Anorganic bovine bone (ABB) vs. autologous bone (AB) plus ABB in maxillary sinus grafting. A prospective non-randomized clinical and histomorphometrical trial.

Christian M. Schmitt Tobias Moest Rainer Lutz Friedrich W. Neukam Karl Andreas Schlegel

Anorganic bovine bone (ABB) vs. autologous bone (AB) plus ABB in maxillary sinus grafting. A prospective non-randomized clinical and histomorphometrical trial

Authors’ affiliation: Christian M. Schmitt, Tobias Moest, Rainer Lutz, Friedrich W. Neukam, Karl Andreas Schlegel, Department of Oral and Maxillofacial Surgery, University of Erlangen-Nuremberg, Erlangen, Germany

Key words: AB, ABB, anorganic bovine bone, augmentation, autologous bone, Bio-Oss, bone

Corresponding author: Christian M. Schmitt Department of Oral and Maxillofacial Surgery University of Erlangen-Nuremberg Gl€ uckstr. 11, 91054 Erlangen, Germany Tel./Fax: 0049- 9131/85-43770 e-mail: [email protected]

after sinus floor augmentation with anorganic bovine bone (ABB, Bio-Ossâ) and ABB plus

graft, bone regeneration, bone substitute material, dental implants, sinus floor elevation Abstract Objectives: This investigation focused on histological characteristics and 5-year implant survival autologous bone (AB) with a ratio of 1/1. Material and methods: Nineteen consecutive patients with bony atrophy of the posterior edentulous maxilla and a vertical bone height ≤4 mm were prospectively included in this study. In the first surgical stage, the maxillary sinus was non-randomized either augmented with ABB alone (n = 12) or a 1/1 mixture of ABB and AB (n = 7). After a mean healing period of 167 days, biopsies were harvested in the region of the grafted sinus with a trephine burr and implants were placed simultaneously, ABB n = 18 and ABB + AB n = 12. The samples were microradiographically and histomorphometrically analyzed judging the newly formed bone (bone volume, BV), residual bone substitute material volume (BSMV), and intertrabecular volume (soft tissue volume, ITV) in the region of the augmented maxillary sinus. Implant survival was retrospectively evaluated from patient’s records. Results: No significant difference in residual bone substitute material (BSMV) in the ABB group (31.21 7.74%) and the group with the mixture of ABB and AB (28.41 8.43%) was histomorphologically determined. Concerning the de novo bone formation, also both groups showed statistically insignificant outcomes; ABB 26.02 5.23% and ABB + AB 27.50 6.31%. In all cases, implants were installed in the augmented sites with sufficient primary stability. After a mean time in function of 5 years and 2 months, implant survival was 93.75% in the ABB and 92.86% in the ABB + AB group with no statistically significant differences. Conclusion: The usage of ABB plus AB to a 1/1 ratio leads to an amount of newly formed bone comparable with the solitary use of ABB after grafting of the maxillary sinus. Considering that ABB is a non-resorbable bone substitute, it can be hypothesized that this leads to stable bone over time and long-term implant success. Importantly, in the sole use of ABB, bone grafting and therefore donor site morbidities can be avoided.

Date: Accepted 10 March 2014 To cite this article: Schmitt CM, Moest T, Lutz R, Neukam FW, Schlegel KA. Anorganic bovine bone (ABB) vs. autologous bone (AB) plus ABB in maxillary sinus grafting. A prospective nonrandomized clinical and histomorphometrical trial. Clin. Oral Impl. Res. 00, 2014, 1–8 doi: 10.1111/clr.12396

Implant placement in the edentulous posterior maxilla is often limited due to bone loss and increasing pneumatization of the maxillary sinus. Several augmentation procedures of the posterior maxillary have been described and established. Nowadays, the technique of sinus floor elevation is commonly used (Summers 1994; Jensen et al. 1998). Sinus floor elevation can be performed as a one- or twostage approach with simultaneous or delayed implant placement (Chao et al. 2010). The implant survival rate is not dependent on the

© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

use of either a simultaneous or a delayed protocol for implant placement in an augmented sinus (Jensen et al. 1998; Wallace & Froum 2003; Del Fabbro et al. 2008; Chao et al. 2010). The decisive factor for choosing one protocol over the other is the implant stability (Peleg et al. 1998, 1999; Del Fabbro et al. 2004, 2008). A two-step procedure is recommended in cases of severe atrophy with less residual bone in which primary implant stability cannot be guaranteed (Del Fabbro et al. 2008; Kang 2008).

