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Review Article

Osseointegration and more e A review of literature

S. Nubesh Khana,*, Mythili Ramachandranb, Swaminathan Senthil Kumarc, Viswanathan Krishnanc, Rajasekar Sundaramc

ABSTRACT
Implant placement in bone is presently associated with dened expectations of success based on dened clinical and radiographic endpoints. This successful outcome has been correlated to the histologically represented bone-implant interface and is commonly referred to as "osseointegration". The concept of osseointegration has thus signicantly broadened from its original sense to its denition as a direct structural and functional connection between living alveolar bone and the dental implant as a load-carrier. Today, osseointegration is a term regarded as synonymous with clinical success. To explain the micromechanisms involved in osseointegration, it is necessary to know concepts of biology, physiology, anatomy, surgery and tissue regeneration. Osseointegration is observed in several areas, including not only dental implants, but also maxillofacial implants, replacement of damaged joints and placement of articial limbs. Among the important requirements for osseointegration are the existence of a biocompatible surface, the presence of alveolar bone in the potential recipient sites and no traumatic surgery. According to Brnemark et al, the phenomenon of osseointegration is due to new bone formation in close contact with the implant. To achieve this end, protocols were developed, since several parameters have to be dened, from the choice of the metal to the placement and preservation of the prosthesis. Thus, osseointegration depends on the material used in the implant, the machining conditions, the surface nish, the type of bone that receives the implant, the surgical technique, design of the prosthesis and the patient care. The aim of the present review is to discuss current status of osseointegration in the eld of dental implants. 2012 Indian Journal of Dentistry. All rights reserved. Keywords: Bone, Dental implants, Osseointegration, Stability

INTRODUCTION
Dentists and scientists have for a long time been researching materials and techniques for providing predictable, efcient and effective methods of restoring a depleted dentition. Amongst the most versatile of these are osseointegrated implants.1 It is of great clinical importance, as it would provide early xation with long-term implant stability, and it would minimize the risk of aseptic loosening; a serious complication in reconstructive surgery, thus reducing patient morbidity and health care cost. Dental implant in the past offered limited hope with an inconsistent prognosis. However, as a result of 30 years of biological and technical research and 20 years of clinical research in osseointegration, there is dependable hope. However, because osseointegrated implants make direct contact with
a *

bone, with no intervening connective tissue the traditional concepts of xed and removable dentures may not apply.2 Implant surfaces have been developed in the last decade in a concentrated effort to provide bone in a faster and improved osseointegration process. Several surface modications have been developed and are currently used with the aim of enhancing clinical performance, including turned, blasted, acid-etched, oxidized, plasma-sprayed and hydroxyapatite-coated surfaces, as well as combinations of these procedures. Among the several parameters inuencing the success of the implants, implantebone interface plays an important role in prolonging the longevity and improving the function of the implant-supported prosthesis. There are several modalities to improve implantebone interface to promote faster and more effective osseointegration. Despite impressive gains in long-term predictability with titanium

Post Graduate Student, b Professor & HOD, c Professor, Department Of Periodontia, Annamalai University, Chidambaram, Tamil Nadu, India. Corresponding author. Tel.: 91 9095130825, 91 9995333320, email: drnubesh@gmailcom Received: 27.12.2011; Accepted: 30.3.2012 2012 Indian Journal of Dentistry. All rights reserved.

doi: 10.1016/j.ijd.2012.03.012

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dental implants, achieving immediate xation in soft bone is a continuing challenge to implant dentistry. It is, therefore, important to have an open mind as more is learned about the principles of osseointegration.

OSSEOINTEGRATIONeA REALITY
In 1952, Professor Per-Ingvar Branemark, a Swedish surgeon, while conducting research into the healing patterns of bone tissue, accidentally discovered that when pure titanium comes into direct contact with the living bone tissue, the two literally grow together to form a permanent biological adhesion. He named the phenomenon osseointegration. Originally, osseointegration was dened as direct bone deposition on the implant surfaces, a fact also called funcAlbrektsson et al dened tional ankylosis.3 osseointegration as a phenomenon where intimate contact between bone and biomaterials occurs at the optical microscopy level, enabling surgical implants to replace load bearing organs restoring their form and function. Osseointegration can be compared with direct fracture healing, in which the fragment ends become united by bone, without intermediate brous tissue or brocartilage formation. A fundamental difference, however, exists: osseointegration unites bone not to bone, but to an implant surface: a foreign material. Thus the material plays a decisive role for the achievement of union.3 Since Branemark initial observations, osseointegration has been intensively studied and the research is ongoing. Currently, an implant is considered as osseointegrated when there is no progressive relative movement between the implant and the bone with which it has direct contact. Essentially, the process of osseointegration reects an anchorage mechanism whereby non-vital components can be reliably incorporated into living bone and which persist under all normal conditions of loading.4

