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Coral hydroxyapatite versus tricalcium phosphate β in sinus augmentation: A comparative clinical study

Boyne and James[1] introduced the sinus elevation procedure in the early 1980s to overcome the anatomical limitation and to achieve vertical bone height in the atrophic areas of the posterior maxilla to facilitate the insertion of dental implants. This procedure contributed significantly to the use of dental implants. Although lifting the sinus membrane is a relatively safe pre-prosthetic surgery, there are some potential problems associated with the technique. Placing the implant in the posterior maxilla often requires surgery in the subantral area because the bone volume is insufficient.


INTRODUCTION
Boyne and James [1] introduced the sinus elevation procedure in the early 1980s to overcome the anatomical limitation and to achieve vertical bone height in the atrophic areas of the posterior maxilla to facilitate the insertion of dental implants. This procedure contributed significantly to the use of dental implants. Although lifting the sinus membrane is a relatively safe pre-prosthetic surgery, there are some potential problems associated with the technique. Placing the implant in the posterior maxilla often requires surgery in the subantral area because the bone volume is insufficient.
Tatum [2] described the enlargement of the maxillary sinus for the insertion of implants in this region for the first time. This surgical procedure allows the implant to be placed by increasing the height of the alveolar bone in this area. A variety of graft materials have been used to enlarge the bottom of the maxillary sinus. Autogenic bone grafts are considered the gold standard because they are not immunogenic and have osteogenic, osteoinductive and osteoconductive properties [1, 3 -6] . However, there are several disadvantages, including donor site morbidity, lameness when the graft is removed from the iliac crest, prolonged healing time, second surgery, the need for general and hospital anesthesia, higher treatment costs, and unpredictable absorption of the graft [7,8] .
These disadvantages have led to the search for suitable graft materials, which are a biocompatible, and osteoinductive or at least osteoconductive alternative to autogenous bone replacement in the procedure for enlarging the sinus floor. Various bone graft materials such as alloplastics (hydroxyapatite, b-tricalcium phosphate and bioactive glass) [9 -14] , xenografts (bovine or coral hydroxyapatite) [15 -20] , or allografts (freeze-dried demineralized bone) [21] are currently in use as an alternative or supplement to autogenous bone. These biomaterials serve as a scaffold for additional bone formation. However, bone reconstruction is slower than with autogenous bone grafts [22] . tricalcium phosphate (b-TCP), a ceramic alloplastic [26 -28] . Several authors have reported that b-TCP is a satisfactory graft material for increasing the maxillary sinuses [11 -14, 22] . The choice of augmentation material is a crucial factor in sinus augmentation. Choosing one of these materials for maxillary sinus augmentation remains controversial and no consensus has yet been reached.
The aim of this clinical study was to compare the biological yields (quantity and density) of the new CHA graft material with the synthetic b-TCP material, in patients with simultaneous atrophic maxillary sinus augmentation and implantation.

MATERIALS AND METHODS
The study consisted of 20 patients (10 men and 10 women) who were edentulous or partially edentulous in the posterior maxilla and required the placement of implants. The mean age of the patients was 41.8 ± 12.5 years (range: 25 -63 years).
The main criterion for admission to the study group was a residual alveolar ridge height of 5 -6 mm and a width of 68-mm. Panoramic X-rays and computed tomography (CT) were taken from the patients. These x-rays were used to assess the width and height of the remaining alveolar ridge ( Figure 1). The surgical phase was planned as a sinus augmentation procedure in connection with the placement of the implant. The patient exclusion criteria were poor oral hygiene, intensive smoking (approx. 15 cigarettes / day), uncontrolled diabetes mellitus or other systemic diseases and acute maxillary sinus infection. All patients were in good health and without any disease that could affect the outcome of the treatment. Patients were fully informed about the procedures including operations, transplant materials and implants. Written and informed consent was obtained. The research protocol has been approved by the Ethics Committee of the Faculty of Dentistry.

