By Jennie McKee
Locally delivered bisphosphonates may enhance bone formation
“Bisphosphonates are known to have potential for increasing bone stock by suppressing osteoclastic activity,” said J. Dennis Bobyn, PhD. By enhancing local bone formation, contended Dr. Bobyn, these drugs may provide better mechanical fixation for total joint implants.
Dr. Bobyn and his colleagues studied the impact of adding zoledronic acid (ZA) to the hydroxyapatite coating of cementless metal implants. They found that direct elution of the ZA from the implants strongly enhances net local bone formation. They present their results in Scientific Exhibit 33, “Locally delivered bisphosphonate for enhancement of bone formation and implant fixation.” The scientific exhibit builds upon a study that received the Otto Aufranc Award from the Hip Society in 2005.
Histologic sections taken from the same animal 1 year after surgery show bone formation around a control implant that was not dosed with ZA (left) compared to the additional bone that formed around an implant dosed with 0.20 mg of ZA.
Courtesy of J. Dennis Bobyn, PhD
Series of studies
The investigators performed a series of complementary studies to investigate whether delivering a potent bisphosphonate (ZA) directly from implants to bone would enhance peri-implant bone formation and implant fixation. They selected ZA because of its potency and prolonged duration of its bone-forming effect.
“We have also shown,” noted Dr. Bobyn, “that the drug remains very local, with only minute exposure systemically that is subtherapeutic.”
Adding dissolved ZA to the hydroxyapatite coating of the highly porous, metallic implants initially immobilized the bisphosphonate. Researchers performed in vitro and canine implant studies to determine the following:
- ZA elution characteristics (using 14C labeled ZA) in water
- local bone response, persistence of bone formation, and the dose effect on bone formation
- the degree of local ZA retention and systemic distribution after elution
Evaluating the effect of ZA—and its clinical utility
Researchers also measured mineral content, elastic modulus, and hardness to determine how ZA affected bone properties.
Elution studies found an initial burst release of the drug (approximately 40 percent within 15 minutes), followed by a much slower progressive release (55 percent by 12 weeks). Results of the canine implant studies showed that bone enhancement persisted between 12 and 52 weeks and that 0.05 mg ZA was statistically equivalent to 0.20 mg ZA for increasing bone ingrowth, peri-implant bone, and interface bone.
“Radiolabeled drug studies showed that ZA elution remained extremely localized to the immediate peri-implant region,” said Dr. Bobyn, who added that ZA levels at remote skeletal sites were up to 300-fold less than those adjacent to the implant. “We measured moderate mechanical property changes in the peri-implant trabecular bone closest to the source of ZA elution, and insignificant changes in the adjacent cortical bone.”
Dr. Bobyn summed up the importance of the studies’ results.
“The additional bone that forms within, on, and around porous implants provides more rapid and substantially increased mechanical fixation,” said Dr. Bobyn. “The use of ZA with cementless implants could have utility in all joint replacement procedures, especially revision cases where bone stock needs to be restored and implant stability is more tenuous than in primary cases.
“In addition,” he continued, “it has potential for use in structurally weak, osteoporotic bone and in bone sites that are more challenging for bone ingrowth fixation.”
Scientific Exhibit 33 can be viewed in the Venetian/Sands Expo Hall D from 7 a.m. to 5:30 p.m.
Copresenters of this scientific exhibit include Michael Tanzer, MD; Kimberly McKenzie, BSc, Dorota Karabasz, RN; and Jan J. Krygier, CET. Drs. Bobyn and Tanzer report ties to Zimmer.