Effects of Zoledronic Acid Treatment on Fracture Healing, Morbidity and Mortality in Elderly Patients with Osteoporotic Hip Fractures
Serdar Sargin, Mehmet N Konya, Anil Gulcu, Ahmet Aslan
Fracture healing, Harris Hip Score, Osteoporotic hip fracture, RUSH score, Zoledronic acid
Citation Information :
Sargin S, Konya MN, Gulcu A, Aslan A. Effects of Zoledronic Acid Treatment on Fracture Healing, Morbidity and Mortality in Elderly Patients with Osteoporotic Hip Fractures. 2019; 14 (3):126-131.
Background: In this study, the effects of zoledronic acid (ZolA) administered at different times to patients undergoing surgical treatment for hip fracture were investigated. Materials and methods: Ninety patients who underwent surgical treatment for osteoporotic (OP) hip fractures between February 2013 and September 2016 in our hospital were included in the study. After surgical treatment, patients were allocated into three groups: group I—patients who had osteosynthesis using proximal femoral nail (PFN) for an intertrochanteric fracture of the femur were given ZolA within 1 week after fracture and before discharge; group II—patients who had osteosynthesis using the PFN for an intertrochanteric fracture of the femur were given ZolA within 1 month after fracture post-discharge; group III—patients in the same age group who had a hemiarthroplasty (HA) for an intertrochanteric fracture of the femur were administered ZolA before discharge. In addition, all patients were given daily oral calcium and vitamin D3. The Radiographic Union Score for Hip (RUSH), Harris Hip Score (HHS), and bone mineral density (BMD) were used at the follow-up as evaluation criteria, and complications were noted. Results: There were no significant differences between groups in terms of demographic data and laboratory outcomes (p > 0.05). Radiographic Union Score for Hip scores were similar between groups I and II (p > 0.05). Fracture union occurred by the sixth month in all patients whose results were evaluated. No statistically significant difference was found between three groups (p > 0.05). There was no difference between the three groups in the hip and vertebrae BMD and t scores (p > 0.05). When t and BMD scores before treatment were compared with those at 1 year after treatment, a benefit from ZolA treatment was observed in all three groups (p < 0.05). Conclusion: This study shows that the timing of ZolA administration has no effect on fracture healing and complication incidence in elderly patients with hip fractures. In addition, ZolA was found to be beneficial in increasing BMD of both femur and vertebra in all groups, but there was no significant difference between the groups. Clinical significance: The study demonstrated that ZolA may be used early in the treatment of osteoporotic hip fractures with PFN.
Tuzun S, Eskiyurt N, Akarirmak U, et al. Incidence of hip fracture and prevalence of osteoporosis in Turkey: the FRACTURK study. Osteoporos Int 2012;23(3):949–955. DOI: 10.1007/s00198-011- 1655-5.
Inan U, Tekcan A, Seber S, et al. Degree of osteoporosis affects the fracture site in older patients with proximal femur fractures. Turkish Journal of Geriatrics/Türk Geriatri Dergisi 2011;14(3):204–207.
Bayrak A, Bayrak SK, Duramaz A, et al. Demographic and clinical results of proximal femoral fractures. Acta Medica Alanya 2017. 38.
Aslan A, Gülcü A, Özmeriç A. Outcomes of treatment in patients with elderly postmenopausal osteoporosis: comparision of oral and parenteral Bisphosphonates. Turk Osteoporoz Dergisi 2018;24(2):53. DOI: 10.4274/tod.73645.
Eriksen EF, Lyles KW, Colón-Emeric CS, et al. 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(7): 1308–1313. DOI: 10.1359/jbmr.090209.
Turker M, Aslan A, Cirpar M, et al. Histological and biomechanical effects of zoledronate on fracture healing in an osteoporotic rat tibia model. Eklem Hastalik Cerrahisi 2016;27(1):9–15. DOI: 10.5606/ehc.2016.03.
Lyles KW, Colón-Emeric CS, Magaziner JS, et al. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med 2007;357(18):1799–1809. DOI: 10.1056/NEJMoa074941.
