The report, based on laboratory animal studies conducted at the UPMC's Musculoskeletal Research Center, was presented Sunday by investigators Arun S. Shanbhag, Ph.D., Carl T. Hasselman, M.D., and Harry E. Rubash, M.D., at the Orthopaedic Research Society meeting of biomedical scientists, in conjunction with the annual gathering of the American Academy of Orthopaedic Surgeons (AAOS) this week in San Francisco.
Nearly 500,000 joint replacement operations are done in the United States each year, including those for hips and knees, according to Dr. Rubash, associate professor and chief of adult reconstructive surgery in the UPMC's department of orthopaedic surgery. About 10 percent of them within 10 years require additional surgeries, each costing $40,000 to $60,000, to replace the components and surrounding bone that have been 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 Dr. Shanbhag, assistant professor of orthopaedic surgery and mechanical engineering at the University of Pittsburgh.
"Our biggest surgical problem is bone loss associated with the loosened implants," said Dr. Rubash. "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, explained Dr. Shanbhag, who is also a core faculty member of the bioengineering program at Pitt.
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. The researchers first had to synthetically create microscopic debris particles identical to those which normally accumulate around a human artificial joint implant over several years. No researchers have ever before been able to produce these particles suitable for scientific study. This breakthrough allowed the investigators to design an appropriate animal model in which to inject the particles to simulate particle disease and thus test the effectiveness of the drug in preventing joint implant failure, according to Dr. Shanbhag.
Interim results from a study to evaluate the effect of alendronate in preventing bone loss and loosening in hip joints in humans who have had hip replacement surgery will be available this year, according to Dr. Rubash. Also this year, he said, the UPMC will be participating in one of two multi-national human clinical trials to study the effect of alendronate in hip and knee replacements. "We look forward to these exciting and promising clinical trials whose results could have major implications for orthopaedic surgery," added Dr. Rubash. Alendronate, developed and manufactured by Merck & Co., Inc., under the brand name Fosamax (TM), is commonly indicated to treat osteoporosis in postmenopausal women and also indicated in the United States to treat patients with Paget's disease of the bone. Recent clinical studies with Fosamax confirm the safety and efficacy of the drug in building bone and preventing hip and spine fractures in postmenopausal women with an existing spinal fracture and in preventing the bone loss that leads to osteoporosis in postmenopausal women who do not yet have the disease. Merck filed for a new indication for Fosamax for the prevention of osteoporosis in postmenopausal women in April 1996.
Drs. Shanbhag, Hasselman and Rubash will share their research findings also at the Hip Society meeting on Sunday, Feb. 16, another session of the AAOS gathering. The Hip Society will honor the UPMC team with the 1997 John Charnley Award, named after England's Sir John Charnley, inventor of the artificial hip. The award is given each year to a paper based on innovative clinical or basic research encompassing important advances in the management of hip disorders.