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Schmitt et al ABB vs. AB + ABB in sinus lifting

Despite surgical approaches and techniques for maxillary sinus augmentation, recent and ongoing research is focusing on alternative materials and grafts used for such procedure (Klijn et al. 2010). Comparing materials with each other, autologous bone can still be considered the gold standard in maxillary sinus augmentation with regard to newly formed bone (Schmitt et al. 2013). Advantages like osteoinductive and osteoconductive properties of the autologous grafting material are well studied. Donor side morbidity, prolonged surgery time and additional surgical risks are common disadvantages (Raghoebar et al. 2007; Weibull et al. 2009) that still favor research with alternative bone substitute materials and especially their sole use in sinus floor grafting (Schmitt et al. 2013). Importantly autologous bone grafting can be avoided. In general, bony defect configuration and defect sizes are factors that influence the outcome of bone augmentation procedures and have to be considered prior to surgery. Especially, non-space-making one-walled bony defects, often called “critical size bony defects”, are challenging, and regeneration potential is limited (Wang & Al-Shammari 2002). In these cases, autologous bone is recommended for vertical bone regeneration due to their osteoinductive properties (Simion & Fontana 2004; Rocchietta et al. 2008). In terms of sinus floor grafting, the height of the residual bone is often used as indicator for the degree of bony atrophy of the posterior maxilla (Schmitt et al. 2014). Until today, the usage of autologous bone or additive of autologous bone to any kind of bone substitute material is recommended when residual alveolar height is low (Klijn et al. 2010). However, defect configuration tremendously differs from defects of the alveolar ridge, and the question arises whether an indication for autologous bone in sinus grafting exists at all (Del Fabbro et al. 2008; Klijn et al. 2010; Jensen et al. 2012b). In terms of using autologous bone alone, augmented bone is subject to conversion processes. The healing process after autologous bone transplantation is well researched and takes place in different successive steps. First, resorptive processes dominate in the context of inflammation. In the course of further healing, the graft is vascularized and the proliferating cells can penetrate the transplanted bone. The transplanted bone is resorbed and replaced successively with new bone (Burchardt 1983, 1987; Schmitt et al. 2014). This leads to an undesirable early loss of bone volume after grafting in the first year

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Clin. Oral Impl. Res. 0, 2014 / 1–8

(Schmitt et al. 2014). This might also affect bone volume loss after sinus floor grafting. To avoid severe bone resorption in the early healing phase of autologous grafts, the usage of additional agents such as membranes and non-resorbable bone substitutes was already proclaimed by some authors based on their clinical experience (von Arx & Buser 2006; Wiltfang et al. 2014). Several studies in patients with high atrophic posterior maxillary situations have shown that bone substitute materials, that is, biphasic calcium phosphate (BCP), anorganic bovine bone (ABB) and mineralized cancellous bone allograft (MCBA), are quite comparable in terms of newly formed bone and clinical outcome (Cordaro et al. 2008; Schmitt et al. 2013). Especially, the use of non-resorbable bone substitute materials such as anorganic bovine bone results in a composite consisting of residual bone substitute material and newly formed bone, but not in a homogenous bone structure (Merkx et al. 2003; Petrungaro & Amar 2005; Schmitt et al. 2013). No evidence indicates whether this situation is an advantage or a disadvantage. As a possible advantage, this structure could represent a type of protection against bone resorption, guaranteeing long-term stability of the augmented maxillary sinus. The aim of the following study was the clinical and histological investigation of anorganic bovine bone (ABB) substitute material alone and ABB plus autologous bone (AB) for the augmentation of the maxillary sinus in cases with high maxillary atrophy and a residual bone height of less or equal to 4 mm. Additionally, we set out to clarify the significance of mentioned bone grafts for implant survival after 5 years in function. It is hypothesized that there will be no significant differences in histological and clinical outcome with the addition of autologous bone to ABB, and the sole use of ABB is suitable for augmentation of the maxillary sinus in terms of histological appearance and implant survival. To create a comparable initial situation, a two-stage procedure with initial grafting of the maxillary sinus and a delayed implant placement was planned.

