A probe into implant dentistry research : Past , present and future

s of scientific publications from January 2011 to January 2012 were accessed online and analysed to gain information on research category, type of study and research design, research topic, interventions and outcome variables. A total of 747 abstracts were analysed. The results are summarised in Table 3, organised according to research category, study type and research design. Research category and study type The largest proportion (60%) of research during the assessed one-year period could be assigned to the clinical research category (research on humans). Other studies were approximately equally distributed between animal-based (18%) and laboratory (in vitro) research (21%). Clinical research is generally classified into three main study types: systematic reviews, experimental studies and observational studies. Most of the research contributions (76.6%). could be classified as observational studies. Only 30 (6.7%) systematic reviews and 75 (16.7%) experimental studies were published during the assessed period. Page 2 of 7 TABLE 1: Summary of studies identified by database search, organised according to research categories and publication date. Research category 1960–1969 1970–1979 1980–1989 1990–1999 2000–2012 Total N n N n N n N n N n N n Clinical 126 5 810 15 2221 13 6199 148 12 744 731 22 100 912 Animal 32 3 295 20 631 29 1391 67 3047 238 5396 357 Laboratory 1 0 5 1 11 0 29 0 91 11 137 12 N, Total number of studies; n, number of publications available in free full text. TABLE 2: Summary of some types of clinical research study in the field of implant dentistry conducted between 1960 and 2012, as found during a database (Medline) search. Type of clinical research 1960–1969 1970–1979 1980–1989 1990–1999 2000–2012 Total N n N n N n N n N n N n Systematic reviews/meta-analysis 0 0 0 0 0 0 10 0 115 6 125 6 Randomised controlled trials 0 0 0 0 12 0 159 9 749 37 920 47 Non-randomised clinical trials 0 0 14 0 75 0 462 24 1460 56 2011 81 Multicentre trials 0 0 0 0 5 0 114 1 271 10 390 11 Comparative (analytical) studies 1 0 25 2 124 2 827 27 1956 92 2933 123 Case reports 18 0 110 0 363 1 1144 8 2616 112 4251 131 N, Total number of studies; n, number of publications available in free full text. TABLE 3: Analysis of studies conducted from January 2011 to January 2012. Research category Study type Sub-study type Research design Total Description n % Description n % Description n %   N % Clinical research Systematic reviews 30 6.7 Quantitative meta-analysis 5 1.1 448 60.0 Qualitative 25 5.6 Experimental 75 16.7 Randomised controlled trial 45 10.0 Non-randomised controlled trial 30 6.7 Observational 343 76.6 Analytical (with comparison group) 132 29.5 Prospective cohort 80 17.9 Retrospective cohort 45 10.0 Case–control 7 1.6 Descriptive (no comparison group) 210 47.0 Cross-sectional (prevalence) 63 14.0 Case series 54 12.0 Case reports 94 21.0 Animal research 141 18.9 Laboratory (in vitro) research 158 21.0 Total abstracts 747 100.0 n, number of studies; N, Total number of studies.

• observing interventions and their outcomes and asking questions as to why they are happening • describing who, what, why, when and where to get insight into or find answers to specific interventions or treatment modalities and outcomes in a population • predicting the prognosis, survival or outcome of therapies or interventions • determining the underlying causes and relationships between different biological processes that leading to the observed events, conditions or outcomes of interest • finding possible explanations to why and how certain events or outcomes are happening • debating the significance of the research or identifying gaps, which may direct research into new areas of interest • synthesising and critically appraising a collective body of evidence on a specific research question to present evidence-based data that can facilitate clinical guidelines and recommendations.
These endeavours culminate in the scholarly activity of publishing research findings in peerreviewed journals.
The value of research lies in its clinical and economic benefits to the individual and collective community.Research also has a scholarly benefit in that it contributes to developing science, technology and education and thus increasing the standing of the profession.However, research is meaningless if the results are not valid (i.e.inaccurate or unreliable), have no relevance to patients in real-world clinical situations, and are not easily accessible to the end users, namely clinicians, educators and researchers. 1