Sinus floor augmentation
Twenty single-stage sinus augmentation with simultaneous implantation were performed under local anesthesia [3] . Patients received antibiotics as 1 g of amoxicillin for prophylaxis 1 hour before surgical exposure of the sinus floor. A crestal incision was made slightly palatally throughout the edentulous area. Vertical release cuts were made at the front and back. A mucoperiosteal flap was then raised, which allowed easy access to the lateral wall of the maxillary sinus. A lateral maxillary antral window was made by a round diamond mill with continuous cooling using a sterile saline solution.
After the Schneiderian, membrane was exposed, the mouth window slowly moved to the medial side of the chest. Using sinuses of different shapes and sizes, the sinus membrane gradually separated.
The sinus membrane was protected during the preparation of the implantation site. With the help of the surgical stent, a pilot drill was used to determine the position of the implant in the alveolar ridge. The implantation site was expanded with conical osteotomes. By using the smallest osteotome for the first time, followed by ever-larger osteotomes, the diameter of the implant site became slightly smaller than that of the implant. The osteotome technique was used to increase the bone density around the implant site and to support the stability of the primary implant [10] .
The space created between the maxillary alveolar ridge and the sinus floor was filled with 2.5 -3 g CHA (Via San Benedetto, 1837-40018 San Pietro in Casale BO Italia) or 2.5 -3 g b-TCP (Sunstar Americas, Inc., formerly John O. Butler Company). The choice of whether the maxillary sinus would contain the CHA test substance or the b-TCP load was made at random distribution ( Figure 2). The study population was originally planned with 24 patients (12 patients per group). The patients were randomly divided into one of two groups according to the order of admission. However, in the b-TCP group, two patients were lost during the follow-up and two patients disagreed with postoperative computed tomography in Group 1, and CHA was used for the 10 patients (5 men) and (5 women). While Group 2, b-TCP was used as a graft material for maxillary sinus augmentation.
All transplant materials were mixed with blood from the surgical site before they were placed in the open sinus cavity. No membrane was used to cover the lateral window. Complete wound closure was achieved with 30/ resorbable sutures (Ethicon US, LLC. 2017. 085133 -171129).

Postoperative care
Patients were advised not to wear their prosthesis 2 to 3 weeks after surgery until the prosthesis was covered with a soft lining (Sofreliner S, Tokuyama Corp., Tokyo, Japan). Antibiotics (1 g clavulanic amoxicillin twice daily) were prescribed for 10 days and pain relievers as needed. Chlorhexidine gluconate 0.12 % mouthwash (3M, ESPE, Peridex and PerioMed are registered trademarks of 3M or 3 M Deutschland GmbH.) Twice a day for 1 week for all patients. The sutures were removed 2 weeks after the operation.
Patients with sinus perforation identified during surgery received decongestants 1 week after surgery. Patients who experience symptoms of congested nose or have had a common cold were advised not to travel by plane until the symptoms have resolved. Postoperative visits were scheduled monthly to review the healing process. After an average healing of 10.5 months (range: 9 -12 months), the inserts of 50 implants were as follows: 30 implants at the CHA site and 20 implants in the b-TCP site. The second surgical step was done 9 months later. A full ceramic crown was then placed. The 2-year follow-up showed no signs or symptoms of implant failure ( Figure 3). The CT scans were recorded before surgery ( Figure 1), immediately after surgery and 9 months after surgery ( Figure 4) and analyzed with the RIS-PACS software by an experienced radiologist who was unfamiliar with the surgery and the distribution of each biomaterial to assess the height of the ridge and changes in the density of the bone substitute material in the sinus cavity.
bone substitute material in the sinus cavity.

Radiographic images
The images were taken for preoperative diagnosis and planning immediately after augmentation with implant insertion and postoperative sinus augmentation by 9 months using standardized low-dose computed tomography (Sensation 16 and Volume Zoom, Siemens) (Healthcare, Erlangen, Germany) and an effective dose of 110 mA. The following parameters were used: tube voltage: 120 kV, sampling time: 3 to 10 s, layer thickness: 2 mm (0.75 mm) with sagittal and coronal reconstruction and table movement / inclination: 0, 9.

