Bone Graft Osseous Changes After Maxillary Sinus Floor Augmentation: A Systematic Review

Implant therapy is considered to be a conventional treatment for edentulous and partially edentulous patients. Rehabilitation of an atrophic posterior maxilla is challenging. This is because of not only the reduced remaining maxillary bone height, associated with ridge resorption and sinus pneumatization, but also low bone density.¹  Implant-supported rehabilitations are especially difficult in the posterior maxilla when it is associated with large or enlarged maxillary sinuses.. Enlarged sinuses may even inhibit the placement of short implants (∼4 mm) because of the lack of adequate bone height. Therefore, in cases in which the remaining bone height is insufficient, augmentation of the maxillary sinus floor is necessary before implant placement.² 

Maxillary sinus augmentations (ie, sinus lift procedures) are among the most commonly performed and reliable augmentation procedures used in implant dentistry.³  In clinical practice, a lateral window is opened into the maxillary sinus, the sinus membrane is carefully lifted, and autogenous bone or a bone substitute is positioned between the sinus floor and the sinus membrane and left to heal for 6 months or more before placing the implants. This technique, with some minor alterations, is widely used and called the “2-stage technique,” the first stage being augmentation of the maxillary sinus floor, and the second stage being the placement of dental implants.⁴ 

Characteristics of bone-graft materials that support increases in bone volume are biocompatibility, mechanical strength, osteoconductive properties, minimal immune response, and controlled resorption.^5,6  To overcome specific negative factors, several augmentation materials are currently used. The most commonly used bone-graft materials include autogenous bone grafts (AB; in particulates or in blocks), allografts (AG), xenografts (XG), alloplasts (AP), synthetics, or combinations of several types of allografts or biomaterials. Each material has case- and clinician-perceived benefits and drawbacks. As a result, the selection and recommendation of the ideal bone-graft material for maxillary sinus augmentation remains a controversial subject.^2,7 

However, despite the clinical establishment of the augmentation technique and graft materials, research is still ongoing to determine the optimal bone substitute or graft for sinus floor augmentation. In reconstructive surgery, autogenous bone is normally considered the gold standard, primarily because of its osteogenic, osteoinductive, and osteoconductive properties and remodeling capabilities. However, there are also disadvantages to the use of autogenous bone, which include the availability of donor bone and the frequent need to gather large quantities from extraoral sites. To limit the disadvantages, bone substitutes have been used including AG, XG, AP, and composite materials.^8,9  Ideally, augmentation with bone substitutes would involve good bone tissue integration, osteoinduction, and long-term stability. However, such a bone substitute material does not yet exist.

The variety of available grafting materials makes it difficult for clinicians to understand the diversity of types and characteristics; thus, there is a need for a current systematic overview of what is known.⁷  The amount of newly formed bone is an important criterion when evaluating grafting materials, as is the total bone volume and adequate bone density. All should result in a greater bone-to-implant contact, which should eventually lead to higher implant survival rates.¹⁰ 

Intraoral and panoramic radiographs can be used to calculate vertical dimensions of bone grafts, but they cannot provide any 3-dimensional (3D) bone change information.¹¹  Computerized tomographic (CT) scans are needed to assess the short- and long-term outcomes after bone grafting in the maxillary sinus. Radiologic analyses of graft volume and density is an interesting investigative method for clinicians and scientists, as it is a supported by technology that is minimally invasive. This is particularly true with the ongoing improvements to CT scans, such as digital volume tomography or cone-beam computerized tomography (CBCT). Bone changes can be measured (detected) from the time of bone graft placement and followed up with long-term analyses. The principle volumetric bone changes occur during the first 2 postoperative years.^12–14 

Many systematic reviews have evaluated the use of different biomaterials in maxillary sinus augmentation procedures, but most either compared a limited number of different types of bone grafts applied in animals and not humans, compared clinical or histomorphometric outcomes, or evaluated only vertical bone height. The objective of the present systematic review was to evaluate osteogenic volumetric gain in lateral window access sinus floor augmentations in the atrophic posterior maxilla, using CT scans, and following the use of various bone-grafting materials either separately or in combination.

This systematic review followed the PRISMA Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-analyses of Health Care Interventions (the PRISMA-P Checklist; Supplementary File 1).¹⁵ 

The databases MEDLINE, EMBASE, CINAHL, Cochrane Central Registry of Controlled Trials (CENTRAL), and SCOPUS were comprehensively searched for all potentially eligible randomized controlled trials (RCTs), without language restrictions, and from the beginning of each database until June 2021. The detailed search strategy is shown below.