The growth of implant dentistry research between 1960 and 2012
Research and scholarship has seen significant growth in all the research categories related to implant dentistry over the past 50 years (Table 1).One could say that implant dentistry was conceptualised in the early sixties, born in the seventies, experienced its infancy period during the eighties and entered adolescence in the nineties.The 21st century can be seen as the maturation period of implant dentistry research, with greater focus being placed on content, quality and consolidation.The significant growth is striking in all research categories.
A basic search of the MEDLINE database for the period 1960-2012, using search terms related to implant dentistry (dental implant surgery, oral implant surgery, oral implantology, dental implantology, implant dentistry, dental implants, and oral implants), yielded a total of 27 625 hits.The largest proportion of this body of scientific evidence (57.5%) was produced during the last decade.
Of this repository of research data, only 1282 (4.6%) studies are available to users as free full text.This indicates that clinical scientific data are not freely available to the general practitioner, who relies on the internet for online access to research.Researchers or clinicians who wish to access research publications have to subscribe to journals, have access to libraries at academic institutions or purchase articles online from publishing houses, all of which are costly.
The database search yielded a total of 22 091 hits in the clinical research categories and 5396 hits in the animal research categories (Table 1).The studies found describing laboratory or in vitro research are not a true reflection of research in this field because their scope differs significantly from that of clinical and animal research and a different set of keywords would be required to identify adequately representative studies.

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A summary of the types of clinical research conducted during the past 50 years is presented in Table 2. Clinical research is dominated by case reports (19.2%).In comparison, only 4.2% randomised controlled trials (RCTs) and 0.6% systematic reviews were described.The search also yielded a meagre 95 hits for clinical guidelines, consensus reports or position papers, of which only two are available as free full text.

Current trends in implant dentistry research: 2011-2012
A bibliometrical analysis of 12 top-impact subject journals was also performed to establish current trends in implant dentistry research.The selected journals were:     Observational studies are divided into two subgroups: analytical studies, which have comparison groups, and descriptive studies, which do not have comparison groups.

Research category and study type
The core of published clinical research sorted within the latter group (47%).
Not all evidence is judged to be of equal value.The different hierarchies of research design provide information with different strengths and value in the decision-making process. 1,2evels of evidence are graded according to research design.Meta-analysis and systematic reviews represent the highest levels of evidence, whereas case reports are at the bottom of the evidence ladder.The classification of research designs as depicted in Table 3 is generally also considered to be the hierarchy of strength of evidence, with meta-analysis at the top and case reports at the bottom of the evidence ladder. 2 Considering research design as an indicator of the quality of research produced in implant dentistry, the scale is tilted towards lower quality of evidence.Ideally one would like to see a shift away from descriptive studies towards core research, namely analytical and experimental research.Only 10% of studies identified by the database search were RCTs.Quality RCTs, the gold standard in clinical research, is the backbone of systematic reviews and evidence-based dentistry.
The evidence gleaned from animal and laboratory research is generally considered to be lower along the evidence hierarchy than clinical research because it is indirect evidence.However, depending on the type of research question that is addressed, laboratory and animal research may have a great impact on driving clinical interventions.Laboratory and animal research is also the driving force behind new innovations and descriptions of biological processes.

Research topics, interventions and outcomes
Clinical research topics are dominated by surgical interventions (50.5%), followed by prosthetic (18.1%) and bioengineering interventions (16.3%) (Table 4).Studies conducted with a high level of evidence (e.g. an RCT) but which lack rigorous methodology have the potential to generate evidence that is inaccurate or unreliable and could thus introduce significant potential harm to the patient. 4imilarly, systematic reviews based on studies lacking rigorous methodology also carry a risk of producing evidence that is unreliable or of poor quality.
Vere and Joshi conducted a systematic review to assess the quality of RCTs of dental implant surgery and prosthodontics. 5heir review identified important methodological flaws and inappropriate statistical analyses that compromised the quality of RCTs.They concluded that: '[R]andomised controlled trials of treatment interventions of dental implant surgery and prosthodontics published between 2004 and 2008 are poorly reported and, by themselves, provide little unbiased evidence to support the clinical decisions that we make'.
In another study, Pandis and co-workers investigated the quality of research published in six major clinical dental specialty journals. 6They showed that the reporting on the key quality criteria (study type, randomisation, sample calculation, confounding concerns, statistical analysis, effect measurement and confidence intervals) was lacking, which could imply low research validity.
If we want to improve patient care through evidence-based dentistry, researchers will have to make concerted efforts to improve their methodological conduct and quality of research.Explicit guidance in this regard can be obtained from the CONSORT statement guidelines (for clinical trials) and the STROBE statement (for reporting observational studies). 7,8,9,10,11 12om an ethical point of view, authors need to be direct and disclose sufficient, relevant information to permit informed judgement of the internal (accuracy and reliability) and external (relevance in the real-world clinical situation) validity of clinical research.

