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Histological comparison between implants retrieved from patients with and without osteoporosis
Int. J. Oral Maxillofac. Surg. 2008; 37: 321–327 doi:10.1016/j.ijom.2007.11.019, available online at http://www.sciencedirect.com
Leading Clinical Paper Dental Implants
Histological comparison between implants retrieved from patients with and without osteoporosis
J. A. Shibli1, K. C. D. S. Aguiar1, L. Melo1, S. d’Avila1, E. G. Zeno´bio2, M. Faveri1, G. Iezzi3, A. Piattelli3 1 Department of Periodontology, Dental Research Division, Guarulhos University, Guarulhos, Sa˜o Paulo, Brazil; 2Department of Periodontology, Dental Research Division, Pontific Catholic University of Minas Gerais, Brazil; 3Department of Oral Medicine and Pathology, Dental School, University of Chieti, Chieti, Italy
J. A. Shibli, K. C. D. S. Aguiar, L. Melo, S. d’Avila, E. G. Zeno´bio, M. Faveri, G. Iezzi, A. Piattelli: Histological comparison between implants retrieved from patients with and without osteoporosis. Int. J. Oral Maxillofac. Surg. 2008; 37: 321–327. # 2007 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved. Abstract. The aim of this restrospective histologic study was to evaluate the bone-toimplant contact of loaded implants retrieved from patients with and without osteoporosis. The evaluated material consisted of 22 threaded, cylindrical, loaded dental implants retrieved from 21 patients: 7 from 7 women with postmenopausal osteoporosis (osteoporosis group) and the remaining 15 from 14 patients without history of osteoporosis or other metabolic diseases (control group). Histologic analysis revealed bone tissue in the threads of the retrieved implants, with variations in the percentage of bone-to-implant contact for the implants retrieved from both groups. The pristine bone was mostly mature bone and/or lamellar and compact, and numerous osteocytes were observed in the lacunae, although areas of woven bone could be distinguished. In some specimens, there were areas of newly formed bone exhibiting different degrees of maturation and remodeling. The mean bone-toimplant contact was 46.00 11.46% and 47.84 14.03% for the osteoporosis group and control group, respectively. The results of this histomorphometric study suggest that osteoporosis may not be a contra-indication for implant placement, at least after osseointegration has been established.
The successful outcome of dental implantation is influenced by a number of confounding factors such as the boneremodeling response, implant design and topography, clinical protocols, and the patient’s level of physical activity6,19. Bone quality is another important factor, with a higher failure rate having been 0901-5027/040321 + 07 $30.00/0
observed in implants placed at type IV bone12,14,23. Osteoporosis is a disease that influences the quality of bone tissue such that it may become susceptible to fracture. Although this disease may have an influence on periodontal attachment loss15, there are no clinical studies that present a clear
Keywords: dental implants; osteoporosis; human histology; retrieved implants; osseointegration. Accepted for publication 23 November 2007 Available online 11 February 2008
association between implant failure and osteoporosis1,24. Earlier animal studies have described the deleterious effect of osteoporosis on the osseointegration process7,8,22 mainly with regard to trabecular bone volume. It has been demonstrated that resorption and remodeling of the alveolar bone, not only
# 2007 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
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after extraction of the tooth but also after dental implant placement, are accelerated following experimental ovariectomy8,20. Concern over dental implants being contraindicated in patients with osteoporosis is based on the assumption that this metabolic disease affects the jaws in the same way as it affects other parts of the skeleton, such as the lumbar spine, femur, neck and forearm15,25. The mechanism by which osteoporosis acts on peri-implant bone is based on the decrease in both cancellous bone volume and bone-toimplant contact, consequently reducing the bone tissue available to support dental implants22. Osteoporosis is thought to be a result of an altered bone-remodeling process, i.e. bone-tissue formation decreases while resorptive capacity remains constant16. Osteoporosis may represent a contraindication or risk factor for osseointegration, but this is still controversial1,2,5,13,24. The objective of this retrospective histologic study was to evaluate bone-toimplant contact in loaded implants retrieved from patients with and without osteoporosis. Materials and Methods
Over a time period of 4 years (March 2003–March 2007), a total of 22 threaded, cylindrical dental implants of different brands were retrieved for different reasons: infection, inflammation and bone loss, mechanical failures of implant components (fracture of implant neck and fracture of abutment screw), and iatrogenic reasons, i.e. paresthesia or hyperesthesia of lower lip. (Fig. 1) The patients were referred for prosthetic treatment and/or maintenance care. After diagnosis of failure of the implant restoration and/or extensive bone loss (>75% of the length of the implant), these failed implants were scheduled for removal. All the retrieved implants were considered ‘‘problematic’’ according to the local Institutional Review Board (IRB). Implants were not removed if bone loss was <75% of the length, they were working as ‘‘sleeping’’ implants, or informed consent from the patient to remove the implant was not obtained. The ‘‘non-problematic’’ implants were treated according to their prognosis: peri-implantitis or kept in the jaws without occlusal function (submerged). Dental implants with clinical mobility and/or loss of osseointegration were excluded from this study. Lack of osseointegration was recorded as the slightest mobility tested by rotating and moving every dental implant back and
Fig. 1. A) Radiographic view of fractured implant abutment screw (arrow) in anterior maxilla in patient with osteoporosis. The other implant presented no osseointegration (*) and was not included in the study. B) Clinical view of the implant (!).