A combination of MeSH terms and free keywords were used as followed: “(Computed tomography OR CBCT OR Computerized tomographic image) AND (new bone formation OR volumetric bone gain OR bone regeneration OR graft volume OR graft density) AND (bone atrophy OR Atrophic posterior maxilla) AND allografts OR autogenous bone grafts OR Xenografts OR alloplastic OR growth factors) AND (lateral sinus left OR lateral window OR lateral osteotomy OR sinus augmentation OR sinus elevation OR maxillary sinus lift OR maxillary sinus floor augmentation OR MSFA OR bone grafts OR graft materials OR bone substitutes OR bone transplantation) AND (randomized clinical study OR randomized controlled trial).”

Based on the PICOTS elements, studies that met the following inclusion criteria were included.

• (P) Problem/population: adult patients having an atrophic posterior maxilla who underwent maxillary sinus floor augmentation by a lateral sinus lift

• (I) Intervention: studies that used the following grafting materials during the maxillary sinus floor augmentation by a lateral sinus lift: AG, AP, XG, combinations of AG+XG, AG+AP, and XG+growth factors

• (C) Comparator: AB (autogenous bone graft)

• (O) Outcome: the primary outcome was the graft volume on CT scans, and the secondary outcome was the bone density on CT scans

• (T) Time: images captured immediately after operation (t1) and at 6-month follow-up (t2)

• (S) Study design: RCTs that reporting the outcomes of interest

The exclusion criteria included RCTs that assessed volumetric bone gain via histomorphometric means or conventional X rays and nonrandomized clinical studies, case series, cohort studies, and review articles as well as publications using duplicated data.

The retrieved publications from each database were documented and exported to the Rayyan web application (www.rayyan.ai), and duplicated articles were deleted. The process of initial (title and abstract) and final (full text) screening was performed using the Rayyan QCRI online tool, which provides independent access for retrieved publications so that each author (W.A., G.A.) could work independently. In case of a disagreement, a third reviewer (E.A.) was consulted.

The process of data collection was carried out independently by 2 researchers (W.A., G.A.), and the extraction table was revised by a third author (E.A.). Any disagreements were tackled by discussion. The data were extracted as follows: study ID (author and year of publication), participants (number, gender), type of graft material, outcome measures, and follow-up period.

The assessment of each included study was performed independently by the two authors (E.A., G.A.) according to the Cochrane risk of bias (ROB) tool, that is, the domain-based evaluation described in the Cochrane Handbook for Systematic Reviews of Interventions. The domains were recorded as “yes” (low ROB), “unclear” (uncertain ROB), or “no” (high ROB).¹⁶ 

Numerical data were described as mean ± standard deviation (SD). Comparison between the mean at baseline and after 6 months was performed using the Wilcoxon signed-rank test. A P value ≤.05 was considered statistically significant using SPSS.

A total of 1278 citations were identified from the literature search. Duplicates were removed automatically (n = 600). The 678 remaining records were screened for the title and abstract, resulting in 289 publications. The full-text versions of all these publications were read, resulting in 7 RCTs^17–23  with a short-term observation period that fulfilled the criteria and were included in the present systematic review (Figure).

In the 7 included RCTs, a total of 214 patients underwent lateral sinus lift elevation augmented with AB (n = 37), AG (n = 47), XG (n = 41), AP (n = 33), or a combination of AB+XG (n = 17), AB+AP (n = 27), and XG+growth factors (n = 12). Most of the patients were women. Most of the included studies used a split-mouth randomized prospective clinical trial design, had a 6-month follow-up period, and assessed the outcome using volumetric CBCT scans. In addition to CBCT analyses, histological evaluation was conducted in 2 of the 7 studies^24,25  (Table 1).

Two studies showed a low ROB,^26,27  and 5 studies^{14,24,25,27,28}  showed an unclear ROB when assessed by the ROB tool (Supplementary File 2).

At the baseline, the highest mean (±SD) was recorded in the AG+XG (2.880 ± 0.980), whereas the lowest mean was detected with XG+growth factors (1.68 ± 0.420). Likewise, the highest mean (±SD) was recorded in AG+XG (2.60 ± 0.97), while the lowest value was recorded in the XG+growth factors (1.10 ± 0.25) 6 months postoperatively.

Within the same category, there was a significant difference (P < .001) in the mean volumetric changes of the bone grafts at the 2 time points, immediately after augmentation and 6 months postoperatively. The topographical analyses of all included grafts revealed a volumetric reduction in all types after 6 months as compared with baseline. Regarding single-graft augmentation, the mean volumes of AB, AG, XG, and AP were 2.153, 2.560, 2.551, and 2.146, respectively, immediately after augmentation, while after 6 months, the mean volume decreased to 1.252, 1.786, 2.047, and 1.553, respectively.

