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| Year : 2021 | Volume
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| Issue : 1 | Page : 61-68 |
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| Osteotome-mediated sinus floor elevation using an in situ hardening biphasic calcium phosphate bone graft substitute compared to xenograft: A randomized controlled clinical trial |
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Ashish Kakar1, Bappanadu H Sripathi Rao2, Nikhil Deshpande3, Shashikanth Hegde2, Anil Kohli4, Aditya Patney5, Harsh Mahajan5
1 Department of Periodontics, Yenepoya University Dental College, Mangalore, Karnataka; Senior Consultant, Department of Dentistry, Indraprastha Apollo Hospitals, New Delhi, India
2 Department of Periodontics, Yenepoya University Dental College, Mangalore, Karnataka, India
3 Department of Dentistry, Inspire Dental, Mumbai, India
4 Department of Conservative Dentistry and Endodontics, Dr. Soni's Dental Clinic, New Delhi, India
5 Department of Radiology, Mahajan Imaging Center, New Delhi, India
Click here for correspondence address and email
| Date of Submission | 08-Nov-2019 |
| Date of Decision | 23-May-2020 |
| Date of Acceptance | 17-Mar-2021 |
| Date of Web Publication | 13-Jul-2021 |
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 Abstract | | |
Aim: To assess osteotome-mediated sinus floor elevation (OMSFE) with simultaneous implant placement using an in situ hardening biphasic calcium phosphate (BCP) compared to xenograft as a control. Methods: Patient in need for sinus floor augmentation in one or both sinuses were selected for this randomised controlled clinical trial. Sites presenting a residual sinus floor height of 3–6 mm and eligible for OMSFE were randomly assigned to receive either BCP (test) or xenograft particles (control). CBCT scans were performed before and at the time of implant loading (180 days). The difference in sinus floor height gain between the two groups was set as the primary endpoint parameter for equivalence testing. The implant insertion torque (ITV) was recorded and Implant stability quotients (ISQ) was assessed upon implant placement, abutment connection (160 days) and implant loading (180 days). Results: A total of 54 sinus lifts were performed in 42 patients including 12 bilateral cases. Four implants failed (two in each group) and a total of six patients were lost to follow-up. Statistical analysis of sinus floor height revealed no significant differences (p < 0.05) between groups at baseline nor at 180 days after augmentation. There was no statistical difference in sinus floor height gain between the two groups as supported by the 90% confidence intervals of the difference between groups. Good primary implant stability was confirmed in both treatment groups by ITV and ISQ measurements. Conclusions: Within the limits of this study, it can be concluded that OMSFE using in situ hardening BCP particles results in equivalent sinus floor height gain than using xenograft particles but offers an easier application.
Keywords: BCP; biomaterials, biphasic calcium phosphate particles, bone graft substitutes, OMSFE, poly (lactic-co-glycolic acid), sinus floor augmentation, xenograft
How to cite this article:
Kakar A, Sripathi Rao BH, Deshpande N, Hegde S, Kohli A, Patney A, Mahajan H. Osteotome-mediated sinus floor elevation using an in situ hardening biphasic calcium phosphate bone graft substitute compared to xenograft: A randomized controlled clinical trial. Indian J Dent Res 2021;32:61-8 |
How to cite this URL:
Kakar A, Sripathi Rao BH, Deshpande N, Hegde S, Kohli A, Patney A, Mahajan H. Osteotome-mediated sinus floor elevation using an in situ hardening biphasic calcium phosphate bone graft substitute compared to xenograft: A randomized controlled clinical trial. Indian J Dent Res [serial online] 2021 [cited 2023 Sep 24];32:61-8. Available from: https://www.ijdr.in/text.asp?2021/32/1/61/321389 |
| Introduction | |  |
The posterior edentulous maxilla presents special challenges to the implant surgeon due to the presence of the maxillary sinus. After tooth loss, the maxillary bone resorbs both in the horizontal dimension, associated with the remodeling of the buccal bone plate, and in the vertical dimension.[1] The vertical bone loss is often more important than in other areas and results in the enlargement of the sinus at the expense of the alveolus related to two phenomena: 1) The increased osteoclastic activity of the periosteum of the Schneiderian membrane and 2) an increase in the positive intra-antral pressure during respiration due to the loss of the tooth.[2]
To restore these large vertical atrophies for subsequent implant placement, various techniques for maxillary sinus augmentation have been developed. They all consist of creating an intraoral access to the sinus and elevating the Schneiderian membrane to create space for bone growth. Therefore, the sinus can be approached through a lateral window or a crestal approach.[3],[4],[5] The lateral window approach is more invasive and associated with more postoperative complications such as swelling, pain and a long edentulous healing period but provides good intra-surgical visibility and allows for large augmentations with bone substitutes.[6] To reduce the invasiveness of the procedure and the complications rate for maxillary sinus augmentation, various techniques for accessing the sinus directly from the crestal approaches such as osteotome-mediated sinus floor elevation (OMSFE), piezoelectric internal sinus elevation (PISE), hydraulic sinus condensing (HSC) technique, internal sinus manipulation (ISM) procedure, crestal window technique (CWT) and hydrodynamic piezoelectric internal sinus elevation (HPISE) have been introduced.[7] However, all these approaches still necessitate the additional application of bone graft substitutes if a sinus floor height gain of more than 1-2 mm has to be achieved.
