Polytherapy versus monotherapy in the treatment of tibial non-unions: a retrospective study.

BACKGROUND: Treating tibial non-unions efficiently presents a challenge for orthopaedic trauma surgeons. The established gold standard involves implanting autologous bone graft with adequate fixation, but the addition of biologicals according to the so-called diamond concept has become increasingly popular in the treatment of non-unions. Previous studies have indicated that polytherapy, which involves implanting mesenchymal stem cells, bioactive factors and osteoconductive scaffolds, can improve bone healing. This study aims to evaluate the efficacy of polytherapy compared with monotherapy in treating tibial non-unions of varying severity. MATERIALS AND METHODS: Data from consecutive tibial non-unions treated between November 2014 and July 2023 were retrospectively analysed. The Non Union Scoring System (NUSS) score before non-union surgery, and the Radiographic Union Score for Tibial fractures (RUST), scored at 1, 3, 6, 9, 12 and 18 months post-surgery, were recorded. Initially, a comparison was made between the polytherapy and monotherapy groups. Subsequently, patients receiving additional surgical non-union treatment were documented, and the frequency of these treatments was tallied for a subsequent per-treatment analysis. RESULTS: A total of 34 patients were included and divided into a polytherapy group (n = 15) and a monotherapy group (n = 19). The polytherapy group demonstrated a higher NUSS score (44 (39, 52) versus 32 (29, 43), P = 0.019, z = -2.347) and a tendency towards a higher success rate (93% versus 68%, P = 0.104) compared with the monotherapy group. For the per-treatment analysis, 44 treatments were divided into the polytherapy per-treatment group (n = 20) and the monotherapy per-treatment group (n = 24). The polytherapy per-treatment group exhibited a higher NUSS score (48 (43, 60) versus 38 (30, 50), P = 0.030, z = -2.173) and a higher success rate (95% versus 58%, P = 0.006) than the monotherapy per-treatment group. Within the monotherapy per-treatment group, the NUSS score displayed excellent predictive performance (AUC = 0.9143). Setting the threshold value at 48, the sensitivity and specificity were 100.0% and 70.0%, respectively. CONCLUSIONS: Polytherapy is more effective than monotherapy for severe tibial non-unions, offering a higher success ratio. The NUSS score supports decision-making in treating tibial non-unions. LEVEL OF EVIDENCE: Level III.

Mid-term clinical results of chronic cavitary long bone osteomyelitis treatment using S53P4 bioactive glass: a multi-center study.

Introduction: Chronic osteomyelitis is a challenging condition in the orthopedic practice and traditionally treated using local and systemic antibiotics in a two-stage surgical procedure. With the introduction of the antimicrobial biomaterial S53P4 bioactive glass (Bonalive®), chronic osteomyelitis can be treated in a one-stage procedure. This study evaluated the mid-term clinical results of patients treated with S53P4 bioactive glass for long bone chronic osteomyelitis. Methods: In this prospective multi-center study, patients from two different university medical centers in the Netherlands were included. One-stage treatment consisted of debridement surgery, implantation of S53P4 bioactive glass, and treatment with culture-based systemic antibiotics. If required, wound closure by a plastic surgeon was performed. The primary outcome was the eradication of infection, and a secondary statistical analysis was performed on probable risk factors for treatment failure. Results: In total, 78 patients with chronic cavitary long bone osteomyelitis were included. Follow-up was at least 12 months (mean 46; standard deviation, SD, 20), and 69 patients were treated in a one-stage procedure. Overall infection eradication was 85 %, and 1-year infection-free survival was 89 %. Primary closure versus local/muscular flap coverage is the only risk factor for treatment failure. Conclusion: With 85 % eradication of infection, S53P4 bioactive glass is an effective biomaterial in the treatment of chronic osteomyelitis in a one-stage procedure. A major risk factor for treatment failure is the necessity for local/free muscle flap coverage. These results confirm earlier published data, and together with the fundamentally different antimicrobial pathways without antibiotic resistance, S53P4 bioactive glass is a recommendable biomaterial for chronic osteomyelitis treatment and might be beneficial over other biomaterials.

