certain known risk factors such as gender, ASA score, site of surgery (knee) and revision surgery. The use of antibiotic loaded calcium sulfate beads as prophylaxis was not beneficial in reducing PJI rates in our cohort. We acknowledge the limitations of our study: a small sample group, in a single institution with heterogeneity in terms of diagnosis and surgical site. We recognize the need for a multicentric study with a larger cohort to validate these findings. For any tables or figures, please contact the authors directly

Aim. Multispecies biofilms are associated with difficult periprosthetic joint infections (PJI), particularly if they have different antibiotic sensitivities. We aimed to determine if we could generate and kill a multispecies biofilm consisting of a Gram negative and Gram positive pathogen in-vitro with antibiotic loaded calcium sulfate beads containing single or combination antibiotics. Methods. To establish whether we could co-culture mixed species biofilms various combinations of Pseudomonas aeruginosa (PA), Enterococcus faecalis (EF), Staphylococcus aureus (SA) and Enterobacter faecalis (EF) were grown together on 316L stainless steel coupons and agar plates. Based on this screen we focused on PA + EF and challenged them with high purity calcium sulfate beads (Stimulan Rapid Cure) loaded with vancomycin (V), alone tobramycin (T) alone or vancomycin and tobramycin in combination (V+T). Bioluminescence, light imaging, plate count, confocal microscopy and scanning electron microscopy were used to quantify growth. Results. On 316LSS the V loaded bead reduced both EF and PA by approximately 2 logs compared to unloaded control beads. A T alone loaded bead eliminated PA from the dual species biofilm and caused a 2-log reduction in EF. The V+T-beads reduced PA by 9-logs and EF by 8.3 logs. In terms of total CFUs V+T beads reduced the bioburden by 8.4 logs compared to V or T alone. which resulted in 2.1 and 2.6 log reductions respectively. (* P<0.05, *** P<0.001). On agar PA dominated the culture for the unloaded and V loaded beads. However, when challenged with a T loaded bead both species were able to coexist and a zone of killing was generated in both species in the multispecies biofilms. However, this zone was smaller and included more tolerant variants than the zone generated by V+T-loaded beads. Conclusions. There were species proportion differences between biofilms grown on agar and 316LSS demonstrating the importance of growth conditions on species interactions. Antibiotics against strains with differing sensitivities can shift species interactions. High purity calcium sulfate beads containing tobramycin a broad-spectrum Gram positive and negative antibiotic vancomycin, a Gram-positive targeted antibiotic killed a larger percentage of a multispecies in an in-vitro biofilm than either single gram-specific antibiotic alone, demonstrating the advantage of using combination antibiotics for treating multispecies biofilms

Osteoarthritis (OA) is a multifactorial debilitating disease that affects over four million Canadians. Although the mechanism(s) of OA onset is unclear, the biological outcome is cartilage degradation. Cartilage degradation is typified by the progressive loss of extracellular matrix components - aggrecan and type II collagen (Col II) – partly due to the up-regulation of catabolic enzymes - aggrecanases a disintegrin and metalloprotease with thrombospondin motifs (ADAMTS-) 4 and 5 and matrix metalloproteinases (MMPs). There is currently no treatment that will prevent or repair joint damage, and current medications are aimed mostly at pain management. When pain becomes unmanageable arthroplastic surgery is often performed. Interest has developed over the presence of calcium crystals in the synovial fluid of OA patients, as they have been shown to activate synovial fibroblasts inducing the expression of catabolic agents. We recently discovered elevated levels of free calcium in the synovial fluid of OA patients and raised the question on its role in cartilage degeneration. Articular cartilage was isolated from 5 donors undergoing total hip replacement. Chondrocytes were recovered from the cartilage of each femoral head or knee by sequential digestion with Pronase followed by Collagenase and expanded in DMEM supplemented with 10% heat-inactivated FBS. OA and normal human articular chondrocytes (PromoCell, Heidelberg, Germany) were transferred to 6-well plates in culture medium containing various concentrations of calcium (0.5, 1, 2.5, and 5 mM CaCl2), and IL-1β. Cartilage explants were prepared from the same donors and included cartilage with the cortical bone approximately 1 cm2 in dimension. Bovine articular cartilage explants (10 months) were used as a control. Explants were cultured in the above mentioned media, however, the incubation period was extended to 21 days. Immunohistochemistry was performed on cartilage explants to measure expression of Col X, MMP-13, and alkaline phosphatase. The sulfated glycosaminoglycan (GAG, predominantly aggrecan) content of cartilage was analyzed using the 1,9-dimethylmethylene blue (DMMB) dye-binding assay, and aggregan fragmentation was determined by Western blotting using antibody targeted to its G1 domain. Western blotting was also performed on cell lysate from both OA and normal chondrocytes to measure aggrecan, Col II, MMP-3 and −13, ADAMTS-4 and −5. Ca2+ significantly decreased the proteoglycan content of the cartilage explants as determined by the DMMB assay. The presence of aggrecan and Col II also decreased as a function of calcium, in both the human OA and bovine cartilage explants. When normal and OA chondrocytes were cultured in medium supplemented with increasing concentrations of calcium (0.5–5 mM Ca2+), aggrecan and Col II expression decreased dose-dependently. Surprisingly, increasing Ca2+ did not induce the release of MMP-3, and −13, or ADAMTS-4 and-5 in conditioned media from OA and normal chondrocytes. Interestingly, inhibition of the extracellular calcium-sensing receptor CaSR) reversed the effects of calcium on matrix protein synthesis. We provide evidence that Ca2+ may play a direct role in cartilage degradation by regulating the expression of aggrecan and Col II through activation of CaSR