forward. This study was reviewed by the local IRB. The study met requirements for exemption from IRB review, which included obtaining informed consent from the patients. Of the 22 implants retrieved from 21 patients (mean age 61.19 7.65 years) included in this study, 7 implants were obtained from 7 women with postmenopausal osteoporosis determined by DPXIQ AP in the lumbar spine and femoral neck. The diagnosis of osteoporosis was established for these patients, based on criteria used by the World Health Organization: T-score <2.5 SD. According to their files, all the patients claimed that the dental implants were placed at the same time as, or after, osteoporosis was diagnosed by bone densitometry. After their diagnosis of osteoporosis, the patients (according to anamnesis) received a diet and some medications with calcium, but glucocorticosteroids or other immunosuppressive drugs were not used. Only one patient received treatment with estrogen. The remaining 15 dental implants were obtained from 14 patients without bone
densitometry, clinical history of osteoporosis or other metabolic diseases that could affect osseointegration healing. Histological Processing and Evaluation
The implants were removed using an internal 4.25-mm-wide trephine, and together with surrounding bone tissues were immediately stored in 10% buffered formalin and processed to obtain thin ground sections with the Precise 1 Automated System (Assing, Rome, Italy). The specimens were dehydrated in an ascending series of alcohol rinses and embedded in a glycol methacrylate resin (Technovit1 7200 VLC, Kulzer, Wehrheim, Germany). After polymerization, the specimens were sectioned longitudinally along the major axis of the implant with a high-precision diamond disk at about 150 mm and ground down to about 30 mm. Two slides were obtained for each implant. The slides were stained with basic fuchsin and toluidine blue. Histomorphometry of bone-to-implant contact
Osseointegration in osteoporosis subjects
323
Table 1. Patients with osteoporosis: retrieved implant data Implant length Time in Loading Implant Age diameter time situ surface (years)/ (mm) Patient Gender topography (months) (months) 61/f 66/f 76/f 59/f 63/f 61/f 62/f
1 2 3* 4 5 6 7 *
Machined Machined Machined Machined SAS Machined Machined
66 59 55 69 48 76 55
60 52 50 63 43 70 48
10 4.0 10 3.75 13 3.75 10 4.0 11 4.0 10 3.75 10 3.50
Implant position
Indications of implant
Bone-to% Length implant of remaining contact (%mean SD) osseointegration
Mandible Mandible Maxilla Maxilla Mandible Mandible Mandible
Single tooth Full denture FDP FDP Full denture FDP Full denture
51.25 3.16 50.08 2.01 27.89 2.22 37.95 1.25 52.43 1.91 62.51 1.96 39.89 0.65
100 85 24 75 19 100 15
Claimed reason for removal Mechanical Mechanical Bone Loss Mechanical Bone Loss Mechanical Bone Loss
Therapy with estrogen; f: female; SAS: sandblasted acid-etched surface; FPD: fixed partial denture.
percentage was performed using a light microscope (Laborlux S1, Leitz, Wetzlar, Germany) connected to a high-resolution video camera (3CCD1, JVC KY-F55B, Milan, Italy), and interfaced to a monitor and personal computer (Intel Pentium III 1200 MMX). This optical system was associated with a digitizing pad (Matrix Vision GmbH, Milan, Italy) and a histometry software package with image-capturing capabilities (Image-Pro Plus1 4.5, Media Cybernetics Inc., Immagini & Computer Snc, Milan, Italy). The measurements14,23 of bone-to-implant contact were performed at a magnification of about x160. Mean and standard deviation of the histometric variable values were calculated for both slides of each implant and then for each group.
showed a lack of connecting bridges between the thin bone trabeculae and the implant surface. On the sandblasted acid-etched surface implants, a thin layer of bone trabeculae was interposed between the old bone and the implants. The areas close to the surfaces showed a thin layer of dense connective tissue between the bone and the implants. In some sections, blood vessels were detected close to the retrieved implant surface (Fig. 6).
Some sections presented surface debris or particle inclusions in the surrounding tissue close to the bone area. Some sections displayed inflammatory cells (lymphocytes, macrophages and giant cells) near the implant surface, mainly in the implants retrieved due to peri-implantitis (Figs. 7 and 8). No foreign body reaction was found in the area of bone-to-implant contact, although epithelial downgrowth was observed at the interface. The evaluation of bone-to-implant contact revealed
Results
Information about patient age, gender, time of loading, etc., is presented in Tables 1 and 2. The main reason for removal was mechanical complications for 45% of the 22 histologically evaluated implants. All implants included in this study were clinically stable. The histologic evaluation revealed bone tissue in the threads of the retrieved implants, with variations in the percentage of bone-to-implant contact for the implants retrieved from both groups (osteoporosis and control). The bone tissue surrounding the implants was healthy for both groups (Figs. 2 and 3). The pristine bone was mostly mature bone and/or lamellar and compact, and numerous osteocytes were observed in the lacunae, although areas of woven bone could be distinguished. In some specimens, there were areas of newly formed bone exhibiting different degrees of maturation and remodeling (Figs. 4 and 5). Occasionally, osteoblasts were connected to the newly formed bone, indicating ongoing bone formation. Inside the implant threads, a variable apposition of bone could be found. Some samples
Fig. 2. A) Ground section of the retrieved implant from patient with osteoporosis depicted in Fig. 1. B) Ground section of the retrieved implant from a patient without osteoporosis. Acid fuchsin and toluidine blue, original magnification x16.
