Clinical StudyA retrospective cohort analysis of the effects of renin-angiotensin system inhibitors on spinal fusion in ACDF patients
Introduction
The renin-angiotensin system (RAS) is well known for its significant role in circulatory homeostasis; and therefore, RAS blocker drugs are commonly used in the treatment of cardiovascular diseases [1], such as arterial hypertension, which affects 50% to 80% of spinal fusion patients [2]. Recent evidence suggests an association between RAS blockers and bone metabolism, particularly in the context of bone healing. In animal models, angiotensin-II (AngII) has been shown to decrease bone mass, while blockage of RAS signaling (mainly via angiotensin-II receptor blockers [ARBs]) seems to counteract these effects. For example, in ovariectomized mice, Zhou et al. [3] demonstrated that AngII accelerated osteoporotic bone resorption, while treatment with AT1R and AT2R blockers relieved AngII-induced osteoporosis. In ovariectomized rats that underwent transverse osteotomy of the proximal metaphysis of the femur, Rajkumar et al. reported that angiotensin-converting enzyme inhibitors (ACEIs) and ARBs increased the consolidation of experimental osteoporotic fractures and the average value of the microcirculation in the fracture zones [4]. In addition, clinical studies have suggested a potential correlation between the use of RAS blockers and reduced osteoporotic fracture risk. Chen et al. [5] reported a significantly higher incidence of osteoporotic fractures in hypertensive patients not treated with RAS inhibitors compared to those who were treated. This association between RAS inhibitors and bone metabolism may play a critical role in spinal fusion patients who also suffer from arterial hypertension. The purpose of this study was to determine whether there is a correlation between the use of antihypertensive medication, particularly AngII inhibitors, and outcomes in anterior cervical discectomy and fusion (ACDF) surgery.
Section snippets
Study design, setting, and participants
We performed a retrospective study according to Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement [6] guidelines to investigate whether there is a correlation between spinal fusion outcomes in a cohort of ACDF patients and treatment with AngII inhibitors. A chart review of patients who underwent ACDF at a single institution was performed, with prior Institutional Review Board approval (IRB00178932). A cohort of adult patients of both sexes, with symptomatic
Demographic and clinical data
A total of 200 patients with cervical degenerative disorders who underwent ACDF were identified, including 85 females (42.5%) and 115 males (57.5%), with a median age of 53.7 (range 24–90) years. Median follow-up was 21.7 months (range 12.2–44.3). Out of the included patients, 32 smokers (16%), 39 diabetic patients (19.5%), and 82 hypertensive patients (41%) were identified. Out of the 82 hypertensive patients, 77 (93.9%) were taking antihypertensive drugs (28 [36.4%] received ARBs, 27 [35.1%]
Discussion
In this study, the statistical analysis revealed RAS blockade to be a significant factor for fusion in ACDF patients. With a median follow-up of 22 months, patients treated with ARBs presented a significantly higher fusion rate (p = .04), while patients treated with ACEIs displayed a higher rate of fusion failure (p = .02). As in previous studies [14], [15], smoking was also correlated with a higher rate of pseudarthrosis (p < .001). Age, hypertension status, and treatment with ACEIs were
Conclusions
In our cohort of ACDF patients, treatment with ARBs was associated with an increased fusion rate, while treatment with ACEIs and smoking were identified as risk factors for pseudarthrosis. Further preclinical and clinical studies are warranted to confirm the beneficial effects of ARBs and deleterious influence of ACEIs on spinal fusion.
Acknowledgment
The authors would like to acknowledge research funding from the Gordon & Marylin Macklin Foundation.
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Author disclosures: AP-P: Nothing to disclose. FS: Nothing to disclose. CH: Nothing to disclose. WI: Nothing to disclose. SR: Nothing to disclose. EC: Nothing to disclose. AB: Nothing to disclose. S-fLL: Research Support (Investigator Salary, Staff/Materials): Chordome Foundation (Research material, cell lines, animal models); Grants: AO Spine (C). NT: Royalties: Globus Medical (E); Depuy Synthes (E); Stock Ownership: Globus Medical (F); Consulting Globus Medical (D); Scientific Advisory Board/Other Office: Globus Medical (B); Endowments; Fellowship Support: AO North America (E). TFW: Grants: Ely Lilly and Company (D); Gordon & Marylin Macklin Foundation (F).
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These authors contributed equally to this work.