Introduction. Antibiotic loaded absorbable calcium sulphate beads (ALCSB) are an increasingly popular adjunct in the treatment of musculoskeletal infections including osteomyelitis and peri-prosthetic joint infections (PJI). Limited data exist regarding the clinical indications and biochemical outcomes of ALCSB in PJI cases. Aims. To determine the proportion of organisms that were sensitive to the gentamicin and vancomycin that we add to the ALCSB as a part of our treatment protocol and to determine the prevalence of postoperative hypercalcaemia when used for treatment of hip and knee DAIR (debridement and implant retention) and revision arthroplasty for PJI. Methods. A retrospective review of 160 hip and knee revisions using ALCSB performed between June 2015 and May 2018 at a tertiary unit was performed. 10–40 cc of ALCSB was used for each case containing vancomycin and gentamicin. Data recorded included patient demographics, comorbidities, indication for surgery, operative intervention, microbiological results and serum biochemistry for calcium levels. Results. The cohort consisted of 91 males and 69 females, with a mean age of 69.0 years (21.3 to 93.1) and mean BMI of 34.7(12.6 to 48.1). 56 (35%) had single-stage revision, 45 (28.1%) had first stage revision, 35 (21.9) had DAIR, 19 (11.9%) had second stage revision and 5 (3.1%) other procedures. Organisms included staphylococcus aureus (30.0%), culture-negative (27.5%), staphylococcus epidermidis (18.1%), and pseudomonas aeruginosa (3.1%). 54.3% were sensitive to both vancomycin and gentamicin, 25.0% to vancomycin only and 8.6% to gentamicin only. 11.9% (19/160) of patients had transient post-operative hypercalcaemia (normal range 2.2–2.7mmol/L), peaking at day 6–7 and resolved with hydration by day 10 postoperatively. Preoperatively, 26.9% had albumin <35 g/L and 49.3% had some degree of renal impairment with an eGFR <90 ml/min. Conclusion. The use of ALCSB allows local delivery of vancomycin and gentamicin in lower limb PJI. Organisms were sensitive to this antibiotic combination in 88% cases. Care must be taken to monitor calcium for 10 days post-operatively