Use of contemporary biomaterials in chronic osteomyelitis treatment: Clinical lessons learned and literature review.

Chronic osteomyelitis has always been a therapeutic challenge for patient and surgeon due to the specific problems related with bone infection and bacterial biofilm eradication. Other than being the cause of infection or facilitating spread or persistence of infection, biomaterials are also becoming a tool in the treatment of infection. Certain novel biomaterials have unique and ideal properties that render them perfectly suited to combat infection and are therefore used more and more in the treatment of chronic bone infections. In case of infection treatment, there is still debate whether these properties should be focused on bone regeneration and/or their antimicrobial properties. These properties will be of even greater importance with the challenge of emerging antimicrobial resistance. This review highlights indications for use and specific material properties of some commonly used contemporary biomaterials for this indication as well as clinical experience and a literature overview.

The Implantation of Bioactive Glass Granules Can Contribute the Load-Bearing Capacity of Bones Weakened by Large Cortical Defects.

Bioactive glass (BAG) granules (S53P4) have shown good clinical results in one-stage treatment of osteomyelitis. During this treatment, a cortical window is created, and infected bone is debrided, which results in large defects that affect the mechanical properties of the bone. This study aimed to evaluate the role of BAG granules in load-bearing bone defect grafting. First, the influence of the geometry of the cortical window on the bone bending stiffness and estimated failure moments was evaluated using micro finite element analysis (µFE). This resulted in significant differences between the variations in width and length. In addition, µFE analysis showed that BAG granules contribute to bearing loads in simulated compression of a tibia with a defect grafted with BAG and a BAG and bone morsel mixture. These mixtures potentially can unload the cortical bone that is weakened by a large defect directly after the operation by up to approximately 25%, but only in case of optimal load transfer through the mixture.

Antibiotic-Loaded Polymethylmethacrylate Beads and Spacers in Treatment of Orthopedic Infections and the Role of Biofilm Formation.

Polymethylmethacrylate (PMMA) also referred as (acrylic) bone cement is a non-degradable biomaterial that has been used in clinical orthopedic practice for several decades. PMMA can be used in a plain formulation, but is often used in an antibiotic-loaded formulation in (primary and revision) arthroplasty and in treatment of orthopedic infections as prosthetic joint infections (PJI) and chronic osteomyelitis. In treatment of PJIs antibiotic-loaded PMMA is often used as a carrier material for local antibiotic delivery in addition to treatment with systemic antibiotics. In this case, the antibiotic-loaded PMMA is often used as a spacer or as a bead chain. Since the introduction of PMMA as an antibiotic carrier there is a tremendous amount of scientific and clinical papers published, which studied numerous different aspects of antibiotic-loaded PMMA. This paper will review the research regarding basic principles of antibiotic-loaded PMMA as mechanism of action, antibiotic-release capacities, choice of antibiotics and influences on mechanical properties of PMMA. Subsequently, concerns regarding the application of antibiotic-loaded PMMA, biofilm formation, antibiotic resistance and local or systemic toxicity will be discussed. In addition to these subjects, the role of antibiotic loaded PMMA in clinical treatment of PJIs and chronic osteomyelitis is discussed in the final part of this paper.

One Week of Hospitalization Following Elective Hip Surgery Induces Substantial Muscle Atrophy in Older Patients.

