Timing of Bisphosphonate Initiation After Fracture: What Does the Data Really Say?

Abstract

Introduction: Osteoporosis is often not clinically recognized until after a fracture occurs. Individuals who have 1 fracture are at increased risk of future fractures. Prompt initiation of osteoporosis treatment following fracture is critical to reducing the rate of future fractures. Antiresorptives are the most widely used class of medications for the prevention and treatment of osteoporosis. Many providers are hesitant to initiate antiresorptives in the acute post-fracture period. Concerns include interference with bone remodeling necessary for successful fracture healing, which would cause increased rates of non-union, malunion, and refracture. While such concerns should not extend to anabolic medications, physicians may also hesitate to initiate anabolic osteoporosis therapies due to high cost and/or lack of familiarity. This article aims to briefly review the available data and present a digestible narrative summary to familiarize practicing orthopaedic surgeons with the essential details of the published research on this topic. Results: The results of 20 clinical studies and key pre-clinical studies related to the effect of anti-resorptive medications for osteoporosis on fracture healing are summarized in the body of this narrative review. Discussion & Conclusions: While few level I studies have examined the impact of timing of initiation of osteoporosis medications in the acute post-fracture period, the few that have been published do not support these concerns. Specifically, data from level I clinical trials indicate that initiating bisphosphonates as early as 2 weeks post-fracture does not increase rates of non-union or malunion. By reviewing the available data, we hope to give clinicians the confidence to initiate osteoporosis treatment promptly post-fracture.

Early bisphosphonate therapy post proximal femoral fracture fixation does not impact fracture healing: a systematic review and meta‐analysis

“…Studies on existing bisphosphonate users who suffer a fracture have concluded that there is some delay in radiographic union, however this does not seem to translate into issues with symptoms or clinical healing. 37 This effect is not replicated with bisphosphonate-naïve patients commenced on treatment post-fracture. 37 Early animal models seemed to indicate that bisphosphonate initiation following fractures resulted in delays of conversion from woven bone to mature lamellar bone and increased fracture bridging and callus size, but no delays to callus formation itself 13,20,[38][39][40] however there was some discrepancies between studies.…”

“…37 This effect is not replicated with bisphosphonate-naïve patients commenced on treatment post-fracture. 37 Early animal models seemed to indicate that bisphosphonate initiation following fractures resulted in delays of conversion from woven bone to mature lamellar bone and increased fracture bridging and callus size, but no delays to callus formation itself 13,20,[38][39][40] however there was some discrepancies between studies. 31 A systematic review and meta-analysis in 2015 on early bisphosphonate therapy in all types of fractures in adult humans found no delays in radiological or clinical union time or rates of delayed or non-union.…”

Orthogeriatrics: a vital requirement for improving fragility fracture patient care internationally with particular reference to Turkey

“…Osteoporosis treatment should be started during hospitalization for fracture, given the reports appraising beneficial and non-hazardous osteoporosis medications when commenced in this state. Studies have shown that the early administration of bisphosphonates within the first 2 weeks after fracture does not delay fracture healing [4,5,[41][42][43][44]. In cases where vitamin D is sufficient, and there is no other contraindication, oral bisphosphonates, zoledronic acid, and denosumab within the first 2 weeks and teriparatide within the first week after the fracture, during the hospitalization, can be started [4,5].…”

Secondary Prevention of Osteoporosis: If Not Now, When?

“… 10 While the long-term benefits are clear, there are those who question the benefit of early initiation of therapy on fractures, showing that they may not necessarily improve the rates of fracture non-union or malunion. 11 …”

“…10 While the long-term benefits are clear, there are those who question the benefit of early initiation of therapy on fractures, showing that they may not necessarily improve the rates of fracture non-union or malunion. 11 Osteoporosis treatment after hip fracture was discussed previously in a well-received commentary. 12 Variations among countries and health care systems are great, and there are reports of a decrease in drug treatment for the secondary prevention of osteoporosis.…”