Non-steroidal anti-inflammatory drugs and the risk of a second hip fracture: a propensity-score matching study

Po-Yao Chuang, Shih-Hsun Shen, Tien-Yu Yang, Tsan-Wen Huang, Kuo-Chin Huang, Po-Yao Chuang, Shih-Hsun Shen, Tien-Yu Yang, Tsan-Wen Huang, Kuo-Chin Huang

Abstract

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed for elderly patients, particularly after a hip fracture. However, we are not clear about the effect of NSAIDs on the risk of a second hip fracture because of confounding factors.

Methods: This was a Taiwan National Health Insurance Research Database-based study using propensity-score matching (PSM) to control for confounding. Enrollees were selected from patients with a hip fracture during 1996-2004 and followed longitudinally until December 2009. After PSM for comorbidities and bisphosphonate therapy, 94 patients with a second hip fracture were assigned to the Cases group and 461 without it to the Controls group. The target drugs are NSAIDs; paracetamol and dexamethasone are used for comparison.

Results: The correlation between the mean daily-dose (MDD) ratios of NSAIDs and the probability values of the current statistical tests were highly negative (Pearson's r = -0.920, P = 0.003), which indicated that the higher the MDD ratios, the greater the risks of a second hip fracture. A Kaplan-Meier survival analysis showed a time-dependent trend of increasing risk of a second hip fracture in patients taking NSAIDs (P < 0.001). Moreover, patients ≥ 60 years old had a higher risk of a second hip fracture than did those <60 and taking the NSAIDs diclofenac (P = 0.016) and celecoxib (P = 0.003) and the corticosteroid dexamethasone (P = 0.018), but not those taking analgesic paracetamol (P = 0.074).

Conclusions: We conclude that taking NSAIDs after a fragility hip fracture dose- and time-dependently significantly increases the risk of a second hip fracture, especially in elderly patients. To lower the risk of a second hip fracture, any underlying causes for excessively using NSAIDs should be treated and thus fewer NSAIDs prescribed after a first hip fracture.

Keywords: Fragility hip fracture; Non-steroidal anti-inflammatory drugs; Population-based study; Propensity-score matching; Second hip fracture.

Figures

Fig. 1
Fig. 1
A flowchart of the patient selection process
Fig. 2
Fig. 2
Correlation between the fold increase of the mean daily dose (MDD) of NSAIDs and of the log value of the probability of the current statistical hypothesis tests
Fig. 3
Fig. 3
Kaplan-Meier survival estimates with a second hip fracture (SHFx) as an endpoint. Survival free of a second hip fracture for a total patients, b male patients, c female patients, d patients who took and did not take paracetamol, NSAIDs, and dexamethasone, and e patients who took paracetamol, f diclofenac, g celecoxib, and h dexamethasone. * P < 0.05