OBJECTIVES: Short successive periods of skeletal muscle disuse have been suggested to substantially contribute to the observed loss of skeletal muscle mass over the life span. Hospitalization of older individuals due to acute illness, injury, or major surgery generally results in a mean hospital stay of 5 to 7 days, during which the level of physical activity is strongly reduced. We hypothesized that hospitalization following elective total hip arthroplasty is accompanied by substantial leg muscle atrophy in older men and women. DESIGN AND PARTICIPANTS: Twenty-six older patients (75 ± 1 years) undergoing elective total hip arthroplasty participated in this observational study. MEASUREMENTS: On hospital admission and on the day of discharge, computed tomographic (CT) scans were performed to assess muscle cross-sectional area (CSA) of both legs. During surgery and on the day of hospital discharge, a skeletal muscle biopsy was taken from the m. vastus lateralis of the operated leg to assess muscle fiber type-specific CSA. RESULTS: An average of 5.6 ± 0.3 days of hospitalization resulted in a significant decline in quadriceps (-3.4% ± 1.0%) and thigh muscle CSA (-4.2% ± 1.1%) in the nonoperated leg (P < .05). Edema resulted in a 10.3% ± 1.7% increase in leg CSA in the operated leg (P < .05). At hospital admission, muscle fiber CSA was smaller in the type II vs type I fibers (3326 ± 253 µm2 vs 4075 ± 279 µm2, respectively; P < .05). During hospitalization, type I and II muscle fiber CSA tended to increase, likely due to edema in the operated leg (P = .10). CONCLUSIONS: Six days of hospitalization following elective total hip arthroplasty leads to substantial leg muscle atrophy in older patients. Effective intervention strategies are warranted to prevent the loss of muscle mass induced by short periods of muscle disuse during hospitalization.

2-stage revision of 120 deep infected hip and knee prostheses using gentamicin-PMMA beads.

Background and purpose - A 2-stage revision is the most common treatment for late deep prosthesis-related infections and in all cases of septic loosening. However, there is no consensus about the optimal interval between the 2 stages. Patients and methods - We retrospectively studied 120 deep infections of total hip (n = 95) and knee (n = 25) prostheses that had occurred over a period of 25 years. The mean follow-up time was 5 (2-20) years. All infections had been treated with extraction, 1 or more debridements with systemic antibiotics, and implantation of gentamicin-PMMA beads. There had been different time intervals between extraction and reimplantation: median 14 (11-47) days for short-term treatment with uninterrupted hospital stay, and 7 (3-22) months for long-term treatment with temporary discharge. We analyzed the outcome regarding resolution of the infection and clinical results. Results - 88% (105/120) of the infections healed, with no difference in healing rate between short- and long-term treatment. 82 prostheses were reimplanted. In the most recent decade, we treated patients more often with a long-term treatment but reduced the length of time between the extraction and the reimplantation. More reimplantations were performed in long-term treatments than in short-term treatments, despite more having difficult-to-treat infections with worse soft-tissue condition. Interpretation - Patient, wound, and infection considerations resulted in an individualized treatment with different intervals between stages. The 2-stage revision treatment in combination with local gentamicin-PMMA beads gave good results even with difficult prosthesis infections and gentamicin-resistant bacteria.

Good results in postoperative and hematogenous deep infections of 89 stable total hip and knee replacements with retention of prosthesis and local antibiotics.

BACKGROUND: Deep postoperative and hematogenous prosthesis infections may be treated with retention of the prosthesis, if the prosthesis is stable. How long the infection may be present to preclude a good result is unclear. PATIENTS AND METHODS: We retrospectively studied 89 deep-infected stable prostheses from 69 total hip replacements and 20 total knee replacements. There were 83 early or delayed postoperative infections and 6 hematogenous. In the postoperative infections, treatment had started 12 days to 2 years after implantation. In the hematogenous infections, symptoms had been present for 6 to 9 days. The patients had been treated with debridement, prosthesis retention, systemic antibiotics, and local antibiotics: gentamicin-PMMA beads or gentamicin collagen fleeces. The minimum follow-up time was 1.5 years. We investigated how the result of the treatment had been influenced by the length of the period the infection was present, and by other variables such as host characteristics, infection stage, and type of bacteria. RESULTS: In postoperative infections, the risk of failure increased with a longer postoperative interval: from 0.2 (95% CI: 0.1-0.3) if the treatment had started ≥ 4 weeks postoperatively to 0.5 (CI: 0.2-0.8) if it had started at ≥ 8 weeks. The relative risk for success was 0.6 (CI: 0.3-0.95) if the treatment had started ≥ 8 weeks. In the hematogenous group, 5 of 6 infections had been treated successfully. INTERPRETATION: A longer delay before the start of the treatment caused an increased failure rate, but this must be weighed against the advantage of keeping the prosthesis. We consider a failure rate of < 50% to be acceptable, and we therefore advocate keeping the prosthesis for up to 8 weeks postoperatively, and in hematogenous infections with a short duration of symptoms.