Daptomycin has a unique mechanism of action against Gram-positive bacteria. Daptomycin is only bactericidal in the presence of calcium ions. [1]. Kanellakopoulou et al [2] investigated elution of daptomycin from calcium sulfate. The results indicated above MIC elution concentrations out to 28 days. Experience reports that the ability for calcium sulfate to set hard when combined with daptomycin can be problematic.[3] This study aimed to investigate the combination of daptomycin with a synthetic recrystallised form of calcium sulfate and investigate zone of inhibition (ZOI) testing against susceptible organisms. 6mm hemispherical beads, were prepared using a commercially available calcium sulfate hemihydrate powder (CSH) – CaSO4 ·1/2H2O. [4] In order to combine daptomycin [5] with the CSH and enable it to set hard, 7mls of saline solution was added to 20g CSH powder and mixed for 80 seconds to initiate the setting reaction. Then 1g of daptomycin powder was added and mixed for a further 30 seconds. The resultant paste was applied to a bead mat and allowed to set. Tryptone soya agar plates were seeded with 0.2ml of a 10e6 – 10e8 cfu/ml suspension of the relevant organism. The plates were incubated at 33 °C ± 2 °C for 30 minutes. The plates were then removed from the incubator and the beads placed on the surface. The plates were then incubated at 33 °C ± 2 °C for 24 hours before examination for the absence of growth as seen by a clear zone around the test sample. Triplicate samples were tested against Staphylococcus epidermidis, Staphylococcus aureus, MRSA, VRE Enterococcus faecium and Propionibacterium acnes. Repeat tests were carried out for beads that had been stored at 37 °C for 21 days to simulate in-vivo conditions. Setting times for the CSH/daptomycin beads were approximately 20 minutes. ZOIs indicating efficacy were seen for all samples both ‘fresh’ and ‘incubated’ with MRSA and Propionibacterium acnes having the largest ZOIs at 31–33mm. A mixing protocol was established to enable set beads to be formed with daptomycin loaded calcium sulfate. As assessed by ZOI testing, the eluted antibiotic maintained efficacy against susceptible pathogens. Results obtained in-vitro may not be indicative of in-vivo performance

Aim. Infection rates after revision THA vary widely, up to 12%. In countries that use antibiotic-loaded cemented stems in combination with perioperative IV antibiotics, infection rates in registry studies are lower. In many countries, however, cementless revision implants are preferred. Our aim was to apply an antibiotic-loaded calcium sulfate coating to cementless revision stems to reduce periprosthetic joint infection (PJI). This study sought to answer two questions: 1) Does the coating of cementless revision stems with calcium sulfate inhibit osteointegration in THA? 2) Does the antibiotic-loaded calcium sulfate coating of revision stems reduce the incidence of PJI?. Method. From Dec. 2010 to Dec. 2015, 111 consecutive revision femoral stems were coated with commercially pure calcium sulfate. 10cc of calcium sulfate was mixed with 1g of vancomycin powder and 240mg of tobramycin liquid and applied to the stem in a semi-firm liquid state immediately prior to stem insertion. The results are compared to a designated control cohort (N=104) performed across the previous 5 years. The surgical methods were comparable, but for the stem coating. All patients were staged preoperatively using the Musculoskeletal Infection Society Staging System and followed for at least 1 year. Results. In the study group of coated stems, there were 46 A hosts, 56 B hosts, and 9 C hosts. In the control group, there were 45 A hosts, 52 B hosts, and 7 C hosts. Both cohorts had 0 cases of aseptic loosening. The overall rate of PJI in the study cohort was 2.7%. Of the 111 revisions, 69 were aseptic (PJI=1.4%) and 42 were second stage revisions for infection (PJI=4.8%). PJI occurred in 2.2% of A hosts, 1.8% of B hosts, and 11.1% of C hosts. In the control cohort, the overall rate of PJI was 7.7%. Of the 104 revisions, 74 were aseptic (PJI=1.4%) and 30 were second stage revisions for infection (PJI=23.3%). PJI occurred in 6.7% of A hosts, 5.8% of B hosts, and 28.6% of C hosts. The results show a reduction in PJI from 7.7% in the control group to 2.7% in the study group and were found to be statistically significant at p-value<0.1 (p=0.09). Conclusions. The application of antibiotic-loaded calcium sulfate to cementless revision femoral stems does reduce PJI. Importantly, this coating did not inhibit osteointegration of the femoral stem. The reduced infection rate in this study supports the concept that bacteria frequently contaminate and reside within the femoral canal