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Table 2. Patients without osteoporosis (control group): retrieved implant data Implant length Loading Time Implant Age diameter time in situ surface (years)/ (mm) Patient Gender topography (months) (months) 1* 2 3 4 5 6 7 8 9* 10 11 12 13 13 14
54/f 45/m 65/f 53/f 49/f 66/m 74/f 59/f 54/f 66/f 59/f 63/m 59/m 59/m 71/f *
Machined SAS Machined Machined SAS Machined Machined Machined Machined TPS Machined Machined Machined Machined Machined
110 66 47 74 16 98 105 54 81 77 120 96 126 126 87
102 60 41 68 12 90 98 47 75 70 112 90 120 120 80
13 3.75 12 4.0 13 3.75 10 3.75 10 4.0 10 3.75 13 3.75 10 4.0 10 3.75 11 4.0 10 3.75 10 3.75 13 3.75 13 4.0 8.0 3.75
Implant position
Indications of implant
Bone-to% Length implant of remaining contact (%mean SD) osseointegration
Mandible Mandible Maxilla Maxilla Mandible Mandible Maxilla Mandible Mandible Maxilla Maxilla Mandible Maxilla Maxilla Maxilla
Full denture FPD FPD Full denture Single tooth FDP Full denture FDP FDP Full denture FDP FDP FDP FDP FDP
21.46 1.45 43.75 0.55 49.00 1.56 37.31 2.01 63.33 0.98 39.63 1.63 38.71 1.74 41.01 0.71 46.74 2.10 39.01 0.56 79.56 1.12 46.66 0.06 58.69 1.74 64.89 1.65 47.96 0.98
24 100 98 19 100 18 19 64 26 20 100 13 54 76 22
Claimed reason for removal Peri-implantitis Mechanical Mechanical Bone Loss Iatrogenic Bone Loss Bone Loss Mechanical Peri-implantitis Peri-implantitis Mechanical Bone Loss Mechanical Mechanical Bone Loss
Smoker; m: male, f: female; SAS: sandblasted acid-etched surface; TPS: titanium plasma spray; FPD: fixed partial denture.
similar means for the two groups (Fig. 9): 46.00 11.46% and 47.84 14.03% for the osteoporosis group and control group, respectively. Discussion
Fig. 3. Presence of cement lines (arrows) and blood vessel (arrowhead) in ground section of implant retrieved because of mechanical failure from patient without osteoporosis. Acid fuchsin and toluidine blue, original magnification x100.
Fig. 4. Ground section from patient of osteoporosis group depicting mostly compact pristine bone and some osteocytes present in the lacunae. Osteoid layer with osteoblasts (arrows). Acid fuchsin and toluidine blue, original magnification x100.
The percentages of bone-to-implant contact presented in this article were, with few exceptions, similar for both osteoporosis and non-osteoporosis patients. Although some clinical investigations have suggested that osteoporosis is not always a risk factor for osseointegration of dental implants, osteoporosis is now regarded as a relative contraindication for oral rehabilitation using dental implants1,2,5,9,13. Several studies point to the role of local and systemic factors in the long-term success of dental implants, but less is known about factors affecting the stability of oral implants after the abutment placement process and occlusal load17,24. In this retrospective histologic study, it was possible to evaluate the bone-toimplant contact in patients classified as type 1 osteoporosis (postmenopausal osteoporosis) according to criteria established by the World Health Organization. It is important to note that, according to patient anamnesis, the diagnosis of osteoporosis was made mainly after implant placement. In addition, is important to note that the control group was characterized according to their anamnesis and clinical evaluation, since these patients have no bone densitometry. However, our retrospective histologic study may offer an idea about the histology of periimplant bone retrieved from patients with osteoporosis. Some authors2,10, based on several lines of evidence from human and animal studies7,8,20,22, revised their classi-
Osseointegration in osteoporosis subjects
Fig. 5. Ground section of implant from osteoporosis patient. Presence of cavity with multinuclear giant cell (arrows) in contact with implant surface. Acid fuchsin and toluidine blue, original magnification x100.
Fig. 6. Ground section of control group depicting close contact between mature compact bone and implant surface. Note the presence of nerve bundles and blood vessels. Acid fuchsin and toluidine blue, original magnification x100.
Fig. 7. Presence of bacteria in peri-implant soft tissue in implant retrieved because of periimplantitis. Acid fuchsin and toluidine blue, original magnification x100.
