Tolerability of the first infusion of once-yearly zoledronic acid within one to two weeks after hip fracture surgery

Kashii, Masafumi; Kamatani, Takashi; Abe, Shingo; Yoshida, Ayanori; Yamamoto, Kengo; Koizumi, Kota; Mizuno, Naoko; Kuriyama, Kohji; Yoshikawa, Hideki

Affiliations

¹Department of Orthopedic Surgery, Toyonaka Municipal Hospital, Toyonaka, Osaka, Japan

²Department of Rehabilitation, Toyonaka Municipal Hospital, Toyonaka, Osaka, Japan

Abstract and keywords

Objective: Once-yearly infusions of zoledronic acid (ZA) 5 mg may be optimal for secondary fracture prevention after hip fracture (HF), but there are crucial side effects of ZA. This study assessed the tolerability of the first infusion of once-yearly ZA within one to two weeks after HF surgery and to identify risk factors for acute-phase reactions (APRs) and the decrease in serum calcium (Ca) concentration.

Methods: We analyzed 84 patients (average age: 83 years, 18 men and 66 women) who met the inclusion criteria. The patients underwent the first infusion of ZA one to two weeks after HF surgery and received antipyretic analgesics and active vitamin D analog.

Results: APRs occurred in ten patients (11.9%) and all these patients had pyrexia (>37.5 °C) and/or other symptoms. The asymptomatic hypocalcemia (serum Ca < 8.3 mg/dL) incidence was 6.0% at 7 days after ZA infusion. Compared with female patients without APRs, female patients with APRs had significantly higher levels of serum 25-dihydroxyvitamin D at baseline and serum C-reactive protein on the day ZA was administered (day 0). Multiple linear regression analyses showed that serum level of tartrate-resistant acid phosphatase-5b were significantly associated with an absolute decrease in serum corrected Ca from day 0 to day 7.

Conclusions: The first infusion of ZA within one to two weeks after HF surgery was well tolerated with the combined use of antipyretic analgesics and active vitamin D analog. Higher inflammatory condition after surgery which is more likely sensitized by ZA administration may increase the risk of APRs, and high bone turnover may increase hypocalcemia risk.

Keywords: Acute-phase reaction; Hip fracture; Hypocalcemia; Osteoporosis; Zoledronic acid

Links

DOI: 10.1016/j.bone.2021.116298

PubMed: 34906743

WoS: 000773552300016

History

Received: 2021-10-3

Revised: 2021-12-7

Accepted: 2021-12-9

Online: 2021-12-11

Cited Works (6)

Year	Entry
2020	Conley RB, Adib G, Adler RA, Åkesson KE, Alexander IM, Amenta KC, Blank RD, Brox WT, Carmody EE, Chapman‐Novakofski K, Clarke BL, Cody KM, Cooper C, Crandall CJ, Dirschl DR, Eagen TJ, Elderkin AL, Fujita M, Greenspan SL, Halbout P, Hochberg MC, Javaid M, Jeray KJ, Kearns AE, King T, Koinis TF, Koontz JS, Kužma M, Lindsey C, Lorentzon M, Lyritis GP, Michaud LB, Miciano A, Morin SN, Mujahid N, Napoli N, Olenginski TP, Puzas JE, Rizou S, Rosen CJ, Saag K, Thompson E, Tosi LL, Tracer H, Khosla S, Kiel DP. Secondary fracture prevention: consensus clinical recommendations from a multistakeholder coalition. J Bone Miner Res. January 2020;35(1):36-52.
2019	Balasubramanian A, Zhang J, Chen L, Wenkert D, Daigle SG, Grauer A, Curtis JR. Risk of subsequent fracture after prior fracture among older women. Osteoporos Int. January 2019;30(1):79-92.
2008	Russell RGG, Watts NB, Ebetino FH, Rogers MJ. Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy. Osteoporos Int. June 2008;19(6):733-759.
2012	Eisman JA, Bogoch ER, Dell R, Harrington JT, McKinney RE Jr, McLellan A, Mitchell PJ, Silverman S, Singleton R, Siris E; ASBMR Task Force on Secondary Fracture Prevention. Making the first fracture the last fracture: ASBMR task force report on secondary fracture prevention. J Bone Miner Res. October 2012;27(10):2039-2046.
2007	Lyles KW, Colón-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; HORIZON Recurrent Fracture Trial. Zoledronic acid and clinical fractures and mortality after hip fracture. NEJM. November 1, 2007;357(18):1799-1809.
2009	van Geel TACM, van Helden S, Geusens PP, Winkens B, Dinant G-J. Clinical subsequent fractures cluster in time after first fractures. Ann Rheum Dis. January 2009;68(1):99-102.