analysis by Cochran et al, the maxillary arch success rates for rough-surface implants were observed to be signicantly greater than the success rate in mandible for these implants, which may suggest that difference in success rates due to implant surface characteristics are more likely to be found in lower bone densities.6 Glauser et al in a clinical study compared the implant stabilities of machined and oxidized implants subjected to immediate loading in the posterior maxilla during 6 months by means of Resonance Frequency Analysis.7 The results found surface-modied implants to maintain implant stability during the rst 3 months of healing in contrast to the machined surface implants. Glauser et al reported a failure rate of 17.3% after 1 year and analysis of the losses showed that most failures occurred in the posterior maxilla.8 Rocci et al also reported more failures with machined implants than with oxidized implants when subjected to immediate loading in the posterior mandible.9 It may be that although surface texturing of implants do not directly contribute to initial implant stability, it may reduce the risk of stability loss and consequently facilitating wound healing (secondary osseointegration).10 2) Primary stability and adequate load Primary implant stability is considered to play a fundamental role in successful osseointegration.11 In a review by Sennerby L. et al, primary implant stability has been reported to be inuenced by the bone quality and quantity, the implant geometry, and the site preparation technique.12 Friberg et al reported an implant failure rate of 32% for those implants that showed inadequate initial stability.13 Ivanoff et al in a rabbit study investigated the inuence of primary stability on osseointegration by placing titanium implants so that some were primarily stable, some showed rotational mobility, and some were totally mobile.14 Primary implant stability is now generally accepted as an essential criterion for obtaining osseointegration. By means of Resonance Frequency Analysis, initial implant stability can be quantitatively assessed and followed with time as a function of implants stiffness in bone.

PREREQUISITES FOR OSSEOINTEGRATION

1) Material and surface properties Osseointegration requires a bio-inert or bioactive material and surface congurations that are attractive for bone deposition. Titanium, either commercially pure or in certain alloys, is generally recognized as being bio-inert and used extensively in both dental and orthopedic surgery. A bioactive material is thought to cause a favorable tissue reaction, either by establishing chemical bonds with tissue components (hydroxyapatite) or by promoting cellular activities involved in bone matrix formation. Cooper et al suggested that surface topography may affect the amount of bone formed at the interface.5 In a meta-

STAGES OF OSSEOINTEGRATION
Direct bone healing, as it occurs in defects, primary fracture healing and in osseointegration is activated by any lesion of the pre-existing bone matrix. Once activated, osseointegration follows a common, biologically determined program that is subdivided into 3 stages.3 1) Incorporation by woven bone formation; 2) Adaptation of bone mass to load (lamellar and parallelbered bone deposition);

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3) Adaptation of bone structure to load (bone remodeling). 1) Incorporation by woven bone formation The rst bone tissue formed is woven bone. It is often considered as a primitive type of bone tissue and characterized by a random, felt-like orientation of its collagen brils, numerous, irregularly shaped osteocytes and, at the beginning, a relatively low mineral density. Woven bone is the ideal lling material for open spaces and for the construction of the rst bony bridges between the bony walls and the implant surface. Woven bone usually starts growing from the surrounding bone towards the implant, except in narrow gaps, where it is simultaneously deposited upon the implant surface. Woven bone formation clearly dominates the scene within the rst 4e6 weeks after surgery. 2) Adaptation of bone mass to load (deposition of parallelbered and lamellar bone) Starting in the second month, the microscopic structure of newly formed bone changes, either towards the wellknown lamellar bone or towards an equally important but less known modication called parallel-bered bone. Lamellar bone is certainly the most elaborate type of bone tissue. Packing of the collagen brils into parallel layers with alternating course (comparable to plywood) gives it the highest ultimate strength. Parallel-bered bone is an intermediate between woven and lamellar bone: the collagen brils run parallel to the surface but without a preferential orientation in that plane. As far as the growth pattern is concerned, both parallel-bered and lamellar bone cannot form a scaffold like woven bone, but merely grow by apposition on a preformed solid base. Considering this last condition, three surfaces are qualied as a solid base for deposition of parallel-bered and lamellar bone: woven bone formed in the rst period of osseointegration, pre-existing or pristine bone surface and the implant surface. Woven bone formed in the rst period of osseointegration: Deposition of more mature bone on the initially formed scaffold results in reinforcement and often concentrates on the areas where major forces are transferred from the implant to the surrounding original bone. Pre-existing or pristine bone surface: This becomes obvious in sites where implants are surrounded by cancelous bone. Quite frequently, the trabecule become necrotic due to the temporary interruption of the blood supply at surgery. Reinforcement by a coating with new, viable bone compensates for the loss in bone quality (fatigue), and again may reect the preferential strain pattern resulting from functional load. The implant surface: Bone deposition in this site increases the bone-implant interface and thus enlarges the