Analyzing software
The CT scans were analyzed using the RIS-PACS AW Suite 2.0 software (General Electric Healthcare, Chalfont St. Giles, UK) to determine the dimensions and density of the ridge before and 9 months after insertion of biomaterials and the Implantation. RIS-PACS software system is suitable for viewing and processing multidimensional images of various devices (tomosynthesis by magnetic resonance, CT etc.) and enables the analysis and processing of images in DICOM format.
First, the images, data and names of the patients were anonymized to ensure an objective and blind analysis. The software shows computer tomography in three different projections (coronal, axial and sagittal) as a series of twodimensional sections, depending on the thickness of the section. In addition, a three-dimensional scan could be generated from the various two-dimensional slides.
In the present study, based on the multitude of software tools, the "density measurement" was used to assess the change in the density of the directly elevated materials and 9 months after sinus augmentation. In addition, the increase in the density of the bone substitute material and the initial density of the initial ridge (reference bone) were analyzed with the software tool "density measurement" (Figure 3).
The analysis of the amount and density of the graft using the above software was carried out as follows: An area was marked in the transplanted bone substitute material and in the reference bone of the original ridge to measure the graft. Comparison of the initial CT scan of the initial ridge density with that obtained immediately and 9 months after the operation revealed a quantitative and qualitative assessment of the newly formed mineralized tissues in the sinus cavity.

Statistics
Statistical analysis was performed with the software package SPSS version 25.0 (IBM SPSS Statistics for Windows, version 25.0. Armonk, NY: IBM Corp., USA). Mean ± SD, minimum and maximum for quantitative variables were used for descriptive statistics. For analytical statistics: the t-test of independent samples was used to assess the differences in the means of the quantitative variables between the two groups, while the t-test of the matching samples was used to compare the means of the quantitative variables within from the same group. Statistical methods were verified in which a significant value of p < 0.05 and a very significant value of p < 0.001 were assumed. (Table 1) shows a detailed assignment of the number and positions of the implant, on the other hand the data on the patient population, the length of the healing period, changes in bone height in enlarged sinus in the base given in the tables (2a, 2b, 3a, 3b, 3c, 4a, 4b).        CT scans were performed immediately and 9 months after insertion and showed dense mineralized material in the sinuses surrounding the implants. In many cases, it has been difficult to delineate the boundary between the original sinus floor and the newly formed tissue. The initial height of the bone under the sinus floor, measured using the original CT images, varied between 5 and 6 mm with an average of 5.4 ± 0.52 mm in the CHA group and 5.3 ± 0.48 in b-TCP study group. In the postoperative evaluation of the second CT scan 9 months after the operation, the height of the CHA radiopaque tissue increased significantly (P < 0.001) to 9 -12 mm with an average increase of 4.6 ± 1.17 mm (Figure 5), while the height of the radiopaque b-TCP tissue increased to 11-14 mm with a significant average increase of 7.1 ± 1.1 mm (P < 0.001) (Figures 6 and 7).

Changes in bone density of the grafts GROUP 1
The CHA xenograft showed an increase in bone density in all patients. The average density of CHA grafts increased significantly from an average of 515 HU (± 105.54 HU) immediately after the increase to 670 HU (± 115.95 HU) 9 month after the increase (P < 0.001).
The comparison of the bone density in the area of interest preoperatively and 9 months after the increase showed a bone density that was not significantly preoperatively below an average of 690 HU (± 90.68 HU) to 670 HU (± 115.95 HU) 9 months after augmentation surgery. The average percentage of the density of the grafted area after 9 months compared to the initial density of the alveolar ridge at the implantation site was -2.89 % with no significant decrease (P = 0.373) (Figure 8).

GROUP 2
Radiological analysis of the b-TCP graft showed a higher bone density in all patients. The average density of the b-TCP graft increased significantly from an average of 880 HU (± 88.82 HU) immediately after the antral grafting to 1170 HU (± 147.57 HU) 9 months post operatively (P < 0.001).
The comparison of the bone density in the area of interest preoperatively and 9 months after the increase showed a significantly higher bone density from an average of 715 HU (± 151.01 HU) preoperatively to 1170 HU (± 147, 57 HU) 9 months post operatively. The average percentage of the density of the grafted area after 9 months compared to the initial density of the alveolar ridge at the implantation site was 63.6% with a significant increase (P < 0.001) (Figure 8). Ellegaard et al. [31] questioned the need for sinus augmentation procedures without graft material. The authors reported a good success rate with 38 implants that were used in the sinus lift procedure without graft material in the premolar / molar areas with a vertical bone height of up to 3 mm. However, the small number of implants in this study compared to the highest number (50 implants) in the present study did not provide solid evidence of the superiority of this technique.
In their conclusions, the authors themselves emphasized that this technique should only be used in patients with high demands on oral hygiene, since the relatively short implants increases the risk of early failure due to inflammation and marginal bone loss.
Various clinical studies and case reports [32 -34] have shown that although maxillary sinus grafting with different graft materials can be clinically successful. Its familiar to emphasize the autogenous bone still provides the best osteogenic potential and bone biomechanical properties.
However, the quantitative limitations of autogenous bone extracted from intraoral sites often force the doctor to look for other types of grafts to get the appropriate amount of graft material.

