Introduction

Teeth loss in the maxillary arch leads to progressive bone atrophy, and enlargement of maxillary sinus cavities can significantly increase the difficulty of the replacement of natural teeth with dental implants [1]. Nowadays, sinus floor elevation surgical procedure has become increasingly popular procedures before the placement of dental implants in posterior maxillae [2]. The first sinus lift procedure was performed by Tatum in 1976 which modified the Caldwell-Luc technique by preparing a lateral bony window to dissect and elevate the maxillary sinus Schneiderian membrane [3].

There are a lot of bone graft materials that are typically used for bone formation in the maxillary sinuses. In 1989 was clear that the ideal graft should be nontoxic, nonantigenic, noncarcinogenic, strong, resilient, easily fabricated, able to permit tissue attachment, resistant to infection, readily available, and inexpensive [4].

Graft materials in dentistry can be subdivided into four subcategories: autografts, allografts, xenografts, and phytogenic materials [5].

Speaking about autografts there are no histocompatibility and immunogenicity issues, thus they represent the highest degree of biological safety. Cancellous autograft bone contains osteoblasts and progenitor cells with considerable osteogenic potential [5]. Using autograft to maximize bone remodeling performance and healing potential, a combination of cancellous and cortical bone should be used [6]. The best alternative to an autograft is the use of allograft materials. Allografts exhibit good histocompatibility [5]. Xenografts have variable resorption rates, a lack of viable cells and biological components, and the need for tissue treatment processes that enable the retention of osteoinductive cells [7]. Phytogenic material has been shown to possess osteoinductive properties, increased alkaline phosphatase activity, and thus promote bone calcification and remodeling processes [8]. Nowadays, the market can be found synthetic materials which display only osteointegration and osteoconductive properties [9]. In this category of materials, we can find calcium phosphate ceramics (hydroxyapatite (HA), beta-tricalcium phosphate (β-TCP), biphasic calcium phosphate (BCP), bioglass) and others [10]. Moreover, it is noticed that TPC has good osteoconduction, radiopacity allowing monitoring of healing, good resorbability, and low immunogenicity but has poor mechanical properties in particular compressive strength. However, compared with BCP, BCP has osteoinduction and comparatively greater mechanical strengths than either TCP [5]. An animal study showed that the BCP ceramic exhibited similar tissue integration compared to the TCP group [11]. Due to different statements found in the literature, it was decided to clarify and evaluate alloplastic grafts (calcium phosphate ceramics – β-TCP and BCP) after maxillary sinus lift to see which material retains better bone volume.

Materials and Methods

A systematic review of the literature was performed between April 3, 2017, and April 3, 2022, according to the PRISMA selection criteria. The research was conducted independently by all authors in electronic databases, including PubMed Medline, Science Direct, Wiley Online Library, The Cochrane Library, and references of relevant studies. Databases were searched using the query: (β-TCP OR beta-tricalcium phosphate OR biphasic calcium phosphate) AND sinus AND (lift OR augmentation) AND (histomorphometric OR histomorphometry).

The protocol for the review was registered prospectively in the PROSPERO, registration number: CRD42022316448.

Interventions included a two-stage sinus floor elevation using β-TCP or BCP as the bone substitute. Comparison groups included a two-stage sinus floor elevation using a different autograft, allograft, xenograft, alloplastic material, or combinations of these substances.

This systematic review included studies in which the patients were augmented maxillary sinus using BCP or β-TCP and the percentage of newly-formed bone and the percentage of a residual bone substitute were histomorphometrically evaluated from bone biopsies obtained during implantation.

Clinical studies with humans published less than 5 years ago, written in the English language, and describing histomorphometric assessment of native bone and bone graft changes after maxillary sinus lift were analyzed in this systematic review. All meta-analyses, systematic and narrative reviews, letters to the editor, case reports or case series, animal, in vitro studies, or those with incomparable results, were excluded.

The PICO criteria for the present review were as follows:

• Patients: Patients for whom lateral maxillary sinus floor augmentation is indicated
• Intervention: Open sinus floor elevation.
• Comparison: Two-stage sinus floor elevation using a different graft material: BCP, β-TCP, autograft, allograft xenograft, or alloplastic material, or combinations of these substances.
• Outcome: Histomorphometric and histological analysis of newly formed bone and residual graft particles after sinus floor elevation using different grafting materials focusing on results of BCP or β-TCP.

The titles and abstracts after applying pre-established selection criteria first were analyzed, followed by the full-text review and analysis of complete articles. Any disagreements between reviewers over the inclusion of studies in the systematic review were resolved by discussion until a consensus was reached.

Quality assessments were also evaluated in included studies. The tool used for randomized controlled trials: RoB 2 tool: A revised Cochrane risk of bias tool for randomized trials [12], a tool used for observational studies: ROBINS-I Risk of Bias in Non-Randomized Studies - of Interventions (ROBINS-I) [13].