Graft biomaterials 7
Superstructure or abutment or crown materials 6 Implant material characteristics 1

CAD or CAM guided surgery 6
Instruments or piezo tips or torque drivers or implant drills 5 Prosthetic techniques 9 5.7

Evidence-based dentistry: Bridging the gap between research and real-world dental practice
Together, the electronic database revolution, the significant growth in research and the demand for reliable and accurate information have allowed a paradigm shift towards evidencebased dentistry, aimed at reducing the gap between clinical research and real-world practice.
Evidence-based dentistry involves the integration of three key elements, namely best available research evidence, clinical expertise, and patient values and preferences, into treatment decision-making. 13st available evidence implies using the highest quality evidence that is available.The highest quality evidence is derived from meta-analysis, systematic reviews and RCTs.Systematic reviews, which collect, appraise and combine all relevant clinical evidence, should therefore be used when available rather than an individual study, as observational studies provide less reliable data owing to their research designs being more prone to bias. 2 However, if high-quality studies are not available studies with lower levels of evidence can be considered.
Clinical expertise is the ability of the clinician to use clinical skills and knowledge to identify a patient's unique situation and diagnosis, considering the individual risks and benefits of potential treatments.Patient values are the unique preferences, concerns and expectations that a patient adds to the clinical encounter.
If future clinical decisions in implant dentistry are to be evidence based, it is important that there should be an increase in the quantity as well as the quality of systematic reviews across all research areas in implant dentistry.The best available evidence is obtained through the process of qualitative and quantitative systematic review of published research findings.Researchers and clinicians should expand their ability to perform critical appraisal and synthesis of research and the associated quality before integrating research findings in clinical decision-making.
Reviews should address clinically relevant problems, include focused questions and follow a well-designed protocol to facilitate proper search strategies, quality assessment of primary research, pooling of data and testing of heterogeneity.
Grading of Recommendation Assessment, Development, and Evaluation (GRADE) is a system for rating the quality of evidence in systematic reviews and grading the strength of recommendations in clinical guidelines. 14Research evidence, irrespective of the study design, does not necessarily imply that the quality of the evidence is high.Similarly, although the design of case-control studies is generally considered to yield lower-quality evidence, such studies do not necessarily have to be excluded from the clinical decision-making process.

Development and standardisation of patientcentred core outcome
Numerous problems exist with regard to the current state of outcome measures in implant dentistry research. 15Future research should aim to focus on the identification, definition and quantification of patient-centred core outcomes.A core set of well-defined, validated and feasible outcome measures are recommended to promote improved quality in implant dentistry research.Standardised core outcome measures would permit researchers to combine data from multiple studies for meta-analysis, thus facilitating critical appraisal and development of appropriate clinical guidelines. 15mmon outcomes of interest (end points) measured in clinical implant research include new bone formation, bone regeneration, bone dimensional changes, marginal bone loss, bone healing, and bone-to-implant contact.These are surrogate end points and are of limited relevance to patients. 16ue end points, such as absence of pain, discomfort and complications, improved aesthetic and masticatory function and phonetics, simplicity and ease of maintenance, and implant survival are true, patient-centred end points and provide meaningful information to the clinician.Hujoel puts this in perspective: 'We must remember that research is conducted for the benefit of patients, not the convenience of researchers, and strive to use true end points wherever possible'. 16e Academy of Osseointegration recommends that a core set of outcome variables be gathered in all technology assessment research to combine and compare data from different studies. 15It is agreed that outcome variables should be addressed in the following areas or domains: • proceduralsimplicity of technique, duration and adverse effects • psychologicalpatient satisfaction, aesthetics, treatment preference and quality of life • longevityimplant stability, prostheses stability, survival and/or success, biologic complications, mechanical complications and adverse effects • physiological and functionalspeech, mastication, nutritional needs, motor and sensory function, bone stability and soft tissue stability • economicinitial cost of intervention and that of maintenance.

