Long-term safety of eldecalcitol in Japanese patients with osteoporosis: a retrospective, large-scale database study

J Bone Miner Metab. 2022 Mar;40(2):275-291. doi: 10.1007/s00774-021-01276-5. Epub 2022 Jan 18.

Abstract

Introduction: This real-world study evaluated whether long-term use of eldecalcitol (ELD) increases the risk of adverse events (AEs), namely, hypercalcemia, acute kidney injury (AKI), and urolithiasis, and analyzed the ELD-induced risk of rare AEs such as osteonecrosis of the jaw (ONJ) and atypical femoral fracture (AFF).

Materials and methods: Patient records were retrieved from Medical Data Vision (MDV) and Japan Medical Data Center (JMDC) databases. The ELD-treated osteoporosis patient cohort (ELD cohort) was analyzed to determine the incidence rate of the aforementioned AEs. The patient cohort that was prescribed active vitamin D3 other than ELD (AVD cohort) was analyzed as the reference.

Results: Incidence rates of hypercalcemia, AKI, and urolithiasis in the ELD cohort were 0.942, 0.517, 2.465 events per 100 person-years, respectively, in the MDV dataset, and 0.687, 0.155, 3.785, respectively, in the JMDC dataset. The incidence rates of these AEs in the ELD cohort remained relatively constant throughout ELD treatment. A small number of patients experienced ONJ or AFF during ELD or AVD treatment. The number of ONJ and AFF cases in the both cohorts decreased over time. The two cohorts showed no difference in the concomitant use of anti-bone resorptive agents such as bisphosphonates and denosumab.

Conclusion: The risk of hypercalcemia and AKI associated with ELD use observed in this retrospective analysis is similar to that reported previously in the Japanese post-marketing surveillance of ELD. Furthermore, ELD, similar to AVD, may not increase the risk of ONJ and AFF.

Keywords: Adverse events; Atypical femoral fracture; Osteonecrosis of the jaw; Osteoporosis; Real-world database study.

MeSH terms

  • Acute Kidney Injury / chemically induced
  • Bisphosphonate-Associated Osteonecrosis of the Jaw
  • Bone Density Conservation Agents* / adverse effects
  • Diphosphonates / adverse effects
  • Femoral Fractures
  • Humans
  • Hypercalcemia / chemically induced
  • Japan / epidemiology
  • Osteoporosis* / drug therapy
  • Osteoporosis* / epidemiology
  • Retrospective Studies
  • Urolithiasis / chemically induced
  • Vitamin D* / adverse effects
  • Vitamin D* / analogs & derivatives

Substances

  • Bone Density Conservation Agents
  • Diphosphonates
  • Vitamin D
  • eldecalcitol