Can an anti-fracture agent heal fractures?

Anti-fracture agents typically prevent fractures by augmenting bone mass and enhancing skeletal integrity. These agents exert their effects by means of anti-catabolic or anabolic actions. Because fracture healing involves bone formation as well as bone resorption, it is reasonable to hypothesize that agents that affect these activities may also modulate skeletal repair. Bisphosphonates, agents that inhibit bone resorption, may enhance the healing of fractures or permit patients with fractures to bear weight earlier by delaying the conversion of calcified cartilage to woven bone, or woven bone to lamellar bone. In doing so, they increase the size of the fracture callus and small increases in the radius of fracture callus can have dramatic positive effects on fracture callus stiffness and strength. Another possibility is that certain hypertrophic nonunions fail to unite because of excessive remodeling of the callus. Use of a bisphosphonate may modulate this catabolic activity, uncouple it from the associated bone formation and promote healing. Inhibitors of RANKL have undergone far less investigation but may also act on osteoclast precursors to down-regulate bone resorption. Parathyroid hormone may enhance fracture repair by promoting chondrogenesis early in the healing process and osteogenesis at a later time. The former effect improves callus geometry while the latter effect improves bone quality as well as quantity. Several anecdotal reports and one randomized, controlled trial have suggested that parathyroid may enhance skeletal repair in specific clinical settings. Although these reports are based on solid scientific data, there are limited clinical data at this time. The use of anti-fracture agents for the enhancement of fracture healing will ultimately depend upon high quality evidence from well-designed, well-controlled clinical trial