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fication and proposed a unitary model for the pathophysiology of involutional osteoporosis, because estrogen deficiency is responsible for bone loss in both postmenopausal women and aging men. Consequently, in osteoporosis, the decreased net bone volume, as well as the reduced ability to withstand optimal load may be affected by a combination of modulated cellular activities, influenced by lower levels of estrogen in postmenopausal osteoporosis20. Bone-to-implant integration gradually increases, and once it is established the accumulated rate of bone attachment to implants is maintained. Unlike regular bone remodeling that occurs in the trabecular area, this phenomenon is not accompanied by apparent turnover or resorption bone18. Reports on histometric evaluations of retrieved oral implants of the same design are rare3. Previous studies3,4,11,21 evaluated the quality and quantity of periimplant bone around several retrieved implants with different designs, host conditions, implant surfaces and causes of failure. Direct comparison with the present study is therefore difficult. It must be emphasized that the histometric evaluation performed in our study considered only the patient group (control or osteoporosis) of the retrieved implants without taking into account the implant surface topography or reason for implant removal. The main difference among the retrieved implants was not the host’s condition (osteoporosis or non-osteoporosis) but the presence of an inflammatory infiltrate in the peri-implant tissue, as well as the presence of bacteria on the coronal part of the retrieved implants, because of periimplantitis. Another important aspect was the time of loading. All implants were loaded at least 1 year before their removal, and they were stable at the time of removal. This condition could explain the higher mean bone-to-implant contact when compared with previous studies3,21. In some clinical investigations, factors such as patient gender and age were not correlated with long-term failures5,12. This may suggest that once bone-to-implant integration is established, there may be not a significant number of clinical failures1. The presence of the dental implant may create a distinct and unique cellular environment, and a scaffold for bone-marrow osteogenic cells to form new bone tissue6, mainly in the earlier stages, depending on the microstructure of the implant surface topography6,14,23, loading time and force17. Implant-supported prostheses in the jawbone are affected not only by systemic
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6. 7.
8.
9. Fig. 8. Retrieved implant from the maxilla of osteoporosis patient depicting bone-resorptive area with osteoclasts (arrowhead) and presence of fibrous connective tissue. Acid fuchsin and toluidine blue, original magnification x100. 10.
11.
12.
Fig. 9. Mean and standard deviation of bone-to-implant contact for retrieved implants from patients with and without (control) osteoporosis.
factors but also by many local factors, such as the periodontal condition of the remaining teeth, number and distribution of dental implants in the arch, occlusion and bite forces. There may be some differences in bone healing and remodeling between the long bones and the jawbones after dental implant placement22,24. According to several investigations, in patients with postmenopausal osteoporosis the rate of trabecular bone loss is greater, despite the rate of cortical bone loss being only slightly above normal. In conclusion, the results of this retrospective histomorphometric study suggest that osteoporosis may not present a contraindication for implant placement, at least once osseointegration has been established. These results should be considered with caution, and further prospective studies are needed with a larger sample of patients with disorders such as postmenopausal and/or senile osteoporosis.
References 1. Amorim MA, Takayama L, Jorgetti V, Pereira RM. Comparative study of axial and femoral bone mineral density and parameters of mandibular bone quality in patients receiving dental implants. Osteoporos Int 2006: 17: 1494–1500. 2. Becker W, Hujoel PP, Becker BE, Willingham H. Osteoporosis and implant failure: an exploratory case-control study. J Periodontol 2000: 71: 625–631. 3. Bolind P, Johansson CB, Balshi TJ, Langer B, Albrektsson T. A study of 275 retrieved Branemark oral implants. Int J Periodontics Restor Dent 2005: 25: 425–437. 4. Bolind PK, Johansson CB, Becker W, Langer L, Svetz Jr EB, Albrektsson TO. A descriptive study on retrieved nonthreaded and threaded implant designs. Clin Oral Implants Res 2005: 16: 447– 455. 5. Dao TT, Anderson JD, Zarb GA. Is osteoporosis a risk for osseointegration
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of dental implants? Int J Oral Maxillofac Implants 1993: 8: 137–144. Davies JE. Mechanisms of endosseous integration. Int J Prosthodont 1998: 11: 391–401. Duarte PM, Cesar Neto JB, Goncalves PF, Sallum EA, Nociti FH. Estrogen deficiency affects bone healing around titanium implants: a histometric study in rats. Implant Dent 2003: 12: 340– 346. Duarte PM, de Vasconcelos Gurgel BC, Sallum AW, Filho GR, Sallum EA, Nociti Jr FH. Alendronate therapy may be effective in the prevention of bone loss around titanium implants inserted in estrogen-deficient rats. J Periodontol 2005: 76: 107–114. Eder A, Watzek G. Treatment of a patient with severe osteoporosis and chronic polyarthritis with fixed implantsupported prosthesis: a case report. Int J Oral Maxillofac Implants 1999: 14: 587– 590. Elsubeihi ES, Heersche JNM. Effects of postmenopausal osteoporosis on the mandible. In: Zarb G, Lekholm U, Albrektsson T, Tenenbaum H, eds: Aging, osteoporosis and dental implants. Chicago, IL: Quintessence Publishing 2002: 207–215. Esposito M, Thomsen P, Ericson L, Lekholm U. Histopathological observations on early oral implant failures. Int J Oral Maxillofac Implants 1999: 14: 798– 810. Friberg B, Jemt T, Lekholm U. Early failures in 4641 consecutively placed Bra¨nemark dental implants. A study from stage I surgery to the connection of completed prostheses. Int J Oral Maxillofac Implants 1991: 6: 142–146. Fujimoto T, Niimi A, Nakai H, Ueda M. Osseointegrated implants in a patient with osteoporosis: a case report. Int J Oral Maxillofac Implants 1996: 11: 539–542. Grassi S, Piattelli A, Ferrari DS, Figueiredo LC, Feres M, Iezzi G, Shibli JA. Histologic evaluation of human bone integration on machined and sandblasted acid-etched titanium surfaces in type IV bone. J Oral Implantol 2007: 33: 8–12. Jeffcoat MK, Chesnut CH. 3rd Systemic osteoporosis and oral bone loss: evidence shows increased risk factors. J Am Dent Assoc 1993: 124: 49–56. Keller JC, Stewart M, Roehm M, Schneider GB. Osteoporosis-like bone conditions affect osseointegration of implants. Int J Oral Maxillofac Implants 2004: 19: 687–694. Kronstrom M, Palmqvist S, Soderfeldt B. Prosthodontic decision making among general dentists in Sweden. III: The choice between fixed partial dentures and single implants. Int J Prosthodont 2000: 13: 34–40. Marco F, Milena F, Gianluca G, Vittoria O. Peri-implant osteogenesis in
Osseointegration in osteoporosis subjects health and osteoporosis. Micron 2005: 36: 630–644. 19. Okamura A, Ayukawa Y, Iyama S, Koyano K. Effect of the difference of bone turnover on peri-titanium implant osteogenesis in ovariectomized rats. J Biomed Mater Res A 2004: 70: 497–505. 20. Ozawa S, Ogawa T, Iida K, Sukotjo C, Hasegawa H, Nishimura RD, Nishimura I. Ovariectomy hinders the early stage of bone-implant integration: histomorphometric, biomechanical, and molecular analyses. Bone 2002: 30: 137–143. 21. Piattelli A, Scarano A, Piattelli M. Histologic observations on 230 retrieved dental implants: 8 years´ experience (1989-1996). J Periodontol 1998: 69: 178–184.
