Biologic Principles. Osseointegration. Theodoros Katsaros LSU Periodontics 2/25/2014

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1 Biologic Principles Osseointegration Theodoros Katsaros LSU Periodontics 2/25/2014

2 An implant object never becomes incorporated into bone, Collins 1954 When any metallic object is implanted in bone a layer of fibrous tissue will always develop, Soutam & Selwyn 1970

3 Osseointegration Observed initially by Branemark in 1969 and proposed as term in 1977.

4 Definition Direct functional and structural connection between living bone and the surface of a load carrying implant. First definition by Albrektsson et al. 1981

5 Definition Schroeder described the rigid fixation of the implant to the jaw bone using the term functional ankylosis.

6 Definition The solid incorporation observed radiologically presents itself, light microscopically (up to x10 3 ), as an immediate growing in of the bone into the rough implant surface. There is no evidence of the formation of a soft tissue bed. Electron microscope (up to x10 6 ) pictures reveal that the bone closely anchored to the titan plasma surface. Schroeder et al. 1976

7 Definition A process in which clinically asympotomatic rigid fixation of alloplastic materials is achieved and maintained in bone during functional loading. Zarb and Albrektsson, 1991

Bone to implant interface In osseointegrated areas two layers can be observed with the transmission electron microscopy (TEM): 1.

8 Bone to implant interface In osseointegrated areas two layers can be observed with the transmission electron microscopy (TEM): nm bonding zone, partially calcified amorphous substance containing proteoglycans and glycosaminoglycans nm thick layer with randomly distributed Type I collagen fibrils. (Possible role in osseointegration)

9 Albrektsson et al. 1991

10 Albrektsson et al. 1991

11 Bone classification In macroscopic level it is classified in Cortical: more mineralized, lower turnover rate (3-7.7%/year), max vascular penetration rate 0.05mm/day Cancellous: less mineralized, higher turnover rate ( %/year), more vascular, contains bone marrow, max vascular penetration rate 0.5mm/day

12 Lekholm & Zarb 1985

13 Bone Classification In the microscopic level bone is classified in: Woven bone is present in the adults in bone healing, grows faster up to 100μm/day, random orientation of its collagen fibrils, poor biomechanical capacity Lamellar bone, is created by woven bone is organized in parallel layers of collagen fibrils, with dense mineralization.

14 Bone Classification Woven bone offers stable scaffold, solid surface, source of osteoprogenitor cells, ample blood supply for cell function and matrix mineralization. Takes months all woven bone to be replaced

15 Carranza s Clinical Periodontology; Newman, Takei et al., 2012, 11 th edition, Elsevier Woven Bone Lamellar Bone

16 Bone healing Bone can heal through Repair, which leads to formation of a fibrous tissue that differs in morphology or function from the original tissue Regeneration that leads to complete restoration of morphology and function.

17 Bone healing Bone healing is regulated by growth factors (GFs) and other cytokines. Bone morphogenetic proteins (BMPs) are a group of at least 20 polypeptides (GFs) that induce bone formation by stimulating the cellular events of mesenchymal progenitor cells

18 Bone healing Mainly BMP -2, -4, -6, -7 and -9 have osteoinductive activity and induce de novo bone formation by themselves. Other GFs related are IGF-I and II, TGFβ-1, PDGF and FGF-2.

19 Bone healing Bone matrix serves as reservoir for these GFs and BMPs, and are activated during matrix resorption by MMPs, while the acidic environment during inflammatory process also leads to activation of GFs. This leads to chemoattraction, migration, proliferation and differentiation of mesenchymal cells in osteoblasts.

20 Bone healing 1. Blood clotting 2. Wound cleansing 3. Tissue formation 4. Tissue modeling and remodeling

21 Modeling and remodeling Processes of bone resorption and apposition that occur throughout life and allow the bone to adapt to external and internal demands Modeling: allows change in initial bone architecture (extraction sockets). It is suggested it can be initiated by external loads too. Remodeling: represents a change that occurs within the mineralized bone without alteration of tissue architecture (during bone formation, when old bone is replaced by new bone).