Material and methods Inclusion and exclusion criteria

Study participants were prospectively recruited from the implant patient collective of the Department of Oral and Maxillofacial Surgery at Friedrich-Alexander-University ErlangenNuremberg from 2007 to 2008. The selected

patients had unilateral free-end edentulous situations in the maxillary with residual bone height less or equal to 4 mm as measured by panoramic radiography. A minimum of a 3month healing period after tooth extraction was assumed. Patients were invited to participate if they were >18 years old, periodontally and systemically healthy, and had good plaque control. They were excluded if they were smokers, or had any systemic disease that would negatively influence wound healing. The patients were divided into two groups: the test group received ABB (consisting of 12 patients/sinuses) and the control group received AB + ABB with a 1/1 ratio (consisting of seven patients/sinuses). Ethical approval (No. 3275) was obtained from the ethics committee of the medical faculties of the Friedrich-Alexander-University ErlangenNuremberg. Used material

The ABB bone substitute material Bio-Ossâ (Geistlich Biomaterials GmbH, Baden-Baden, Germany) is a natural, non-antigenic, porous bone mineral matrix produced by removing all organic components from bovine bone. Due to its natural structure, Bio-Ossâ is physically and chemically comparable with the mineralized matrix of human bone (Tapety et al. 2004). The anorganic bone matrix of Bio-Ossâ contains macroscopic and microscopic structures with an interconnecting pore system that serves as a physical scaffold for the immigration of osteogenic cells (Tapety et al. 2004). Its osteoconductive properties could be shown in various studies (Piattelli et al. 1999; Schlegel et al. 2003; Degidi et al. 2007; Traini et al. 2007). BioOssâ is known to be a non-resorbable bone substitute (Schlegel 1996; Schlegel & Donath 1998; Schlegel et al. 2003; Traini et al. 2007). In the recent study, ABB (Bio-Ossâ) was used with a diameter of 1–2 mm. Presurgical measures

Before sinus grafting and implant placement (delayed protocol), conventional panoramic radiography (Orthophosâ XG; Sirona Dental Systems GmbH, Bensheim, Germany) was performed to evaluate the expansion of the maxillary sinus and the vertical residual bone height prior sinus lifting and the augmented bone height prior implant insertion. The surgical procedure was performed under local anesthesia (Ultracainâ UDSf; adrenaline 1:100,000; Sanofi-Aventis GmbH, Frankfurt, Germany). All patients received oral preoperative antibiotics (either one dose Augmentanâ 875/125 mg, Western Pharma GmbH,



Quettingen, Germany or one dose Clindamycinâ 600 mg, HEXAL AG, Holzkirchen, Germany) one hour before surgery. Bone harvesting

In the group, with the mixture of ABB and AB, the bone was harvested from the chin of patient jaws. Access preparation was carried out with a paracrestal labial incision in the anterior region of the lower jaw and preparation of a mucoperiosteal flap. The autologous bone was collected with a trephine bur (Hager & Meisinger GmbH, Neuss, Germany), a hammer, and a chisel (KLS Martin GmbH & Co. KG, Tuttlingen, Germany). After removal, the defect was filled with a collagen sponge (Lyostyptâ; B. Braun Melsungen AG, Melsungen, Germany), and the mucoperiosteal flap was repositioned and sutured with Vicryl 4/0. The harvested bone was particulated using a bone mill (Quentin Dental Products, Leimen, Germany), and the 1 : 1 mixture of AB and ABB was performed with a measuring cup with a size of 1 cm3. Sinus floor elevation