References

    1. Kanis JA, Odén A, McCloskey EV, Johansson H, Wahl DA, Cooper C. A systematic review of hip fracture incidence and probability of fracture worldwide. Osteoporos Int. 2012;23(9):2239–2256. doi: 10.1007/s00198-012-1964-3.
    1. Ryg J, Rejnmark L, Overgaard S, Brixen K, Vestergaard P. Hip fracture patients at risk of second hip fracture: a nationwide population-based cohort study of 169,145 cases during 1977–2001. J Bone Miner Res. 2009;24(7):1299–1307. doi: 10.1359/jbmr.090207.
    1. Shen SH, Huang KC, Tsai YH, et al. Risk analysis for second hip fracture in patients after hip fracture surgery: a nationwide population-based study. J Am Med Dir Assoc. 2014;15(10):725–731. doi: 10.1016/j.jamda.2014.05.010.
    1. Lönnroos E, Kautiainen H, Karppi P, Hartikainen S, Kiviranta I, Sulkava R. Incidence of second hip fractures. A population-based study. Osteoporos Int. 2007;18(9):1279–1285. doi: 10.1007/s00198-007-0375-3.
    1. Khosla S, Amin S, Orwoll E. Osteoporosis in men. Endocr Rev. 2008;29(4):441–464. doi: 10.1210/er.2008-0002.
    1. Pietschmann P, Rauner M, Sipos W, Kerschan-Schindl K. Osteoporosis: an age-related and gender-specific disease - a mini-review. Gerontology. 2009;55(1):3–12. doi: 10.1159/000166209.
    1. Vestergaard P, Rejnmark L, Mosekilde L. Hip fracture prevention: Cost-effective strategies. Pharmacoeconomics. 2001;19(5 Pt 1):449–468. doi: 10.2165/00019053-200119050-00002.
    1. Raisz LG. Potential impact of selective cyclooxygenase-2 inhibitors on bone metabolism in health and disease. Am J Med. 2001;110(Suppl 3A):43S–45S. doi: 10.1016/S0002-9343(00)00684-7.
    1. Kawaguchi H, Pilbeam CC, Harrison JR, Raisz LG. The role of prostaglandins in the regulation of bone metabolism. Clin Orthop Relat Res. 1995;313:36–46.
    1. Raisz LG. Prostaglandins and bone: physiology and pathophysiology. Osteoarthritis Cartilage. 1999;7(4):1–3. doi: 10.1053/joca.1998.0230.
    1. Kawaguchi H, Pilbeam CC, Vargas SJ, Morse EE, Lorenzo JA, Raisz LG. Ovariectomy enhances and estrogen replacement inhibits the activity of bone marrow factors that stimulate prostaglandin production in cultured mouse calvariae. J Clin Invest. 1995;96(1):539–548. doi: 10.1172/JCI118066.
    1. Jee WS, Ma YF. The in vivo anabolic actions of prostaglandins in bone. Bone. 1997;21(4):297–304. doi: 10.1016/S8756-3282(97)00147-6.
    1. Faye-Petersen OM, Johnson WH, Jr, Carlo WA, et al. Prostaglandin E1-induced hyperostosis: clinicopathologic correlations and possible pathogenetic mechanisms. Pediatr Pathol Lab Med. 1996;16(3):489–507. doi: 10.1080/15513819609168686.
    1. Rashiq S, Logan RF. Role of drugs in fractures of the femoral neck. BMJ. 1986;292(6524):861–863. doi: 10.1136/bmj.292.6524.861.
    1. van Staa TP, Leufkens HG, Cooper C. Use of nonsteroidal anti-inflammatory drugs and risk of fractures. Bone. 2000;27(4):563–568. doi: 10.1016/S8756-3282(00)00361-6.
    1. Thompson DD, Rodan GA. Indomethacin inhibition of tenotomy-induced bone resorption in rats. J Bone Miner Res. 1988;3(4):409–414. doi: 10.1002/jbmr.5650030407.
    1. Rossini M, Viapiana O, Adami S, et al. Medication use before and after hip fractures: a population based cohort and case-control study. Drugs Aging. 2014;31(7):547–553. doi: 10.1007/s40266-014-0184-2.
    1. Vestergaard P, Hermann P, Jensen JE, Eiken P, Mosekilde L. Effects of paracetamol, non-steroidal anti-inflammatory drugs, acetylsalicylic acid, and opioids on bone mineral density and risk of fracture: results of the Danish Osteoporosis Prevention Study (DOPS) Osteoporos Int. 2012;23(4):1255–1265. doi: 10.1007/s00198-011-1692-0.
    1. Carbone LD, Tylaysky FA, Cauley JA, et al. Association between bone mineral density and the use of nonsteroidal anti-inflammatory drugs and aspirin: impact of cyclooxygenase selectivity. J Bone Miner Res. 2003;18(10):1795–1802. doi: 10.1359/jbmr.2003.18.10.1795.
    1. Mann B, Wood E. Confounding in observational studies explained. Open Epidemiol J. 2012;5:18–20. doi: 10.2174/1874297101205010018.
    1. Rosenbaum PR, Rubin DB. The central role of the propensity score in observational studies for causal effects. Biometrika. 1983;70(1):41–55. doi: 10.1093/biomet/70.1.41.
    1. Dehejia RH, Wahba S. Propensity score-matching methods for nonexperimental causal studies. Rev Econ Statistics. 2002;84(1):151–161. doi: 10.1162/003465302317331982.
    1. Cheng CL, Kao YH, Lin SJ, Lee CH, Lai ML. Validation of the national health insurance research database with ischemic stroke cases in Taiwan. Pharmacoepidemiol Drug Saf. 2011;20(3):236–242. doi: 10.1002/pds.2087.
    1. The Anatomical Therapeutic Chemical (ATC) classification system and the Defined Daily Dose (DDD).
    1. Goodman SN. Toward evidence-based medical statistics. 1: The P value fallacy. Ann Intern Med. 1999;130(12):995–1004. doi: 10.7326/0003-4819-130-12-199906150-00008.
    1. Bauer DC, Orwoll ES, Fox KM, et al. Aspirin and NSAID use in older women: effect on bone mineral density and fracture risk. Study of Osteoporotic Fractures Research Group. J Bone Miner Res. 1996;11(1):29–35. doi: 10.1002/jbmr.5650110106.
    1. Wilkin TJ, Devendra D. Bone densitometry is not a good predictor of hip fracture. BMJ. 2001;323(7316):795–797. doi: 10.1136/bmj.323.7316.795.
    1. Rochon PA, Gurwitz JH. Optimising drug treatment for elderly people: the prescribing cascade. BMJ. 1997;315(7115):1096–1099. doi: 10.1136/bmj.315.7115.1096.
    1. Ekman EF. The role of the orthopaedic surgeon in minimizing mortality and morbidity associated with fragility fractures. J Am Acad Orthop Surg. 2010;18(5):278–285. doi: 10.5435/00124635-201005000-00004.
    1. Kannus P, Parkkari J, Niemi S, et al. Prevention of hip fracture in elderly people with use of a hip protector. N Engl J Med. 2000;343(21):1506–1513. doi: 10.1056/NEJM200011233432101.
    1. McLellan AR, Gallacher SJ, Fraser M, McQuillian C. The fracture liaison service: success of a program for the evaluation and management of patients with osteoporotic fracture. Osteoporos Int. 2003;14(12):1028–1034. doi: 10.1007/s00198-003-1507-z.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa