Effect of bisphosphonate initiation at week 2 versus week 12 on short-term functional recovery after femoral neck fracture: a randomized controlled trial

Aasis Unnanuntana, Panai Laohaprasitiporn, Atthakorn Jarusriwanna, Aasis Unnanuntana, Panai Laohaprasitiporn, Atthakorn Jarusriwanna

Abstract

The appropriate time to initiate bisphosphonate treatment after a fragility fracture has not yet been established. In this study, we found no significant differences in short-term functional recovery between femoral neck fracture patients who received bisphosphonate treatment at 2 versus 12 weeks after hemiarthroplasty.

Introduction: Bisphosphonate is the mainstay therapy for prevention and treatment of osteoporosis. The aim of this study was to investigate the effect of bisphosphonate initiation on short-term functional recovery in femoral neck fracture patients at 2 versus 12 weeks after hemiarthroplasty.

Methods: One hundred patients were randomly allocated into two groups in a parallel group designed, randomized, controlled trial. Both groups received risedronate 35 mg/week at either 2 or 12 weeks after hemiarthroplasty. All patients received calcium and vitamin D supplementation. Functional recovery was assessed by de Morton Mobility Index, Barthel Index, EuroQol 5D, visual analog scale, 2-min walk test, and timed get-up-and-go test at 2 weeks, 3 months, and 1 year after surgery.

Results: At the 3-month follow-up, all functional outcome measures showed significant improvement in both groups. There were no statistically significant differences in any of the functional outcomes between groups at both the 3-month and 1-year follow-ups. Although patients who received bisphosphonate initiation at week 2 had lower serum calcium level at 3 months and more overall adverse events than patients in the week 12 group, no patients in either group discontinued their prescribed medications.

Conclusions: While underpowered, the findings of this study suggest that there were no significant differences in short-term functional recovery or significant adverse events between the two bisphosphonate groups. Thus, the initiation of bisphosphonate therapy may be considered as early as 2 weeks after femoral neck fracture. It is important that low serum calcium and vitamin D status must be corrected with calcium and vitamin D supplementation prior to or at the time of bisphosphonate initiation.

Clinical trial registration number: This study was registered in the database via the Protocol Registration and Results System (PRS) (NCT02148848).

Keywords: Bisphosphonate; Femoral neck fracture; Hemiarthroplasty; Randomized controlled trial; Risedronate.

Conflict of interest statement

Conflicts of interest

None.

Figures

Fig. 1
Fig. 1
Consolidated Standards of Reporting Trials (CONSORT) diagram showing the flow of patients in the study. The group with bisphosphonate initiation at week 2 received bisphosphonate at 2 weeks after surgery. The group with bisphosphonate initiation at 12 weeks received bisphosphonate at 12 weeks after surgery
Fig. 2
Fig. 2
Mean change in scores from baseline to 12 months after surgery. a de Morton Mobility Index. b Barthel Index. c EuroQol visual analog scale. d Visual analog scale. e Two-minute walk test. f Timed get-up-and-go test. The error bars indicate the standard error. The p values at the top of each graph indicate the significance level of each functional outcome in the bisphosphonate initiation at week 2 group between the indicated time points. The p values at the bottom of each graph indicate the significance level of each functional outcome in the bisphosphonate initiation at week 12 group between the indicated time points

