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Significance of Osteogenic Surface Coatings on Implants to Enhance Osseointegration Under Osteoporotic-like Conditions Fawad Javed, BDS, PhD,* Fahim Vohra, BDS, MClinDent,† Sohail Zafar, BDS, MSc, PhD,‡ and Khalid Almas, BDS, MSc§
t is well acknowledged that the quality and quantity of host bone, presence of sufficient primary stability at the time of implant placement and formation of a direct bone-to-implant contact (BIC) are critical parameters that govern the overall success and survival of implants.1–4 However, implant surface characteristics (including surface topography, energy, chemistry, and roughness) also play significant roles in enhancing osseointegration and BIC. Studies have reported that increasing surface roughness of implants favors osteoblastic proliferation, collagen synthesis, and expression of integrins in the extracellular matrix, thereby improving the mechanisms associated with osseointegration.5–12 In this regard, some studies placed localized organic and inorganic osteogenic coatings on implant surfaces in an attempt to
I
*Assistant Professor, Engineer Abdullah Bugshan Research Chair for Growth Factors and Bone Regeneration, 3D Imaging and Biomechanical Laboratory, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia. †Assistant Professor, Department of Prosthetic Dental Sciences, College of Dentistry, King Saud University, Riyadh, Saudi Arabia. ‡Assistant Professor, Department of Dental Biomaterials, College of Dentistry, Taibah University, Madinah, Saudi Arabia. §Professor, Division of Periodontology, College of Dentistry, University of Dammam, Dammam, Saudi Arabia.
Reprint requests and correspondence to: Fawad Javed, BDS, PhD, Engineer Abdullah Bagshan Research Chair for Growth Factors and Bone Regeneration, 3D Imaging and Biomechanical Laboratory, College of Applied Medical Sciences, King Saud University, PO Box 60169, Riyadh 11545, Saudi Arabia, Phone: +966 50 968 6328, Fax: +96614678639, E-mail: [email protected] ISSN 1056-6163/14/02306-679 Implant Dentistry Volume 23 Number 6 Copyright © 2014 by Lippincott Williams & Wilkins DOI: 10.1097/ID.0000000000000161
Purpose: The aim was to assess the significance of osteogenic surface coatings on implants to enhance osseointegration under osteoporoticlike (OP-like) conditions. Methods: To address the focused question “Do osteogenic surface coatings on implants enhance osseointegration under OP-like conditions?” PubMed/MEDLINE and Google-Scholar databases were searched from 1995 up to and including February 2014 using various keywords. Unpublished data, letters to the editor, review articles, and articles published in languages other than English were excluded. Results: Of the 28 studies identified, 11 experimental studies were included. These studies were performed on bilaterally ovariectomized animals. In all studies, implant surface roughness was increased by various osteogenetic surface coat-
ings including alumina, hydroxyapatite, calcium phosphate, and zoledronic acid. Nine studies reported that compared with noncoated surfaces, osteogenic coatings on implant surfaces increases bone volume and bone-to-implant contact (BIC) under OP-like conditions. In 2 studies, there was no difference in BIC around hydroxyapatite-coated implants placed in animals with and without OP-like conditions. Conclusion: Osteogenic coatings on implant surfaces enhanced osseointegration in animals with OP-like conditions. However, additional clinical studies are warranted to assess the role of osteogenic coatings in increasing osseointegration in patients with osteoporosis. (Implant Dent 2014;23:679–686) Key Words: bone-to-implant contact, coating, implant surface, osseointegration and osteoporosis
improve implant surface activity and osteopromotive activity.13–23 Osteoporosis is a metabolic disease of bone characterized by low bone mineral density (BMD) and reduced bone mass due to impaired bone metabolism and imbalanced osteoblastic and osteoclastic activities.24,25 In osteoporotic bone, osteoblasts demonstrate impaired proliferative, synthetic, and reactive
ability to cellular mediators.24,26,27 Underlying causes of osteoporosis include premenopausal and postmenopausal estrogen deficiency, excessive glucocorticoid intake, eating disorders such as anorexia nervosa and celiac disease.28,29 Although the bone quality and strength are compromised in osteoporotic patients (compared with healthy individuals) because of low BMD and
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osteoregenerative capacity of osteoporotic bone, osteoporosis is not considered a contraindication for implant placement.30,31 Because optimal bone volume (BV) and BIC are critical in establishing implant stability in bones with low BMD, and that implant surface topography influences the mechanisms of osseointegration, it is hypothesized that implant surfaces with osteogenic coatings increase osteoblastic activity thereby enhancing BV and BIC under osteoporotic-like (OP-like) conditions as compared with implants with noncoated surfaces.13,14,32,33 The aim of this study was to review the significance of osteogenic coatings on implant surfaces in enhancing osseointegration under OP-like conditions.
