Hip fractures among the elderly are a significant and rapidly growing public health problem. The prevailing view is that most hip fractures are the consequence of age-related bone loss or osteoporosis. However, because over 90% of hip fractures are the result of falls, we have undertaken a falls surveillance study to determine if factors related to the mechanics of falling are associated with increased risk of hip fracture. Case subjects with hip fracture and control subjects without hip fracture were sampled from falls recorded at the Hebrew Rehabilitation Center for Aged, a chronic care facility. Fall information was obtained by interview of the subject and witnesses if the fall was witnessed. Data were analyzed by multiple logistic regression. Increased risk of hip fracture from a fall was associated with impacting on the hip or side of the leg and potential energy associated with the fall. Quetelet, or body mass index, was inversely related to fracture risk. The adjusted odds ratio of hip fracture for a fall involving impact on the hip region was 21.7 (95% confidence interval, 8.2-58). The potential energy associated with these falls was an order of magnitude greater than the average energy required to fracture elderly, cadaveric, proximal femurs in earlier in vitro experiments. We conclude, therefore, that a fall from standing height should no longer be considered minimal trauma but rather trauma of sufficient magnitude to pose a high risk of hip fracture if impact occurs on the hip and if energy-absorbing processes are inadequate.(ABSTRACT TRUNCATED AT 250 WORDS)

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An experimental biodegradable bone cement [poly(propylene fumarate)-methylmethacrylate] (PPF-MMA) has been compared in vivo with polymethylmethacrylate (PMMA) as a carrier agent for local release of antibiotics. This approach is potentially applicable to the treatment of chronic osteomyelitis where the clinical goal is to achieve sustained high concentrations of antibiotics locally in the infected bone. In our experiments, gentamicin- and vancomycin-impregnated cylindrical PMMA and PPF-MMA cement specimens were implanted subcutaneously in rats, and blood and wound fluid samples were obtained over a 2-week period. Antibiotic levels were determined using immunoassays, and microbiologic activity was confirmed with agar diffusion techniques. The biodegradable PPF-MMA cement achieved and maintained considerably higher wound antibiotic levels than did PMMA cement. Vancomycin levels for the PPF-MMA cement were greater than 20 times those for the PMMA cement at all sampling times from 24 h to 14 days. For both cements, the serum antibiotic concentrations remained safely below maximum levels recommended for parenteral therapy. Mechanical testing of the PPF-MMA cement showed that admixture of 3% by weight of antibiotic did not adversely affect material properties. We conclude that this experimental biodegradable bone cement (PPF-MMA) can be used as a carrier to achieve high sustained local levels and low serum levels of antibiotics. Because it is biodegradable and thus does not require a secondary procedure for removal, it has special potential for use in treatment of chronic osteomyelitis.

A biodegradable, particulate composite bone cement containing gentamicin and vancomycin was used for both treatment and prophylaxis of Staphylococcus aureus osteomyelitis in rats. Osteomyelitis was established by inoculating S. aureus into holes that were drilled in the proximal tibiae and were filled with polymethylmethacrylate (PMMA) cylinders. The cylinders were left in place for 3 weeks. The infections were serially evaluated by clinical and radiographic examination and by quantitative culture for colony forming units (CFUs) at the time the rats were killed. For treatment, cements containing antibiotic were implanted in animals that had established osteomyelitis and were left in place for an additional 3 weeks. Sites treated with biodegradable cement containing antibiotics exhibited significantly fewer CFUs in comparison with controls (p < 0.01). Sites treated prophylactically with the biodegradable cement developed no infections as evaluated by clinical or radiographic criteria or by quantitative culture. At this relatively early time, no significant difference in therapeutic effectiveness was found when either the biodegradable cement or PMMA was used as a carrier for antibiotics.

Acute and chronic osteomyelitis can be difficult to treat by conventional means. Current methods of treatment involve the use of systemic antibiotics, the local implantation of non-degradable drug carriers, and surgical débridement. Each method has specific drawbacks. We report on the use of a new controlled release system utilizing gentamicin and bioerodible, biocompatible polymers (polyanhydrides) designed for drug delivery applications for the treatment of clinical osteomyelitis. We compared this system's ability to reduce bacterial levels in infected bone with that of conventional non-degradable delivery systems based on polymethylmethacrylate (PMMA) and gentamicin. Polyanhydride copolymers of bis-carboxyphenoxypropane and sebacic acid P loaded with gentamicin sulfate and PMMA/gentamicin matrices were implanted in the long bones of Sprague-Dawley rats infected with a strain of Staphylococcus aureus. After 3 weeks of implantation, the polymeric delivery devices were removed and quantitative cultures were used to determine bacterial levels in bone. The polyanhydride/gentamicin matrices demonstrated significant degradation over the 3 week implantation period. Levels of bacteria, measured in colony forming units, were significantly lower in bone implanted with the polyanhydride/gentamicin release system than in long bones of control animals without an implant (p < 0.01), of animals with a polyanhydride polymer implant alone (p < 0.01), and of animals with a PMMA/gentamicin implant (p = 0.03). Bioerodible polyanhydrides show promise as a new treatment modality for infections in bone.