load-transmitting surface. Extension of the bone-implant interface and reinforcement of pre-existing and initially formed bone compartments are considered to represent an adaptation of the bone mass to load. 3) Adaptation of bone structure to load (bone remodeling and modeling) Bone remodeling characterizes the last stage of osseointegration. It starts around the third month and, after several weeks of increasingly high activity, slows down again, but continues for the rest of life. In cortical, as well as in cancelous bone, remodeling occurs in discrete units, often called a bone multicellular unit, as proposed by Frost. Remodeling starts with osteoclastic resorption, followed by lamellar bone deposition. Resorption and formation are coupled in space and time. Remodeling in the third stage of osseointegration contributes; to an adaptation of bone structure to load in two ways: a) It improves bone quality by replacing pre-existing, necrotic bone and/or initially formed more primitive woven bone with mature, viable lamellar bone. b) It leads to a functional adaptation of the bone structure to load by changing the dimension and orientation of the supporting elements.

FACTORS WHICH DETERMINE THE SUCCESS OF OSSEOINTEGRATION

Albrektsson et al rst referred to the six important factors which determine the success of osseointegration. These are: implant biocompatibility, design characteristics, implant surface characteristics, state of the host bed, surgical technique, and implant loading conditions. LeGeros and Craig categorized these factors into biomaterial, biomechanical and biologic determinants.1 1) Biomaterial factors The biocompatibility of the material is of great importance and a predictor of osseointegration, as it is essential to establish stable xation with direct bone-implant contact and no brous tissue at the interface. Pure Titanium (Ti) is widely used as an implant material as it is highly biocompatible, it has good resistance to corrosion, and no toxicity on macrophages or broblasts, lack of inammatory response in peri-implant tissues and its surface is composed of an oxide layer and has the ability to repair itself by reoxidation when damaged. Other materials have also been proposed either as alternative to Ti or as alloy systems, including tantalum, aluminum, nionium, nickel, zirconium, and hafnium.1 Two forms of titanium (Ti) are principally used

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for endosseous dental implants. They are commercially pure titanium (cpTi, at least 99.5% pure Ti) and a titanium alloy, titanium-aluminum-vanadium (Ti-6AI-4V). CpTi is available in four grades which vary in their oxygen content. Grade I cpTi is the purest and therefore the softest. Grade 4 cpTi has the most oxygen at 0.4% by weight, and is the material used for dental implants. Ti is the material of choice in implant dentistry. Its excellent corrosion resistance is due to the surface which oxidizes spontaneously upon contact with air or tissue uids. This layer, normally approximately 2e5 nm thick is primarily TiO2. Williams described a biocompatible material as one which possesses the ability to perform an appropriate host response in a specic application, and consequently, Stanford and Keller proposed that the term osseointegration reects the results of a lack of a negative tissue response to Ti, rather than the presence of an advantageous one.1 Rahal et al showed that Ti does not have the ability to induce osteogenesis from potential osteogenic precursor cells in mice marrow.15 Larsson et al showed that bone healing around machined Ti implants takes place by a gradual mineralization process directed towards, but does not start, at the implant surface.16 Ti is a reactive material, and Hanawa found that it naturally forms calcium phosphate on its oxide layer in a neutral electrolyte solution simulating body uids.1 2) Biomechanical factors There are numerous designs of implant systems currently available. However, the original Branemark implant system is the best documented and researched implant system in current use. The Branemark implant system was based on a two stage surgical procedure followed by the construction of either a xed or removable precision attached prosthesis. It is assumed that when an implant is osseointegrated, the titanium implant and bone may be regarded as having a perfect t, similar to the ankylosis of teeth in bone, with no stress in either material prior to loading.1 3) Biologic factors Esposito et al (1999) dened biological failures related to biological process, and mechanical failures related to fractures of components and prostheses.17 Patient factors are important determinants of implant failure. Ekfeldt et al (2001) identied the patient risk factors leading to multiple implant failures and concluded that a combination of several medical situations could provide a contraindication to implant treatment.17 Diabetic patients experience delayed wound healing, which logically affects the osseointegration process. Fiorellini et al (2001)18 demonstrated a lower success rate of only