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):431–441. DOI: 10.1007/s00198-014-2903-2.
Colón-Emeric C, Nordsletten L, Olson S, et al. Association between timing of Zoledronic acid infusion and hip fracture healing. Osteoporos Int 2011;22(8):2329–2336. DOI: 10.1007/s00198-010-1473-1.
Einhorn TA. The science of fracture healing. J Orthop Trauma 2005;19(Suppl. 10):S4–S6. DOI: 10.1097/00005131-200511101-00002.
Gerstenfeld LC, Sacks DJ, Pelis M, et al. Comparison of effects of the Bisphosphonate alendronate versus the RANKL inhibitor denosumab on murine fracture healing. J Bone Miner Res 2009;24(2):196–208. DOI: 10.1359/jbmr.081113.
Kim T, Ha Y, Kang B, et al. Does early administration of bisphosphonate affect fracture healing in patients with intertrochanteric fractures? J Bone Joint Surg Br 2012;94(7):956–960. DOI: 10.1302/0301-620X.94B7.29079.
Bhandari M, Chiavaras M, Ayeni O, et al. Assessment of radiographic fracture healing in patients with operatively treated femoral neck fractures. J Orthop Trauma 2013;27(9):e213–e219. DOI: 10.1097/BOT.0b013e318282e692.
Bhandari M, Chiavaras MM, Parasu N, et al. Radiographic union score for hip substantially improves agreement between surgeons and radiologists. BMC Musculoskelet Disord 2013;14(1):70. DOI: 10.1186/1471-2474-14-70.
Nilsdotter A, Bremander A. Measures of hip function and symptoms: harris hip score (HHS), hip disability and osteoarthritis outcome score (HOOS), oxford hip score (OHS), lequesne index of severity for osteoarthritis of the hip (LISOH), and american academy of orthopedic surgeons (AAOS) hip and knee questionnaire. Arthritis Care Res (Hoboken) 2011;63(Suppl 11):S200–S207. DOI: 10.1002/acr.20549.
Tang P, Hu F, Shen J, et al. Proximal femoral nail antirotation versus hemiarthroplasty: a study for the treatment of intertrochanteric fractures. Injury 2012;43(6):876–881. DOI: 10.1016/j.injury.2011.11.008.
Aslan A, Karakoyun O, Güler E, et al. Evaluation of bone mineral density, osteoporosis prevalence and regional risk factors in Turkish women living in Kastamonu: KASTÜRKOS study. Eklem hastaliklari ve cerrahisi= Joint diseases & related surgery 2012;23(2):62–67.
Matos MA, Tannuri U, Guarniero R. The effect of zoledronate during bone healing. J Orthop Traumatol 2010;11(1):7–12. DOI: 10.1007/s10195-010-0083-1.
Li J, Mori S, Kaji Y, et al. Effect of bisphosphonate (incadronate) on fracture healing of long bones in rats. J Bone Miner Res 1999;14(6):969–979. DOI: 10.1359/jbmr.19184.108.40.2069.
Li C, Mori S, Li J, et al. Long-term effect of incadronate disodium (YM-175) on fracture healing of femoral shaft in growing rats. J Bone Miner Res 2001;16(3):429–436. DOI: 10.1359/jbmr.2001.16.3.429.
Bauss F, Schenk RK, Hort S, et al. New model for simulation of fracture repair in full-grown beagle dogs: model characterization and results from a long-term study with ibandronate. J Pharmacol Toxicol Methods 2004;50(1):25–34. DOI: 10.1016/j.vascn.2003.11.003.
Munns CF, Rauch F, Zeitlin L, et al. Delayed osteotomy but not fracture healing in pediatric osteogenesis imperfecta patients receiving pamidronate. J Bone Miner Res 2004;19(11):1779–1786. DOI: 10.1359/JBMR.040814.