Aim. Treatment principles of chronic osteomyelitis include debridement, clean sampling, excision of dead bone, stabilization, dead space management, soft tissue closure and systemic antibiotic therapy. Dead space management becomes very complicated, if the bone infection is caused by multi-resistant bacteria. The aim of this investigation was to evaluate the effect of a new vancomycin-loaded hydroxyapatite / calcium sulfate composite. *. in the treatment of chronic osteomyelitis (OM) caused by multi-resistant bacteria. Method. From June 2015 to November 2015, 7 patients (4 males, 3 females, average age 52.6y) were treated according to the above mentioned principles using the new vancomycin-loaded hydroxyapatite / calcium sulfate composite. *. Infections were caused by methicillin-resistant Staphylococcus aureus (MRSA), multi-resistant Staphylococcus epidermidis (MRSE) and polymicrobial, vancomycin-sensitive bacteria. We used a two-stage protocol with debridement, excision of bone and external stabilization in the first stage, followed by bone defect reconstruction. To fill the residual bone defects, in 3 patients the new vancomycin-loaded hydroxyapatite / calcium sulfate composite. *. (10mL) was used on its own and in 4 patients combined with 18mL of an unloaded calcium sulfate / hydroxyapatite composite. **. Post-operative follow-up was evaluated clinically and by radiographs and CT scans at 6, 14 and 24 weeks. Results. In 6 of 7 patients rapid control of infection was achieved. Soft tissue reactions and prolonged white wound drainage (caused by calcium sulfate dissolution) was seen in 3 of 7 patients. In 6 of 7 patients recurrence of infection has not been observed so far. Radiographs showed different elution intervals of the radiocontrast agent (Iohexol), depending on anatomical location. Bone remodelling or replacement of the composite by new bone was not uniform in the patients and showed specific radiographic signs. In addition to the so-called „puddle sign“, we found septae, membranes, vacuoles and sometimes arc-like structures. Therefore, we suggest the name “arc-sign” for these formations. Conclusions. During the follow-up of the first 7 patients treated with the unloaded calcium sulfate / hydroxyapatite composite. **. in 6 of 7 cases no recurrence of infection was observed. This is very promising in the difficult situation of bone infections caused by multi-resistant bacteria. Follow-up radiographs and CT-scans showed specific patterns during the resorption of the composite and the formation of new bone, which have not been described in other bone graft substitutes so far. The bone defects are not completely filled yet, but the affected bones are clinically stable and patients can ambulate with full weight bearing

In bone and joint infections, several materials can be used for local antibiotic elution at site of infection. Polymethylmethacrylate (PMMA) cement is often used. Recently the use of antibiotic impregnated dissolvable synthetic pure calcium sulphate beads [Stimulan R]1 has been used as an alternative, due to several perceived advantages. We present our experience of using Calcium sulphate beads in infections involving the upper limb. From Jan 2012 to Jan 2015, we used Calcium sulphate beads in 7 complex upper limb infections including 1 elbow replacement, 2 infected non unions, 2 shoulder replacement, 1 wrist fusion and I ORIF elbow. We used combination of Vancomycin and Gentamicin in the beads, using manufacturer's mixing guide for optimum setting. Arthroplasty infections underwent explantation, addition of antibiotic impregnated calcium sulphate beads in the joint space, followed by a second stage, and systemic antibiotics. Fracture non-union cases had surgical debridement, calcium sulphate beads and systemic antibiotics. Follow up (6months to 2 years) indicate no recurrence of infection in any case. The most common organisms isolated were Coagulase negative staphylococcus and Staphylococcus aureus. Others included Group B Streptococcus, Serratia marscesens and Corynebacterium spp. In 2 of 7 cases there was significant drainage from the wound. This settled without further input. For fracture non-union fixation, there was no need to do second procedure to remove beads as they dissolve. In cases of staged revisions, the beads were inserted at first stage with microbiological clearance at 2nd stage. At present there are no reports in the literature of the use of this product in the upper limb. Our experience suggests use of dissolvable pure Calcium sulphate beads impregnated with selected antibiotics, is an effective adjunct to current treatments. Aseptic drainage has been reported and this was seen in some of our cases. It is postulated that the use of Calcium sulphate beads in more superficial joints may lead to more drainage. It may be necessary to avoid packing any beads in the subcutaneous spaces and using lower volumes in upper limb. Further work will include long-term follow up and any evidence of relapse or recurrence of infection

