May 2012, Volume 33, Issue 5
Published by AEGIS Communications
Analysis of Bone Formation After Sinus Augmentation Using ß-Tricalcium Phosphate
Implant placement in the edentulous maxilla often represents a clinical challenge due to insufficient bone height after crestal bone resorption and maxillary sinus pneumatization. Several graft materials have been evaluated for augmenting the maxillary sinus to compensate for the lost vertical dimension. Allografts are readily available without the risk of disease transmission and the need for a second site surgery. The aim of this case series was to systematically evaluate the development and maturation of augmented bone in the maxillary sinus using ß-tricalcium phosphate. In 21 to 40 weeks post-sinus elevation, bone biopsies were taken and implants placed simultaneously. All specimens were demineralized and subjected to staining procedures (ie, Hematoxylin and Eosin [H&E], Goldner’s staining, and tartrate-resistant acid phosphatase [TRAP]). Total bone increased over time, whereas the amount of graft material diminished. A lack of inflammatory reaction was noticed with the use of this graft material. In addition, TRAP staining revealed the presence of osteoclasts surrounding the remaining particles. During a 12-month follow-up, no implant failure or complications were observed.
Implant placement in the edentulous maxilla often represents a clinical challenge due to insufficient bone height after crestal bone resorption. In the past, clinicians developed surgical augmentation techniques that used existing space in the maxillary sinus to restore bone height and subsequently create a sufficient implant bed.1,2 Several modifications of the originally described sinus augmentation procedure were developed; however, the basic principle of increasing maxillary bone height by placing graft material in the maxillary sinus after detaching the Schneiderian membrane remained the same.3,4 Grafting materials can be categorized into four groups: autogenous bone, allografts (human), xenografts (nonhuman species), and alloplasts (synthetic materials).5-10 The use of autogenous bone requires a second surgical site at the time of sinus augmentation, which may lead to morbidity. Allografts and xenografts are taken from human cadavers and animals, respectively, whereas alloplasts are synthetic and, therefore, readily available. ß-tricalcium phosphate, an alloplast, has been widely used in bone-grafting procedures as a bone substitute. It is a biocompatible material that can be replaced gradually by bone tissue.11,12
Previous studies used ß-tricalcium phosphate in sinus augmentation procedures.11 Implants were placed simultaneously or delayed after a healing period. However, an in-depth analysis of ß-tricalcium phosphate and bone formation over time is still missing. Therefore, the aim of this study was to follow the development and maturation of grafted bone in the maxillary sinus for several months. In the cases described herein, patients had been edentulous or partially edentulous for a long period and, therefore, presented with insufficient bone dimensions for future implant-supported restorations. Implants were placed at different time points starting 21 to 40 weeks after sinus augmentation surgery. Bone cores were taken at the time of implant placement to analyze bone structure and identify the amount of remaining graft particles.
Materials and Methods
The study was reviewed and approved by the Boston University Medical Center Institutional Review Board (IRB) prior to study initiation. The IRB-approved informed consent was obtained from all the enrolled participants. In addition, before surgery, surgical consents were obtained from the patients after they received detailed information, including possible risks and complications associated with sinus augmentation.
This article reports on cases selected from a bigger study in which patients returned for implant placement at different time points and, therefore, the opportunity arose to study bone healing and graft remodeling. Healthy participants (N = 6; two women, four men, ages 30 to 65) with the need for rehabilitation of their dentition in the posterior maxilla were included in this case series. One patient was totally edentulous in the posterior maxilla; five were partially edentulous in the posterior maxilla. One patient received bilateral sinus augmentation and the other patients received unilateral grafts. The interocclusal distance was taken into consideration, and the crown–implant ratio was ≤ 1.
Medical history was evaluated to establish eligibility. The following criteria excluded patients from participation: systemic diseases or a history of systemic diseases that could affect healing (eg, diabetes mellitus, cancer); regular use of medications that could affect healing (eg, anti-inflammatory medications, nonsteroidal anti-inflammatory drugs, steroids) or bleeding (eg, aspirin, clopidogrel, warfarin); untreated periodontal disease (> two remaining teeth with > 4-mm probing pocket depths); smoking status (current or cessation < 2 years ago); pregnancy/lactation; planned pregnancy; and contraindications for sinus lift procedure (eg, sinusitis).
