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 presented their results in Scientific Exhibit 33, “Locally Delivered Bisphosphonate for Enhancement of Bone Formation and Implant Fixation.” The scientific exhibit, which won an Award of Excellence at the 2009 AAOS Annual Meeting, built on a study that received the Otto Aufranc Award from the Hip Society in 2005.
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.”
Dissolved ZA was added to the hydroxyapatite coating of the highly porous, metallic implants to initially immobilize 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 (Fig. 1).
“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 found 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,” he said.
“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.”
Copresenters included Michael Tanzer, MD; Kimberly McKenzie, BSc, Dorota Karabasz, RN; and Jan J. Krygier, CET. The authors reported the following disclosures: Dr. Bobyn—Zimmer and Stryker; Dr. Tanzer—Zimmer.
Jennie McKee is a staff writer for AAOS Now. She can be reached at email@example.com