22 Remodeling is 9x faster per year within 1mm of the implant surface, than was the the rate in areas further from the implant. Garetto et al 1995 This high turnover rate around implants, maintains tissue and inhibits microdamage, and may be responsible for high success rates. Huja et al 1999 Mangano et al 2013

23 BMU: Bone Multicellular Unit, contains osteoclasts, vascular structures and osteoblasts.

24 Factors that may interfere with bone healing 1. Failure of vessels to proliferate into the wound 2. Improper stabilization of the coagulum and granulation tissue in the defect 3. Ingrowth of non-osseous or fibrous tissues with a high proliferative activity 4. Bacterial contamination

25 Implant surface ØWithin ns titanium oxide TiO 2 is formed on implant surface after contact with atmosphere Ø A ØProtects implant surface from corrosion ØInteracts with biological elements (attracts Ca +, fibronectin bind to it) is and is thought to play key role in osseointegration

26 Implant surface Ions because of ionic leakage from metal surfaces can bind to proteins and create allergens. Although potentially significant for other metals (e.g. aluminum) this leakage is less than 100ppm for titanium and no specific side effects have been reported in the literature. In vitro studies showed that 0.08μg titanium ions can be released, times less than our body s daily absorption from other sources Lautenschlager & Monaghan 1993

27 Healing after implant placement follows the stages of bone healing

of mesenchymal cells and macrophages from the

28 Healing after implant placement Healing process starts with blood clot formation and migration of mesenchymal cells and macrophages from the bone marrow within 3 days. 0.66mm à Primary stability

29 Primary Stability At the time of placement and is related to the surface of implant - primary bone contact

30 1 st week: Osteoclasts first seen at Day 4 Bone formation first time observed at Day 7, starting from the original cortex (Distant osteogenesis) Formation of capillaries which take part with the fibroblasts in granulation tissue formation. BMPs and other GFs already have a role in bone healing.

31 2 nd week Bone in direct contact with the implant because of initial contact due to insertion. Active osteoclastic resorption of old bone. 25% of bone surface covered with osteoclasts

32 3 rd week (Peak of resorption) Immature bone continues to form Most of the old bone close to the interface undergoes resorption During this phase only a small amount of newly formed bone (woven bone, weak) is in contact with the implant surface Therefore mechanical strength of the implant bone complex is poor. Lowest stability measurements for all bone types (Barewall et al, 2003)

33 4 th week Bone resorption decreases and bone formation increases. New bone trabeculae, still fine and fragile First osteon formation b/w implant threads Important phase (weeks 2-4) for immediate loaded implants

34 6 th week Still active bone formation, spongy bone increases in thickness and becomes more compact ( peri implant corticalization ) New osteons form b/w implant threads

35 2 nd Month Most of the old peri-implant bone tissue is removed 15-20% of new bone formation 40% covered with osteoid Ongoing bone remodeling Majority of immediate loaded implant failures occur at this time. à Secondary stability

36 Secondary Stability The result of the formation of secondary bone contact of woven and then lamellar bone

37 Raghavendra et al. 2005

38 3 rd Month High rate of bone formation activity, more than 50% of the bone coated with band of osteoid. Continuous bone layer covers the biggest part of implant surface. Till now bone formation and resorption do not proceed at the same rate as it occurs in normal bone remodeling

39 4-8 Months Most of the peri-implant bone has become dense. At 8 months remodeling is reduced

40 Degree of direct bone to implant contact is between 60-99%, with no tendency to increase with a longer time of insertion. Albrektsson et al 1993 Bone to implant contact (BIC) ranges 37-76%, in implants retrieved after at least 20 years of function. Mangano et al 2013

41 Many remodeling areas and cement lines (line visible in microscopic examination) dividing bone in different maturation stages, primary and secondary osteons present and no osteolytic lesions. Bone immediately adjacent to implants maintained structure and biomechanical properties after 20 years in vivo. Mangano et al 2013

42 Cortical bone presented an increase in elastic modulus and hardness during the first 5 years after implant placement, and presented stable biomechanical properties thereafter. Indication that bone remodeling has achieved full maturity after this period. Baldassari et al 2012

43 How can we assess implant osseointegration?

44 The gold standard is given by histologic measurements that allow the measuring of the bone to implant contact fraction.

45 Ø Small angle X-ray scattering (SXAS): give information about bone mineralization but no information about mechanical properties ØNanoidentation: investigates biomechanical properties in the microscopic scale ØScanning acoustic microscopy (SAM): qualitative assessment of the biomechanical microstructural properties of bone-implant interface ØMicro Brillouin scattering: uses the photo acoustic interaction between a laser beam and a sample to measure bone speed of sound

46 Implant Stability Assessment ØX-ray and MRI based techniques ØInvasive biomechanical methods ØNon invasive biomechanical methods

47 Implant Stability Assessment X-ray and MRI based techniques Limited resolution of clinical X-ray based techinques due to metal artifacts related to the presence of the implant metallic components Shalabi et al MRI has also been proposed but is also of limited interest due to magnetic fields disturbance Gill & Shellock, 2012 Hecht et al Knothe Tate et al. 2008

tissue cell X-ray or MRI based techniques are

48 Implant Stability Assessment X-ray and MRI based techniques Maximum resolution level of radiography is 0.1mm which is ten times the size of a soft tissue cell X-ray or MRI based techniques are not commonly used in order to assess the biomechanical properties of bone to implant interface