In the edentulous posterior maxilla, a paracrestal and an anterior buccal vertical releasing incision was made and a full-thickness flap was raised to access the facial sinus wall. This was followed by the preparation of an approximately 4-mm high and 10-mm wide slot-shaped opening of the basal maxillary sinus, and the Schneiderian membrane was elevated as already described by Schlegel et al. (2006b). Afterward, a collagen matrix was inserted (Lyostypt â; B. Braun Melsungen AG) to create a barrier between the Schneiderian membrane and the used bone grafts. In the test group, the bone substitute material ABB (Bio-Ossâ; 1–2 mm in diameter) and in the control group the 1 : 1 mixture of ABB and AB were inserted up to the palatal sinus wall in the resulting space (Fig. 1). The maxillary sinus was vertically augmented about approximately 10 mm. After augmentation of the maxillary sinus, the external window was covered with a collagen membrane (BioGideâ, Geistlich AG, Baden-Baden, Germany) and the mucoperiosteal flap was repositioned and fixed using resorbable sutures (Vicryl 4/ 0). After surgical intervention, postoperative panoramic radiography was performed to visualize the region of interest. All patients received postoperative nose drops for ten days (Otrivenâ nose drops 1-1-1; Novartisâ Consumer Health GmbH, Munich, Germany) and were instructed not to blow through the nose for 2 weeks. Postoperative care was carried out on the first and tenth postoperative days

and appropriate oral hygiene: twice daily tooth brushing, except in the augmented region, and twice daily antiseptic rinsing with chlorhexidine (0.2%) (Chlorhexamed, GlaxoSmithKline, B€ uhl, Germany) for 10 days was prescribed. Ibuprofen (Ibuhexal 600 mg, HEXAL, Holzkirchen, Germany) was prescribed for 3 days (three times a day) postoperatively and then taken as needed. After ten days, the sutures were removed. Implantation and biopsies

After a mean healing period of 167 days, the surgical area was anesthetized. Access preparation was performed as already described in stage-one surgery. Implant bed preparation was performed using a surgical template, during which a biopsy was taken using a trephine bur (outer diameter 3.5 mm, inner diameter 3.4 mm, Straumann AG, Basel, Switzerland), Fig. 2. Drilling with the trephine bur was performed as apically as possible already described and published in a previous work (Schmitt et al. 2013). Thus, residual maxillary bone and the whole augmented sinus were included in the biopsies

(a)

(Fig. 2). The biopsy was stored in paraformaldehyde until further processing. The trephine sites were used for implant placement after definitive treatment of the implant site. The lengths of the inserted implants were chosen after measuring the total vertical bone heights of the implant sites by measuring the whole lengths of the harvested biopsies. Postoperative panoramic radiography was performed after surgery and indicated that the implants were in the augmented sinus, respectively; the biopsies had been harvested in the region of augmentation. Postoperative care was carried out as described in stage-one surgery. Microradiography and light microscopy

The biopsies were dehydrated in graded alcohol at room temperature in a dehydration unit (Shandon Citadel 1000â; Shandon GmbH, Frankfurt, Germany) and embedded in a methacrylate-based resin (Technovitâ 9100 New; Haereus Kulzer, Hanau, Germany). The embedded bone samples were prepared for histomorphometrical evaluation according to an established cutting and grinding method (Schlegel & Donath 1998; Schlegel et al. 2006a,b; Stockmann et al. 2012). Samples were cut in the median longitudinal axis and further processed with a precision sawing and grinding machine (Exakt Apparatebau GmbH, Norderstedt, Germany) and ground to thin sections of 120 lm. Samples

(b)

Fig. 1. Exemplary presentation of stage-one surgery in the ABB + AB group; grafting of the maxillary sinus with a combination of autologous bone (AB) and anorganic bovine bone (ABB) with a 1/1 ratio. 1a showing the graft before insertion in the maxillary sinus and 1b showing the completion of the grafting procedure.


Fig. 2. Stage-two surgery showing the biopsy harvesting procedure in the augmented region. After access preparation, the biopsy was harvested with a trephine burr in the region of the later implant site.