New frontiers in implant dentistry research
Bioengineering, tissue engineering and nanotechnology are expected to revolutionise implant dentistry in a dramatic way over the next two decades.The primary focus of these emerging research frontiers will be aimed at exploring innovative ways of enhancing bone regeneration and osseointegration, modulation of the host immune response, reducing healing time and preventing peri-implant disease.
Bioengineering is clearly setting the tone in innovative research.The arrival of nanotechnology has opened up new opportunities for the development and manipulation of implant surface topography.Bio mimicking the nanopatterned surface topography of the extracellular matrix components of bone tissue could promote cell attachment, proliferation and differentiation, thereby significantly enhancing new bone formation and attachment to implant surfaces.
Multilayered biodegradable polypeptide nanofilms are currently being developed for surface coatings on implants or as scaffold material. 17Nanofilms or coatings can be loaded and used as carriers of antibiotics or other biologically active therapeutic or modulating molecules such as interleukins, bone morphogenic proteins, growth factors, catabolic enzymes or matrix metallo-proteinases.
Tissue engineering, and in particular mesenchymal stem cell therapy, has the potential to offer enormous opportunities in the areas of alveolar bone and soft tissue regeneration and repair to deliver predictable implant site development and implant therapy to compromised patients. 15In addition, stem cell therapy could reduce donor site morbidity because it would replace autogenous tissue harvesting.
Nanotechnology will have an impact across the entire practice of implant dentistry.new generation of 'bioactive' implants are capable of modulating cellular responses at the molecular level.Beside the advances to implant surface topography itself, nanotechnology offers useful possibilities with regard to diagnostic imaging methodologies, implant site preparation, restoration and aesthetics, wound healing, delivery of modulating therapeutic molecules and drugs, management of peri-implant disease and surgical and restorative techniques.As nanotechnologies mature, they will become more customised, allowing them to be guided towards specific patients, treatment sites or clinical indications. 15e Academy of Osseointegration further cites vertical ridge augmentation and the prevention and treatment of peri-implantitis as the two most challenging issues that should be prioritised as a future research focus in implant dentistry therapy. 15ere should be an increased quest for basic experimental research (i.e.laboratory or bench research, materials research and animal studies) to characterise and develop new materials and fundamental biological principles, and to understand biological mechanisms at cellular and molecular level.These studies should be conducted according to the same rigorous methodologies as applied in controlled experimental clinical research to improve the quality of evidence. 4

Open access to peer-reviewed research articles
It is imperative that the wealth of research information be used and integrated into mainstream clinical practice in a more efficient and accessible manner.Open access to peerreviewed research articles will undoubtedly be the future platform for authors' scholarly reporting and provide access to research for readers. 18The aim of an open-access journal is to provide wider and easier access to readers and a larger audience and impact for authors by removing price barriers such as subscriptions, licensing fees or pay-per-view fees, and permission barriers associated with copyright and licensing restrictions, thus allowing 'free availability and unrestricted use' of peer-reviewed research. 18The only constraint on the reproduction and distribution is that the authors are appropriately acknowledged and cited for their work.
According to Suber: 18 'We have already reached the point at which even affluent research institutions cannot afford access to the full range of research literature.Priced access to journal articles would not scale down with continuing, explosive growth of knowledge even if prices were low today and guaranteed to remain low forever'.
Open access to peer-reviewed articles provides authors with an audience larger than that of any subscriptionbased journal, no matter how prestigious or popular, and undeniably increases the visibility and impact of the work. 18r readers, open access provides barrier-free access to literature needed for research or clinical purposes, without any constraints of access to or budgets of academic libraries.
For those involved in post-graduate clinical education, open access eliminates the need for payment or permissions to reproduce and distribute content to students or participants in clinical training.For academic institutions, open access thus increases visibility of their faculty and research, reduces their expenses with regard to journal subscriptions and, most importantly, advances their mission to share knowledge. 18cording to Suber: 18 'The most important 'royalty-free literature' for open access purposes is the body of peer-reviewed scientific and scholarly research articles and their preprints.Scholars write journal articles because advancing knowledge in their fields advances their careers.They write for impact, not for money.It takes nothing away from a disinterested desire to advance knowledge to note that it is accompanied by a strong self-interest in career-building'.
Open access increases the return on investment in research, making the results of funded research more widely available, retrievable and useful to authors, readers and the public at large.