22. Qi MC, Zhou XQ, Hu J, Du ZJ, Yang JH, Liu M, Li XM. Oestrogen replacement therapy promotes bone healing around dental implants in osteoporotic rats. Int J Oral Maxillofac Surg 2004: 33: 279–285. 23. Shibli JA, Grassi S, Cristina de Figueiredo L, Feres M, Marcantonio Jr E, Iezzi G, Piattelli A. Influence of implant surface topography on early osseointegration: A histological study in human jaws. J Biomed Mater Res B Appl Biomater 2007: 80: 377– 385. 24. van Steenberghe D, Jacobs R, Desnyder M, Maffei G, Quirynen M. The relative impact of local and endogenous patient-related factors on implant failure
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up to the abutment stage. Clin Oral Implants Res 2002: 13: 617–622. 25. Wasnich RD. Vertebral fracture epidemiology. Bone 1996: 18(Suppl):179S– 183S. Address: Prof. Jamil Awad Shibli Centro de Po´s-graduac¸a˜o Pesquisa e Extensa˜o – CEPPE Universidade Guarulhos-UnG R. Dr. Nilo Pec¸anha 81 – Pre´dio U – 68 Andar 07011-040 Guarulhos SP Brazil Fax: +55 11 64641758 E-mail: [email protected]
Leading Clinical Paper Dental Implants
Histological comparison between implants retrieved from patients with and without osteoporosis
J. A. Shibli1, K. C. D. S. Aguiar1, L. Melo1, S. d’Avila1, E. G. Zeno´bio2, M. Faveri1, G. Iezzi3, A. Piattelli3 1 Department of Periodontology, Dental Research Division, Guarulhos University, Guarulhos, Sa˜o Paulo, Brazil; 2Department of Periodontology, Dental Research Division, Pontific Catholic University of Minas Gerais, Brazil; 3Department of Oral Medicine and Pathology, Dental School, University of Chieti, Chieti, Italy
J. A. Shibli, K. C. D. S. Aguiar, L. Melo, S. d’Avila, E. G. Zeno´bio, M. Faveri, G. Iezzi, A. Piattelli: Histological comparison between implants retrieved from patients with and without osteoporosis. Int. J. Oral Maxillofac. Surg. 2008; 37: 321–327. # 2007 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved. Abstract. The aim of this restrospective histologic study was to evaluate the bone-toimplant contact of loaded implants retrieved from patients with and without osteoporosis. The evaluated material consisted of 22 threaded, cylindrical, loaded dental implants retrieved from 21 patients: 7 from 7 women with postmenopausal osteoporosis (osteoporosis group) and the remaining 15 from 14 patients without history of osteoporosis or other metabolic diseases (control group). Histologic analysis revealed bone tissue in the threads of the retrieved implants, with variations in the percentage of bone-to-implant contact for the implants retrieved from both groups. The pristine bone was mostly mature bone and/or lamellar and compact, and numerous osteocytes were observed in the lacunae, although areas of woven bone could be distinguished. In some specimens, there were areas of newly formed bone exhibiting different degrees of maturation and remodeling. The mean bone-toimplant contact was 46.00 11.46% and 47.84 14.03% for the osteoporosis group and control group, respectively. The results of this histomorphometric study suggest that osteoporosis may not be a contra-indication for implant placement, at least after osseointegration has been established.
