A long-lasting bisphosphonate partially protects periprosthetic bone, but does not enhance initial stability of uncemented femoral stems: A randomized placebo-controlled trial of women undergoing total hip arthroplasty

Abstract

Low bone quality may compromise the success of cementless total hip arthroplasty in high-risk patients such as elderly women. Zoledronic acid is a long-lasting antiresorptive agent, which is known to reduce short-term periprosthetic bone loss. However, its effect on femoral stem stability is not well known. Forty-nine female patients with a mean age of 68 years (range, 51-85 years) scheduled to undergo cementless total hip arthroplasty due to osteoarthritis were randomized in this double-blind, placebo-controlled trial to receive a single postoperative infusion of zoledronic acid or placebo. Patients were evaluated for up to four years postoperatively for femoral stem migration measured by radiostereometric analysis, bone mineral density (BMD) measured by dual X-ray absorptiometry, functional recovery, and patient-reported outcome scores. Implant survival was determined at nine years postoperatively. Zoledronic acid did not reduce the femoral stem migration that occurred predominantly during the settling period of the first 3-6 months. Subsequently, all femoral stems were radiographically osseointegrated. Zoledronic acid maintained periprosthetic BMD, while the expected loss of periprosthetic bone during the first 12 months was found in controls. Thereafter, periprosthetic BMD of Gruen zone 7 decreased even in the zoledronic acid group but remained 14.6% higher than that in the placebo group at four years postoperatively. Functional recovery was comparable across the groups. At nine years postoperatively, no revision arthroplasty had been performed. In conclusion, in women at high-risk for low BMD, zoledronic acid had a long-lasting, partially protective effect on periprosthetic bone loss, but the treatment did not enhance the initial femoral stem stability.

Effect of Denosumab on Femoral Periprosthetic BMD and Early Femoral Stem Subsidence in Postmenopausal Women Undergoing Cementless Total Hip Arthroplasty

“…Denosumab increased bone mineral density in the greater and lesser trochanters as well as in the entire periprosthetic region above baseline levels. This type of strong response has not been observed in trials with oral risedronate or intravenous zoledronic acid . The successful inhibition of periprosthetic bone resorption had no detectable effect on femoral stem migration; these findings are in line with the results of our study on zoledronic acid, which had no effect on migration of a double‐tapered straight femoral stem in postmenopausal women.…”

“…All subjects of our trial received vitamin D and calcium supplementation because denosumab may cause hypocalcemia as an adverse event. For unknown reasons, total hip arthroplasty may also cause temporary asymptomatic postoperative hypocalcemia . On the other hand, vitamin D deficiency may impair osteoblastic functions .…”

“…The discontinuation of denosumab caused no adverse events. The maintenance of treatment response and prevention of a rebound increase in bone resorption call for efficient aftertreatment protocols, such as the single infusion of long‐lasting zoledronic acid . Before clinical use of denosumab in hip arthroplasty patients, the execution of large clinical trials should be focused on clinically relevant endpoints.…”

“…However, postmenopausal women with low bone mineral density (BMD), as elderly patients with hip fractures, are prone to temporary stem migration. Initial subsidence and rotation does not ultimately prevent stem osseointegration, and osseointegrated stems do not develop late mechanical loosening . Bisphosphonates have failed to reduce femoral stem subsidence in various patient populations, including postmenopausal women .…”

“…Initial subsidence and rotation does not ultimately prevent stem osseointegration, and osseointegrated stems do not develop late mechanical loosening . Bisphosphonates have failed to reduce femoral stem subsidence in various patient populations, including postmenopausal women . Postmenopausal women with low BMD also suffer from aggravated early periprosthetic bone resorption, which may appear radiographically as late bone loss around the osseointegrated femoral stems .…”