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were x-rayed using the Faxitronâ Cabinet Xray System (Faxitron X-ray Corporation, Lincolnshire IL, USA) on dental films (Kodak Insightâ, Rochester, NY, USA) at 13.5 kV, 2.5 mA, with an exposure time of 2.5 min. The film was developed and scanned using a flat-bed scanner (Epson Perfection 4990â; Seiko Epson Corporation, Seoul, Korea) at 1200 dpi and 12-bit grayscale and stored in compressed tif file. Digital processing (contrast) was carried out with Adobe Photoshop CS2â (Adobe Corp., San Jose, CA, USA). For light microscopy, bone sections were reduced to 30 lm, polished, treated with continuous agitation using a magnetic stirrer for 14 min with hydrogen peroxide, rinsed under cold tap water, dried, and stained for 5 min in toluidine blue-o solution (Sigma-Aldrich, St. Louis, MO, USA). After dyeing, the samples were digitized at 4800 dpi and 16-bit colors using a flat-bed scanner.

Implant survival and clinical outcome

All patients participating to the study were included in an oral hygiene follow-up program standardized offered to all implant patients at the Department of Oral and Maxillofacial Surgery, University of ErlangenNuremberg. The individual hygiene plan included oral hygiene motivations and hygiene instructions as well as professional care at least once a year by a dental hygienist but individually adapted to patients needs. In every visit, treatment related data were collected with a dental documentation software impDat (Kea Software GmbH, Munich, Germany). Between October and November 2013, patient‘s records and data retrieved by impDat documentation were retrospectively reviewed to detect implant failures/loss after loading and implant or graft-related complications or treatments. Statistical analysis

Histomorphometry

Prior histomorphometric evaluation, toluidine blue-o histologies were examined with light microscopy to determine the region of augmented and residual bone. Visualization of the augmented region in the maxillary sinus and the residual maxillary bone was significant for the evaluation of the region of interest (ROI), the region of the augmented maxillary sinus. Quantitative evaluation was carried out via Bioquant Osteoâ (BIOQUANT Image Analysis Corporation, Nashville, TN, USA). For analyses, microradiographic and histological images were used to detect the residual anorganic bovine bone substitute material (BSMV), the newly formed bone volume (BV), and the intertrabecular volume (ITV) in the region of interest (ROI), the augmented maxillary sinus, defined as tissue volume (TV). Microradiographic images were suitable for the detection of residual bone substitute particles due to their higher density compared with newly formed bone and inserted autologous bone. Measurements of residual autologous bone, which was inserted for grafting in a prior defined amount, were not possible with microradiographic images due to the similarity in radiographic appearance of the transplant and the newly formed bone. Therefore, histologies were used. The following parameters in the ROIs (TV, tissue volume) were evaluated (Fig. 3) 1. Residual bone substitute material volume/tissue volume (BSMV/TV) 2. Newly formed bone volume/tissue volume (BV/TV) 3. Intertrabecular volume (soft tissue components)/tissue volume (ITV/TV)

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Results were transferred into the spreadsheet program Excel 2007 (Microsoft Corp., Redmond, WA, USA). Statistical analysis was performed using the statistical package SPSS for Windows version 19.0 (Microsoft Corp.). Descriptive statistics include frequency values (absolute and relative abundances, %) and metric data (arithmetic mean, standard deviation, and median). To eliminate dependency in statistical comparisons between groups (ABB and AB + ABB) in cases harvesting more than one biopsy per sinus, means were calculated for each sinus and used for statistical analyses. A standardized nonparametric

(a)

(b)

(c)

Mann–Whitney test was carried out to determine statistical significance between groups, which was defined as P < 0.05.

Results Data set and surgical outcome

Nineteen patients participated in this study; one sinus was treated in each patient, and at least one biopsy was harvested per sinus. Patients mean age was 54.5 years (median 54 years), ranging from 33 to 62 years. Radiological bone height at baseline was 2.2 mm 1.15 mm (median 2 mm). Twelve patients/sinuses were treated in the ABB group, and 18 biopsies were harvested in total in the augmented regions as well as 18 implants inserted in the grafted areas. The combination group (ABB + AB) consisted of seven patients/sinuses, 14 biopsies were harvested in total, and the same number of implants was placed in the augmented maxillary sinuses. In stage-one surgery, maxillary sinus grafting procedures and bone harvesting could be performed without any complications. A perforation of the Schneiderian membrane was not observed in any patient. The postoperative course was uneventful in every case. Patients who underwent removal of bone from the chin (n = 7) demonstrated subjective more swelling and felt more stressed after the operation than the other patients. Hypoesthesia in the distribution of the nerve was not observed. In stage-two surgery, 32 implants were inserted in the grafted maxillary sinuses in