The management of chronic osteomyelitis is fraught with difficulties; a multi-disciplinary team approach is recommended for optimum outcome. Thorough debridement, dead space management and organism targeted antibiotic therapy the gives best clinical results. Calcium sulphate beads impregnated with antibiotic is an absorbable option for prolonged local antibiotic elution and dead space management. This study aims to analyse the early results of single stage management of osteomyelitis with antibiotic impregnated calcium sulphate beads. Following surgical debridement, calcium sulphate impregnated typically with tobramycin and/or vancomycin is inserted to obliterate the dead space. Intravenous antibiotics – typically teicoplanin and piperacillin-tazobactam – are administered until culture results permit rationalisation to narrow spectrum agents. Patients are followed up in Infectious Diseases and Orthopaedic clinics for a period of 12 months and discharged if quiescence is achieved. We conducted a retrospective analysis of our prospective database to identify patients treated with our single stage protocol for chronic osteomyelitis. We excluded patients that had (1) less than 6 months of follow up, (2) incomplete metal-ware removal, (3) patients lost to follow up. Fourteen patients (9 men, 5 women) with mean age of 41 (16–73) years and mean follow up of 9 (6–12) months were included in study. Eleven patients had previous surgeries involving internal fixation; the rest were primary osteomyelitis. Seven patients had washouts and removal of metal-ware procedures for osteomyelitis prior to referral to the bone infection service. Clinical, radiographic, and laboratory (microbiological, biochemical and haematological) methods were used to monitor response to treatment. Cierney-Mader classification determined that 8 patients were classed as type A (normal hosts); 4 as BS (systemically compromised); 2 as BLS (locally and systemically compromised). Anatomic analysis suggested 7 were Type 1 (medullary osteomyelitis); the remaining 7 were type 3 (localised disease). Five patients were staged IA; three each staged IIIA and IIIBS; and one each staged IBs, IBLS, IIIBLS. Staphylococcus Aureus was the commonest causative organism. Follow up radiograph monitoring indicated absorption of the beads by 3 months. There has been no evidence of recurrence based on clinical, radiographic and blood based parameters in all patients. Short-term results of single stage osteomyelitis treatment with calcium sulphate beads impregnated with antibiotics are promising

Introduction. Temporary use of antibiotic-impregnated polymethylmethacrylate (PMMA) bone cement spacers in two-stage revisions is considered to be standard of care for patients with a chronic infection of a joint replacement. Spacers should be wear resistant and load-bearing to avoid prolonged immobilisation of the patient and to reduce morbidity. Most cement spacers contain barium sulphate or zirconium dioxide as radio-opaque substrate. Both are quite hard materials that may negatively influence the wear behaviour of the spacer. Calcium carbonate is another radio-opaque substrate with lower hardness potentially increasing the wear resistance of the spacer materials. The purpose of the study was to compare a prototype PMMA knee spacer (calcium carbonate loaded) with a commercially available spacer (containing barium sulphate) regarding the wear performance and particle release in a knee wear simulator. Material and Methods. Spacer K (TECRES, Italy) was used as barium sulphate (10%) containing spacer material. A prototype material (Heraeaus Medical, Germany) with 15% calcium carbonate was compared. Both were gentamicin impregnated, ready-made for clinical application (preformed) and consist of a tibial and a femoral component. Force-controlled simulation was carried out on an AMTI knee simulator. The test parameters were in accordance to ISO 14243–1 with a 50% reduced axial force (partial weight bearing). Tests were carried out at 37 °C in closed chambers filled with calf serum. Tests were run for 500,000 cycles at a frequency of 1 Hz. For wear analysis, gravimetric wear measurements according to ISO 14243–2 and wear particle analysis according to ASTM F1877–05 were performed. Results. Fig. 1 presents the results of the gravimetric wear measurements. For the Spacer K cement a mean articular wear mass of 375.53±161.22 mg was determined after 500.000 cycles (femoral components: 149.55±17.30 mg, tibial components: 225.98±153.01 mg). The prototype cement showed lower mean total wear of 136.32±37.58 mg (femoral components: 74.32±33.83 mg, tibial components: 61.99±15.74 mg). However, a statistically significant lower wear rate was only seen for the femoral components (p=0,027). In Fig. 2 isolated PMMA wear particles are shown and the morphological characteristics are given in Tab. 1. Discussion and conclusion. The prototype material showed better wear performance in terms of gravimetric wear and particle release. Thus calcium carbonate seems to be a promising material as radio-opaque substrate in PMMA spacers. Nevertheless, the wear amount released from both spacer materials is much higher as compared to conventional total knee replacements with polyethylene inserts. In this context biological reactions against PMMA particles and an increased release of cytokines have been reported in vitro [1] and furthermore, the promotion of osteolysis has been shown in vivo in the presence of PMMA particles [2]. As a clinical consequence we suggest excessive debridement during removal of the cement spacer components to reduce the risk of third body wear for the final joint replacement. Beside the wear performance further studies are essential to prove the mechanical stability and the antibiotic release kinetics for the prototype cement

