DAICY Trial - Dual vs. Single-Antibiotic Impregnated Cement in Hemiarthroplasty for Femoral Neck Fracture: A Register-based Cluster-randomized Cross-over Controlled Trial

In Sweden, hip fractures annually affect close to 20,000 elderlies, often frail patients. Although the incidence of this injury seems to be stabilizing or even slightly declining, hip fractures cause an annual economic burden of no less than 800 million € in Sweden alone and the costs are increasing.

Femoral neck fractures (FNFs) are mainly a fragility fracture in the elderly and frail, predominantly affecting women after menopause but reports have indicated an increased incidence in elderly men. The average age of patients suffering a hip fracture has been increasing over the last decade and is around 80 years with an exponential increase of incidence with age. The lifetime risk of hip fracture in Sweden is 20% for women and 11% in men. A hip fracture is related to a doubled risk of death during the first year after fracture in comparison to age-matched controls.

FNFs are classified according to the degree of fracture displacement and the most widely used is the Garden classification. As displacement increases, the risk of disruption of the blood supply to the femoral head increases. Displaced fractures represent two thirds of the FNFs. With a disrupted vascular supply, the risk for healing disturbances, complications and reoperations increases when treated with internal fixation with screws or pins. For displaced fractures in elderly patients treated with internal fixation, failure rates of 35-50% have been reported in the literature. The most frequent complications are avascular necrosis and pseudarthrosis due to disrupted vascular supply of the femoral head and mechanical failure due to inadequate fixation. Long-term follow-up studies have emphasized the superiority of replacing the joint by hip arthroplasty in comparison to internal fixation in regard to hip function. Hip arthroplasty with either a total or hemiarthroplasty is a reliable option due to its ability to restore hip function and reduce the need for secondary surgery after an FNF. In hip arthroplasty implants are fixed to the bone with or without the use of bone cement (polymethyl methacrylate). Uncemented fixation in FNF patients has been linked to an increased risk for periprosthetic femoral fractures. In Sweden cemented hip arthroplasties are most frequently used and are regarded as the gold standard for FNF patients.

Bone cement or polymethyl methacrylate (PMMA) is widely used for implant fixation in orthopaedic procedures. PMMA acts as a void-filler that creates a tight space which holds the implant against the bone and acts as a 'grout'. Bone cements have no adhesive properties and rely instead on close mechanical interlock between the irregular bone surface and the prosthesis. PMMA is an acrylic polymer that is formed by mixing 2 sterile components, a liquid methyl methacrylate monomer and a powdered methyl methacrylate-styrene polymer. When mixed the liquid monomer polymerizes around the pre-polymerized powder particles to form hardened PMMA. An exothermic reaction generate heat in the process which reaches temperatures of around 82-86 °C in the body. In order to make the cement visible on radiographs, a contrast agent is added (zirconium dioxide or bariumsulphate).

Bone cement has proven useful as carrier of specific active substances, e.g., antibiotics added to the powder component. Antibiotics are delivered directly to the surgical site which in turn give a high concentration and low systemic concentration well below the clinical routine dosages for systemic single injections. Various antibiotics have been successfully mixed and used with bone cements like gentamycin, clindamycin etc. Compared to intramuscular administration, systemic concentration levels of gentamycin are low with bone cement, usual maximum concentrations below 1 μg/ml (<10%) without any detectable systemic levels after 7 days. In Sweden, antibiotic loaded cement is routinely used and represents the standard of care in cemented primary total hip arthroplasty, always in combination with systemic prophylaxis to reduce the risk for revision surgery due to periprosthetic joint infection (PJI). The type of antibiotic impregnated bone cement varies between regions, countries and type of surgical procedure performed.