Introduction

Patients with syndromic craniosynostosis undergo multiple surgical interventions to expand intracranial volume and improve skull dysmorphology [1,2,3]. While the type and timing of interventions remain a matter of debate, these patients are at increased risk of re-operation when compared to patients with single-suture, nonsyndromic craniosynostosis [4, 5]. As such, these patients are at particular risk for persistent bone defects and frontal contour irregularities as they progress to skeletal maturity which may precipitate the request for onlay, contouring cranioplasty.

Choice of reconstructive material utilized in secondary cranioplasty is hotly debated, and this study is not designed to answer which technique is optimal, but rather to describe our experience with carbonated calcium phosphate (CCP) bone cement. Autologous grafts, such as rib [6], iliac [7], and calvarium [8], have the benefits of being host-derived, with calvarial grafts providing a particularly natural contour. However, potential drawbacks of these grafts include donor site morbidity and resorption [9,10,11,12]. In recent decades, alloplastic reconstructive materials such as CCP cement and polyetheretherketone (PEEK) have been used as substitutes to autogenous grafts [13, 14]. CCP demonstrates structural similarity to bone matrix and, to an extent, is replaced via ingrowth of native bone [15, 16]. While aesthetic outcomes of CCP cranioplasty are favorable, the risk of CCP infection ranges from 10 to 50% based on defect size and proximity to sinus cavities [13, 16,17,18,19,20]. This wide range of infection rates is also attributable to heterogenous study populations. At our institution, CCP is used for a variety of cranial defects, most commonly partial thickness contour irregularities, including those caused by cranial vault reconstruction for craniosynostosis, trauma, and neurosurgical interventions, and our previously reported complication rate is 13.2% [19].

The ongoing need for secondary craniosynostosis surgery and the wide range of complications observed after cranioplasty call for focused examinations in specific sub-populations to further delineate indications and contraindications for the use of CCP cement. Patients with syndromic craniosynostosis are of specific interest as they often have a greater number of prior reconstructive surgeries, the potential need for greater volumes of CCP, and intrinsically abnormal bone homeostasis due to FGFR2 or TWIST gene mutations [21,22,23]. Indeed, existing literature has suggested that patients with syndromic craniosynostosis have a higher incidence of persistent postoperative defects following reconstruction with demineralized bone matrix than nonsyndromic patients [24]. The purpose of this study is to investigate the aesthetic outcomes and risk profile associated with CCP cement cranioplasty in patients with syndromic craniosynostosis.

Methods

Patient selection and study variables

Following approval from the Institutional Review Board, patients with a diagnosis of syndromic craniosynostosis treated with secondary frontal cranioplasty utilizing CCP cement from 2009 to 2022 at our institution were identified. Only patients with reconstructions of the forehead and frontotemporal region were included. Both partial and full thickness cranial defects were included. For all patients, the methodology of cement application has been previously described [19, 25, 26]. Information obtained for each patient included demographics, syndromic diagnosis, prior surgical history including age at initial fronto-orbital advancement (FOA), age at secondary contouring cranioplasty, operative duration, defect area and location (frontal, temporal, parietal), mass of cement used, length of postoperative hospital stay, complications, and most recent clinical follow-up. Defect area was determined by intraoperative measurements of total cranioplasty construct area, and mass of cement used was acquired from operative reports. Clinical photographs were obtained preoperatively (T1), at less than 6 months postoperatively (T2) and at > 1 year postoperatively (T3, Fig. 1). Forehead contour in each photograph was scored I–IV utilizing the Whitaker classification system [5, 27]. Scores were averaged across two craniofacial surgeons, and photographs were not scored if patient hair significantly obscured the forehead contour. All postoperative complications were noted. For each complication, the elapsed time from the initial operation was recorded as well as the outcome of the complication (operative or nonoperative). Complications were classified as infectious, cement exposure/extrusion, or contour abnormalities.

Fig. 1
figure 1

(Left) Preoperative photographs of a patient with Crouzon syndrome who underwent prior FOA with noticeable frontal bone irregularities and temporal narrowing. (Middle) Same patient 6 months after contouring cranioplasty with 20 g of CCP cement demonstrating improved forehead contour. (Right) Same patient at postoperative year 4 demonstrating stable forehead contour

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Data analysis

Data analysis was conducted in JASP (Version 0.16.3; JASP Team, 2020). Demographic variables and operative data were assessed with descriptive statistics. Whitaker scores were assessed between T1, T2, and T3 with paired-sample t-tests. Patients demonstrating improved postoperative Whitaker scores were compared to patients without improved scores with unpaired t-tests to identify factors associated postoperative aesthetic improvement. CCP cement use, defect size, and rate of complications in patients with syndromic craniosynostosis undergoing contouring cranioplasty in the present cohort was compared to the complication rate observed in age-matched patients with nonsyndromic craniosynostosis using previously published institutional data [19].