Aim. Bone and implant-associated infections caused by microorganisms that grow in biofilm are difficult to treat because of persistence and recurrence. Systemic administration of antibiotics is often inefficient because the poor vascularization of the site of infection. This issue has led to the development of biomaterials capable to locally deliver high doses of therapeutic agents to the injured bone with minimal systemic effects. In this context, calcium sulphate/hydroxyapatite (CS/HA) bone graft substitutes are widely used being safe, osteoconductive and resorbable biomaterials that can be easily enriched with consistent amounts of antibiotics. In this in vitro study, the capability of the eluted antibiotics to select the tested bacterial strains for antibiotic resistance was evaluated to confirm the safe use of the product. Method. S. aureus, S. epidermidis and P. aeruginosa isolated in our Institute from bone and joint infection with different resistance phenotypes were used. 6 × 2.5 mm CS/HA discs were generated by pouring the antibiotic loaded formulations in a mold and were used as a modified disk diffusion test. The resistance selection was evaluated by subculturing cells growing on the edge of the zone of inhibition (ZOI) for seven days. Minimum inhibitory concentrations (MICs) of gentamicin and vancomycin were determined by broth microdilution method before and after the selection of resistance assay. In addition, MICs were assessed after seven day passage on antibiotic free agar plates to evaluate if eventual decrease of antibiotic susceptibility was stable or only transient. Results. Commonly, no adaptation in presence of both CS/HA formulations was observed by analysing ZOI on agar medium. The kinetic of decrease of the ZOI was similar between the strains, with the exception of gentamicin resistant staphylococci in presence of gentamicin loaded CS/HA, which was faster with respect to the susceptible strains. Conclusions. The present study shows that elution of gentamicin and vancomycin from CS/HA bone graft substitutes did not induce a decrease in susceptibility to these antibiotics in an in vitro setting, suggesting the safe use of the product

Purpose. Infections in orthopaedic surgery are costly, debilitating complications. The search for new treatments and prevention strategies has led to the use of antibiotic-filled calcium sulfate (CaS) as a bone void filler that is both safe and effective. The purpose of this study was to examine the available data on the efficacy of this technology. Methods. A literature search was performed for studies that evaluated the use of antibiotic-loaded CaS cement in orthopaedics published between inception of the databases to 2017. Selected studies included randomized controlled trials (RCTs) and observational studies published in the English language that met the following criteria: 1) patients underwent an orthopaedic procedure; 2) CaS cement with an antibiotic was used; and 3) at least one of our outcomes were mentioned. Outcomes included resolution of infection, complications related to treatment, subsequent surgeries, overall infection rate, fracture union rate, clinical outcomes, and wound complications. A total of 17 studies were included. Results. Ten studies examined the use of antibiotic-eluting CaS cement with surgical debridement to treat osteomyelitis and reported resolution rates ranging from 80–100%. Two studies examined CaS for prophylaxis of infection after open fracture, with subsequent infection rates ranging from 0–22%. Two studies examined infected non-unions with CaS used as an adjunct to surgery with an 87.5% infection clearance rate. Finally, three studies examined the use of local antibiotic release from CaS in the repair of infected TKAs or THAs, with success rates ranging from 52–93.3%. Conclusion. Initial results support the use of CaS with surgical debridement for osteomyelitis and infected non-unions. Results are mixed for CaS use in the prophylaxis of infection after open fractures and for PJIs, thereby necessitating further research. Overall the studies were small, retrospective, and lacked controls. Further research should focus on RCTs to minimize bias and investigate for non-inferiority. For any figures or tables, please contact authors directly