49 Implant Stability Assessment Invasive biomechanical methods Ø Tensional test Ø Push out/pull out test ØRemoval torque analysis Park, J-W Lee, Kim, J-H Lee, 2011

50 Implant Stability Assessment Non invasive biomechanical methods ØEmpirical approaches ØImpact based approaches Ø Resonance frequency analysis Ø Quantitative ultrasounds methods

51 Implant Stability Assessment ØEmpirical approaches: Hitting the implant with an instrument and listen to the noise made by the system Insertion torque during the surgical procedure

52 Implant Stability Assessment ØImpact based approaches PerioTest device (Schulte et al. 1980) was originally used for evaluation of tooth mobility.

53 Implant Stability Assessment Ø Impact based approaches Measurement leads to PerioTest value (PTV), -8 to 50 PTV correlates to mobility and level of marginal bone

Implant Stability Assessment Ø Impact based approaches No correlation was found between PTV and BIC Different criteria to assess implant and teeth mobility Limited range of measurements applies to

54 Implant Stability Assessment Ø Impact based approaches No correlation was found between PTV and BIC Different criteria to assess implant and teeth mobility Limited range of measurements applies to implants (àlow sensitivity) PTV strongly influenced by the position of impact location and by the angle of the device relatively to the implant axis à Difficult to use PerioTest for monitoring purposes due to reproducibility and precision error related issues.

Uses an L-shaped transducer or a Smartpeg, which is a piece screwed in the implant

55 Implant Stability Assessment Ø Resonance frequency analysis Measurement of the first resonance frequency of the bone implant system. Uses an L-shaped transducer or a Smartpeg, which is a piece screwed in the implant abutment Measurement gives an index called Implant Stability Quotient (ISQ 0-100), system is commercialized under the name Osstell

bone measurements assessed empirically by the

56 Implant Stability Assessment Ø Resonance frequency analysis A correlation was shown between initial ISQ value and 1. cutting torque 2. bone measurements assessed empirically by the surgeon during implant placement 3. Cortical bone thickness 4. Anatomical region of implantation

57 Implant Stability Assessment Ø Resonance frequency analysis Limitations: 1. Only captures the first resonance frequency, which is of limited value from a structural mechanics point of view ( oversimplification ) 2. Sensitivity of ISQ value to the implant stability depends on the implant type 3. Relationship between ISQ values and BIC remains unclear 4. Fixation and orientation of the transducer (or smartpeg) influence significantly the ISQ values 5. ISQ values are related to the bone properties at the scale of the organ, but properties at the scale of μm are critical for osseointegration 6. No criteria for implant failure

58 Implant Stability Assessment ØQuantitative Ultrasound (QUS) Methods Used to assess bone mineral status, enamel thickness Several studies show the potentiality of QUS to investigate bone quality around implants, further work is necessary

59 Factors for reliable osseointegration 1. Implant biocombatibility 2. Implant design 3. Implant surface 4. State of host bed 5. Surgical technique 6. Loading conditions Albrektsson et al. 1981

60 Several implant designs and implant surfacesà Same biologic sequence in different time intervals and different outcomes Osteoconductive implant surface à Contact osteogenesis Davies, 2003

61 Engelke et al, 2004 State of Host Bed 100μm 150 μm 250μm Lateral force of 30 N

62 There is significant relationship between Lekholm & Zarb index placement torque, ISQ and PTV values Quirynen et al, 2006 Oh and Kim, 2012

63 Mandibular Implants are generally placed in better quality bone Several studies indicate that although initial implant stability is lower in poor quality bone, this difference decreases during osseointegration period. No significant increase in stability for Type I bone in the first 10 weeks, while type IV increases 27% between 3-10 weeks (Barewall et al, 2003, Davies, 2003)

64 Surgical Technique Avoid overheating of bone (more than 44 o C) ØAdequate irrigation ØSharp drills ØAvoid multiple drillings with the same drill ØSlow speed

65 Placement method (one- or two-stage) does not seem to affect osseointegration. The differences that may observed may be attributed to implant design characteristics. Boioli et al 2001

66 Compression necrosis: Theory that increased torque can impede blood circulation and lead to bone necrosis. Both animal and human studies have failed to confirm this theory. It could only be confirmed in osteotome site preparation.