In terms of composite bone-grafting materials, a similar trend has been reported. The difference was significant (P < .001). In particular, the mean volume of AG+XG, AG+AP, and XG+growth factors were 2.880, 2.030, and 1.68, respectively, at baseline, while after 6 months, the mean volume had decreased to 2.60, 1.523, and 1.10 respectively (Table 2).

At the 6-month follow-up, there was a significantly greater amount of bone volume after AB when compared withi AB+XG, XG, AP, and AG+XG (P < .001). However, no significant difference between AG, AG+AP, and XG+growth factors was found (Table 3).

At the 6-month follow-up, there was a significantly greater amount of bone volume after AG when compared with XG (P = .025), AG+XG (P < .001), AG+AP (P = .012), and XG+growth factors (P < .001). However, no significant difference was found after AG when compared with AP and AG+AP (Table 4).

At the 6-month follow-up, there was a significantly greater amount of bone volume after XG when compared with AG+XG and XG+growth factors (P < .001). Also, there was a significant difference after XG compared with AP and AG+AP (P < .05; Table 5).

A significantly smaller amount of bone volume after AP was apparent when compared with AG+XG as well as XG+growth factors (P < .001). However, no significant difference was found after AP when compared with AG+AP at the 2 follow-up points (Table 5).

At the 6-month follow-up, there was a significantly greater amount of bone volume after AG+XG compared with AG+AP and XG+growth factors (P < .001). In addition, there was a significantly greater amount of bone volume after AG+AP compared with a combination of XG+growth factors (P < .001; Table 6).

The outcome of alveolar bone grafting has traditionally been studied using 2-dimentional (2D) imaging, such as periapical, occlusal, and panoramic radiographs. However, 2D images of a 3D defect allow only measurement of bone height and do not measure the defect volume or the percentage of bone fill in the defect.²⁹  The use of 3D CT to measure bone graft volumetric reduction is relatively new, being used for approximately 10 years and, despite its importance, rarely presented in the literature. In fact, when it comes to the use of 3D CT for measurements of grafted maxillary sinus, its use becomes even more important for monitoring dimensional changes to bone volume following maxillary sinus floor augmentation.²⁶ 

Presurgical 3D scans allow volume measurements that can determine the amount of graft material needed. Postsurgical 3D scans are useful for determining correct implant placement.²⁹  Volumetric and dimensional stability of the grafting material represents an important factor for successful long-term implant treatment outcomes following maxillary sinus floor augmentation.³⁰  In the present study, the bone volume of a grafted maxillary sinus was measured in 3D to verify the volume contraction rate after 6 months of healing. CBCT scans were used to evaluate the volumetric gain of the various bone-grafting materials (either alone or in combination) for a lateral window sinus floor elevation performed in the atrophic posterior maxilla.

The dimensional changes of different types of graft materials reported in the literature may not only influence the resulting bone volume after maxillary sinus augmentation but also affect the stability of the actual implants.³¹  The general conclusion throughout the literature was that all bone-grafting materials and material combinations are prone to some resorption before dental implant placement. Most bone resorption and volumetric loss takes place in the period immediately after the augmentation procedure and before the placement of dental implants.³² 

The results of this systematic review showed that there was a highly significant difference in the mean volumetric changes of bone grafts immediately after augmentation and 6 months postoperatively. The topographical analysis of all included graft materials revealed a volumetric reduction after 6 months when compared with recorded baseline means. This is in agreement with a previous systematic review and clinical study that concluded that volumetric reductions of the augmented area was inevitable regardless of the grafting material used.^33,34  These results are also in agreement with Kirmeier et al,³⁴  who stated that there is an average shrinkage of approximately 26% after 2 weeks compared with the initial volume. Klein et al³⁵  demonstrated a statistically significant increase in volume in all maxillary sinuses. There may be various reasons for these contradictory results in bone volume changes after maxillary sinus augmentations. First, although numerous methods have been tried, there is no standardized measurement of bone volume after maxillary sinus augmentation using serial CBCT images. Accurate measurements of graft materials through 3D analysis software are difficult because of the variations in the degree of opacity in the ossified bone at the bone boundaries. Second, the patient's position cannot be replicated exactly for each serial CBCT image capture. Last, reliable volume measurements and standardized bone quality evaluations are difficult to accomplish due to errors of manual segmentation.^34,35 

AB is generally accepted as the gold standard for alveolar ridge augmentation.^8,9  However, pronounced volumetric reductions of the augmented area have been reported in several studies following maxillary sinus augmentation, which are in agreement with this review. This review showed significant differences in mean graft volume between AB and the other studied graft materials (AB+XG, XG, AP, and AG-XG) at the 6-month follow-up. Furthermore, this study did not reveal any significant differences in mean graft volumes between AB and AG, AG+AP, or XG+growth factors. Therefore, the volumetric stability of AB seems to be less preserved than other used grafting materials when used individually. However, the volumetric stability of AB is approximate to the composite grafting materials, which is in agreement with Shahbang et al,³³  who assessed the volumetric changes of grafted sinuses over time and found that the highest amount of volume reduction was reported for AB (up to 45%), followed by AG and other grafting materials. Thus, AB combined with a slow bone substitution rate graft material seems to diminish AB resorption and improve the long-term volumetric stability of the augmented area.^36,37 

An experimental study in minipigs assessing maxillary sinus augmentation with different compositions of AB and XG revealed that the augmented area was preserved after the addition of XG and the volumetric reduction significantly influenced by the ratio of XG to AB.³⁸  Another review indicated that the volumetric stability of the augmented area was significantly improved by combining AB with a nonresorbable XG.³⁰  These conclusions seem to be in accordance with the results of the present systematic review indicating that the volumetric stability of the augmented area was significantly improved with AG+XG or AG+AP combinations. The improvement showed a greater preservation of bone-grafting material in combination rather than in isolation graft materials. Based on these findings, it is recommended to “over-reconstruct” the grafted site when using AP or AG to compensate for shrinkage. The smallest graft volumetric change was found with the the use of XG+AP.²⁴ 

One interesting finding in the current review showed that although there was a significant difference between AG and AP immediately postoperatively, after 6 months there was no statistical difference found. Also, after 6 months, statistically significant differences with a greater bone volume in AG were then compared with each of XG, AG+XG, AG+AP, and XG+growth factors. This is in accordance with a study reporting AG with the lowest percentage of residual bone when compared with AP and XG. On the other hand, Kim et al³⁹  did not report any significant differences between AG and AG+XG in bone volume loss after 6 months. However, the present review showed a significant difference with a greater bone volume only after AG and not after AG+XG. This difference in outcome might be explained by the small number of participants in the study.³⁹ 

With respect to XG, after 6 months, the statistical analyses showed that there was a significantly greater bone volume, in comparison with AG+XG, XG+growth factors, AP, and AG+AP. This does not agree with Kwon et al.,⁴⁰  who showed that the average volume of bovine graft material (ie, XG) decreased during the follow-up period, although this was not statistically significant. This difference may be due to the fact that the study by Kwon et al⁴⁰  was a retrospective clinical study and not a systematic review.

Biomimetic enhancement factors and stem cell technologies have been introduced to the field of implant dentistry in the past decade.⁴¹  As indicated in previous studies, the application of biomimetic enhancement factors and stem cell technologies may reduce the time necessary for graft maturation, but it is unlikely to result in any dramatic changes in the volume of new bone formation.^42,43  In the current review, the effect of adding growth factors to other grafting materials was evaluated with XG; however, the results showed more resorption of the bone graft in the groups with growth factors.

It is noteworthy to mention that the observational period of the 7 included studies of the present systematic review was 6 months. Sufficient long-term data are needed to verify whether volumetric changes are limited to the initial postoperative period (6 months to 2 years) or not. Consequently, further randomized controlled trials with longer observational periods are needed before final conclusions can be drawn about the volumetric stability of different grafting materials following maxillary sinus floor augmentation.

The present systematic review has several limitations. First, most included studies did not provide information regarding residual ridge height between the sinus floor and the crest of the alveolar ridge. Residual ridges provide support to the grafted sinus and consequently affects the amount of new bone formation. Second, the current study did not differentiate between the different types or brands of bone grafts but rather dealt with bone grafts in general, “AB, AG, XG . . . etc.” Finally, only a limited number of studies were included to compare the tomographic volumetric gain between different grafting materials at 6 months of healing.

The volumetric gain of various grafting materials is important to consider before their use in maxillary sinus augmentation procedures, as they will contribute to the density and volumetric stability results of the future graft. In the current review, the topographical examination showed a volumetric reduction, such as shrinkage, in all graft types 6 months from immediate postplacement values and that there were no significant advantages regarding volumetric gain using graft combinations. Finally, among the graft combinations, AG+XG appeared to result in the greatest volumetric osseous increase. Although AB is considered the gold standard bone-grafting material, it demonstrated a high resorption rate and less volumetric gain compared with other grafting materials. Moreover, AG and XG showed a significant difference with less volumetric gain than AP alone or in combination with other grafting materials. No difference was detected between AP and AG+AP. However, there was significantly less volumetric gain for AP alone compared with AG+XG and XG-growth factors combinations. As a result, these findings suggest significant advantages to new bone formation using grafting materials in combination. To achieve a better understanding of topographical variables related to various grafting materials, more clinically focused RCTs, with sufficient statistical power to control for confounding factors, are needed.