The use of bisphosphonates to meet orthopaedic challenges.

The anti-resorptive properties of bisphosphonates have been explored to manage several conditions that traditionally have required a surgical solution. In osteonecrosis, their use is predicated on the principle that bone collapse occurs during the revascularisation phase of the disease. If the associated resorptive activity were modulated, the resultant preserved joint architecture may improve clinical outcome and reduce the need for joint replacement. Pre-clinical and small-scale clinical studies have given non-conclusive support for this principle. Adequately powered clinical trials with relevant long-term endpoints are still required to firmly clarify the clinical efficacy of this treatment. Several clinical studies have shown that bisphosphonates can reduce periprosthetic bone loss and, in some situations, enhance implant fixation in the early period after joint replacement. This may be advantageous in settings where osseointegration is problematic. However, the ultimate goals of their use in joint replacement has been to reduce the incidence of late periprosthetic inflammatory osteolysis, the main cause of prosthesis failure. Population-based observational studies have associated bisphosphonate use with a lower incidence of revision surgery, supported by pre-clinical data. However, clinical trials have, to date, failed to demonstrate any efficacy for the human disease. The timing of bisphosphonate administration for secondary prevention after acute osteoporotic fracture has been subject to extensive investigation, with pre-clinical studies showing increased callus formation but decreased remodelling and no effect on the restoration of mechanical integrity of bone. Meta-analysis of clinical trial data indicates that early administration of bisphosphonate after acute fracture does not adversely affect fracture union, pain or functional outcomes. Finally, bisphosphonates have also been explored as a treatment for complex regional pain syndrome type-I. A recent meta-analysis has shown a beneficial effect on visual analogue scale pain scores, but an increase in mild adverse events.