References

    1. Kanis JA, Oden A, McCloskey EV, Johansson H, Wahl DA, Cooper C. A systematic review of hip fracture incidence and probability of fracture worldwide. Osteoporos Int. 2012;23:2239–2256. doi: 10.1007/s00198-012-1964-3.
    1. Cooper C, Campion G, Melton LJ., 3rd Hip fractures in the elderly: a world-wide projection. Osteoporos Int. 1992;2:285–289. doi: 10.1007/BF01623184.
    1. Dhanwal DK, Dennison EM, Harvey NC, Cooper C. Epidemiology of hip fracture: worldwide geographic variation. Indian J Orthop. 2011;45:15–22. doi: 10.4103/0019-5413.73656.
    1. Johnell O, Kanis JA. An estimate of the worldwide prevalence, mortality and disability associated with hip fracture. Osteoporos Int. 2004;15:897–902. doi: 10.1007/s00198-004-1627-0.
    1. Brauer CA, Coca-Perraillon M, Cutler DM, Rosen AB. Incidence and mortality of hip fractures in the United States. JAMA. 2009;302:1573–1579. doi: 10.1001/jama.2009.1462.
    1. Scaf-Klomp W, van Sonderen E, Sanderman R, Ormel J, Kempen GI. Recovery of physical function after limb injuries in independent older people living at home. Age Ageing. 2001;30:213–219. doi: 10.1093/ageing/30.3.213.
    1. Kanis JA, Johnell O, De Laet C, Johansson H, Oden A, Delmas P, Eisman J, Fujiwara S, Garnero P, Kroger H, McCloskey EV, Mellstrom D, Melton LJ, Pols H, Reeve J, Silman A, Tenenhouse A. A meta-analysis of previous fracture and subsequent fracture risk. Bone. 2004;35:375–382. doi: 10.1016/j.bone.2004.03.024.
    1. Edwards BJ, Bunta AD, Simonelli C, Bolander M, Fitzpatrick LA. Prior fractures are common in patients with subsequent hip fractures. Clin Orthop Relat Res. 2007;461:226–230.
    1. Haentjens P, Autier P, Barette M, Boonen S. The economic cost of hip fractures among elderly women. A one-year, prospective, observational cohort study with matched-pair analysis. Belgian Hip Fracture Study Group. J Bone Joint Surg Am. 2001;83-a:493–500. doi: 10.2106/00004623-200104000-00003.
    1. Woratanarat P, Wajanavisit W, Lertbusayanukul C, Loahacharoensombat W, Ongphiphatanakul B. Cost analysis of osteoporotic hip fractures. J Med Assoc Thail. 2005;88(Suppl 5):S96–104.
    1. Elliot-Gibson V, Bogoch ER, Jamal SA, Beaton DE. Practice patterns in the diagnosis and treatment of osteoporosis after a fragility fracture: a systematic review. Osteoporos Int. 2004;15:767–778. doi: 10.1007/s00198-004-1675-5.
    1. Molvik H, Khan W. Bisphosphonates and their influence on fracture healing: a systematic review. Osteoporos Int. 2015;26:1251–1260. doi: 10.1007/s00198-014-3007-8.
    1. Jung A, Bisaz S, Fleisch H. The binding of pyrophosphate and two diphosphonates by hydroxyapatite crystals. Calcif Tissue Res. 1973;11:269–280. doi: 10.1007/BF02547227.
    1. Boonekamp PM, van der Wee-Pals LJ, van Wijk-van Lennep MM, Thesing CW, Bijvoet OL. Two modes of action of bisphosphonates on osteoclastic resorption of mineralized matrix. Bone Miner. 1986;1:27–39.
    1. Russell RG, Xia Z, Dunford JE, Oppermann U, Kwaasi A, Hulley PA, Kavanagh KL, Triffitt JT, Lundy MW, Phipps RJ, Barnett BL, Coxon FP, Rogers MJ, Watts NB, Ebetino FH. Bisphosphonates: an update on mechanisms of action and how these relate to clinical efficacy. Ann N Y Acad Sci. 2007;1117:209–257. doi: 10.1196/annals.1402.089.
    1. Roberts KC, Brox WT, Jevsevar DS, Sevarino K. Management of hip fractures in the elderly. J Am Acad Orthop Surg. 2015;23:131–137. doi: 10.5435/JAAOS-D-14-00432.