Greiner SH, Wildemann B, Back DA, et al. Local application of Zoledronic acid incorporated in a poly(D,L-lactide)-coated implant accelerates fracture healing in rats. Acta Orthop 2008;79(5):717–725. DOI: 10.1080/17453670810016768.
Rozental TD, Vazquez MA, Chacko AT, et al. Comparison of radiographic fracture healing in the distal radius for patients on and off bisphosphonate therapy. J Hand Surg Am 2009;34(4):595–602. DOI: 10.1016/j.jhsa.2008.12.011.
Amanat N, Brown R, Bilston LE, et al. A single systemic dose of pamidronate improves bone mineral content and accelerates restoration of strength in a rat model of fracture repair. J Orthop Res 2005;23(5):1029–1034. DOI: 10.1016/j.orthres.2005.03.004.
Little DG, McDonald M, Bransford R, et al. Manipulation of the anabolic and catabolic responses with OP-1 and Zoledronic acid in a rat critical defect model. J Bone Miner Res 2005;20(11):2044–2052. DOI: 10.1359/JBMR.050712.
Bransford R, Goergens E, Briody J, et al. Effect of Zoledronic acid in an L6-L7 rabbit spine fusion model. Eur Spine J 2007;16(4):557–562. DOI: 10.1007/s00586-006-0212-y.
Kates SL, Ackert-Bicknell CL. How do bisphosphonates affect fracture healing? Injury 2016;47:S65–S68. DOI: 10.1016/S0020-1383(16) 30015-8.
Li C, Wang H-R, Li X-L, et al. The relation between Zoledronic acid infusion and interbody fusion in patients undergoing transforaminal lumbar interbody fusion surgery. Acta Neurochir (Wien) 2012;154(4):731–738. DOI: 10.1007/s00701-012-1283-7.
Li Y, Zhao WB, Wang DL, et al. Treatment of osteoporotic intertrochanteric fractures by Zoledronic acid injection combined with proximal femoral nail anti-rotation. Chin J Traumatol 2016;19(5):259–263. DOI: 10.1016/j.cjtee.2016.07.001.
Cengiz Ö, Polat G, Karademir G, et al. Effects of zoledronate on mortality and morbidity after surgical treatment of hip fractures. Adv Orthop 2016;2016:3703482. DOI: 10.1155/2016/3703482.
Maiettini D, Bisaccia M, Caraffa A, et al. Feasibility and value of radiographic union score hip fracture after treatment with intramedullary nail of stable hip fractures. Acta Inform Med 2016;24(6):394–396. DOI: 10.5455/aim.2016.24.394-396.
Güler A, Doğukan M, Kaya R, et al. Retrospective evaluation of the effects of albumin and hemoglobin values on the duration of hospital stay and mortality in elderly patients operated for hip fracture. Adiyaman Üniversitesi Sağlik Bilimleri Dergisi 2018;4(1):637–647.
Atay T, Ceylan BG, Özmeriç A, et al. The effects of related factors on one-and two-year mortality after a hip fracture in elderly Turkish patients. Balkan Med J 2010;27(2):127–131.
Zuradelli M, Masci G, Biancofiore G, et al. High incidence of hypocalcemia and serum creatinine increase in patients with bone metastases treated with Zoledronic acid. Oncologist 2009;14(5): 548–556. DOI: 10.1634/theoncologist.2008-0227.
Langmann GA, Perera S, Ferchak MA, et al. Inflammatory markers and frailty in long-term care residents. J Am Geriatr Soc 2017;65(8): 1777–1783. DOI: 10.1111/jgs.14876.
Pieper CF, Colon-Emetic C, Caminis J, et al. Distribution and correlates of serum 25-hydroxyvitamin D levels in a sample of patients with hip fracture. Am J Geriatr Pharmacother 2007;5(4):335–340. DOI: 10.1016/j.amjopharm.2007.12.004.
Lv QB, Gao X, Liu X, et al. The serum 25-hydroxyvitamin D levels and hip fracture risk: a meta-analysis of prospective cohort studies. Oncotarget 2017;8(24):39849–39858. DOI: 10.18632/oncotarget. 16337.