Research Article: Corticosteroid Is Associated with Both Hip Fracture and Fracture-Unrelated Arthropathy

Date Published: January 26, 2017

Publisher: Public Library of Science

Author(s): Feng-Chen Kao, Yao-Chun Hsu, Chien-Fu Jeff Lin, Ying-Ying Lo, Yuan-Kun Tu, Ping-Hsun Wu.

http://doi.org/10.1371/journal.pone.0169468

Abstract

We aimed to investigate whether and how corticosteroid use was associated with serious hip arthropathy.

This population-based cohort study analyzed the Taiwan National Health Insurance Research Database and screened the one-million random sample from the entire population for eligibility. The steroid cohort consisted of 21,995 individuals who had used systemic corticosteroid for a minimum of 6 months between January 1, 1997 and December 31, 2006. They were matched 1:1 in propensity score on the index calendar date with controls who never used steroid. All participants were followed up until occurrence of serious hip arthropathy that required arthroplasty, withdrawal from the national health insurance, or the end of 2011. Surgical indication was classified as fracture-related and -unrelated. The cumulative incidence of hip arthroplasty was estimated by the Kaplan Meier method. The association with steroid exposure was explored by the Cox proportional hazard model.

Cumulative incidences of hip arthroplasty after 12 years of follow-up were 2.96% (95% confidence interval [CI], 2.73–3.2%) and 1.34% (95% CI, 1.2–1.51%) in the steroid users and non-users, respectively (P<0.0001). The difference was evident in fracture-related arthroplasty with 1.89% (95% CI, 1.71–2.09%) versus 1.10% (95% CI, 0.97–1.25%), but more pronounced in fracture-unrelated surgery, 1.09% (95% CI, 0.95–1.24%) versus 0.24% (95% CI, 0.19–0.32%). Multivariate-adjusted Cox regression analysis confirmed steroid use was independently associated with both fracture-related (adjusted hazard ratio [HR], 1.65; 95% CI, 1.43–1.91) and unrelated arthroplasty (adjusted HR, 4.21; 95% CI, 3.2–5.53). Moreover, the risk for fracture-unrelated arthropathy rose with steroid dosage, as the adjusted HR increased from 3.30 (95% CI, 2.44–4.46) in the low-dose subgroup, 4.54 (95% CI, 3.05–6.77) in intermediate-dose users, to 6.54 (95% CI, 4.74–9.02) in the high-dose counterpart (Ptrend<0.0001). Corticosteroid use is associated with long-term risk of hip arthroplasty, particularly for fracture-unrelated arthropathy.

Partial Text

Corticosteroid may induce bone disease that is associated with substantial morbidity and mortality[1]. For instance, osteoporosis is a well-recognized complication that can precipitate fracture of the weight-bearing bones [2, 3]. Previous studies have established that glucocorticoid use is a risk factor of vertebral and hip fracture[4]. However, the detrimental effect of corticosteroid on bone health extends beyond demineralization. It may also reduce osteocytes’ life span, impair the balance between osteoclast and osteoblast, and compromise skeletal angiogenesis[5–7]. As another complication of steroid exposure, osteonecrosis reportedly affects femoral heads in 8~10% of the users[8]. An epidemiological survey from Japan estimated that among 2,500~3,300 new cases of non-traumatic osteonecrosis every year, 34.7% were induced by corticosteroid[9]. How steroid duration, dosing frequency, and cumulated dosage might impact the risk of osteonecrosis, however, remains controversial[10–12].

This population-based study revealed a significant association of corticosteroid with subsequent hip arthropathy that entailed surgical intervention. Cumulatively at 12 years of follow-up, 2.96% (95% CI, 2.73–3.20%) of steroid users would require hip arthroplasty, significantly higher than 1.34% (95% CI, 1.2–1.51%) of their propensity score-matched controls (P < .0001). Our study further revealed that the excessive risk conferred by steroid use was more pronounced for fracture-related arthropathy, although it was also significant for hip fracture. A four-fold risk (adjusted HR, 4.21; 95% CI, 3.2–5.53) of receiving fracture-unrelated hip surgery (mainly driven by AVN) was shown in the multivariate-adjusted analysis that took age and comorbidity in to account. Moreover, the association was significant in a dose-dependent manner. Collectively, these findings contribute to bridge the knowledge gap pertaining how this extensively prescribed medication may raise the risk of serious hip diseases at a population scale. Our data not only caution against prolonged exposure to steroid, but also indicate the unmet need of effective strategies capable of preventing adverse orthopedic events in individuals who cannot spare steroid.   Source: http://doi.org/10.1371/journal.pone.0169468