In this respect, alloplastic graft materials have shown to be an effective alternative to xenografts providing predictable short- and long-term results in terms of bone regeneration capacity.[8] Alloplasts are synthetic, biocompatible bone graft materials free of any risk of transmitting infections or diseases that cannot be completely excluded when xenografts or allografts are used. One of the most promising groups of alloplastic bone substitutes are porous calcium phosphate ceramics. Calcium phosphate ceramic materials can be produced in two different crystalline phases and admixed to produce biphasic calcium phosphate (BCP) with different phase ratios. Bone graft substitutes consisting of pure beta tri-calcium phosphate (β-TCP) phase resorb completely and are gradually replaced by the body's own tissue, whereas materials containing hydroxyapatite phase do not resorb and remain integrated with the host's bone.[9],[10],[11],[12] A meta-analysis of the histomorphometric data obtained from bone biopsies harvested after sinus augmentation using different graft materials revealed that biopsies from sites augmented with β-TCP showed the highest percentage of new bone in the grafted sites among the biomaterials. The amount of bone found was close to sites augmented with autologous bone.[8] These positive results are probably due to the fact that β-TCP materials completely resorb in the body and are completely replaced by host bone leaving no biomaterials in the site. However, a shortcoming of the fast resorption of β-TCP seems to be their incapability to protect the augmented tissue from mechanical forces present in the sinus, which was reported to result in a significant reduction of the initially augmented volume over time.[13],[14] Therefore, non- or slowly resorbing bone substitutes containing a HA phase such as BCPs or xenografts might present a better choice for bone augmentation in sites subjected to mechanical stress like the sinus.
Still, the application of particulate bone graft substitutes through the 3-mm access in the crestal approach remains challenging because loose granules might be spilled or expelled through the same opening due to the respiration of the patient. Coating such alloplastic graft granules with PLGA can enhance the handling properties of the material transferring the bone substitute in a gluey, moldable mass after mixing with a bioactivator. The bioactivator is washed out from the coating of the granules by the bleeding in situ, which allows the PLGA to harden again and to entrap the particles in a solid but porous scaffold. The self-stabilized graft may greatly reduce the micromotion of the bone substitute granules in the augmented site, which might be beneficial for de novo bone formation. A possible positive effect of the stabilization on bone generation has already been reported in both animal and clinical studies by comparing coated and uncoated BCP granules.[15]
This randomised clinical trial was designed to assess if OMSFE using alloplastic in situ hardening BCP bone substitutes can provide equivalent results in terms of sinus floor augmentation than xenograft granules but at the same time offer an easier handling.
| Materials and Methods | | |
Patients
A positive ethical vote (Approval Number YOEC83/8/4/2015) was obtained from the Yenepoya University Ethics Committee, Mangalore, India, before starting the recruitment of patients. Patients, 18 years or older, with severely atrophic maxilla or maxillae presenting a residual sinus floor height of 3–6 mm were selected. Patients were examined for medical contraindications, such as acute or recurrent sinusitis, severe allergic rhinitis and uncontrolled systemic diseases. All patients were systemically healthy at the time of consultation and had no history of sinus pathology. Furthermore, the patients were mentally able to understand the nature and the conduct of the study and to comply with the instructions given by the clinician.