67 Insertion torque of 32 Ncm improves implant prognosis Ottoni et al, 2005 Favorable clinical results can be achieved with a 25 Ncm insertion torque Norton, 2011

68 Loading conditions Immediate loaded implants should not be subjected to restorative procedures (torque- un torque abutments) during the first 2-3 months Too large micromovements (more than 150μm) during healing period can disrupt osseointegration process and lead to fibrous tissue formation Stress/strain stimulates the bone to model/remodel as long as its level does not exceed a threshold that causes bone destruction Greenstein et al, 2013 Trisi et al, 2002

69 For experienced surgeons there is data from several Oral Implant Systems with good results with direct or rapid loading, however the more rapid the loading, the greater the biologic challenge Dr T. Albrektsson

70 References Giannobile, et al. Bone as a Tissue (CH 4). Clinical Periodontology and Implant Dentistry, Lindhe, J.; Lang, K. 5th Edition, 2008, Blackwell Munksgaard (Volume 1). Lindhe, Berglundh, Lang. Osseointegration (CH 5). Clinical Periodontology and Implant Dentistry, Lindhe, J.; Lang, K. 5th Edition, 2008, Blackwell Munksgaard (Volume 1). Boioli L et al: A meta-analytic, quatitative assessment of osseointegration establishment and evolotuin of submerged and non-submerged endosseous titanium oral implants. Clin Oral Implants Res. 12: , 2001 Albrektsson T et al: The long term efficacy of currently used dental implants: A review and proposed criteria of success. Int J Oral Max Implants 1:11-26, 1986 Albrektsson, T et al: Biological aspects of implant dentistry: Osseointegration. Periodontology :58-73, 1994 Trisi, P., Rebaudi A: Progressive bone adaptaion of titanium implants during and after orthodontic load in humans. Int J Periodontics Restorative Dent Feb; 22(1):31-43 Abrahamsson I, Berglundh, T, et al. Early bone formation adjacent to rough and turned endosseous implant surfaces. An experimental study in the dog Clinical Oral Implants Research, 15 (2004), pp

71 References Berglundh T, Abrahamsson I, et al. Bone healing at implants with a fluoridemodified surface: an experimental study in dogs. Clinical Oral Implants Research, 18 (2007), pp Mathieu V, Vayron R, et al. Biomechanical determinants of the stability of dental implants: Influence of the bone-implant interface properties. J Biomech Jan 3;47(1):3-13. doi: /j.jbiomech Epub 2013 Oct 10. Greenstein G, Cavallaro J, Tarnow D. Assessing bone's adaptive capacity around dental implants: a literature review. J Am Dent Assoc Apr;144(4): Mangano C, Piattelli A, et al. Evaluation of peri-implant bone response in implants retrieved for fracture after more than 20 years of loading. A case series. J Oral Implantol Aug 21. [Epub ahead of print] Barewal R et al: Resonance Frequence Measurment on Implant Stability in Vivo on Implants with a Sandblasted and Acid Etched Surface. Int J Oral Maxillofac Implants 2003; 18: Jong-Chul Park, Jung-Woo Lee, Soung-Min Kim and Jong-Ho Lee (2011). Implant Stability - Measuring Devices and Randomized Clinical Trial for ISQ Value Change Pattern Measured from Two Different Directions by Magnetic RFA, Implant Dentistry - A Rapidly Evolving Practice, Prof. Ilser Turkyilmaz (Ed.), ISBN: , InTech, Available from: practice/implant-stability-measuring-devices-andrandomized-clinical-trial-for-isq-value-change-pattern-measu

72 References Alsaadi, G et al: A Biomechanical assessment of the relation between the oral implant stability at insertion and subjective bone quality assessment. J Clin Periodontol 2007; 34: Raghavendra S, Wood M, Taylor T Early wound healing around endosseous implants: A review of the Literature. Int J Oral Maxillofac Implants 2005;20: Carranza s Clinical Periodontology; Newman, Takei et al., 2012, 11 th edition, Elsevier Oh J, Kim S, Clinical study of the relationship between implant stability measurements using Periotest and Osstell mentor and bone quality assessment. Oral Surg Oral Med Oral Pathol Oral Radiol Mar;113(3):e35-40 Lautenschlager EP, Monaghan P. Titanium and titanium alloys as dental materials. Int Dent J Jun;43(3): Immediate Loading: A New Era in Oral Implantology Testori, Tiziano; Galli, Fabio; Del Fabbro. 2010, Quintessence Publishing

73 Thank you

Pressure Necrosis And Osseointegration: An Editorial White Paper*

Pressure Necrosis And Osseointegration: An Editorial White Paper* Alan Meltzer, DMD, MScD; Harold Baumgarten, DMD; Tiziano Testori, MD, DDS; Paolo Trisi, DDS, PhD Published by Pressure Necrosis And Osseointegration: