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

Abstract

OBJECTIVEDecompressive 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.METHODSIn 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.RESULTSA 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.CONCLUSIONSHypertensive 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.

Cranial bone flap resorption—pathological features and their implications for clinical treatment

“…A possible contamination and subsequent low-grade infection with Propionibacterium acnes has been discussed as a potential risk factor as well [6,37]. Schütz et al were further able to show that hypertensive patients treated with ACE inhibitors had a lower ABR rate than patients treated with other antihypertensive medication or patients who do not suffer from arterial hypertension [35].…”

Lisinopril-Induced CD34 Bone Healing Marker

“…More research is needed to fully understand the relationship between lisinopril and bone healing, and to determine the mechanisms by which lisinopril may affect bone healing. [13][14][15][16][17][18] There has been some research on the potential effects of lisinopril on the CD34 bone healing marker. CD34 is a protein that is expressed by cells called mesenchymal stem cells, which are involved in tissue repair and regeneration.…”

Risk factors for bone flap resorption after autologous bone cranioplasty

“…[ 11 , 12 ] BFR can lead to weakening, loosening and significant disintegration of the implanted autologous bone, which eventually results in loss of the bone coverage. [ 13 ] Revision surgery with replacement of synthetic material is necessary in severe cases of BFR and second surgery could be associated with higher expenses and poor clinical outcomes. [ 14 , 15 ] It would be reasonable to identify high-risk group that might suffer BFR and take preventive measures or choose alloplastic material cranioplasty for those patients.…”

“…Previous reports have found that younger age, bone flap fragmentations, and hydrocephalus shunt implantation to be associated with higher incidence of BFR. [ 11 , 16 – 18 ] Other potential risk factors, such as bone flap size, preservation of bone flap, and time interval between DC and cranioplasty [ 13 , 17 , 19 , 20 ] need to be assessed in a systematic approach. Therefore, we will undertake a systematic review and meta-analysis of studies presented data on risk factors for BFR requiring a second surgery after autologous cranioplasty.…”