Patients underwent sinus augmentation using ß-tricalcium phosphate (SynthoGraft™, www.synthograft.com) that was mixed with the patient’s blood drawn via venipuncture during surgery before implantation into the sinus cavity. The maxillary sinus was accessed using a lateral window approach.2
Briefly, a midcrestal incision was made with mesial- and distal-releasing incisions extending into the buccal fold. The mucoperiosteal flap was reflected in a full-thickness manner, and care was taken to completely release the tissue for a tension-free access to the lateral wall of the maxillary sinus. An oval window was outlined on the lateral wall of the sinus using a round diamond bur and continuous sterile saline irrigation. Afterward, the outlined bony plate was carefully pushed inward, detaching the Schneiderian membrane from its underlying surface (Figure 1). A collagen membrane CollaTape® (Zimmer Dental Inc., www.zimmerdental.com) was placed after sufficient membrane elevation, and a venous blood sample was taken (5 mL) from the patient and mixed with ß-tricalcium phosphate. Afterwards, the graft was gently packed until the space between the sinus membrane and the bony walls of the sinus was completely filled (Figure 2). The window was covered with a collagen membrane (Resorbable Collagen Membrane, Bicon Dental Implants, www.bicon.com) that overlapped its outlines and, therefore, protected the grafted side. The mucoperiosteal flap was positioned back to cover the surgical site and secured with nonresorbable suture material (Gore-Tex® Suture 4.0, W.L. Gore & Associates, Inc., www.goremedical.com) using single interrupted sutures. Patients were prescribed antibiotics (500 mg amoxicillin three times daily for 7 days; 300 mg clindamycin four times daily was prescribed for patients sensitive to penicillin) and chlorhexidine digluconate mouth rinse twice a day for 21 days postoperatively.
Twenty-one to 40 weeks after sinus augmentation, computer tomography (CT) scans were taken and placement of dental implants was planned according to bony dimensions in the posterior maxilla. Bone cores were taken using a 2.75-mm trephine bur from the future implant sites at the time of placement.
Histology and Histomorphometry
All specimens were placed in 10% formalin and demineralized using 10% EDTA in 0.1-M Tris at pH 6.95. Afterwards, they were processed in a standard ethanol dehydration sequence and embedded in paraffin. Sections (6-µm thick) were obtained and subjected to staining procedures with Hematoxylin and Eosin (H&E), Goldner’s staining, and tartrate-resistant acid phosphatase (TRAP) according to previously described procedures (Figure 3 through Figure 6).13 Slides were analyzed using light microscopy for total surface area, the surface area that consisted of bone, and the surface area that consisted of graft material (all in mm2 and expressed as % of the total surface). Osteoclasts were identified and counted as number per mm2. Means were compared by using one-way analysis of variance (ANOVA) or Student’s t-test. P < .05 was considered significant.
All implants were placed, achieving primary stability and restored 4 months after placement. During a 12-month follow-up, no implant failures or complications were observed.
CT was used to evaluate the bony architecture before and after sinus augmentation (Table 1). For this purpose, CT scans were taken immediately before sinus augmentation and subsequently before implant placement. Bone levels after augmentation were significantly higher than the baseline measurements (3.21 ± 0.9 before augmentation, 13.86 ± 1.1 after augmentation, P < .0001).
Implants were placed at different time points to evaluate bone maturation and graft material throughout various stages of bone remodeling. Time points were grouped into early and late implant placement. H&E and Goldner’s stainings enabled identification of bone content and the amount of remaining graft. Analysis of the slides demonstrated the presence of vital woven bone in the grafted area at all time points (total bone surface: 34% ± 9.7% at 21 to 30 weeks and 52% ± 7.8% at 38 to 40 weeks, P < .05). In addition, the amount of graft particles was decreasing gradually (total graft surface: 18.6% ± 11.9% at 21 to 30 weeks and 16.1% ± 9.4% at 38 to 40 weeks). Notably, no inflammatory reaction was noticed around the graft material at all time points.
The authors used TRAP staining to reveal the presence of osteoclasts surrounding bone and graft particles. They detected a gradual decrease in the number of osteoclasts around bone (osteoclast number: 2.6 ± 1.4 per mm2 at 21 to 30 weeks and 1.1 ± 0.5 per mm2 at 38 to 40 weeks) (Figure 7). Parallel to this, fewer osteoclasts were detectable around graft particles over time (6.4 ± 1.1 per mm2 at 21 to 30 weeks and 1.4 ± 1 per mm2 at 38 to 40 weeks, P < .05) (Figure 8).
Taken together, a systematic analysis of augmented bone and graft material at different stages of remodeling revealed an increase of bone and a decrease of overall graft material over time. Graft particles appeared well integrated, and no inflammatory reaction was detectable around the augmentation material.
In the past, augmentation of the maxillary sinus has been an established method to create adequate implant housing. Clinical situations that have been severely compromised due to issues such as trauma and tooth loss can now be restored with functional adequate fixtures. The authors present a case series that aims to investigate bone graft maturation and remodeling after augmenting the maxillary sinus with an alloplastic graft material, ß-tricalcium phosphate. Patients exhibited a remaining bone height of approximately 1 mm to 2 mm in the posterior maxilla when they presented at the clinic. After augmentation, implants were placed, achieving primary stability, and were restored 4 to 6 months later. During a 12-month follow-up period, no implant failure was observed. Furthermore, CT scan evaluation revealed the new hard-tissue level in the sinus.
ß-tricalcium phosphate is an alloplast with osteoconductive properties.12,14,15 It has been shown that cells can use it as a scaffold and its pores facilitate rapid vascularization and ingrowth. In addition, it has been suggested that the graft material should be impregnated with the patient’s blood. Studies have demonstrated that the ß-tricalcium phosphate crystals can preserve the integrity of blood cells and, hereby, the graft can gain some osteoinductive properties.15
Handschel et al performed an analysis of several studies to investigate the amount of bone in core biopsies of future implant sites. Sites had been grafted prior to implant placement with ß-tricalcium phosphate or various other materials. The authors found comparable amounts of viable bone in all groups at 9 months post-sinus augmentation surgery.16 Other studies compared the use of autogenous bone to ß-tricalcium phosphate. Autogenous bone has previously been considered the gold standard in bone augmentation surgeries due to its osteogenic properties.5,10 However, limited availability, a second-site surgery, and donor-site morbidity are the drawbacks of using this material in bone grafting procedures. Zijderveld et al conducted a prospective human clinical study to determine bone formation after grafting with either autogenous bone or ß-tricalcium phosphate. Both materials created an implant bed that was able to provide sufficient stability at the time of placement and up to 1-year follow-up.17 In line with this study, Szabo et al reported similar ossification patterns after using autogenous bone grafts and ß-tricalcium phosphate in bilateral maxillary sinus elevation procedures.18 However, as noted by Suba et al, graft biodegradation of ß-tricalcium phosphate was less when compared to autogenous bone.19 Nevertheless, this did not interfere with implant stability. In an evaluation of the amount of height reduction during a 4- to 5-year period, it was demonstrated that both grafts preserved their height after maxillary sinus augmentation in a similar way. After an initial height reduction within the first 1.5 years, subsequent changes were minimal in both groups.20
Simunek et al evaluated the occurrence of new bone formation after performing maxillary sinus augmentation using either ß-tricalcium phosphate, autogenous bone, bovine bone, or a combination of ß-tricalcium phosphate with autogenous bone. They reported the occurrence of new vital bone in all groups; however, its amount was highest in the autogenous group followed by bovine bone and the ß-tricalcium phosphate combined with autogenous bone group.21 Nevertheless, in contrast to both materials, ß-tricalcium phosphate can be produced in unlimited quantities.
Further studies evaluated the suitability of ß-tricalcium phosphate for alveolar reconstruction at additional oral sites. Within 5 years, ß-tricalcium phosphate was used for grafting mandibular cyst defects, periodontal defects, and secondary/tertiary alveolar clefts. Complete radiologic replacement of ß-tricalcium phosphate with autogenous bone was found approximately 12 months after its placement, indicating its osteoconductive properties and value in various bone grafting procedures.22
How do these findings affect today’s clinical practice? ß-tricalcium phosphate is clinically easy to use and appears to cause no persistent inflammatory reaction in surrounding bone when used for sinus augmentation. Furthermore, this material seems to provide adequate stability at time of implant placement, has no risk of disease transmission, and can be produced in unlimited quantities. Therefore, augmentation of the maxillary sinus with ß-tricalcium phosphate represents a viable option for increasing vertical bone height in the posterior maxilla prior to implant placement.
This research was sponsored by a General Clinical Research Center grant (M01 RR00533) and a Clinical and Translational Science Institute grant (UL1 RR025771).
1. Tatum H Jr. Maxillary and sinus implant reconstructions. Dent Clin North Am. 1986;30(2):207-229.
2. Boyne PJ, James RA. Grafting of the maxillary sinus floor with autogenous marrow and bone. J Oral Surg. 1980;38(8):613-616.
3. Summers RB. A new concept in maxillary implant surgery: the osteotome technique. Compend Contin Educ Dent. 1994;15(2):152-162.
4. Davarpanah M, Martinez H, Tecucianu JF, et al. The modified osteotome technique. Int J Periodontics Restorative Dent. 2001;21(6):599-607.
5. Block MS, Kent JN. Sinus augmentation for dental implants: the use of autogenous bone. J Oral Maxillofac Surg. 1997;55(11):1281-1286.
6. Wheeler SL. Sinus augmentation for dental implants: the use of alloplastic materials. J Oral Maxillofac Surg. 1997;55(11):1287-1293.
7. Froum SJ, Tarnow DP, Wallace SS, et al. Sinus floor elevation using anorganic bovine bone matrix (OsteoGraf/N) with and without autogenous bone: a clinical, histologic, radiographic, and histomorphometric analysis—Part 2 of an ongoing prospective study. Int J Periodontics Restorative Dent. 1998;18(6):528-543.