A multimodality approach is needed for management of infected joint replacement prostheses and infected skeletal metalwork. We present our results in six patients managed surgically with standard techniques, with the addition of a local antibiotic delivery system using absorbable Calcium Sulphate beads. A retrospective study was undertaken of 6 patients with established musculoskeletal infection in relation to existing metalwork. Two patients had infection in the hip replacement prosthesis, three had infected prosthetic knee joints and one had infection in a femoral locking plate. All were treated with extensive debridement, revision / retention of implants, parenteral antibiotics and local antibiotics. Patients were followed up in clinic for resolution of inflammatory markers and subsidence of signs of infection. Control of infection was achieved in five patients at average 19 months followup. One patient had persistent infection and has undergone further surgery. In this preliminary study, we found local antibiotic delivery using absorbable calcium sulphate beads to be an effective adjuvant to standard debridement, parenteral antibiotics and revision of implants

Bone and joint infections of the lower limbs cause significant morbidity for patients. Infection is a devastating complication for prosthetic joint replacements. In this large case series from a single centre in the NE of England, we present our experience of using antibiotic impregnated dissolvable synthetic pure calcium sulphate beads [Stimulan R]1 for local elution of antibiotics at the site of infection. At our centre, from August 2012 to Jan 2015, antibiotic impregnated dissolvable synthetic pure calcium sulphate beads [Stimulan R]1 was used for local elution of antibiotics in 45 patients with lower limb bone or joint infections. Tailored plans were made by Orthopedic surgeon and Microbiologist MDTs based on bacteria and sensitivities. Cases included 20 THR, 13 TKR, 5 Hemiarthroplasties, 4 tibial nonunions, 1 infected femoral plate and 2 paediatric osteomyelitis. Organisms isolated – Coagulase negative Staphs, Staph aureus, MRSA, E coli, Enterococcus, Enterobacter cloacae, Serratia and 1 Salmonella typhimurium!!. In our cases, a combination of Vancomycin and Gentamicin was added to Stimulan beads following manufacturer's mixing guide. In 2 cases, we added Ceftazidime to the beads and Daptomycin in 1 case. In bone infections, surgical debridement and systemic antibiotics were also needed. All arthroplasty infections underwent explantation with addition of antibiotic impregnated beads either at single stage or both stages of 2 stage revisions and systemic antibiotics. Follow up (ranging 9months to 2 years) indicates no failure so far. The beads caused no excessive wound drainage. There was no need to remove beads as they dissolve. In the cases where a staged revision was performed, the beads were inserted at first stage and there was microbiological clearance of infection at 2nd stage. Our series includes some experince in paediatric cases too. As far as we are aware, this is the largest series in the UK from a single centre reporting experience with Stimulan in infected bone and joints of the lower limbs. Our experience suggests use of dissolvable pure Calcium sulphate beads impregnated with carefully selected antibiotics, works as an effective adjunct to current treatments and offers flexibility with choice of antiobiotics that can be added locally. Acknowledgements. Biocomposites UK for supporting attendance at EBJIS. Authors control ownership of all data and analysis

Introduction. Osteoporotic intertrochanteric fracture (ITF) is frequent injuries affecting elderly, osteoporotic patients leading to significant morbidity and mortality. Successful prognosis including union and alignment is challenging even though initial successful reduction with internal fixation. Although many factors are related to the patient's final prognosis. Well reduction with stable fracture fixation is still the goal of treatment to improve the quality of life and decrease morbidity in patients with hip fractures, but this in turn depends on the type of fracture and bone quality. Poor bone quality is responsible for common complications, such as failure of fixation, varus collapse and lag screw cut-out, in elderly patients. Kim et al. found that the complication rate when using conventional DHS in unstable ITFs can be as high as 50% because of screw cut-out. We used the dynamic hip screws (DHS) strengthened by calcium phosphate cement (CPC) for treatment femoral intertrochanteric fracture and review the prognosis of our patients. Materials and Methods. From January of 2011 to January of 2014, 42 patients with femoral intertrochanteric fracture underwent surgery with DHS strengthened by CPC. Comparisons were made between the DHS plus CPC group with the other patients with only DHS used in our department. All patients were followed up for an average time of 14.8(6 to 24) months. X-ray was reviewed for the conditions of union and implant failure. Results. In DHS group, fixation failure happened in 3 case, delayed union and coax varus deformity in 2 cases. IN DHS plus CPC group, all fractures healed uneventfully, there is no non-union or malunion in this group. There is only 1 fixation cut-out and 1 secondary lag screw sliding was noted, however, union was still well over fracture site in this case, the patient had no clinical symptoms. Discussion. Residual bony defects present after DHS fixation in intertrochanteric fracture may lead to postoperative complications, including nonunion or implant failure. DHS strengthened by CPC is reliable fixation for old patients with intertrochanteric fracture, We demonstrated that augmentation of the bony defect with dynamic hip screw by reinforced calcium phosphate cement significantly improved the strength of osteoporotic bone, prevent screw loosening, and promote early healing of fracture. The patients can be decreased the risk of refracture and allow early weight bearing, especially in elderly patients with osteoporotic bone