Results

 Twenty-one patients with a diagnosis of syndromic craniosynostosis underwent secondary cranioplasty with CCP by two craniofacial surgeons during the study period. Apert syndrome was the most common diagnosis treated, followed by Pfeiffer, Saethre-Chotzen, Muenke, and Crouzon syndromes. The patient cohort was 81% white and 52% female. Seventy-six percent of patients had bicoronal craniosynostosis, 19% were unicoronal, and 5% were sagittal (Table 1).

Table 1 Diagnostic and surgical characteristics of the patient cohort
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Operative characteristics

Age at surgery was 16.2 ± 2.8 years. Average defect area was 135 ± 112 cm2 and average cranioplasty construct utilized 17.2 ± 7.8 g of CCP cement. In addition to CCP cement, 13 patients’ reconstructions also utilized titanium mesh and 9 utilized cranial bone grafting. Operative duration was 179 ± 66 min. Postoperative length of stay was 1.9 ± 0.8 days and postoperative follow-up was 3.0 ± 3.1 years (Table 1).

Aesthetic outcomes

T1 photographs (n = 19) were taken 3.4 ± 2.4 months preoperatively, T2 photographs (n = 17) were 4.6 ± 3.5 months postoperatively, and T3 photographs (n = 13) were 19.9 ± 10.0 months postoperatively. Ninety-one percent of Whitaker ratings either agreed or fell within one level of disagreement. Average Whitaker score at T1 was 1.9 ± 0.4. Scores decreased at T2 to 1.4 ± 0.5 (p = 0.005). Average Whitaker score at T3 was 1.3 ± 0.3, which was not significantly different from T2 (p = 0.720, Fig. 2). Comparing patients with improved postoperative Whitaker scores to patients without improved scores, those with improved scores had, on average, smaller cranioplasty defect areas than patients without improved scores (89 ± 50 cm2 vs 168 ± 90 cm.2, p = 0.046). There were no differences between patients with and without postoperative aesthetic improvements in terms of number of preceding vault surgeries, age at initial fronto-orbital advancement, or age at secondary cranioplasty (Table 2). 

Fig. 2
figure 2

Whitaker classification scores across T1, T2, and T3. Scores were averaged across two craniofacial surgeons. *p < 0.05, ns = not significant

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Table 2 Comparison between patients experiencing postoperative improvement in forehead contour versus those who did not, as assessed by the Whitaker classification system. Significance (α < 0.05) bolded
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Complications

There were two complications in the patient cohort (9.5%). Both were infectious in nature and necessitated operative removal of CCP cement. Both complications occurred in patients who, in addition to CCP cement, had titanium mesh implanted to cover a full thickness calvarial defect. One complication occurred 4.5 months postoperatively and the other complication occurred 23 months postoperatively. The amount of cement used in these cases were 30 g and 40 g, respectively. These were the two largest masses in the cohort, but we are underpowered to make definitive conclusions regarding the relationship between volume used and complications. There were no complications of cement fragmentation in patients included in this study.

The complication rate of secondary cranioplasty in patients with syndromic craniosynostosis was compared to patients with nonsyndromic craniosynostosis previously published from our institution [19]. In that cohort, patients underwent cranioplasty at 15.0 ± 1.8 years of age. Five out of 65 patients (7.7%) had postoperative infections necessitating CCP cement removal, which was not significantly different than the rate of reoperation noted in the present study (p = 0.790). The cranioplasty construct area in the nonsyndromic patients was 105 ± 76 cm2 which was not significantly lower than the 135 ± 112cm2 seen in syndromic patients (p = 0.273). Similarly, CCP cement mass was not different between syndromic and nonsyndromic patients (17.2 ± 7.8 g vs 14.8 ± 7.7 g, p = 0.242). Ten patients in the present study have had follow-up for more than 3 years postoperatively and 5 have had follow-up for 5 or more years (range 3.0–7.8 years) None has undergone additional contouring cranioplasty or developed an indication for cement removal.

Discussion

There are many options for, and no consensus as to, the optimal reconstructive material for secondary cranioplasty. Alloplastic materials, such as CCP cement, have several advantages yet literature suggests cautious patient selection is necessary to avoid adverse outcomes, namely infection and fragmentation leading to extrusion. The present study was carried out to assess the use of CCP cement in a specific population with a high risk of needing secondary surgery, patients with syndromic craniosynostosis. Additionally, this study aimed to add precision to the risk profile associated with CCP given the ambiguity surrounding the risk profiles of alloplasts in the literature. The results of this study provide evidence that CCP cement reconstruction improves forehead contour with reasonable risk of infection or the need for re-contouring.