The successful outcome of dental implantation is influenced by a number of confounding factors such as the boneremodeling response, implant design and topography, clinical protocols, and the patient’s level of physical activity6,19. Bone quality is another important factor, with a higher failure rate having been 0901-5027/040321 + 07 $30.00/0
observed in implants placed at type IV bone12,14,23. Osteoporosis is a disease that influences the quality of bone tissue such that it may become susceptible to fracture. Although this disease may have an influence on periodontal attachment loss15, there are no clinical studies that present a clear
Keywords: dental implants; osteoporosis; human histology; retrieved implants; osseointegration. Accepted for publication 23 November 2007 Available online 11 February 2008
association between implant failure and osteoporosis1,24. Earlier animal studies have described the deleterious effect of osteoporosis on the osseointegration process7,8,22 mainly with regard to trabecular bone volume. It has been demonstrated that resorption and remodeling of the alveolar bone, not only
# 2007 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
322
Shibli et al.
after extraction of the tooth but also after dental implant placement, are accelerated following experimental ovariectomy8,20. Concern over dental implants being contraindicated in patients with osteoporosis is based on the assumption that this metabolic disease affects the jaws in the same way as it affects other parts of the skeleton, such as the lumbar spine, femur, neck and forearm15,25. The mechanism by which osteoporosis acts on peri-implant bone is based on the decrease in both cancellous bone volume and bone-toimplant contact, consequently reducing the bone tissue available to support dental implants22. Osteoporosis is thought to be a result of an altered bone-remodeling process, i.e. bone-tissue formation decreases while resorptive capacity remains constant16. Osteoporosis may represent a contraindication or risk factor for osseointegration, but this is still controversial1,2,5,13,24. The objective of this retrospective histologic study was to evaluate bone-toimplant contact in loaded implants retrieved from patients with and without osteoporosis. Materials and Methods
Over a time period of 4 years (March 2003–March 2007), a total of 22 threaded, cylindrical dental implants of different brands were retrieved for different reasons: infection, inflammation and bone loss, mechanical failures of implant components (fracture of implant neck and fracture of abutment screw), and iatrogenic reasons, i.e. paresthesia or hyperesthesia of lower lip. (Fig. 1) The patients were referred for prosthetic treatment and/or maintenance care. After diagnosis of failure of the implant restoration and/or extensive bone loss (>75% of the length of the implant), these failed implants were scheduled for removal. All the retrieved implants were considered ‘‘problematic’’ according to the local Institutional Review Board (IRB). Implants were not removed if bone loss was <75% of the length, they were working as ‘‘sleeping’’ implants, or informed consent from the patient to remove the implant was not obtained. The ‘‘non-problematic’’ implants were treated according to their prognosis: peri-implantitis or kept in the jaws without occlusal function (submerged). Dental implants with clinical mobility and/or loss of osseointegration were excluded from this study. Lack of osseointegration was recorded as the slightest mobility tested by rotating and moving every dental implant back and
Fig. 1. A) Radiographic view of fractured implant abutment screw (arrow) in anterior maxilla in patient with osteoporosis. The other implant presented no osseointegration (*) and was not included in the study. B) Clinical view of the implant (!).
forward. This study was reviewed by the local IRB. The study met requirements for exemption from IRB review, which included obtaining informed consent from the patients. Of the 22 implants retrieved from 21 patients (mean age 61.19 7.65 years) included in this study, 7 implants were obtained from 7 women with postmenopausal osteoporosis determined by DPXIQ AP in the lumbar spine and femoral neck. The diagnosis of osteoporosis was established for these patients, based on criteria used by the World Health Organization: T-score <2.5 SD. According to their files, all the patients claimed that the dental implants were placed at the same time as, or after, osteoporosis was diagnosed by bone densitometry. After their diagnosis of osteoporosis, the patients (according to anamnesis) received a diet and some medications with calcium, but glucocorticosteroids or other immunosuppressive drugs were not used. Only one patient received treatment with estrogen. The remaining 15 dental implants were obtained from 14 patients without bone
densitometry, clinical history of osteoporosis or other metabolic diseases that could affect osseointegration healing. Histological Processing and Evaluation
The implants were removed using an internal 4.25-mm-wide trephine, and together with surrounding bone tissues were immediately stored in 10% buffered formalin and processed to obtain thin ground sections with the Precise 1 Automated System (Assing, Rome, Italy). The specimens were dehydrated in an ascending series of alcohol rinses and embedded in a glycol methacrylate resin (Technovit1 7200 VLC, Kulzer, Wehrheim, Germany). After polymerization, the specimens were sectioned longitudinally along the major axis of the implant with a high-precision diamond disk at about 150 mm and ground down to about 30 mm. Two slides were obtained for each implant. The slides were stained with basic fuchsin and toluidine blue. Histomorphometry of bone-to-implant contact
Osseointegration in osteoporosis subjects
323
Table 1. Patients with osteoporosis: retrieved implant data Implant length Time in Loading Implant Age diameter time situ surface (years)/ (mm) Patient Gender topography (months) (months) 61/f 66/f 76/f 59/f 63/f 61/f 62/f
1 2 3* 4 5 6 7 *
Machined Machined Machined Machined SAS Machined Machined
66 59 55 69 48 76 55
60 52 50 63 43 70 48
10 4.0 10 3.75 13 3.75 10 4.0 11 4.0 10 3.75 10 3.50
Implant position
Indications of implant
Bone-to% Length implant of remaining contact (%mean SD) osseointegration
Mandible Mandible Maxilla Maxilla Mandible Mandible Mandible
Single tooth Full denture FDP FDP Full denture FDP Full denture
51.25 3.16 50.08 2.01 27.89 2.22 37.95 1.25 52.43 1.91 62.51 1.96 39.89 0.65
100 85 24 75 19 100 15
Claimed reason for removal Mechanical Mechanical Bone Loss Mechanical Bone Loss Mechanical Bone Loss
Therapy with estrogen; f: female; SAS: sandblasted acid-etched surface; FPD: fixed partial denture.
