Human Studies of Vertical and Horizontal Alveolar Ridge Augmentation Comparing Different Types of Bone Graft Materials: A Systematic Review

Implant placement in patients with atrophic mandible or maxilla is becoming more prevalent.¹  Atrophy or bone loss can be due to periodontal disease, trauma, or postextraction resorption. This loss may not be sufficient from an esthetic or functional perspective for implant placement; thus, bone augmentation might be recommended.¹ 

Bone grafting or bone augmentation is the process of adding bone in anatomically or functionally deficient areas. Bone augmentation is performed for procedures such as sinus augmentation, socket grafting, or alveolar ridge augmentation. The purpose of the new bone is to provide stability and support for the future dental implant. As native bone grows, it replaces the graft material and, with time, results in an integrated region of new bone.²  This process will vary among the different bone substitutes used with relation to their resorption properties; for some bone substitutes, very minimal resorption was reported. New bone may grow by osteogenesis, osteoinduction, or osteoconduction.³  Osteogenesis occurs when osteoprogenitor cells in the graft material can survive transplantation and can differentiate into osteoblasts and later osteocytes.⁴  Osteoinduction is when undifferentiated mesenchymal cells in the native bone are induced into osteoblasts or chondroblasts to grow new bone by surrounding tissue. This is often dependent on bone morphogenic proteins (BMPs).²  Osteoconduction is defined as a material encouraging bone formation from already existing bone or differentiated mesenchymal cells via scaffolding.² 

Bone grafting materials vary by their source. Autogenous bone grafts may be harvested from the patient's iliac crest, mandibular ramus, or other intraoral sites. The donor site chosen is determined based on the volume of graft material required.⁵  Autogenous bone heals in three phases. The first phase is osteogenesis, and here the surviving cells form the osteoid. The second phase is osteoinduction and starts 2 weeks after grafting. The blood vessels from the host bone invade the graft, and native bone cells follow the vessels. Bone formation and resorption are now mediated by BMP. The third phase occurs as the minerals from the graft act as scaffolding for native bone to from a matrix upon. The third phase is synonymous with osteoconduction. These 3 phases overlap and are not separate entities.⁵  Disadvantages of autografts include the need for a second surgical site and the morbidity related to bone harvesting.⁴  Autogenous bone may also require a longer time period for resorption than some synthetics or demineralized freeze-dried bone allografts (DFDBA) mixed with calcium sulfate. This could also be a disadvantage if full graft resorption is desired in a short time frame, which will not occur with autogenous cortical bone grafts.

Allograft material is bone material from another individual of the same species—often cadaveric. The bone material is sterilized, processed, and stored in bone banks.^2,5  Allografts act via osteoinduction and have osteoconductive capabilities as well on native undifferentiated mesenchymal cells. They are known to form bone via osteoconduction by a combination of resorption of the graft matrix and deposition of new bone on the residual scaffold. Osteogenesis is not an option for allografts as the cells are not vital. Some challenges with this type of bone are that the medical history of the donor must be cleared of infections, cancers, and other problems for the recipient's safety. It has been hypothesized that bone formation is slower and may produce less volume for allografts vs autografts as allografts do not conduct osteogenesis.⁵  Those findings, however, are controversial. There are 2 main types of allografts: frozen and freeze-dried (lypholized) or demineralized freeze-dried bone.² 

Xenograft material is bone material from equine, porcine, or bovine sources that is mostly deproteinized and further processed.⁶  The organic components of these materials are removed to mitigate immune reactivity or pathogen transmission. The remaining minerals act as a scaffolding for native bone growth. They might be used in combination with growth factors or allografts to simulate the autogenous bone. Bone formation occurs mostly via osteoconduction.⁷  The resulting crystal structure is described as being rather similar to human cancellous bone.^7,8 

Alloplastic material is entirely synthetic and synthesized from nonorganic sources.⁹  The most prevalent type of alloplasts are bioactive ceramics such as calcium phosphates.²  Ceramics (calcium phosphates, bioglass, calcium sulfate) can be mixed with growth factors and ions to increase bone mineral density and osteoblast proliferation.^2,4  The mode of bone formation for these ceramics is osteoconduction. When transplanted, osteoid is produced directly onto the ceramic surface by native bone and later undergoes remodeling.⁴  Particle sizes and porosity influence the resorption rates of these materials along with other physical properties. Larger particles have a greater expectancy to remain at the augmentation site. Greater porosity has faster resorption rates than osteoclasts and can penetrate the graft more readily than dense material.⁵  Certain ceramics can dissolve via the extracellular matrix as well.