    1. Di Monaco M, Castiglioni C, Di Monaco R, Tappero R. 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. 2015;52:502–507.
    1. Maalouf NM, Heller HJ, Odvina CV, Kim PJ, Sakhaee K. Bisphosphonate-induced hypocalcemia: report of 3 cases and review of literature. Endocr Pract. 2006;12:48–53. doi: 10.4158/EP.12.1.48.
    1. de Morton NA, Davidson M, Keating JL. The de Morton Mobility Index (DEMMI): an essential health index for an ageing world. Health Qual Life Outcomes. 2008;6:63. doi: 10.1186/1477-7525-6-63.
    1. de Morton NA, Harding KE, Taylor NF, Harrison G. Validity of the de Morton Mobility Index (DEMMI) for measuring the mobility of patients with hip fracture during rehabilitation. Disabil Rehabil. 2013;35:325–333. doi: 10.3109/09638288.2012.705220.
    1. Mahoney FI, Barthel DW. Functional evaluation: tha barthel index. Md State Med J. 1965;14:61–65.
    1. Loewen SC, Anderson BA. Predictors of stroke outcome using objective measurement scales. Stroke. 1990;21:78–81. doi: 10.1161/01.STR.21.1.78.
    1. Gresham GE, Phillips TF, Labi ML. ADL status in stroke: relative merits of three standard indexes. Arch Phys Med Rehabil. 1980;61:355–358.
    1. Burgos E, Gomez-Arnau JI, Diez R, Munoz L, Fernandez-Guisasola J, Garcia del Valle S. Predictive value of six risk scores for outcome after surgical repair of hip fracture in elderly patients. Acta Anaesthesiol Scand. 2008;52:125–131. doi: 10.1111/j.1399-6576.2007.01473.x.
    1. O’Sullivan SB, Schmitz TJ. Physical rehabilitation. Philadelphia, PA: F.A. Davis Company; 2007.
    1. Tidermark J, Zethraeus N, Svensson O, Tornkvist H, Ponzer S. Quality of life related to fracture displacement among elderly patients with femoral neck fractures treated with internal fixation. J Orthop Trauma. 2002;16:34–38. doi: 10.1097/00005131-200201000-00008.
    1. Mancuso CA, Choi TN, Westermann H, Briggs WM, Wenderoth S, Charlson ME. Measuring physical activity in asthma patients: two-minute walk test, repeated chair rise test, and self-reported energy expenditure. J Asthma. 2007;44:333–340. doi: 10.1080/02770900701344413.
    1. Stratford PW, Kennedy DM, Maly MR, Macintyre NJ. Quantifying self-report measures’ overestimation of mobility scores postarthroplasty. Phys Ther. 2010;90:1288–1296. doi: 10.2522/ptj.20100058.
    1. Port L, Center J, Briffa NK, Nguyen T, Cumming R, Eisman J. Osteoporotic fracture: missed opportunity for intervention. Osteoporos Int. 2003;14:780–784. doi: 10.1007/s00198-003-1452-x.
    1. von Friesendorff M, Besjakov J, Akesson K. Long-term survival and fracture risk after hip fracture: a 22-year follow-up in women. J Bone Miner Res. 2008;23:1832–1841. doi: 10.1359/jbmr.080606.
    1. von Friesendorff M, McGuigan FE, Besjakov J, Akesson K. Hip fracture in men-survival and subsequent fractures: a cohort study with 22-year follow-up. J Am Geriatr Soc. 2011;59:806–813. doi: 10.1111/j.1532-5415.2011.03399.x.
    1. Cheung WH, Miclau T, Chow SK, Yang FF, Alt V. Fracture healing in osteoporotic bone. Injury. 2016;47(Suppl 2):S21–S26. doi: 10.1016/S0020-1383(16)47004-X.
    1. Xue D, Li F, Chen G, Yan S, Pan Z. Do bisphosphonates affect bone healing? A meta-analysis of randomized controlled trials. J Orthop Surg Res. 2014;9:45. doi: 10.1186/1749-799X-9-45.
