ACE-inhibitors: a preventive measure for bone flap resorption after autologous cranioplasty?

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OBJECTIVE

Decompressive craniectomy (DC) is an established treatment for refractory intracranial hypertension. It is usually followed by autologous cranioplasty (AC), the reinsertion of a patient’s explanted bone flap. A frequent long-term complication of AC is bone flap resorption (BFR), which results in disfigurement as well as loss of the protective covering of the brain. This study investigates risk factors for BFR after AC, including medical conditions and antihypertensive drug therapies, with a focus on angiotensin-converting enzyme inhibitors (ACEIs), which have been associated with a beneficial effect on bone healing and bone preservation in orthopedic, osteoporosis, and endocrinology research.

METHODS

In this single-center, retrospective study 183 consecutive cases were evaluated for bone flap resorption after AC. Information on patient demographics, medical conditions, antihypertensive therapy, and BFR—defined as an indication for revision surgery established by a neurosurgeon based on clinical or radiographic assessments—was collected. A Kaplan-Meier analysis of time from AC to diagnosis of BFR was performed, and factors associated with BFR were investigated using the log-rank test and Cox regression.

RESULTS

A total of 158 patients were considered eligible for inclusion in the data analysis. The median follow-up time for this group was 2.2 years (95% CI 1.9–2.5 years). BFR occurred in 47 patients (29.7%), with a median time to event of 3.7 years (95% CI 3.3–4.1 years). An ACEI prescription was recorded in 57 cases (36.1%). Univariate Kaplan-Meier analysis and the log-rank test revealed that ACEI therapy (2-year event free probability [EFP] 83.8% ± 6.1% standard error vs 63.9% ± 5.6%, p = 0.02) and ventriculoperitoneal (VP) shunt treatment (2-year EFP 86.9% ± 7.1% vs 66% ± 5.0%, p = 0.024) were associated with a lower probability of BFR. Multiple Cox regression analysis showed ACEI therapy (HR 0.29, p = 0.012), VP shunt treatment (HR 0.278, p = 0.009), and male sex (HR 0.500, p = 0.040) to be associated with a lower risk for BFR, whereas bone fragmentation (HR 1.92, p = 0.031) was associated with a higher risk for BFR.

CONCLUSIONS

Hypertensive patients treated with ACEIs demonstrate a lower rate of BFR than patients treated with other hypertensive medications and nonhypertensive patients. Our results are in line with previous reports on the positive influence of ACEIs on bone healing and preservation. Further analysis of the association between ACEI treatment and BFR development is needed and will be evaluated in a multicenter prospective trial.

ABBREVIATIONS AC = autologous cranioplasty; ACEI = angiotensin-converting enzyme inhibitor; BFR = bone flap resorption; CI = confidence interval; CVI = cerebrovascular ischemia; DC = decompressive craniectomy; EFP = event-free probability; HR = hazard ratio; ICH = intracerebral hemorrhage; IQR = interquartile range; mTTE = median time to event; PTH = parathyroid hormone; RAAS = renin-angiotensin-aldosterone system; RR = relative risk; SAH = subarachnoid hemorrhage; TBI = traumatic brain injury; VP = ventriculoperitoneal.
Article Information

Contributor Notes

Correspondence Alessa Schütz: Bern University Hospital, Bern, Switzerland. alessa.schuetz@insel.ch.INCLUDE WHEN CITING Published online November 23, 2018; DOI: 10.3171/2018.6.JNS172605.

A.S. and M.M. contributed equally to this work and share first authorship.

Disclosures Dr. Shucht reports an ownership interest in Trustedoctor.
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