percentage was performed using a light microscope (Laborlux S1, Leitz, Wetzlar, Germany) connected to a high-resolution video camera (3CCD1, JVC KY-F55B, Milan, Italy), and interfaced to a monitor and personal computer (Intel Pentium III 1200 MMX). This optical system was associated with a digitizing pad (Matrix Vision GmbH, Milan, Italy) and a histometry software package with image-capturing capabilities (Image-Pro Plus1 4.5, Media Cybernetics Inc., Immagini & Computer Snc, Milan, Italy). The measurements14,23 of bone-to-implant contact were performed at a magnification of about x160. Mean and standard deviation of the histometric variable values were calculated for both slides of each implant and then for each group.
showed a lack of connecting bridges between the thin bone trabeculae and the implant surface. On the sandblasted acid-etched surface implants, a thin layer of bone trabeculae was interposed between the old bone and the implants. The areas close to the surfaces showed a thin layer of dense connective tissue between the bone and the implants. In some sections, blood vessels were detected close to the retrieved implant surface (Fig. 6).
Some sections presented surface debris or particle inclusions in the surrounding tissue close to the bone area. Some sections displayed inflammatory cells (lymphocytes, macrophages and giant cells) near the implant surface, mainly in the implants retrieved due to peri-implantitis (Figs. 7 and 8). No foreign body reaction was found in the area of bone-to-implant contact, although epithelial downgrowth was observed at the interface. The evaluation of bone-to-implant contact revealed
Results
Information about patient age, gender, time of loading, etc., is presented in Tables 1 and 2. The main reason for removal was mechanical complications for 45% of the 22 histologically evaluated implants. All implants included in this study were clinically stable. The histologic evaluation revealed bone tissue in the threads of the retrieved implants, with variations in the percentage of bone-to-implant contact for the implants retrieved from both groups (osteoporosis and control). The bone tissue surrounding the implants was healthy for both groups (Figs. 2 and 3). The pristine bone was mostly mature bone and/or lamellar and compact, and numerous osteocytes were observed in the lacunae, although areas of woven bone could be distinguished. In some specimens, there were areas of newly formed bone exhibiting different degrees of maturation and remodeling (Figs. 4 and 5). Occasionally, osteoblasts were connected to the newly formed bone, indicating ongoing bone formation. Inside the implant threads, a variable apposition of bone could be found. Some samples
Fig. 2. A) Ground section of the retrieved implant from patient with osteoporosis depicted in Fig. 1. B) Ground section of the retrieved implant from a patient without osteoporosis. Acid fuchsin and toluidine blue, original magnification x16.
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Table 2. Patients without osteoporosis (control group): retrieved implant data Implant length Loading Time Implant Age diameter time in situ surface (years)/ (mm) Patient Gender topography (months) (months) 1* 2 3 4 5 6 7 8 9* 10 11 12 13 13 14
54/f 45/m 65/f 53/f 49/f 66/m 74/f 59/f 54/f 66/f 59/f 63/m 59/m 59/m 71/f *
Machined SAS Machined Machined SAS Machined Machined Machined Machined TPS Machined Machined Machined Machined Machined
110 66 47 74 16 98 105 54 81 77 120 96 126 126 87
102 60 41 68 12 90 98 47 75 70 112 90 120 120 80
13 3.75 12 4.0 13 3.75 10 3.75 10 4.0 10 3.75 13 3.75 10 4.0 10 3.75 11 4.0 10 3.75 10 3.75 13 3.75 13 4.0 8.0 3.75
Implant position
Indications of implant
Bone-to% Length implant of remaining contact (%mean SD) osseointegration
Mandible Mandible Maxilla Maxilla Mandible Mandible Maxilla Mandible Mandible Maxilla Maxilla Mandible Maxilla Maxilla Maxilla
Full denture FPD FPD Full denture Single tooth FDP Full denture FDP FDP Full denture FDP FDP FDP FDP FDP
21.46 1.45 43.75 0.55 49.00 1.56 37.31 2.01 63.33 0.98 39.63 1.63 38.71 1.74 41.01 0.71 46.74 2.10 39.01 0.56 79.56 1.12 46.66 0.06 58.69 1.74 64.89 1.65 47.96 0.98
24 100 98 19 100 18 19 64 26 20 100 13 54 76 22
Claimed reason for removal Peri-implantitis Mechanical Mechanical Bone Loss Iatrogenic Bone Loss Bone Loss Mechanical Peri-implantitis Peri-implantitis Mechanical Bone Loss Mechanical Mechanical Bone Loss
Smoker; m: male, f: female; SAS: sandblasted acid-etched surface; TPS: titanium plasma spray; FPD: fixed partial denture.
similar means for the two groups (Fig. 9): 46.00 11.46% and 47.84 14.03% for the osteoporosis group and control group, respectively. Discussion
Fig. 3. Presence of cement lines (arrows) and blood vessel (arrowhead) in ground section of implant retrieved because of mechanical failure from patient without osteoporosis. Acid fuchsin and toluidine blue, original magnification x100.
Fig. 4. Ground section from patient of osteoporosis group depicting mostly compact pristine bone and some osteocytes present in the lacunae. Osteoid layer with osteoblasts (arrows). Acid fuchsin and toluidine blue, original magnification x100.
