Treatment Effects of Bisphosphonates and Denosumab on Survival and Refracture from Real-World Data of Hip-Fractured Patients

Calcif Tissue Int. 2019 Dec;105(6):630-641. doi: 10.1007/s00223-019-00611-3. Epub 2019 Sep 17.

Abstract

We examined differences in patients' survival after hip fracture (HF) and risk for subsequent HF among patients treated with oral and intravenous bisphosphonates (oBPs, iBPs), denosumab (DMAB), and patients without therapy. We used data from all patients in Austria aged ≥ 50 who sustained a HF between 2012 and 2017 and were followed for a subsequent HF and all-cause mortality until 2017. Antiosteoporotic treatment-naïve patients, who were incident users of BPs and DMAB, were eligible for propensity score matching 1:1 to obtain comparable user groups. We applied competing risk approach and calculated cumulative incidence functions and subdistribution-hazards for refracture. Cox regression models were applied for mortality risk. A total of 54,145 hip-fractured patients were observed (1919 oBPs; 1870 iBPs; 555 DMAB users; and 42,795 untreated patients were included in the matched sets) and followed up for a median (interquartile range) of 22.6 months (26.2). Patients treated with antiresorptive medications had significantly longer survival time than patients without treatment. Receiving treatment significantly decreased a hazard of dying only for women by 17% for iBPs (HR 0.83, 95% CI 0.71-0.98, p = 0.023). For DMAB and oBPs, the results were not statistically significant. Higher risk of a subsequent HF was observed in women on DMAB (SHR 1.77, 95% CI 1.08-2.91) and on iBP (SHR 1.81, 95% CI 1.35-2.41), and in men on oBPs (SHR 2.89, 95% CI 1.58-5.30). Patients who were treated with antiresorptive medications after HF had longer survival than patients without treatment, highlighting the importance of initiation of antiresorptive treatment after HF.

Keywords: Bisphosphonates; Competing risk regression; Denosumab; Hip fracture; Mortality; Subsequent hip fracture.

MeSH terms

  • Aged
  • Bone Density Conservation Agents / pharmacology
  • Denosumab / pharmacology*
  • Diphosphonates / pharmacology*
  • Female
  • Hip Fractures / drug therapy*
  • Hip Fractures / mortality*
  • Humans
  • Male
  • Middle Aged
  • Osteoporosis, Postmenopausal / drug therapy*
  • Treatment Outcome

Substances

  • Bone Density Conservation Agents
  • Diphosphonates
  • Denosumab