Shawn Yee, Mercer University College of Pharmacy
Hip fractures in the elderly population are associated with serious health consequences, which includes significant mortality, loss of mobility, and decreased independence. [1,2] Bisphosphonates are the most commonly used medications for osteoporosis treatment and prevention. [3,2] They work by inhibiting bone resorption and causing osteoclast apoptosis. [4,2] However, due to concerns with correcting low vitamin D and calcium levels as well as potentially negative effects on healing, the appropriateness of early treatment initiation of bisphosphonates is unclear. [5,2]
A recent meta-analysis (N= 10 trials, N= 2,888) that reviewed early versus late initiation of bisphosphonates after surgery for fractures found that fracture healing time was not delayed with early initiation of bisphosphonates. The included studies used alendronate, zoledronic acid, risedronate, and etidronate.  Below is a summary of a randomized controlled trial evaluating the effects of early versus late initiation of risedronate post-hemiarthroplasty. 
|Effect of bisphosphonate initiation at week 2 versus week 12 on short-term functional recovery after femoral neck fracture: a randomized controlled trial|
|Design||Randomized, controlled, parallel group study; N= 100|
|Objective||To analyze the effects of bisphosphonate (BIS) initiation at week two versus week 12 on functional femoral neck fracture recovery|
|Methods||Patients were randomized to receive risedronate 35 mg/week at either week two or week 12 after hemiarthroplasty surgery. All patients received supplementation with vitamin D2 0-60,000 IU/week (depending on serum levels) and calcium 1,000 mg/day. The de Morton Mobility Index (DEMMI), Barthel Index, EuroQol 5D (EQ-5D), visual analog scale, 2-min walk test, and timed get-up-and-go test were used to assess the patient’s functional recovery at baseline, three months post-surgery, and one year post surgery. DEMMI scores range from 0-100 with higher scores indicating greater levels of independent mobility. The Barthel Index describes a patient’s ability to carry out activities of daily living, with higher scores indicating greater likelihood of being able to live at home alone. The EQ-5D shows patient’s self-evaluation of their own health state, with a max score of 100 indicating the best imaginable health state. A visual analog scale was used to evaluate the patient’s level of pain in the past 24 hours, with scores ranging from 0-10 (10 being most painful).
|Duration||June 2013 to June 2015|
|Primary Outcome Measure||Change in the DEMMI score from baseline to three month follow-up|
|Percentage that Discontinued due to Adverse Events: 0% in either group|
|Study Author Conclusions||There was no significant difference in short-term functional recovery between the two bisphosphonate treatment groups, as well as adverse events.|
Based on the data from this study, there is no significant difference in regards to functional recovery or adverse events between initiation of risedronate 35 mg/week at week 2 versus week 12. To note, the number adverse events was higher with early initiation treatment (16.3% versus 5.9%, p= 0.095), but the difference was not statistically significant.
This study only analyzes the short-term effects of recovery, which may not be a long enough period to analyze differences in long-term effects of different initiation times on safety and efficacy. Also, the patients recruited in this study are from Thailand, which is a factor that should be taken into consideration for patients outside of Thailand. However, based on outcomes of the study, early initiation of risedronate at two weeks post-hemiarthroplasty may be appropriate. The results of this study do not definitively show benefit towards either early or late initiation of risedronate. Future studies evaluating the long-term effects and differences between bisphosphonate initiation times may provide further clinical insight into the risks versus benefits.
 Brauer CA, Coca-Perraillon M, Cutler DM, Rosen AB (2009) Incidence and mortality of hip fractures in the United States. JAMA 302:1573–1579.
 Unnanuntana, A., Laohaprasitiporn, P. & Jarusriwanna, A. Effect of bisphosphonate initiation at week 2 versus week 12 on short-term functional recovery after femoral neck fracture: a randomized controlled trial. Arch Osteoporos 2017;12:27.
 Molvik H, Khan W (2015) Bisphosphonates and their influence on fracture healing: a systematic review. Osteoporos Int 26:1251–1260.
 Boonekamp PM, van der Wee-Pals LJ, van Wijk-van Lennep MM, Thesing CW, Bijvoet OL (1986) Two modes of action of bisphosphonates on osteoclastic resorption of mineralized matrix. Bone Miner 1:27–39.
 Di Monaco M, Castiglioni C, Di Monaco R, Tappero R (2015) Time trend 2000-2013 of vitamin D status in older people who sustain hip fractures: steps forward or steps back? A retrospective study of 1599 inpatients. Eur J Phys Rehabil Med 52:502–507.
 Li YT, Cai HF, Zhang ZL. Timing of the initiation of bisphosphonates after surgery for fracture healing: a systematic review and meta-analysis of randomized controlled trials. Osteoporos Int. 2015;26(2):431-41.