Systemic administration of pharmacological agents and bone repair: what can we expect.

Pharmacologic agents that modulate bone formation and bone remodelling are in broad use and development for the treatment of osteoporosis and other disorders of bone fragility. There is significant interest into the effect these agents may have on bone repair and fracture healing and whether these agents may be beneficial or detrimental to bone repair. Bisphosphonates delay callus remodelling, but increased callus volume seen during endochondral bone repair with bisphosphonate use allows for equivalent biomechanical properties for the fractured bone. Teripartide stimulates bone formation and in bone repair appears to have the potential to accelerate fracture callus formation and remodelling, potentially accelerating fracture healing. Animal models of fracture healing have demonstrated accelerated healing with larger callus volume, more rapid remodelling to mature bone, and improved biomechanical properties of the fractured bone. Clinical data with teriparatide has shown mixed results for its ability to stimulate fracture healing. Wnt signalling is one of the major pathways through which cartilage and bone formation is regulated during development. This same pathway has been identified as one of the ways that teriparatide stimulates bone formation. Antibodies to downstream proteins in this pathway, Dkk-1 and sclerostin, show significant promise of accelerating even normal fracture healing in preclinical animal models.