Background:. Delay in fracture healing is a complex clinical and economic issue for patients and health services. Established non-unions are debilitating and often difficult to treat. Bone morphogenic proteins (BMPs) may play an important role in bone and cartilage formation, fracture healing and the repair of other musculoskeletal tissues. There is, however, a paucity of data on the use of BMPs in fracture healing and to date its role remains unclear. Objectives:. To describe the 9-year experience of the Limb Reconstruction Team, Belfast in using BMP 2 for fracture non-unions. Methods:. This is a 9-year retrospective review of 66 episodes of BMP 2 application in 63 patients for fracture non-unions by two surgeons across two sites. Rate of union was calculated as the primary outcome measure. Secondary outcome measures were: time to fracture union, complication rate and re-operation rate. Time to radiological and clinical union was assessed by serial outpatient follow-up. Results:. 63 patients had been treated for an average of 12.7 months (range 2–61) for a variety of fracture non-unions with an average 2.2 operations each (range 0–6) prior to their definitive BMP implantation. 46% were open fractures. A union rate of 89% was achieved in an average of 5 months following BMP application to 45 tibial fractures, 16 femoral fractures, 4 humeral fractures and 1 radial fracture. There was an overall complication rate of 12%: 6% further non-union, 4.5% osteomyelitis and 1.5% heterotopic ossification at the BMP site. Overall there was an 11% re-operation rate, with repeat grafting required in 3 patients. Following repeat BMP grafting in these patients an overall union rate of 95% was achieved. Discussion:. High bony union rates are achievable through the use of the osteo-inductive agent BMP 2 for fracture non-unions. It can provide a reliable intervention for delayed fracture healing in circular frame patients where established non-union is deemed likely

Fracture repair occurs by two broad mechanisms: direct healing, and indirect healing with callus formation. The effects of bisphosphonates on fracture repair have been assessed only in models of indirect fracture healing.

A rodent model of rigid compression plate fixation of a standardised tibial osteotomy was used. Ten skeletally mature Sprague–Dawley rats received daily subcutaneous injections of 1 µg/kg ibandronate (IBAN) and ten control rats received saline (control). Three weeks later a tibial osteotomy was rigidly fixed with compression plating. Six weeks later the animals were killed. Fracture repair was assessed with mechanical testing, radiographs and histology.

The mean stress at failure in a four-point bending test was significantly lower in the IBAN group compared with controls (8.69 Nmm^-2 (sd 7.63) vs 24.65 Nmm^-2 (sd 6.15); p = 0.017). On contact radiographs of the extricated tibiae the mean bone density assessment at the osteotomy site was lower in the IBAN group than in controls (3.7 mmAl (sd 0.75) vs 4.6 mmAl (sd 0.57); p = 0.01). In addition, histological analysis revealed progression to fracture union in the controls but impaired fracture healing in the IBAN group, with predominantly cartilage-like and undifferentiated mesenchymal tissue (p = 0.007).

Bisphosphonate treatment in a therapeutic dose, as used for risk reduction in fragility fractures, had an inhibitory effect on direct fracture healing. We propose that bisphosphonate therapy not be commenced until after the fracture has united if the fracture has been rigidly fixed and is undergoing direct osteonal healing.

Cite this article: Bone Joint J 2013;95-B:1263–8.