(d)

(e)

(f)

Fig. 3. Microradiography (3a) and histology (3d) of a biopsy obtained from a sinus grafted with the sole use of anorganic bovine bone (ABB). Images 3b, c, e, and f showing the evaluation process. One can distinguish between the two portions of the biopsy; residual alveolar bone and the region of interest (ROI), the grafted maxillary sinus (defined as tissue volume, TV). Image b and e showing the quantification of the mineralized tissue and image c and f of the residual bone substitute material (BSMV/TV). Previously defined parameters (BV/TV and ITV/TV) have been calculated accordingly.



the region of the harvested biopsies with sufficient primary stability in both groups and resulted in no wound healing complications. Postoperative panoramic radiographs revealed that all implants were inserted in the grafted sinus and the biopsies were harvested in the region of interest. Harvesting of the biopsies and further sample preparation was carried out without loss under standardized conditions. Implant survival and clinical follow-up

Reviewing patient’s records and data from the implant documentation software left us with data form 17 patients eligible for evaluation (10 in the ABB and 7 in the AB group). One patient of the ABB group did not join the implant hygiene and follow-up program. In the other case (ABB group), there was insufficient data for evaluation. Sixteen implants for evaluation remained in the ABB and 14 in the ABB + AB group. With a mean time in function of 5 years and 2 months 7 months, there was one implant loss in each group, which left us with an implant survival rate of 93.75% in the ABB and 92.86% in the ABB + AB group with no statistically significant differences. Implant data retrieved from the implant documentation software revealed that in the mentioned follow-up, there were no graft-related or implant-related complications or treatments. Histomorphometrical and histological results

Quantitative result of histomorphometry is summarized in Table 1. Microradiographically, the bone substitute material could be well distinguished from the newly formed bone and local bone due to its radiographical appearance. In quantifying the newly formed bone, histologies could sufficiently be used. The nonparametric Mann–Whitney test revealed no statistical significance for intergroup comparison of all evaluation parameters. ABB particles were surrounded from newly formed bone in both groups confirming

the osteoconductivity of used bone substitute material as already documented in multiple studies before (Hallman et al. 2002b; Schlegel et al. 2003; Traini et al. 2007; Cordaro et al. 2008; Froum et al. 2008; Klijn et al. 2010; Jensen et al. 2012a,b; Schmitt et al. 2013).

Discussion Due to several modalities in sinus grafting, that is, external/internal approach, grafting with immediate or delayed implant placement and the variety of used filling materials (autologous bone, mixtures of autologous bone with bone substitute materials and bone substitute materials alone from different origins), the sinus lift procedure still remains an open area of research (Peleg et al. 1999; Crespi et al. 2009; Santagata et al. 2010; Rodriguez Lozano & Moraleda 2011; Rosano et al. 2011). The total replacement of autogenous bone by several bone substitute materials in sinus lifting has been discussed in numerous studies (Esposito et al. 2010; Jensen et al. 2012b). Focusing on the used filler, autologous bone and anorganic bovine bone substitute material (Bio-Oss) are probably the most clinically and histologically studied fillers in terms of sinus lifting (Jensen et al. 2012a,b). However, reviewing the current literature about sinus lifting with Bio-Oss or Bio-Oss mixed with autogenous bone, Jensen et al. 2012b stated that the hypothesis of “no differences” between both mentioned fillers of the maxillary sinus using the lateral window approach can neither be confirmed nor rejected due to insufficient knowledge and data (Jensen et al. 2012b). Comparative studies are rare, and final conclusions about the preferable filler cannot be drawn by date. Following outcomes are of significant concern that might favor the use of one over the other graft: Implant survival, newly formed bone in the augmented region, bone to implant contact, biodegradation and resorption of used

Table 1. Outcome of histomorphometrical evaluation. Evaluation parameters (mean, median, and standard deviation in %) in the region of interest, the grafted maxillary sinus (tissue volume, TV) Group ABB (n = 18)