Numerous studies have been performed to determine if there is a significant difference between these types of bone materials. The aim of this work was to systematically review comparative human studies of vertical and horizontal alveolar ridge augmentation comparing 2 different types of bone graft materials (autogenous, allograft, xenograft, and alloplast) for the purposes of dental implantation.

The research objective was constructed per the PICO framework¹⁰  (Table 1). The search's inclusion criteria were articles that investigated horizontal or vertical alveolar ridge augmentation in human subjects for the purposes of dental implantation. The studies must have directly compared 2 (or more) of the 4 groups of bone grafts (autogenous, allografts, xenografts, and alloplasts) to be included in the review. Studies were limited to retrospective or prospective clinical trials. There were no search limitations on follow-up period, publication date, and sample size to prevent loss of data. Exclusion criteria included studies that compared the same graft types. In addition, sinus augmentations or socket grafting procedure related to bone grafting were excluded. Case report and small case series articles were excluded. Studies that included the same data set were considered as a single publication. The PRISMA protocol was followed for this systematic review.¹¹  The PRISMA diagram is presented in Figure 1.

Full-text articles in English were searched on MEDLINE based on a search query (Figure 2). The articles were included from earliest inception until August 20, 2016. The search method was planned in collaboration with an experienced librarian at John W. Scott Library at the University of Alberta based on the research objective. The search identified papers that were tagged under (1) bone transplantation, (2) dental implantation, and (3) alveolar ridge augmentation. Key search words included “bone graft/grafts/grafted/grafting,” “bone augment/augmented/augmenting/augmentation,” “dental implant/implants/implanted/implanting,” “vertical,” or “horizontal.” The 2 limitations on this query were human studies and comparative studies.

Following title review, abstracts were assessed per inclusion and exclusion criteria. The included full articles were fully assessed, and the significant results were recorded into a chart. Data were recorded on a spreadsheet, including authorship, patient characteristics, compared materials, outcomes, follow-up after augmentation, complications, main results, and limitations/strengths. A 9-item quality and risk of bias assessment tool was used and recorded in a separate spreadsheet.^12,13  The bias assessment recorded any conflicts of interest, clarity of objectives described, and the source of the patients. Conflict of interest was defined as all financial relationships with companies whose products the researchers are evaluating in the transcript.

The MEDLINE search initially identified 219 articles. Following a title- and abstract-based search, 17 articles were selected for full-text review. Upon full review of these articles, only 9 publications were included for data extraction and descriptive analysis in accordance with the inclusion criteria.^14–22 

In the included articles, there were a total of 181 patients who underwent alveolar ridge augmentation for future dental implantation. Of those, 68 patients had mandibular defects and 79 patients had maxillary defects. Table 2 describes the number of graft sites and implants for each bone graft material. Overall, 304 implants were recorded for 196 graft sites in 181 patients. Of those, 15 patients were treated in studies with a split-mouth design; thus, there are 15 more graft sites than patients.^16,19  Three studies did not state if the implants were placed in the maxilla or mandible.^14,19,22  One study had not placed any implants at the time of publication of those patients.¹⁴  Mini-implants were not included in these calculations as they were never loaded with a prosthesis and thus are not comparable with normal dental implants. One study had used a mix of 70% autogenous (ramus) and 30% bovine porous bone mineral as their test graft and was included under the xenograft group.¹⁷  Two studies are based on the same data set; however, the latter is 1 year later of follow-up.^15,20  Both articles contain different results and thus have been kept as 2 separate inclusions.

The main results, subject demographics, and procedures among other criteria from all 9 publications were summarized in Appendix Ia and Ib. Table 3 summarizes the 9-item quality and risk of bias assessment tool results for all 9 publications.

Vertical bone gain differences were not statistically significant between bone materials, except in 1 study.¹⁵  This study found that although the individual vertical bone height for autogenous (iliac crest) and bovine Bio-OSS were significant, the difference between the materials was not significant. Significantly more residual graft was found in the bovine group by 10%–13% vs autogenous.²⁰  Significantly more vital bone and less soft connective tissue was found for autogenous bone vs allogeneic bone.¹⁴  Microvascular density was deemed not to be significantly different between studied materials (autogenous and bovine).¹⁸  Degree or penetration of graft material into native bone was less extensive for allogenic bone than autogenous bone.²¹ 

Bone-to-implant contact was measured in 2 studies, and the difference between materials was not found to be statistically significant. Implant failure rates were not found to be statistically different between bone materials, except in 1 study that found statistically significant worse outcomes (graft failures, implant failures, higher complication rates) for bovine grafts vs autogenous grafts.²²  Complication rates among studies were not found to be different in a statistically significant manner between studied materials among studies. All articles except one used autogenous bone grafts as their control to directly compare another bone graft.¹⁹  A total of 3 studies included smokers.^15,20,22  One study had only 5 patients, and thus the statistical significance was impossible to deduce.¹⁶ 

The measured outcomes varied greatly among studies such that a meta-analysis was not considered feasible. Several studies have solely investigated the integration between the graft types and native bone¹⁶  or compared the microvascular density of the bone grafts,¹⁸  whereas others had directly assessed the success of the implants and prosthesis within each bone graft type.^19,20,22  The follow-up period after implant loading varied and was between 6 and 14 months.

