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March 20, 1997


Research shows drug may prevent need for repeat hip surgeries

The bone-building drug alendronate sodium may reduce the need for costly repeat surgeries by preventing the loosening of hip joints common after total hip replacement surgery, University of Pittsburgh Medical Center (UPMC) research shows.

The report, based on laboratory animal studies conducted at UPMC's Musculoskeletal Research Center, was presented this month by investigators Arun S. Shanbhag, Carl T. Hasselman and Harry E. Rubash at the Orthopaedic Research Society meeting of biomedical scientists, in conjunction with the annual gathering of the American Academy of Orthopaedic Surgeons in San Francisco.

Nearly 500,000 joint replacement operations are done in the United States each year, including those for hips and knees, said Rubash, associate professor and chief of adult reconstructive surgery in UPMC's orthopaedic surgery department.

About 10 percent of these operations require additional surgeries, each costing $40,000 to $60,000, to replace the components and surrounding bone that have broken down and loosened by an inflammatory process generated by the implanted materials.

"Based on our animal study with alendronate, we believe we may have found a way to control the bone destruction around failed joint implants, a previously un-solvable problem that has led to devastating consequences for the nearly 50,000 patients who must undergo joint replacement revision surgery each year in this country," said Shanbhag, a Pitt assistant professor of orthopaedic surgery and medical engineering.

"Our biggest surgical problem is bone loss associated with the loosened implants" Rubash said. "If we could avoid the need for repeat surgeries by a mere 10 percent or decrease the complexity of the procedures by eliminating bone loss, an estimated $200 million would be saved." In total hip replacement, a plastic socket is implanted into the hip, joined by a metal ball anchored into the top of, and down through, the thigh bone. Although the ball-and-socket device that mimics hip joint movement is extremely smooth, tiny particles of wear debris still are released and remain within the space between the ball's anchor and the thigh bone. Within this space, the debris interacts with immune cells that, in turn, secrete bone resorbing substances. This process, called particle disease, leads to erosion of the surrounding thigh bone, painful joint swelling and loosening and, in many cases, implant failure.

The UPMC research, which is the first-ever study of the effect of alendronate on animal hip joint replacements, indicates that the oral prescription drug can prevent this destructive process.


Brain cooling found effective in treating head trauma

Moderate cooling of the brain is the first new treatment shown to be effective for brain trauma, according to a study by Pitt medical center researchers published last month in the New England Journal of Medicine.

More than a dozen previous trials of various medications have failed to show benefit for brain trauma patients.

Investigators from UPMC's Brain Trauma Research Center found that inducing moderate hypothermia — lowering the body temperature from the normal range of 98-99 to 87-88 degrees Fahrenheit — for 24 hours after patients suffer severe traumatic brain injury hastened recovery and lessened disability for those patients compared with patients who did not receive the treatment. The standard measure of mental responsiveness is the Glasgow Coma Scale, developed to assess coma by determining motor, verbal and eye response to stimulus.

Good outcomes were achieved by 56 percent of hypothermia-treated patients compared with 33 percent of the patients treated conventionally. Mortality rates were 20 percent among those who received hypothermia treatment and 24 percent in the other patients.

In a subset of patients who showed some brain activity despite unconsciousness at the time of admission (Glasgow Coma Scale 5, 6 or 7, amounting to 61 percent of those in the study), the results were even more dramatic. Six months after their injuries, 73 percent of patients receiving hypothermia treatment had a good outcome (moderate or no disability) compared with 35 percent of patients in the control group. Mortality also was markedly improved in this group of patients: 9 percent in the hypothermia group, 23 percent in the non-hypothermia group. UPMC researchers believe that hypothermia helps patients in two ways: by reducing swelling due to inflammation and by inhibiting the cascade of neurochemicals (especially glutamate) that kill brain cells.

Principal investigator Donald W. Marion, Pitt associate professor of neurosurgery and chief, neurotrauma service at UPMC's neurological surgery department, said: "This study is significant because it verifies the effectiveness of this treatment after more than 15 studies of other therapies proved ineffective. Now, more people who suffer non-penetrating head trauma may be able to resume a normal life. Hypothermia treatment delivered within six hours of trauma is relatively simple and inexpensive to implement and free of unwanted side effects." Severe brain trauma is a common cause of death and mental impairment, particularly among young people. Annually, 50,000 people suffer such injuries and require long-term care at a cost of more than $20 billion, according to the National Institute of Neurological Disorders and Stroke.

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