85% in diabetic patients, while Olson et al (2000)19 found that the duration of the diabetes had an effect on implant success: more failures occurred in patients who had diabetes for longer periods. Fiorellini et al (2001)18 also observed that most failures in diabetic patients occurred in the rst year after implant loading. The adverse effects of cigarette smoking on implant treatment are well documented. A longitudinal study by Lambert et al (2000) found more failures in patients who smoked, Bain and Moy and Lindquist et al showed that smoking may be directly related to the soft tissue changes and marginal bone loss around dental implants.1 Theoretically, patients with increased age will have more systemic health problems, but there is no scientic evidence correlating old age with implant failure. Although Salonen et al (1993) stated that advanced age was a possible contributing factor to implant failure; other reports have showed no relationship between old age and implant failure.4

THE FUTURE
The search for improved osseointegration in soft bone has helped propel more than 20 years of post-Branemark research in implant design, materials and surfaces. The future now seems to be looking to nanotechnology, like the recent introduction of a chemically-modied implant surface, or biotech concepts such as the possible incorporation of bone morphogenetic proteins onto the implant surface to enhance osseointegration. Certainly it seems there is more development and evolution to come, which will ultimately add to the history of these small metal devices, but only until such time as the very notion of screwing metal into bone becomes historical itself, which it surely will as genetic engineering gathers pace.

REFERENCES
1. Isa ZM, Hobkirk IA. Dental implants: biomaterial, biomechanical and biological considerations. Annal Dent Univ Malaya. 2000;7:27e35. 2. Strnad J, Strnad Z, Sestak J. J Therm Anal Calorim. 2007;88:3. 3. Schenk Robert K, Bluser Daniel. Osseointegration: a reality. Periodontol 2000. 1998;17:22e35. 4. Dimitriou R, Babis GC. Biomaterial osseointegration enhancement with biophysical stimulation. J Musculoskelet Neuronal Interact. 2007;7(3):253e265. 5. Cooper LF. A role of surface topography in creating and maintaining bone at titanium endosseous implants. J Prosthet Dent. 2000;84:522e534. 6. Cochran DL. A comparison of endosseous dental implant surfaces. J Periodontol. 1999;70(12):1523e1539.

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7. Glauser R, Portmann M, Ruhstaller P, Lundgren AK, Hammerle CHF, Gotlow J. Stability measurements of immediately loaded machined and oxidized implants in the posterior maxilla. Appl Osseointegr Res. 2001;2(1):27e29. 8. Glauser R, Ree A, Lundgren A, Gottlow J, Hammerle CH, Scharer P. Immediate occlusal loading of Branemark implants applied in various jawbone regions: a prospective, 1-year clinical study. Clin Implant Dent Relat Res. 2001;3(4): 204e213. 9. Rocci A, Martignoni M, Gottlow J. Immediate loading of Banemark system TiUnite and machined surface implants in the posterior mandible. A randomized open-ended clinical trial. Clin Implant Dent Relat Res; 2003. 10. Vidyasagar Linish, Apse Peteris. Dental implant design and biological effects on bone-implant interface. Stomatologija, Baltic Dental Maxillofac J. 2004;6:51e54. 11. Vidyasagar Linish, Salms Girts. Investigation of initial implant stability with different dental implant designs. A pilot study in pig ribs using resonance frequency analysis. Stomatologija, Baltic Dental Maxillofac J. 2004;6:35e39. 12. Sennerby L, Roos J. Surgical determinants of clinical success of osseointegrated oral implants: a review of the literature. Int J Prosthodont. 1998;11(5):408e420. 13. Friberg B, Jemt T, Lekholm U. Early failures in 4,641 consecutively placed Branemark dental implants: a study from stage

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1 surgery to the connection of completed prostheses. Int J Oral Maxillofac Implants. 1991;6(2):142e146. Ivanoff CJ, Sennerby L, Lekholm U. Inuence of initial implant mobility on the integration of titanium implants. An experimental study in rabbits. Clin Oral Implants Res. 1996;7(2):120e127. Rahal MD, Branemark PI, Osmond DG. Response of bone marrow to titanium implants: osseo integration and the establishment of a bone marrow-titanium interface in mice. Int J Oral Maxillofac Implants. 1993;8:573e579. Larsson C, Thomsen P, Aronsson BO, Rodahl M. Bone response to surface-modied titanium implants: studies on the early tissue response to machined and electropolished implants with different oxide thicknesses. Biomaterials. 1996;17:605e616. Hadi SA, Ashfaq N. Biological factors responsible for failure of osseointegration in oral implants. Biol Med. 2011;3(2): 164e170 [Special issue]. Fiorellini JP, Chen PK, Nevins M, Nevins ML. A retrospective study of dental implants in diabetic patients. Int J Periodontics Restorative Dent. 2000;20:366e373. Olson JW, Shernoff AF, Tarlow JL, Colwell JA, Scheetz JP, Bingham SF. Dental endosseous implant assessments in a type 2 diabetic population: a prospective study. Int J Oral Maxillofac Implants. 2000;15:811e818.