The standard exclusion criteria for bone grafting procedures were applied including systemic chronic disease, alcoholism, drug abuse, pregnancy and breast-feeding. Smokers and patients with any oral tobacco habit were excluded. Patients using dentures were also excluded. Further exclusion criteria incude acute abscesses or active infections localized in the proximity of the prospective surgical field, heavily scarred mucosa at the site, malignant disease, radiotherapy in the last 6 months and chemotherapy during the past 5 years.
Informed consent was obtained from all the patients before enrollment into the study.
The recruitment was performed in three different implantology clinics: 1. Department of Periodontics and Implantology, Yenepoya Dental College and Hospital, Mangalore, India. 2. Global Health Research Group, New Delhi, India and 3. Dental Foundations, Mumbai, India. Test and control treatment were randomly assigned to the 54 treated surgical sites following a central randomisation.
Surgical technique and study conduct
[Figure 1]a, [Figure 1]b, [Figure 1]c, [Figure 1]d, [Figure 1]e, [Figure 1]f, [Figure 1]g, [Figure 1]h, [Figure 1]i, [Figure 1]j, [Figure 1]k, [Figure 1]l, [Figure 1]m, [Figure 1]n, [Figure 1]o, [Figure 1]p, [Figure 1]q, [Figure 1]r, [Figure 1]s, [Figure 1]t, [Figure 1]u, [Figure 1]v, [Figure 1]w, [Figure 1]x represent the surgical technique followed for the study. A site-specific full-thickness mucoperiosteal flap was elevated to expose the underlying crest of bone. A pilot drill was used to the depth 1–2 mm short of the sinus floor to accommodate osteotome to the sinus floor. A small-diameter osteotome was inserted into the prepared bone to compress the sinus floor using a surgical mallet. Wider osteotomes were then inserted continuously into the prepared bone to accommodate the implants. | Figure 1: a: Pre-operative occlusal view, missing upper left second premolar and first molar. b: Pre-operative buccal view. c: Maxillary left first molar area, coronal view. d: Maxillary left first molar area, sagittal view. e: Maxillary left first molar area, axial view showing width. f: Panoramic view. g: Incision and full-thickness flap reflection. h: Initial osteotomy preparation with drill. i: Osteotome-mediated sinus elevation. j: easy-graft CRYSTAL insertion through the osteotomy. k: Nobel Biocare Replace Select CC implant placement. l: Implant placed in second premolar area. m: IOPA showing implant placement and sinus elevation. n: Wound closure with 3.0 black silk Ethicon sutures (Johnson & Johnson). o: Second-stage surgery and placement of healing abutments. p: Peri-implant tissue healing. q: Impression copings in place. r: Abutments placed, occlusal view. s: Abutments placed, buccal view. t: Porcelain fused to metal prosthesis cemented in place, occlusal view. u: Porcelain fused to metal prosthesis cemented in place, occlusal view. v: Post-op CBCT, axial view. w: Post-op CBCT, coronal view. x: Post-op CBCT, sagittal view
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To further elevate the sinus floor, bone graft substitutes were added using the syringe provided by the manufacturer. The osteotome was used to insert the bone graft through the crestal access into the sinus. For a sinus floor elevation of 3–4 mm, 4–6 times of grafting and osteotome insertion were required. In total, 0.4 cc of bone graft material were applied. For the test group, an in situ hardening BCP bone graft substitute (GUIDOR easy-graft CRYSTAL Sunstar Suisse SA, Etoy, Switzerland) was used. The material consists of biphasic calcium phosphate core granules of 60% of hydroxyapatite (HA) and 40% of beta-tricalcium phosphate (β-TCP), which are coated with a thin (10 μm) layer of poly (lactic-co-glycolic acid) (PLGA) and preloaded in a plastic sterile syringe. The device was prepared according to the manufacturer's instructions prior to injecting into the osteotomy site. Briefly, the granules were mixed in the syringe with the provided liquid bioactivator (N-methyl-2-pyrrolidone solution). The bioactivator turns the coated granules into a sticky mass that after application in the osteotomy and upon contact with blood, begins to progressively harden in situ. The last osteotome used for elevation was used to condense and shape the sticky, easy to handle and moldable graft granules in the osteotomy site.