DISCUSSION
Although many studies recommended the two-step procedure for patients with an alveolar bone height of 5 mm or less in the posterior maxilla [29] , this study evaluated the performance of CHA compared to b-TCP bone grafts in one-step sinus augmentation with simultaneous Implant insertion in patients with a bone height of 5 to 6 mm before the transplant. The one-step approach saves the patient from having to perform a second operation, and if done by experienced surgeons, it is predictable. The results of this research suggest that CHA bone grafting and b-TCP provide adequate bone quality and volume for predictable simultaneous implantation in these patients and candidates for use as an alternative to autogenous and allogeneic bone grafts.
With regard to the low ridge height of 5 mm, Peleg et al. [30] stated that the one-step procedure for patients with only 3 mm height of the alveolar bone before antral grafting could be carried out using implants coated with hydroxyapatite and autogenous bone. Then, the onestep, of low ridge height of 5-mm crest protocol used in this study offers the advantages of superior predictability, reducing the number of operations and the time required to complete the functioning implants.
Allografts used as an alternative to autografts have several problems, mainly related to the late reabsorption of freeze-dried dehydrated bone particles, variable inductive properties, and the potential for disease transmission [33] The alternatives to autogenous and allogeneic bone grafts are xenogeneic CHA and Alloplastic b-TCP, which were used in the present study.
Because doctors are in daily contact with bone substitute materials and are more interested in the clinical success, durability and reliability of the products they use than in scientific details, such as cellular reactions. Compared to histological and histomorphometric analysis, the present study, according to the idea of radiological analysis, required less effort for both the researcher and the patient, since it is benefits as "non-invasive " follow up procedure from technical support.
However, it should be mentioned that detailed conclusions on cellular responses to different biomaterials can only be drawn by histological and histomorphometric analyzes, especially during the initial phase of the study, the histological analysis of biopsies remains important and will be no less relevant [35] .
The increase in bone density and ridge volume in both groups represents the increased reorganization of bone replacement materials with the newly formed bone and suggests that condensation processes or the loss of the liquid component causes the increased volume density. However, the evaluation of CT examinations cannot provide any objective information about the degradation or dehydration process.
A possible explanation for the fact that the volume and density appeared to increase, which was significantly higher in both groups 9 month post-operative (compared to the immediate postoperative increase) regardless of cellular reactions, is a combination of manual condensation of bone replacement material and increased dehydration of biomaterials after implantation with simultaneous growth of newly formed bone tissue in the intergranular space.
Compared to the percentage increase in the bone volume in the sinuses with different particulate graft materials, the results reported by several authors have shown great differences [32] . A study by Wheeler et al., found an increase in bone volume from 16.38 % after 4 to 10 months of healing to 45.30 % after 36 months of sinus grafting with porous alloplastic hydroxyapatite alone [36] , whereas in the present study a higher percentage of new bone formation in both groups of alloplastic CHA and b-TCP (85 % and 133.9 % on average) after 9 months of healing of the elevated sinus cavities. Therefore, the radiologically examined amount and the changes in bone density in the present study were significantly different between the two groups. The maximum height and the increase in bone density increased in both groups, but more significantly in the b-TCP group instead of the CHA group during the 9-month observation period.
While many studies have shown biocompatible properties and promising osteogenic results, the use of CHA as a bone substitute and porous bone fill may be limited due to its inherent mechanical weakness and reduced biodegradation [37] . And this is an explanation for the increased increase in quantity and bone density in the CHA study group compared to the b-TCP group.
This is in line with the benefits of reporting on CHA as a bone graft, particularly in terms of its safety, biocompatibility and osteoconductivity. Therefore, CHA can be used as a bone replacement biomaterial in many clinical indications.
The methodology presented can be a reliable and adequate technique for analyzing the volume and density of the CHA and b-TCP bone graft for sinus augmentation with simultaneous implantation.

CONCLUSION
Despite the limited number of cases and short followup time in this clinical trial, it was concluded that the two graft materials had successful biocompatibility and osteoconductivity in sinus augmentation. However, B-TCP appears to be more effective than CHA in osteoconduction.