Table 3 presents the bias assessment tool results. One study was financially supported by Brazilian agencies Fapesp and CNPq.¹⁴  Another study was supported by Bioteck, Arcugnano (VI), but the authors stated the data was their own.²²  All other articles declared no conflict of interest or did not discuss conflict of interests. All studies were conducted at universities except for 1 study at a private clinic¹⁹  and 1 study that collected patients from a private clinic and a university.²²  All studies collected data prospectively. All studies had clear objectives and clearly described their main outcomes.

Autogenous bone appears to be the current gold standard for alveolar ridge augmentation against which other materials are chosen to be compared.^{14–18,21,22}  Per the current review, most studies compared autogenous bone material to another material type. The results of these studies do not suggest that autogenous bone has significantly greater implant or prosthesis success rates. Some studies suggested that autogenous bone has lesser healing time and better compatibility with native bone because of noticeably greater integration although not statistically more significant than its comparators.^14,22  A major implication of this review is that autogenous grafts may not be a clinically superior choice for alveolar ridge augmentation as they are associated with more pain and morbidity.^15,22–24 

These results are in general concurrence with the current comparative literature on bone graft materials. A systematic review of randomized clinical trials of bone graft materials for dental implants showed that there was no significant difference in bone gains between materials.²⁵  The authors also similarly concluded that nonautogenous bone grafts are a feasible alternative to autogenous grafts. Another systematic review and meta-analysis of the effect of bone graft materials on healing time of sinus floor augmentation concluded that autogenous grafts have significantly greater growth of new bone vs xenografts, allografts, or alloplasts.²⁴  However, the authors did conclude that the nonautogenous bone graft materials would be viable alternatives because of lesser morbidity and limited availability.²⁶  A systematic review of clinical outcomes of autogenous bone and other bone substitutes for sinus floor augmentation showed the current evidence does not favor autogenous bone over the others.²⁷  The implications of this article's results are supportive of the current standing of bone augmentation literature in dentistry.

When performing the MEDLINE search, there were no other reviews found of this nature; however, it should be noted that other reviews have looked at bone augmentation materials but not exclusively for human comparative studies for horizontal and vertical augmentation. Furthermore, the results do concur with current bone augmentation literature.

There are several limitations of this review. There were only 9 articles finally included under the stated search query and inclusion/exclusion criteria. Most of the articles (Appendix Ia and Ib) have autogenous bone as one of the compared bone materials. This resulted in less information about the relative efficacy of xenograft, allograft, and alloplast bone materials. A meta-analysis was not possible because of the low number of articles, small sample sizes, variable procedures, and short follow-up periods. These limitations have been cited in similar reviews.²⁵ 

Disappointingly, the follow-up times of the selected publications ranged from 4 months postaugmentation to 16 months postloading of implants. Longer follow-up times are needed to truly assess the long-term success and failure rates of implants in the different bone graft materials' types.

As smokers were included in multiple studies in this review, it is worth discussing the clinical significance of tobacco smokers.^15,19,22  Smoking is associated with greater risk of alveolar bone loss around dental implants.^28–32  However, some articles have shown that although smoking does contribute to peri-implant bone loss, it has not been shown to be correlated with greater implant failures.^33–35  Thus, it is feasible to conclude that including smokers would not be a limitation of these studies.

Future directions of research should have long-term follow-up postaugmentation and postimplantation of at least 5 to 10 years. As nonautogenous bone substitutes are deemed comparable and in some respects advantageous to autogenous bone, future studies should compare nonautogenous bone substitutes to each other to determine if there are differences in vitality, osseointegration, or clinical outcomes.

The results of this systematic review of the literature suggested no clinically significant differences between autogenous bone types and other bone substitutes in terms of implant and prosthesis survival and success. Future studies should be promoted to compare outcomes of dental implants between nonautogenous bone grafts. Longer-term follow-up studies are necessary for our future understanding and decision making in that field.

Abbreviations

BMP

bone morphogenic protein

DFDBA

demineralized freeze-dried bone allograft

The authors report no conflicts of interest.