8. Froum SJ, Wallace SS, Elian N, et al. Comparison of mineralized cancellous bone allograft (Puros) and anorganic bovine bone matrix (Bio-Oss) for sinus augmentation: histomorphometry at 26 to 32 weeks after grafting. Int J Periodontics Restorative Dent. 2006;26(6):543-551.
9. Cammack GV II, Nevins M, Clem DS III, et al. Histologic evaluation of mineralized and demineralized freeze-dried bone allograft for ridge and sinus augmentations. Int J Periodontics Restorative Dent. 2005;25(3):231-237.
10. Pikos MA. Chin grafts as donor sites for maxillary bone augmentation—Part II. Dent Implantol Update. 1996;7(1):1-4.
11. Ozyuvaci H, Bilgic B, Firatli E. Radiologic and histomorphometric evaluation of maxillary sinus grafting with alloplastic graft materials. J Periodontol. 2003;74(6):909-915.
12. Burger EL, Patel V. Calcium phosphates as bone graft extenders. Orthopedics. 2007;30(11):939-942.
13. Helfrich M, Ralston S, eds. Bone Research Protocols (Methods in Molecular Medicine). Totowa, NJ: Humana Press Inc; 2003.
14. Lu JX, Flautre B, Anselme K, et al. Role of interconnections in porous bioceramics on bone recolonization in vitro and in vivo. J Mater Sci Mater Med. 1999:10(2):111-120.
15. Yokozeki H, Hayashi T, Nakagawa T, et al. Influence of surface microstructure on the reaction of the active ceramics in vivo. J Mater Sci Mater Med. 1998;9(7):381-384.
16. Handschel J, Simonowska M, Naujoks C, et al. A histomorphometric meta-analysis of sinus elevation with various grafting materials. Head Face Med. 2009;5:12.
17. Zijderveld SA, Zerbo IR, van den Bergh JP, et al. Maxillary sinus floor augmentation using a beta-tricalcium phosphate (Cerasorb) alone compared to autogenous bone grafts. Int J Oral Maxillofac Implants. 2005;20(3):432-440.
18. Szabó G, Huys L, Coulthard P, et al. A prospective multicenter randomized clinical trial of autogenous bone versus beta-tricalcium phosphate graft alone for bilateral sinus elevation: histologic and histomorphometric evaluation. Int J Oral Maxillofac Implants. 2005;20(3):371-381.
19. Suba Z, Takács D, Matusovits D, et al. Maxillary sinus floor grafting with beta-tricalcium phosphate in humans: density and microarchitecture of the newly formed bone. Clin Oral Implants Res. 2006;17(1):102-108.
20. Zijderveld SA, Schulten EA, Aartman IH, ten Bruggenkate CM. Long-term changes in graft height after maxillary sinus floor elevation with different grafting materials: radiographic evaluation with a minimum follow-up of 4.5 years. Clin Oral Implants Res. 2009;20(7):691-700.
21. Simunek A, Kopecka D, Somanathan RV, et al. Deproteinized bovine bone versus beta-tricalcium phosphate in sinus augmentation surgery: a comparative histologic and histomorphometric study. Int J Oral Maxillofac Implants. 2008;23(5):935-942.
22. Horch HH, Sader R, Pautke C, et al. Synthetic, pure-phase beta-tricalcium phosphate ceramic granules (Cerasorb) for bone regeneration in the reconstructive surgery of the jaws. Int J Oral Maxillofac Surg. 2006;35(8):708-713.
Related Content: A CE article, The Maxillary Sinus: Challenges and Treatments for Implant Placement, is available at dentalaegis.com/go/cced130
About the Authors
Ulrike Schulze-Späte, DMD, PhD
Assistant Professor of Dental Medicine
Division of Periodontics
Section of Oral and Diagnostic Sciences
College of Dental Medicine
New York, New York
Thomas Dietrich, DMD, MD, MPH
Associate Professor of Health Policy & Health Services Researc
Department of Periodontology and Oral Biology
Goldman School of Dental Medicine
The School of Dentistry
University of Birmingham
Birmingham, United Kingdom
Rayyan A. Kayal, BDS, DSc
Department of Basic Oral and Clinical Sciences
Faculty of Dentistry, King Abdulaziz University
Jeddah, Kingdom of Saudi Arabia
Hatice Hasturk, DDS PhD
Associate Research Investigator
Center for Clinical and Translational Research
The Forsyth Institute
Justine Dobeck, BA, MS
The Forsyth Institute
Ziedonis Skobe, PhD
Associate Member of the Staff
Department of Biomineralization
The Forsyth Institute
Assistant Clinical Professor of Oral Medicine and Oral Pathology
Harvard School of Dental Medicine
Serge Dibart, DMD, MS
Professor and Chair
Department of Periodontology and Oral Biology
Advanced Specialty Program in Periodontics
Goldman School of Dental Medicine