For the control group, a bovine xenogeneic particulate bone graft substitute delivered in a syringe was used (Geistlich Bio-Oss Pen, Wolhusen, Switzerland). The granules in the syringe were mixed with normal saline until fully wet. Excess saline was removed by dabbing it against a sterile gauge prior to application in accordance with the manufacturer's instructions for use. The mix was then applied directly from the syringe onto the osteotomy site and condensed in small increments to help elevate the membrane with the last osteotome used.
After grafting the sinus, implants were placed (NobelReplace Tapered, Nobel Biocare AB, Gothenburg, Sweden) according to the manufacturer's surgical protocol.
The mucoperiosteal flap was closed with interrupted non-resorbable 4-0 sutures (Silk, Ethicon, Johnson & Johnson, Somerville, NJ, USA) to achieve soft tissue stability and primary closure. The patients did not wear any prosthesis during the healing period.
Antibiotic therapy consisting of 1 g of Amoxicillin every 12 hours for 4 days and mouth rinsing with 0.2% chlorhexidine every 8 hours for 10 days were prescribed. The suture was removed 2 weeks postoperatively.
In cases with uneventful healing, a vertical crestal incision was made 160 days post-op and a healing abutment was placed. After allowing 20 days for the maturation of the soft tissues, the final restoration was fabricated with a successful functional and aesthetic result (180 days post-op).
CBCT evaluation was performed in all patients prior to the procedure and immediately after implant loading (180 days post-op). Implant stability was assessed immediately after implant placement, after abutment connection (160 days post-op) and after implant loading (180 days post-op).
Endpoint measurements
Measurement of Insertion Torque Values (ITV) and Implant Stability Quotient (ISQ)
Immediately after implant placement, the final seating torque was recorded using the manufacturer's hand ratchet. The primary implant stability was further assessed through the measurement of the implant stability quotient (ISQ) by resonance frequency analysis (Osstell ISQ, Göteborg, Sweden). For each implant, two ISQ measurements were recorded—palatal (or lingual) and buccal—according to the guidelines of the manufacturer.
Assessment of sinus floor height using cone beam computed tomography (CBCT)
CBCT images were taken using the Planmeca Romexis 3D Classic CBCT machine (generator specifications: constant potential, microprocessor controlled, resonance mode, operating frequency: 80–160 kHz, power factor corrector, complies with the standard IEC 60601-2-7, scan time: 12–26 seconds, pixel size: 127 micrometres, X-ray tube: Toshiba D-054SB, focal spot size: 0.5 x 0.5 mm, according to IEC 6036) before the surgical procedure and after implant loading 180 days post-op.
Sinus floor height was measured on CBCT images as the vertical distance implant shoulder to the sinus floor. Changes in sinus floor height were calculated by subtracting the sinus floor height assessed at baseline from the sinus floor height measured after 180 days post-op. The person performing the CBCT analysis did not know which material was placed.
Statistical considerations
Sample size calculations
Sample size calculation was performed using the Simple Interactive Statistical Analysis (SISA) (http://www.quantitativeskills.com/sisa/calculations/samsize.htm). The sample size calculation was based on the clinical data on sinus floor height changes after osteotomy-mediated sinus floor augmentation with xenograft bone substitute reported by Pjetrusson et al. Mean sinus floor height gain with xenograft was reported to be 4.1 mm with a mean standard deviation for the procedure of 2.4 mm.[16] The significance level (alpha) was set to 5% and the power to 80%. Continuity correction was applied due to the expected small sample size. The study hypothesis was set as equivalence sinus floor height changes between the test and control group. A clinical difference of 2 mm was considered to be relevant between the groups corresponding to the equivalence limit.
The sample size calculation revealed that a total of 46 sites (24 per group) should be included. A security margin of 20% (8 sites) was added in the view of the small patient number and possible dropouts. Thus, a minimum of 54 sites were treated.
Statistical analysis
The descriptive statistics for continuous variables will be presented with a number of non-missing observations (n), mean, standard deviation (SD), median, minimum and maximum.
Differences in endpoint variables between treatment groups were assessed by the Wilcoxon rank-sum method using ordinary two-sided tests at the 5% level each along with 95% confidence intervals.