Aims. Calcium sulphate (CaSO. 4. ) is a resorbable material that can be used simultaneously as filler of a dead space and as a carrier for the local application of antibiotics. Our aim was to describe the systemic exposure and the wound fluid concentrations of vancomycin in patients treated with vancomycin-loaded CaSO. 4. as an adjunct to the routine therapy of bone and joint infections. Patients and Methods. A total of 680 post-operative blood and 233 wound fluid samples were available for analysis from 94 implantations performed in 87 patients for various infective indications. Up to 6 g of vancomycin were used. Non-compartmental pharmacokinetic analysis was performed on the data from 37 patients treated for an infection of the hip. Results. The overall systemic exposure remained within a safe range, even in patients with post-operative renal failure, none requiring removal of the pellets. Local concentrations were approximately ten times higher than with polymethylmethacrylate (PMMA) as a carrier, but remained below reported cell toxicity thresholds. Decreasing concentrations in wound fluid were observed over several weeks, but remained above the common minimum inhibitory concentrations for Staphylococcus up to three months post-operatively. . Conclusion. This study provides the first pharmacokinetic description of the local application of vancomycin with CaSO. 4. as a carrier, documenting slow release, systemic safety and a release profile far more interesting than from PMMA. In particular, considering in vitro data, concentrations of vancomycin active against staphylococcal biofilm were seen for several weeks. Cite this article: Bone Joint J 2017;99-B:1537–44

Calcium sulphate (CaSO. 4. ) is a recognised form of delivery of antibiotic for the treatment of bone infection. Complications inherent in the rapid reabsorption are well recognised (predominantly that of wound breakdown and leakage). There is little data on the frequency of these complications. The purpose of this study was to quantify the incidence of wound leakage from CaSO. 4. and the service impact in orthopaedic surgery. Infective limb reconstruction cases managed with gentamicin impregnated CaSO. 4. between 2004–2012 were identified. Co-morbidities and factors influencing wound leakage were recorded. Medical and wound care notes were analysed. Episodes of delayed discharge and unscheduled clinic attendance due to wound leakage were recorded. 80 patients (18 female, 62 male), with a mean age of 45 years (18–80 years, median 46 years) underwent 84 procedures utilising CaSO. 4. 47 were in the tibia, 14 in the femur, 10 in the humerus. A mean of 36 mL (4–150 mL, median 22 ml, unknown in 18 cases) was used. 31 cases (37%) had post-operative wound leakage, the majority from the tibia(55%) and femur(25%). 21 cases (25%) leaked within the first week. Each 10 ml rise in CaSO. 4. volume lead to a 50% rise in leakage incidence. Leak duration ranged from 4 days–10 months. The majority leaked between 1–4 months before ceasing spontaneously and without specific treatment. 14 cases (17%) required a cumulative 32 unscheduled clinic appointments for leakage. Further surgery was required for infection in 7 cases (8.3%). Delayed discharge was not clearly attributable to CaSO. 4. The mode of skin closure and cultured organism did not affect leakage. CaSO. 4. has unpredictable leakage, but is present in 1/3 of patients. Volume of CaSO. 4. impacts on leakage. Leakage usually self-resolves and does not clearly impact on final outcomes. The cost impact of ongoing wound care and additional clinic appointments may be substantial