Conclusion
The ultimate goal of future research initiatives is to produce biomaterials and therapies that will improve current standards of care, customised to patients' preferences and specific needs and improve quality of life.This will require greater integrated and interdisciplinary team work between the fields of bioengineering, tissue engineering, material sciences, biology and clinical sciences.
Research in implant dentistry is not without problems and challenges.Studies in dental implantology are expensive to conduct, difficult to blind, require prolonged follow-up and frequently impossible to undertake owing to ethical constraints.Limited available space in journals also often results in a long publication lag time.Funding for research will increasingly become a major challenge for researchers.
Pooling resources through multicentre trials and collaborative efforts are some of the innovative methods of addressing this challenge.
Research should go the full circle: identification of patientcentred clinical problems, posing focused research questions, proper planning and execution of research, ethical and adequate reporting of findings, synthesising pooled evidence in systematic reviews, and critical appraisal of systematic reviews and evidence-based clinical recommendations, to culminate in the implementation of evidence-based recommendations in practice in an affordable and accessible manner.As members of a profession we have the responsibility to question the value and validity of each of these processes to ensure both that the patient will benefit and that implant dentistry will develop in stature.Research achieves its true value only when quality evidence is available, integrated with clinical expertise and patient preferences to produce clinical guidelines or recommendations that are freely available to clinicians for making clinical decisions about patient care.

TABLE 1 :
Summary of studies identified by database search, organised according to research categories and publication date.

TABLE 2 :
Summary of some types of clinical research study in the field of implant dentistry conducted between 1960 and 2012, as found during a database (Medline) search.

TABLE 3 :
Analysis of studies conducted from January 2011 to January 2012.
n, number of studies; N, Total number of studies.

TABLE 4 :
Clinical research topics and interventions in implant dentistry: January 2011 to January 2012.

TABLE 5 :
Animal research topics and interventions in implant dentistry: January 2011 to January 2012.

Future directions in implant dentistry research Improving the quality of research evidence
Clinicians and researchers need to be more mindful and critical in planning, conducting, reporting and assessing research to ensure that the results are valid, accurate and reliable.To achieve this goal, greater focus needs to be placed on research design and methodology.Understanding what kind of research design is required or has been implemented is a prerequisite to thoughtful planning or critical appraisal of research.Selection of research design depends on the research question the investigator wants to pursue, the clinical setting, the time required to measure an expected outcome, data availability and the availability of resources.One of the fundamental skills required for research and for practising evidence-based dentistry is that of asking well-constructed clinical questions.These should include four critical elements, namely patient or problem (P), intervention or exposure (I), comparator or alternative (C), and outcome or effect (O).3An RCT is the best design to test effectiveness or efficacy of specific interventions or to establish causality.RCTs, when performed properly, are the gold standard for inclusion into systematic review studies and evidence-based dentistry.Properly performed RCTs can minimise bias effectively and eliminate confounding variables, such as age, sex, disease severity, periodontal biotype and bone density, and co-morbidities (smoking, bisphosphanates, diabetes and irradiation), which reduce the validity of the research.

TABLE 6 :
Laboratory research topics and interventions in implant dentistry: January 2011 to January 2012.