The percentages of bone-to-implant contact presented in this article were, with few exceptions, similar for both osteoporosis and non-osteoporosis patients. Although some clinical investigations have suggested that osteoporosis is not always a risk factor for osseointegration of dental implants, osteoporosis is now regarded as a relative contraindication for oral rehabilitation using dental implants1,2,5,9,13. Several studies point to the role of local and systemic factors in the long-term success of dental implants, but less is known about factors affecting the stability of oral implants after the abutment placement process and occlusal load17,24. In this retrospective histologic study, it was possible to evaluate the bone-toimplant contact in patients classified as type 1 osteoporosis (postmenopausal osteoporosis) according to criteria established by the World Health Organization. It is important to note that, according to patient anamnesis, the diagnosis of osteoporosis was made mainly after implant placement. In addition, is important to note that the control group was characterized according to their anamnesis and clinical evaluation, since these patients have no bone densitometry. However, our retrospective histologic study may offer an idea about the histology of periimplant bone retrieved from patients with osteoporosis. Some authors2,10, based on several lines of evidence from human and animal studies7,8,20,22, revised their classi-
Osseointegration in osteoporosis subjects
Fig. 5. Ground section of implant from osteoporosis patient. Presence of cavity with multinuclear giant cell (arrows) in contact with implant surface. Acid fuchsin and toluidine blue, original magnification x100.
Fig. 6. Ground section of control group depicting close contact between mature compact bone and implant surface. Note the presence of nerve bundles and blood vessels. Acid fuchsin and toluidine blue, original magnification x100.
Fig. 7. Presence of bacteria in peri-implant soft tissue in implant retrieved because of periimplantitis. Acid fuchsin and toluidine blue, original magnification x100.
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fication and proposed a unitary model for the pathophysiology of involutional osteoporosis, because estrogen deficiency is responsible for bone loss in both postmenopausal women and aging men. Consequently, in osteoporosis, the decreased net bone volume, as well as the reduced ability to withstand optimal load may be affected by a combination of modulated cellular activities, influenced by lower levels of estrogen in postmenopausal osteoporosis20. Bone-to-implant integration gradually increases, and once it is established the accumulated rate of bone attachment to implants is maintained. Unlike regular bone remodeling that occurs in the trabecular area, this phenomenon is not accompanied by apparent turnover or resorption bone18. Reports on histometric evaluations of retrieved oral implants of the same design are rare3. Previous studies3,4,11,21 evaluated the quality and quantity of periimplant bone around several retrieved implants with different designs, host conditions, implant surfaces and causes of failure. Direct comparison with the present study is therefore difficult. It must be emphasized that the histometric evaluation performed in our study considered only the patient group (control or osteoporosis) of the retrieved implants without taking into account the implant surface topography or reason for implant removal. The main difference among the retrieved implants was not the host’s condition (osteoporosis or non-osteoporosis) but the presence of an inflammatory infiltrate in the peri-implant tissue, as well as the presence of bacteria on the coronal part of the retrieved implants, because of periimplantitis. Another important aspect was the time of loading. All implants were loaded at least 1 year before their removal, and they were stable at the time of removal. This condition could explain the higher mean bone-to-implant contact when compared with previous studies3,21. In some clinical investigations, factors such as patient gender and age were not correlated with long-term failures5,12. This may suggest that once bone-to-implant integration is established, there may be not a significant number of clinical failures1. The presence of the dental implant may create a distinct and unique cellular environment, and a scaffold for bone-marrow osteogenic cells to form new bone tissue6, mainly in the earlier stages, depending on the microstructure of the implant surface topography6,14,23, loading time and force17. Implant-supported prostheses in the jawbone are affected not only by systemic
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6. 7.
8.
9. Fig. 8. Retrieved implant from the maxilla of osteoporosis patient depicting bone-resorptive area with osteoclasts (arrowhead) and presence of fibrous connective tissue. Acid fuchsin and toluidine blue, original magnification x100. 10.
11.
12.
Fig. 9. Mean and standard deviation of bone-to-implant contact for retrieved implants from patients with and without (control) osteoporosis.
factors but also by many local factors, such as the periodontal condition of the remaining teeth, number and distribution of dental implants in the arch, occlusion and bite forces. There may be some differences in bone healing and remodeling between the long bones and the jawbones after dental implant placement22,24. According to several investigations, in patients with postmenopausal osteoporosis the rate of trabecular bone loss is greater, despite the rate of cortical bone loss being only slightly above normal. In conclusion, the results of this retrospective histomorphometric study suggest that osteoporosis may not present a contraindication for implant placement, at least once osseointegration has been established. These results should be considered with caution, and further prospective studies are needed with a larger sample of patients with disorders such as postmenopausal and/or senile osteoporosis.
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up to the abutment stage. Clin Oral Implants Res 2002: 13: 617–622. 25. Wasnich RD. Vertebral fracture epidemiology. Bone 1996: 18(Suppl):179S– 183S. Address: Prof. Jamil Awad Shibli Centro de Po´s-graduac¸a˜o Pesquisa e Extensa˜o – CEPPE Universidade Guarulhos-UnG R. Dr. Nilo Pec¸anha 81 – Pre´dio U – 68 Andar 07011-040 Guarulhos SP Brazil Fax: +55 11 64641758 E-mail: [email protected]