Safety of low dose inpatient zoledronic acid in acute hip fracture patients with advanced chronic kidney disease

Zoledronic acid (ZA), cleared renally, carries a higher nephrotoxicity risk at doses≥4 mg, especially in patients with chronic kidney disease (CKD). While 5 mg is standard for osteoporosis, ZA increases bone mineral density at doses as low as 0.25 mg every 3 mo. Inpatient ZA (IP-ZA) in hip fracture patients reduces mortality and re-fracture risk, but its safety in those with advanced CKD [creatinine clearance rate (CrCl) < 35 mL/min] is unclear. We analyzed real-world data from a large academic healthcare system to assess the safety of reduced-dose IP-ZA (≤3 mg) in hip fracture patients with advanced CKD, compared to propensity-matched controls receiving no anti-osteoporosis medication during index hip fracture hospitalization. The study included 328 IP-ZA patients and 2308 controls, with a primary cohort of 46 IP-ZA patients and 98 matched untreated controls, predominantly female (77.8%), White (92.4%), with a mean age of 89.9 yr and CrCl of 31.1 ± 0.6 mL/min. The IP-ZA group received an average dose of 2.7 ± 0.1 mg (1 patient at 1 mg, 11 at 2 mg, 34 at 3 mg) on postoperative day 2.9 ± 0.3. All patients received standing acetaminophen, calcium (650-1000 mg/d), and vitamin D (1000-2500 IU/d) post-surgery. We monitored daily maximum body temperature, serum creatinine, and serum calcium for five days, starting the day before IP-ZA administration (or postoperative day 2 for controls). IP-ZA did not affect temperature, with new-onset fever (≥38.0 °C, days 2-4) in one IP-ZA patient and two controls. Serum creatinine level remained stable. Serum calcium level in the IP-ZA group decreased from 8.8 ± 0.1 mg/dL to 8.2 ± 0.2 mg/dL by day 5, unchanged in controls; no IP-ZA patient had serum calcium level < 7.5 mg/dL. Hospital length-of-stay (6.2 ± 0.4 vs. 6.5 ± 0.4 d, p = .41) and 30-d readmission rates were similar. This study suggests that reduced-dose IP-ZA is likely safe for patients with hip fracture and advanced CKD who are otherwise at high risk for being untreated.