How do bisphosphonates affect fracture healing?

Bisphosphonates (BPs) have been in use for many years for the treatment of osteoporosis, multiple myeloma, Paget's disease, as well as a variety of other diseases in which there is reduced bone mineral density. Given that bisphosphonates inhibit bone resorption, an important stage of fracture healing; this class of compounds has been widely studied in preclinical models regarding their influence on fracture healing. In animal models, bisphosphonate treatment is associated with a larger fracture callus, coincident with a delay in remodeling from primary woven bone to lamellar bone, but there is no delay in formation of the fracture callus. In humans, de novo use of bisphosphonate therapy after fracture does not appear to have a significant effect on fracture healing. Rarely, patients with long term use of Bisphosphonates may develop an atypical fracture and delay in fracture healing has been observed. In summary, bisphosphonates appear safe for use in the setting of acute fracture management in the upper and lower extremity in humans. While much remains unknown about the effects on healing of long-term bisphosphonates, use prior to "typical" fracture, in the special case of atypical fracture, evidence suggests that bisphosphonates negatively influence healing.