Negative effect of zoledronic acid on tendon-to-bone healing: In vivo study of biomechanics and bone remodeling in a rat model

BACKGROUND AND PURPOSE: Outcome after ligament reconstruction or tendon repair depends on secure tendon-to-bone healing. Increased osteoclastic activity resulting in local bone loss may contribute to delayed healing of the tendon–bone interface. The objective of this study was to evaluate the effect of the bisphosphonate zoledronic acid (ZA) on tendon-to-bone healing. METHODS: Wistar rats (n = 92) had their right Achilles tendon cut proximally, pulled through a bone tunnel in the distal tibia and sutured anteriorly. After 1 week animals were randomized to receive a single dose of ZA (0.1 mg/kg IV) or control. Healing was evaluated at 3 and 6 weeks by mechanical testing, dual-energy X-ray absorptiometry and histology including immunohistochemical staining of osteoclasts. RESULTS: ZA treatment resulted in 19% (95% CI 5–33%) lower pullout strength and 43% (95% CI 14–72%) lower stiffness of the tendon–bone interface, compared with control (2-way ANOVA; p = 0.009, p = 0.007). Administration of ZA did not affect bone mineral density (BMD) or bone mineral content (BMC). Histological analyses did not reveal differences in callus formation or osteoclasts between the study groups. INTERPRETATION: ZA reduced pullout strength and stiffness of the tendon–bone interface. The study does not provide support for ZA as adjuvant treatment in tendon-to-bone healing.