    1. Eriksen EF, Lyles KW, Colon-Emeric CS, Pieper CF, Magaziner JS, Adachi JD, Hyldstrup L, Recknor C, Nordsletten L, Lavecchia C, Hu H, Boonen S, Mesenbrink P. Antifracture efficacy and reduction of mortality in relation to timing of the first dose of zoledronic acid after hip fracture. J Bone Miner Res. 2009;24:1308–1313. doi: 10.1359/jbmr.090209.
    1. Nguyen ND, Eisman JA, Nguyen TV. Anti-hip fracture efficacy of biophosphonates: a Bayesian analysis of clinical trials. J Bone Miner Res. 2006;21:340–349. doi: 10.1359/JBMR.050903.
    1. Lyles KW, Colon-Emeric CS, Magaziner JS, Adachi JD, Pieper CF, Mautalen C, Hyldstrup L, Recknor C, Nordsletten L, Moore KA, Lavecchia C, Zhang J, Mesenbrink P, Hodgson PK, Abrams K, Orloff JJ, Horowitz Z, Eriksen EF, Boonen S. Zoledronic acid in reducing clinical fracture and mortality after hip fracture. N Engl J Med. 2007;357:nihpa40967. doi: 10.1056/NEJMoa074941.
    1. Morin S, Rahme E, Behlouli H, Tenenhouse A, Goltzman D, Pilote L. Effectiveness of antiresorptive agents in the prevention of recurrent hip fractures. Osteoporos Int. 2007;18:1625–1632. doi: 10.1007/s00198-007-0421-1.
    1. Giangregorio L, Papaioannou A, Cranney A, Zytaruk N, Adachi JD. Fragility fractures and the osteoporosis care gap: an international phenomenon. Semin Arthritis Rheum. 2006;35:293–305. doi: 10.1016/j.semarthrit.2005.11.001.
    1. Cadarette SM, Katz JN, Brookhart MA, Levin R, Stedman MR, Choudhry NK, Solomon DH. Trends in drug prescribing for osteoporosis after hip fracture, 1995-2004. J Rheumatol. 2008;35:319–326.
    1. Rabenda V, Vanoverloop J, Fabri V, Mertens R, Sumkay F, Vannecke C, Deswaef A, Verpooten GA, Reginster JY. Low incidence of anti-osteoporosis treatment after hip fracture. J Bone Joint Surg Am. 2008;90:2142–2148. doi: 10.2106/JBJS.G.00864.
    1. Nakayama A, Major G, Holliday E, Attia J, Bogduk N. Evidence of effectiveness of a fracture liaison service to reduce the re-fracture rate. Osteoporos Int. 2016;27:873–879. doi: 10.1007/s00198-015-3443-0.
    1. Harrington JT, Ste-Marie LG, Brandi ML, Civitelli R, Fardellone P, Grauer A, Barton I, Boonen S. Risedronate rapidly reduces the risk for nonvertebral fractures in women with postmenopausal osteoporosis. Calcif Tissue Int. 2004;74:129–135. doi: 10.1007/s00223-003-0042-4.
    1. Roux C, Seeman E, Eastell R, Adachi J, Jackson RD, Felsenberg D, Songcharoen S, Rizzoli R, Di Munno O, Horlait S, Valent D, Watts NB. Efficacy of risedronate on clinical vertebral fractures within six months. Curr Med Res Opin. 2004;20:433–439. doi: 10.1185/030079903125003125.
    1. Glendenning P, Chew GT, Seymour HM, Gillett MJ, Goldswain PR, Inderjeeth CA, Vasikaran SD, Taranto M, Musk AA, Fraser WD. Serum 25-hydroxyvitamin D levels in vitamin D-insufficient hip fracture patients after supplementation with ergocalciferol and cholecalciferol. Bone. 2009;45:870–875. doi: 10.1016/j.bone.2009.07.015.
    1. Geller JL, Hu B, Reed S, Mirocha J, Adams JS. Increase in bone mass after correction of vitamin D insufficiency in bisphosphonate-treated patients. Endocr Pract. 2008;14:293–297. doi: 10.4158/EP.14.3.293.
    1. Peter R, Mishra V, Fraser WD. Severe hypocalcaemia after being given intravenous bisphosphonate. BMJ. 2004;328:335–336. doi: 10.1136/bmj.328.7435.335.
    1. Pioli G, Barone A, Giusti A, Oliveri M, Pizzonia M, Razzano M, Palummeri E. Predictors of mortality after hip fracture: results from 1-year follow-up. Aging Clin Exp Res. 2006;18:381–387. doi: 10.1007/BF03324834.

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