Changes over time within each treatment group were assessed by two-sided Wilcoxon signed-rank tests for paired observations. P values were compared with the 5% level and are complemented by the corresponding non-parametric 95% confidence intervals for the pseudomedian (i.e. the median of all pairwise average changes).
Equivalence testing for the primary endpoint changes in sinus height (mm) was tested by two one-sided Wilcoxon rank-sum tests. If the larger of the two one-sided tests is lower than 5%, we may claim equivalence. This is complemented by the limits of the corresponding 90% confidence interval for the underlying location shift parameter (the theoretical median of all pairwise differences across groups). If it is entirely contained in the interval specified by the equivalence margin of 2 mm, equivalence claim can be supported.
Randomisation
Randomisation was performed using a randomisation list that had been prepared using the website www.randomization.com. Each hemi-maxilla was assigned to a treatment number according to the chronological enrolment of the patients starting with the right hemi-maxilla. This treatment number corresponded to the treatment assigned in the randomisation list.
| Results | | |
A total of 54 OMSFE were performed in 42 patients including 12 bilateral cases. Patients were enrolled in the study between December 2014 and November 2015. Both materials were applied to the sinus through a crestal opening of 3 mm using the osteotomy in sufficient volumes. On average, 0.4 cc of bone graft material were applied. The application of the test material (GUIDOR easy-graft CRYSTAL) was considered easier by the surgeons. The stickiness of the material facilitated the application and prevented the dispersion and loss of graft material in the oral cavity.
[Figure 2] represents the Consort flow diagram for the study. The age of the patients (23 women and 19 men) ranged from 22 to 65 years.
Postoperative healing was uneventful in most cases. Clinically, the same soft tissue healing pattern was observed. However, a total of four implants failed (2 in each groups) during the 180 days follow-up. The failed implants showed a good primary stability when placed in situ, as confirmed by the resonance frequency analysis (ISQ >70) and measured insertion torque values (ITV) (25-50 Ncm). The good primary implant stability may attribute the implant loss to infection of the surgical site.
Among the 42 patients, six patients did not return to follow-up without giving reason. These patients were excluded which corresponded to the loss of additional five sites in the test group and six sites in the control group. In the end, 22 test sites and 21 control sites were evaluated for the statistical analysis of the performance parameters. Descriptive statistics of all the endpoints are presented in [Table 1]. A comparison of the endpoints between the groups and the corresponding P values are listed in [Table 2] and the evaluation of the changes in endpoints within the groups over time in [Table 3].
The primary implant stability was similar in both groups, as confirmed by the mean final seating torque of 36.86 ± 8.62 Ncm for the test group and 34.68 ± 9.61 Ncm for the control group, respectively. Implant stability was slightly reduced between implant placement and abutment connection (160 days) and increased again until loading (180 days) as assessed by resonance frequency measurements [Table 1].
Baseline sinus floor heights at day 0 were between 3 and 6 mm in both groups and averaged 5.01 ± 0.89 mm for the test group and 4.76 ± 0.82 mm for the control group without being statistically significance [p = 0.378, Table 2]. The final sinus floor height after 180 days was 12.26 ± 1.87 mm for the test group and 12.05 ± 1.43 mm for the control without statistical significance (p = 0.0761). However, both the groups showed a highly statistical significant [p < 0.000001, [Table 3]] sinus height gain of 7.25 ± 1.78 mm for the test group and 7.26 ± 1.47 mm for the control, respectively. The difference in sinus height gain between the two groups was set as the primary outcome parameter defined for equivalence testing. The lower and upper 90% confidence intervals (lower CI90 = -0.99 mm, upper CI90 = 0.72 mm) for the underlying location shift parameter (the theoretical median of all pairwise differences across groups = -0.19 mm) of the difference in sinus height gain between the groups was small and well contained within the equivalence limit of 2 mm in the sample size calculation. This fact supports the equivalence claim.
Sinus width did only minimally change in the two groups but was slightly significant in the control group as shown by the P value and the positive lower 95% confidence interval [Table 3].
| Discussion | | |
The present randomised clinical trial assessed the performance of an in situ hardening a biphasic calcium phosphate (BCP) grafting material compared to a xenograft for per crestal sinus floor augmentation using osteotome-mediated sinus floor elevation (OMSFE) technique.