ABB + AB (n = 14)

Evaluation parameters

Mean

Median

SD

Mean

Median

SD

P

BSMV/TV BV/TV ITV/TV

31.21 26.02 42.91

30.43 26.72 41.47

7.74 5.23 8.08

28.41 27.50 44.12

28.01 26.90 41.12

8.43 6.31 7.82

0.68 0.36 0.914

ABB, anorganic bovine bone; AB, autologous bone; SD, standard deviation; BSMV/TV, bone substitute material volume/tissue volume; BV/TV, bone volume/tissue volume; ITV/TV, intertrabecular volume (soft tissue components)/tissue volume; P, P-value for intergroup comparison (ABB and ABB + AB) applying the nonparametric Mann–Whitney test. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

material and volumetric stability over time (Jensen et al. 2012b). Concerning long-term survival of dental implants, there is still a lack of knowledge if a composite of newly formed bone and anorganic bovine bone (Bio-Oss) or a 100 percentage of newly formed bone, that is, with the use of autologous bone alone, has a significant influence. Additionally, literature is inconclusive whether the addition of autologous bone to the anorganic bovine bone has a beneficial effect at all (Hallman et al. 2002b). Implant survival using Bio-Oss and Bio-Oss mixed with autologous bone has exclusively been compared in one study, and no statistically significant histological differences and clinical outcomes were shown after implants have been 1 year in function (Hallman et al. 2002b). Long-term comparative data of implant survival in this constellation do not yet exist. The long-term survival (up to 6 years) of implants placed in augmented sinuses with the sole use of Bio-Oss ranges from 91% to 100% in the literature (Valentini et al. 2000; Valentini & Abensur 2003; Froum et al. 2008). Long-term data about survival of implants placed in sinuses grafted with mixtures of anorganic bovine bone and autologous bone are rare in the literature (Hatano et al. 2004). In our study, we retrospectively retrieved comparable long-term data of implants placed in Bio-Oss and a mixture of Bio-Oss and autogenous bone for sinus lifting. While we report of a very low number of implants, there were comparable survival rates (93.75% in the ABB and 92.86% in the ABB + AB group) after a mean time of 5 years and 2 months in function which might favor the sole use of the bone substitute. By date, this is the only available data about long-term survival of implants placed in augmented sinuses with either BioOss or Bio-Oss mixed with autogenous bone compared in one study. Histological and histomorphometrical outcome revealed that the addition of autologous bone to anorganic bovine bone does not lead to increased new bone formation in the grafted sinus (ABB 26% and ABB + AB 27%). In both groups, there were Bio-Oss remnants to a comparable amount (31.21% in the ABB and 28.41% in the ABB + AB group) surrounded by newly formed bone. Concerning the amount of residual bone substitute material (Bio-Oss) after sinus grafting with the sole use of ABB, our results are similar in comparison with findings in other studies (Valentini et al. 2000; Froum et al. 2006, 2008; Simunek et al. 2008), while other authors reported of more bone formation and

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less residual ABB particles (Hallman et al. 2002b; John & Wenz 2004; Lindgren et al. 2009; Schmitt et al. 2013). Concerning mixtures of autologous bone with anorganic bovine bone histological and histomorphometrical are rare. In the literature, the addition of autologous bone ranges from 20% to 50% (Galindo-Moreno et al. 2010b). With the ratio of 20% autologous bone and 80% BioOss, Hallman et al. 2002b measured an amount of residual bone substitute material of 12% and newly formed bone of 40% with no statistical significant difference compared with the usage of 100% Bio-Oss (residual Bio-Oss 12% and newly formed bone 42%). They concluded that the effect of adding autogenous bone remains unclear but may allow for a reduction in the healing time (Hallman et al. 2002b). With a ratio of 50% Bio-Oss and 50% bone harvested from the maxilla, Galindo-Moreno et al. (2010a) measured a residual bone substitute material amount of 37%25% and newly formed bone of 46 16%. Radiographic analysis additionally revealed that the higher the proportion of remaining ABB, the lower the total vertical resorption of the graft. In the ABB + AB group (50/50), in our study, we had slightly different amounts of newly formed bone with 27% and residual ABB of 28% compared with the present results of the literature. In all cases, different outcomes may be justified by differing measuring methods, healing times, the ratio of the used mixtures, the origin of used autologous bone and treatment of autologous bone, particle sizes of the bone substitute material and how dense the filler is packed into the cavity of the maxillary sinus. However, the usage of ABB alone and the mixture of ABB with autologous bone seems to induce comparable proportions of newly formed bone with a non-significant amount of residual anorganic bovine bone. Anorganic bovine bone was considered to be a non-resorbable bone substitute that leads to a predictable bone formation and longterm volume preservation (Traini et al. 2007). Nine years after sinus grafting with Bio-Oss, Traini et al. 2007 reported that the tissue

