The Association between Polypharmacy and Hip Fracture in Osteoporotic Women: A Nested Case–Control Study in South Korea
Background and Objective
Polypharmacy, regarded as an indicator of potentially inappropriate medications (PIMs), may lead to a higher risk of serious health consequences in elderly patients with osteoporosis. Thus, this study aimed to analyze the association between polypharmacy and hip fracture in patients with osteoporosis because only a limited number of studies have reported on this association, with inconsistent results to date.
In this nested case–control study using a population-based sample cohort, the target cases were female patients with hip fracture diagnosed with osteoporosis and aged ≥ 50 years. Polypharmacy (prescription of an average of five or more daily drugs), PIMs for hip fracture (such as benzodiazepines and glucocorticoids), Charlson Comorbidity Index (CCI) score, and other comorbidities were analyzed during the year preceding the diagnosis of hip fracture. Adjusted odds ratios (ORs) for hip fracture for the variables were also analyzed.
The cases (n = 1003) showed higher exposure rates to polypharmacy, glucocorticoids, and benzodiazepines, and had more severe comorbidity statuses compared with the controls. The ORs for hip fracture adjusted for confounders increased with polypharmacy level, with persistent statistical significance in most analyses. The ORs (95% confidence intervals), with reference to the 0 to < 1 drug group, were 1.65 (1.31–2.08) and 2.11 (1.12–3.96) for the 5 to < 10 and 10 + drug groups, respectively, with adjustment for PIMs, and 1.34 (1.04–1.72) and 1.45 (0.76–2.80) for the 5 to < 10 and 10 + drug groups, respectively, with adjustment for PIMs and CCI score.
The results suggest that polypharmacy is associated with an increased risk of hip fracture after adjustment for confounders in patients with osteoporosis. These results highlight the importance of polypharmacy management in preventing hip fractures in patients with osteoporosis.
The authors thank the Korea Research Foundation for supporting this research (nos. 2015R1C1A2A01052768 and 2018R1D1A1B07043416), and the National Health Insurance Service for providing data for this study (Approval number: NHIS-2018-2-022).
All authors were involved in the conception of the study, and HP and JK directed and executed the research project. HP, SK, and JK designed the statistical analysis, SK and JK executed the analysis, and all authors reviewed the statistical analysis. HP wrote the first draft. All authors contributed to the review, critical analysis, and finalization of this manuscript.
Compliance with Ethical Standards
A National Research Foundation of Korea grant funded by the Korean government (MSIP) provided funding for the study (No. 2015R1C1A2A01052768 and No.2018R1D1A1B07043416), and the funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Conflict of interest
Hae-Young Park, Suji Kim, Hyun Soon Sohn, and Jin-Won Kwon declare that they have no conflicts of interest.
The study protocol was approved by the Institutional Review Board of Kyungpook National University (approval number KNU 2014-0080).
This study was based on a secondary data source and patients were not directly involved in the entire research process, therefore the need for informed consent was waived.
- 2.Jokanovic N, Tan EC, Dooley MJ, Kirkpatrick CM, Bell JS. Prevalence and factors associated with polypharmacy in long-term care facilities: a systematic review. J Am Med Direct Assoc. 2015;16(6):535 e1-12.Google Scholar
- 16.Lee J, Lee JS, Park SH, Shin SA, Kim K. Cohort profile: the national health insurance service-national sample cohort (NHIS-NSC), South Korea. Int J Epidemiol. 2017;46(2):e15.Google Scholar
- 19.Weinstein RS. Clinical practice. Glucocorticoid-induced bone disease. N Engl J Med. 2011;365(1):62–70.Google Scholar
- 21.Vatcheva KP, Lee M, McCormick JB, Rahbar MH. Multicollinearity in regression analyses conducted in epidemiologic studies. Epidemiology (Sunnyvale). 2016;6(2):227.Google Scholar
- 43.Patterson SM, Cadogan CA, Kerse N, Cardwell CR, Bradley MC, Ryan C et al. Interventions to improve the appropriate use of polypharmacy for older people. The Cochrane Database Syst Rev. 2014;(10):CD008165.Google Scholar