Negative effect of zoledronic acid on tendon-to-bone healing.

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.

Tendon to bone tunnel healing--a study on the time-dependent changes in biomechanics, bone remodeling, and histology in a rat model.

Tendons and ligaments attach to bone through a transitional connective tissue with complex biomechanical properties. This unique tissue is not regenerated during healing, and surgical reattachment therefore often fails. The present study was designed to evaluate tendon healing in a bone tunnel and to evaluate the utilized rat model. Wistar rats (n = 61) were operated with the Achilles tendon through a bone tunnel in the distal tibia. Healing was evaluated at 2, 3, 4, and 12 weeks by biomechanical testing, bone mineral density and histology. After 2 weeks median (interquartile range) pull-out force was 2.2 N (1.9). The pull-out force increased chronologically, by 12 weeks fivefold to 11.2 N (11.4). Energy absorption, stiffness, and bone mineral density increased similarly. The histological analyses showed inflammation at early stages with increasing callus by time. Our data showed a slow healing response the first 4 weeks followed by an accelerated healing period, favoring that most of the gain in mechanical strength occurred later than 4 weeks postoperatively. These findings support the concern of a vulnerable tendon bone tunnel interface in the early stages of healing.

The effect of a pre- and postoperative orthogeriatric service on cognitive function in patients with hip fracture: randomized controlled trial (Oslo Orthogeriatric Trial).

BACKGROUND: Delirium is a common complication in patients with hip fractures and is associated with an increased risk of subsequent dementia. The aim of this trial was to evaluate the effect of a pre- and postoperative orthogeriatric service on the prevention of delirium and longer-term cognitive decline. METHODS: This was a single-center, prospective, randomized controlled trial in which patients with hip fracture were randomized to treatment in an acute geriatric ward or standard orthopedic ward. Inclusion and randomization took place in the Emergency Department at Oslo University hospital. The key intervention in the acute geriatric ward was Comprehensive Geriatric Assessment including daily interdisciplinary meetings. Primary outcome was cognitive function four months after surgery measured using a composite outcome incorporating the Clinical Dementia Rating Scale (CDR) and the 10 words learning and recalls tasks from the Consortium to Establish a Registry for Alzheimer's Disease battery (CERAD). Secondary outcomes were pre- and postoperative delirium, delirium severity and duration, mortality and mobility (measured by the Short Physical Performance Battery (SPPB)). Patients were assessed four and twelve months after surgery by evaluators blind to allocation. RESULTS: A total of 329 patients were included. There was no significant difference in cognitive function four months after surgery between patients treated in the acute geriatric and the orthopedic wards (mean 54.7 versus 52.9, 95% confidence interval for the difference -5.9 to 9.5; P = 0.65). There was also no significant difference in delirium rates (49% versus 53%, P = 0.51) or four month mortality (17% versus 15%, P = 0.50) between the intervention and the control group. In a pre-planned sub-group analysis, participants living in their own home at baseline who were randomized to orthogeriatric care had better mobility four months after surgery compared with patients randomized to the orthopedic ward, measured with SPPB (median 6 versus 4, 95% confidence interval for the median difference 0 to 2; P = 0.04). CONCLUSIONS: Pre- and postoperative orthogeriatric care given in an acute geriatric ward was not effective in reducing delirium or long-term cognitive impairment in patients with hip fracture. The intervention had, however, a positive effect on mobility in patients not admitted from nursing homes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01009268 Registered November 5, 2009.