pattern appeared composed by residual ABB particles in close contact to the newly formed bone. This demonstrated both a high level of osteoconductivity and a “biomimetic” behavior over the long term (Traini et al. 2007). Other studies indicate that Bio-Oss undergoes not or only limited resorption (Schlegel 1996; Schlegel & Donath 1998; Piattelli et al. 1999; Yildirim et al. 2000; Jensen et al. 2012b). This probably preserves the volume of the graft over time and might influence long-term implant success. On the other hand, sinus lifting, respectively, bone grafting with the sole use of autologous bone leads to an undesirable bone loss over time due to biodegradation and resorption processes that might compromise dental implant long-term success (Wiltfang et al. 2005; Schmitt et al. 2014). By date, ABB particles are successfully used in combination with autologous bone transplants to protect tremendous bone resorption processes after bone grafting (Wiltfang et al. 2014). The addition of autologous bone to ABB does not seem to change biodegradation processes of Bio-Oss and leads to comparable residual bone substitute material as confirmed in our study and by Hallman et al. (2002b). The background of autologous bone additives to bone substitutes was originally to gain osteoinductive properties of the graft. Today, non-resorbable ABB particles are added to autologous grafts or autologous grafts are covered with ABB particles as a protection to graft resorption and long-term bone preservation (Wiltfang et al. 2014). In terms of implant long-term survival, the volumetric stability of the augmented sinus and therefore the presence of periimplant bone is obviously important. Studies measuring the volumetric stability of grafted sinuses are rare by date. Especially, the volumetric stability of the graft after maxillary sinus floor elevation with autologous bone with Bio-Oss or Bio-Oss alone has never been compared. Hatano et al. (2004) concluded from his radiographic long-term (10 years followup) evaluation of 191 patients after a sinus lifting with a mixture of 2 : 1 autologous

bone to Bio-Oss that the long-term stability of the maxillary sinus graft is an important factor for implant success (Hatano et al. 2004). Other studies also report of limited volumetric graft changes after augmentation with different mixtures of Bio-Oss with autologous bone or autologous bone alone (Hallman et al. 2002a; Kim et al. 2009; Galindo-Moreno et al. 2010a; Schmitt et al. 2014). However, methods are limited to two-dimensional measurements involving radiographs. Three-dimensional measurement methods are needed to confirm volumetric graft changes over time and the assessment whether ABB or ABB mixed with autologous bone is beneficial for graft preservation and implant long-term success. According to our findings and multiple other studies, the sole use of Bio-Oss is suitable in grafting of the maxillary sinus (Hallman et al. 2002b; John & Wenz 2004; Froum et al. 2006). As already reported by Hallman et al. (2002b), our study confirms that the addition of autologous bone to Bio-Oss has no beneficial effect and is comparable with the sole use of Bio-Oss. Due to the small sample number in our study, it should, however, be noted that this study provides only moderate evidence. However, present data and the results of our study might therefore favor the sole use of Bio-Oss for sinus lifting. Importantly, autologous bone harvesting, which is always associated with patient morbidities, is avoided.

Conclusion The effect of adding autologous bone with its osteoinductive properties has no beneficial effect on newly formed bone and long-term implant survival. Bio-Oss alone with comparable histological and clinical outcome is suitable for sinus lifting. Due to its limited biodegradation, it is hypothesized that addition of Bio-Oss to autogenous bone graft or the sole use of Bio-Oss is an advantage for bone preservation and long-term implant success.

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