Biphasic calcium phosphate (BCP) bone graft substitutes benefit from a slower resorption in the body material composed of pure tri-calcium phosphate phase (β-TCP) due to the insoluble hydroxyapatite (HA) phase. BCP with a phase ratio of 60% HA to 40% β-TCP have shown no measurable resorption within the first years after application. Still high amounts of residual BCP material found in bone core biopsies taken after three years of sinus grafting, which were comparable to the amounts of residual xenograft used in study.[17] Considering the fact that intact xenograft particles with no significant changes in particle size could still be detected in large amounts in bone core biopsies harvested 11 years after sinus augmentation.[18] BCP materials are likely to show a similar slow or no resorption over time. Such slow resorbing bone graft substitutes might be needed for a long-term protection of the augmented area in sites subjected to constant pressure such as those exerted in the sinus through pneumatic forces during normal respiration.[13],[14] In the abovementioned study, new bone formation after sinus augmentation with BCP and xenograft were comparable after 3 years. This has been further corroborated by another randomised controlled trial showing similar results for new bone formation and residual BCP or xenograft 6-8 months after sinus grafting.[19]
It is further known that micro-movements in the implanted grafted material disturb bone formation and may lead to mesenchymal cell differentiation to fibroblasts instead of osteoblasts, resulting in the development of fibrous tissue. The impact of grafted site stability on bone healing was previously discussed by Troedhan et al.[20] who evaluated the initial implant stability of implants placed in augmented sinuses with in situ hardening alloplastic bone substitutes or loose particulate biomaterials including xenografts. The authors reported significantly higher implant torque values (ITV) in sites regenerated with in situ hardening alloplasts arguing that the immobilisation of these bone grafting materials in situ allowed for improved vascularisation and mineralisation of the sub-antral scaffold due to the better protection of augmentation towards pressure changes of the sinus at normal breathing. However, the presented clinical study could not corroborate these findings. The ITV measured in our study did not significantly differ between the two groups (test = 36.86 ± 8.62 Ncm, control = 34.68 ± 9.61 Ncm) and were below the ITV previously reported for in situ hardening BCP (ITV = 56.6 ± 3.4). Moreover, the implant stability measured by resonance frequency measurement was not statistically different between both groups at the time point of loading (180 days post-op).
Other authors reported on data from a rabbit sinus model that the in situ stabilization did accelerate bone formation in situ.[15] Unfortunately, the endpoint of new bone formation was not assessed in the present study since no bone biopsies could be taken following a clinical protocol of sinus grafting with simultaneous implant placement. The radiologic assessment performed in the present study showed a significant sinus floor height gain for both the in situ hardening BCP (test) and the loose xenograft (control) granules used with the OMSFE technique (test = 7.25 ± 1.78 mm, control = 7.26 ± 1.47 mm). The interferential statistics showed that both groups performed equivalently in this respect.
Similar results were reported by other authors comparing in situ hardening BCP granules to the same but loose BCP granules using the lateral window approach. The authors reported no significant difference in terms of sinus floor height gain but showed significant higher amounts of mesenchymal stem cells (MSCs, Musashi-1-positive cells) in the augmentation area of the PLGA-stabilized material than found in sinuses augmented with the uncoated, loose BCP particles. The authors concluded that MSCs are pivotal for new bone formation and their increased presence associated with the use of the in situ hardening bone graft substitute should be further investigated.[21]
Although the positive effect of in situ stabilization on bone augmentation performance could not be shown by the clinical radiological outcomes assessed in this study, the authors agree that the application of the in situ hardening material through the small crestal opening was easier than that of the loose xenograft granules. The sticky mass of alloplast could be added in incremental steps to the sinus using the osteotome without losing the particles or particles being ejected from the sinus due to the respiration of the patient.
| Conclusion | | |
Within the limits of this study, it can be concluded that OMSFE using alloplastic in situ hardening biphasic calcium phosphate (BCP) particles results in equivalent sinus floor height gain than using xenograft particles but with the advantage of an easier application.
Acknowledgements
This study was partly supported by a grant provided by Sunstar Suisse SA, Etoy, Switzerland.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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Correspondence Address:
Dr. Ashish Kakar
H-8 Masjid Moth, Greater Kailash 2, New Delhi
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/ijdr.IJDR_857_19
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3] |
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