The patients in the present study experienced postoperative improvement in forehead contour as quantified using the Whitaker classification system [5]. Improvement in cranial contour with this alloplastic material is generally well accepted [19, 24, 28, 29]. The immediate postoperative improvement in this patient cohort was sustained at an average of over 18 months postoperatively, indicating that at least in medium-term follow-up, the aesthetic improvement is durable. Additionally, none of the 10 patients with 3 years or more follow-up underwent additional contouring, providing additional evidence of patient satisfaction.

The rate of infectious complications in the present study was 9.5%, similar to the complication rate observed in patients with nonsyndromic craniosynostosis. This is not necessarily intuitive as syndromic patients generally have a more complex surgical history, which has previously been implicated as a risk for cement infection [19, 20]. Both infections in this cohort occurred within 2 years and none of the patients followed for 3 or more years developed late postoperative infections. This finding, when considering that the cranioplasty construct area was an average of 135 cm2, seems initially at odds with prior research which has suggested that defects over 25 cm2 have increased risk of infection [17, 20, 30]. However, the difference in mass of cement used likely accounts for this finding, as high complication rates have been seen with average CCP cement construction up to 80 g [20]. A separate study reported that mean cement use in cases with infectious complications was 43 g, 20 g greater than cases without infectious complications [26]. Here, the average amount of CCP cement used was 17.2 g. Thin layering likely lowers the infectious risk, as it is known that neovascularization is limited to the periphery of the cement construct [31, 32]. Further, the two patients with infectious complications in this cohort had the largest construct masses at 30 g and 40 g, providing additional evidence that lack of neovascularization in the center of a thick cranioplasty may increase risk of chronic infection. Conversely, no complications were seen when 20 g or less was used.

There are several technical considerations for CCP cement cranioplasty in patients with syndromic craniosynostosis that may serve to mitigate risk while allowing for aesthetic improvement. First is a contraindication for the application of CCP cement to regions communicating with the frontal or ethmoid sinuses or nasal cavity, as previously described [18, 26]. By extension, hardware overlying sinuses is not removed during cranioplasty. Additionally, alloplastic material is rarely placed near the coronal incision during reconstruction, as exposure to skin flora may seed the CCP cement construct. Second, it is critical that CCP bone cement be placed on dry bone. We spend a great deal of time and energy ensuring the surface of the bone is absolutely dry without any small amount of blood. Third, the volume of the overall cranioplasty construct should ideally be kept low, smoothing contour but not providing for large frontal protrusion, in line with prior evidence [19, 26]. In cases of severe dysmorphology and frontotemporal retrusion, staging cranial bone grafting and/or repeat FOA followed by CCP cement cranioplasty may be necessary to avoid the higher risk of large-volume cement cranioplasty. Fourth, as seen in this study, patients with syndromic craniosynostosis may present for secondary cranioplasty with full thickness defects from prior craniotomies. Utilization of titanium mesh to absorb dural pulsations has been suggested to lower the risk of cement fracture [33, 34]. Finally, thin application of cement, on the order of 5 mm or less, is standard at our institution, as the existing histologic evidence does not suggest that this alloplastic material is replaced by native bone to any great extent, even with long-term follow-up [29, 35]. Still, there is limited revascularization and replacement of CCP cement particularly at the periphery of the implant [36], suggesting that optimizing the surface areas to volume ratio with a thin onlay would be more resistant to chronic infection than thick onlays. It is our impression that application of these guiding principles allows for the safe utilization of this reconstructive material, even in patients with complex surgical histories and contour irregularities over a large surface area.

There are limitations to the present study. First, this study is retrospective and cannot assign causality to the findings. Unaccounted for factors may have influenced both the aesthetic ratings and development of complications. Second, surgeon estimates of cement mass used may be unreliable as they are recorded intraoperatively by the surgeon from pre-weighted packaging. Similarly, defect dimensions are estimated from long- and short-sided measurements of the contouring surface and may be inaccurate as they do not account for curvature. Additionally, the Whitaker classification system, used to assess pre- and postoperative forehead contour, has been shown to have high inter-rater variability [27]. Finally, due to the small number of complications, it was not possible to statistically assess factors associated with postoperative CCP cement infection. Still, by narrowly defining a population for investigation, this study has been able to demonstrate aesthetic efficacy and safety of secondary cranioplasty with carbonated calcium phosphate cement in patients with syndromic craniosynostosis and provide additional evidence for the proper usage of this reconstructive material.

Conclusions

Our results suggest that aesthetic forehead ratings improve after CCP contouring cranioplasty, and that the improvement is sustained, at least in the medium-term. Infection and extrusion were uncommon, suggesting that CCP is relatively safe though longer-term follow-up is needed before reaching definitive conclusions regarding safety and efficacy.