A retrospective cohort analysis of the effects of renin-angiotensin system inhibitors on spinal fusion in ACDF patients

Abstract

BACKGROUND CONTEXT

Recently, preclinical and clinical studies suggest an association between renin-angiotensin system (RAS) blockers and bone healing, particularly in the context of osteoporotic bone fractures.

PURPOSE

To determine the correlation between the use of RAS inhibitors and fusion outcomes and neurologic status in anterior cervical discectomy and fusion (ACDF) surgery.

STUDY DESIGN

Retrospective observational study.

PATIENT SAMPLE

Patients who underwent ACDF for degenerative disorders.

OUTCOME MEASURES

Spinal fusion status and neurologic function (modified Japanese Orthopedic Association [mJOA] and Nurick grading scales).

METHODS

A retrospective chart review was performed, including 200 patients who underwent ACDF for degenerative disorders with 1-year minimum follow-up. Demographic data, comorbidities, antihypertensive medication, neurologic examination, and fusion status were collected. Spinal fusion was assessed via plain cervical x-ray, resorting to dynamic radiographs and/or computer tomography (CT) in cases of uncertainty. Preoperative mJOA and Nurick scores and recovery rates were calculated to determine neurologic status.

RESULTS

Of the 200 patients (42.5% females, 57.5% males, median age of 53.7 years), 82 hypertensive patients were identified. Seventy-seven (93.9%) were taking antihypertensive medication as follows: 36.4% angiotensin-II receptor blockers (ARBs), 35.1% angiotensin-converting enzyme inhibitors (ACEIs), and the remaining patients were taking other medication. In the analysis of fusion rates, patients treated with ARBs exhibited a higher fusion rate, while those treated with ACEIs displayed a lower fusion rate compared to untreated nonhypertensive patients (p = .04 and .02, respectively). The difference in fusion rates between ARBs and ACEIs was also significant, with the former displaying higher rates (p < .001). Smoking exhibited a negative correlation with spinal fusion (p < .001). In the multivariate analysis, ARBs remained an independent factor for successful fusion (p = .02), while smoking remained a risk factor for failed fusion (p = .002). In the neurologic examination, ACEIs, hypertension status, and older age correlated with lower modified Japanese Orthopedic Association (mJOA) recovery rates (p = .001, <.001, and <.001, respectively) in the univariate analysis.

CONCLUSIONS

In ACDF patients, we observed that ARBs were associated with higher fusion rates. Conversely, ACEIs and smoking were related to failed fusion. Prospective case-control studies are needed to confirm these RAS inhibitors effects on spinal fusion.

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.