The important data (publications date, augmented sinuses or patients, used bone substitute materials, time until histologic, histomorphometric evaluation, main results, and outcomes) were independently extracted and collected from included articles.

Results and Discussion

Study selection

The literature research resulted in a total of 654 publications. After applying pre-established eligibility criteria, 184 articles were left for screening. After excluding publications with inappropriate titles or content, for full-text assessment 21 articles were involved. Finally, 8 of them fulfilled all inclusion criteria and underwent systematic review (Figure 1).

Studies design and characteristics

In this systematic review, 8 studies were included: 6 randomized clinical trials [14-19], 2 cohort studies [20, 21].

All studies included focused on new bone formation after lateral sinus augmentation using alloplastic graft. Three of them evaluated the effects of β-TCP alone [17, 19, 21] and five clinical trials have assessed the effects of BCP (comprising β-TCP and hydroxyapatite) [14-16, 19, 20]. This review also includes studies evaluating the effects of additional substances such as PRP, PRF [17, 18], or enamel matrix proteins (EMD) [16] on new bone formation after sinus augmentation with an alloplastic graft. The study's design and characteristics are shown in Table 1.

Table 1. Studies design and characteristics.

RCT - randomized clinical trial, CS – cohort study

Quality assessment

Risk of bias evaluation with the RoB 2 tool found that 4 of 6 included randomized studies characterized as low risk, and 2 had some concerns [14-19]. Results of the risk of bias in randomized studies are shown in Figure 2.

Assessing the risk of bias of included publications using the ROBINS-I tool for non-randomized studies is shown in Figure 3. Both involved studies were found to be a moderate risk of bias [20, 21].

Histology

Five studies included in this systematic review histologically described the formation of the new bone [15-18, 20].

The newly formed bone was in close contact with the partially resorbed graft particles although a demarcation line was separated between the rest of the native bone and the grafted sites. Histologically vital bone was composed of lamellar and woven bone with osteocytes in the lacunae [15-18]. Osteoblasts were also observed near the distinctive contours of the newly formed bone [17]. Only a few inflammatory cells, mostly macrophages or lymphocytes, and multinucleated giant cells were observed in a few studies without signs of acute inflammation [16-18, 20]. In a clinical trial by S. Comert Kilic et al. [17], sufficient angiogenesis was declared around the newly formed bone, but in sites grafted with β-TCP and P-PRP a denser network of capillaries was detected compared to β-TCP alone or β-TCP mixed with PRF. In this study was also noted that a lower density of osteoprogenitor cells and a higher density of inflammatory cells were found in β-TCP mixed with the PRF group (P < 0.05) [17].

Histomorphometry

Bone biopsy specimens were taken 6 - 9 months after the sinus lifting procedure [14-21]. The results are presented in Table 2.

Table 2. Studies results.

HA- hydroxyapatite; β-TCP - β-tricalcium phosphate; BCP- biphasic calcium phosphate; EMD- enamel matrix proteins; P-PRP- platelet-rich plasma; PRF- platelet-rich fibrin; MPM- mineralized plasmatic matrix; DBBM- deproteinized bovine bone mineral.

Sinuses augmented with β-TCP showed a mean volume of new bone ranging from 26.92% ± 7.26% to 47.6% ± 9.9% and an average residual volume of graft ranging from 30.39% ± 10.29% to 32.25% ± 8.48% in reviewed articles [17, 18, 21].

Sites augmented with BCP (comprising β-TCP and hydroxyapatite) showed an average bone volume ranging from 23.0% ± 8.80% to 43.4% ± 6.1% and the remaining volume of evaluated grafting material ranged from 16.4 ± 11.4% to 32.9% ± 15.6% [14-16, 19, 20].

The addition of autologous platelet concentrates to the β-TCP graft showed controversial results (Table 3). In the randomized control trial of S. Comert Kilic et al. [17], involving 26 patients was found no statistically significant differences between β -TCP, P-PRP-mixed β -TCP, and PRF-mixed β-TCP groups in terms of mean percentages of bone regeneration, residual grafting particles and soft-tissue area (P > 0.05). I. C. Cinar et al. [18] established statistically significant differences in percentages of newly formed bone and remaining graft material between groups of the β-TCP and β-TCP mixed with PRF (P < 0.05). However, no statistically significant difference was found in the evaluation of soft tissue areas between these two groups (P > 0.05).

The effect of EMD as an adjunct to BCP was not statistically significant compared to graft material alone on new bone formation, residual graft, or soft tissue formation 6 months after lateral sinus augmentation (P > 0.05) [16].

Table 3. Results in studies with additional biomaterials.