MATERIALS
AND
METHODS
Focused Question
The addressed focused question was “Do osteogenic coatings around implant surfaces enhance osseointegration under OP-like conditions?” Eligibility Criteria
The following eligibility criteria were entailed: (1) original studies; (2) clinical and experimental studies; (3) intervention: role of modifications in Titanium (Ti) implant surfaces in enhancing osseointegration in OP-like conditions; (4) articles published only in English language. Letters to the Editor, commentaries, case reports, review articles, and unpublished articles were excluded. Search Strategy
To address the focused question, PubMed/MEDLINE (National Library of Medicine, Bethesda, MD) and GoogleScholar databases were searched from 1995 up to and including February 2014 using different combinations of the following key words: “bone,” “implant surface,” “osseointegration,” “osteoporosis,” and “ovariectomy” (Fig. 1). Titles and abstracts of studies that fulfilled the eligibility criteria were screened by the authors and checked for agreement. Full texts of studies judged by title and abstract to be relevant were read and independently assessed against the selection protocol. After this, reference lists of original and review studies that were found to be pertinent in the
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Fig. 1. A schematic presentation of the literature search strategy used in this study. PubMed/ MEDLINE and Google-Scholar databases were searched from 1995 up to and including February 2014 using various key words. Letters to the editor, reviews, case reports, unpublished studies, and articles published in languages other than English were excluded. Disagreements among the authors regarding study selection were resolved through discussion.
previous step were handsearched and checked for agreement through discussion among the authors. The initial search yielded 28 studies. Seventeen studies, which did not fulfill our eligibility criteria, were excluded (Appendix A). In total, 11 studies were included and processed for data extraction.
RESULTS General Characteristics of the Studies
The general characteristics of the studies that were included in the present
systematic review are summarized in Table 1. All studies were experimental and were performed at University settings.13–23 Rats, rabbits, and sheep were used in 5, 4, and 2 studies, respectively.13–23 In these studies, the mean ages of rats, rabbits, and sheep ranged between 3 to 10 months, 6 to 15 months, and 2 to 7, years, respectively.13–23 In all studies, the animals underwent bilateral ovariectomy (OVX) for the induction of OP-like conditions (Table 2).13–23 The follow-up period after implant placement ranged between 1 and 16 weeks. In studies by Fini et al19 and Mardas et al,20 implants were placed in the
Table 1. General Characteristics of Studies That Fulfilled Our Eligibility Criteria Authors 13
Alghamdi et al Alghamdi et al14 Yang et al15 Qi et al16 Jung et al17 De Benedittis et al18 Fini et al19 Mardas et al20 Vidigal et al21 Gao et al22 Borsari et al23
Study Design
Subjects
Mean Age (mo)
Experimental Experimental Experimental Experimental Experimental Experimental Experimental Experimental Experimental Experimental Experimental
15 rats 24 rats 48 rats 56 rabbits 36 rabbits 36 rats 8 sheep 36 rabbits 20 rabbits 40 rats 15 sheep
3 3 NA NA 15 10 48 6 12 NA Young sheep: 24 Aged sheep: 108 Aged OVX sheep: 84
NA indicates not available; OVX, ovariectomized.
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Table 2. Study Grouping and Implant-Related Characteristics of Studies That Fulfilled Our Eligibility Criteria Authors Alghamdi et al13
Study Groups Group 1: 15 OVX rats
Implants Placed in Femoral condyle
Group 2: 15 rats without OVX Alghamdi et al14
Yang et al15
Qi et al16
Group 1: 13 OVX rats
Group 2: 11 rats without OVX Group 1: 64 OVX rats with simvastatin treatment Group 2: 32 OVX rats without simvastatin treatment
Group 1: 40*‡ OVX rabbits
Femoral condyle
Tibia
Tibia
Group 2: 16*‡ without OVX
Jung et al17
De Benedittis et al18
Group 1: 12 OVX rabbits treated with alendronate-Na tablets Group 2: no treatment in 12 OVX rabbits Group 3: Sham surgery (controls) Group 1: 10 OVX rabbits
Group 2: 10 rabbits without OVX
Implant Surface Modifications Implant I: CaP coated
Implant II: collagen type1 coated Implant III: non-coated Group a: 13 CaP coated and 13 non-coated
Group b: 11 CaP coated and 11 non-coated Group 1a: implants† coated with 10−7 mol/L simvastatin Group 1b: implants† coated with 10−6 mol/L simvastatin Group 2: implants without simvastatin coating Group 1a: OVX alone
Follow-up (wk) 12
BV and BIC were higher around implants I and II than implant III
8
BV and BIC were higher around CaP coated implants in both groups
1, 2, 4, and 12
In groups 1a and 1b, BV increased after 1 wk In group 2, BV increased after 2 wk
12
Group 1b: local ZOL
Parietal bones
Tibia
Group 1c: systemic ZOL Group 1d: local + systemic ZOL Group 2: Sham surgery (controls) In each group, one modSLA and one SLA titanium dome was placed
In each group, implants with 3 types of surfaces were placed
Outcome
At all time points, BV and BIC were higher in groups 1a and 1b than group 2 BV and BIC were higher in groups 1b, 1c, and 1d Highest increase in BV and BIC occurring in group 1d compared with group 2
4 and 16
modSLA Ti surface increased BIC and new bone formation in all groups compared with SLA surfaces
16
No difference in BIC among the implants placed in groups 1 and 2
a) Ti implant b) HA-PS implant c) Implant coated with HA with biomimetic process (continued on next page)
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Table 2. (Continued) Authors Fini et al
Study Groups 19
Mardas et al20
40 OVX rats
Group 1: 5 young sheep
Implants Placed in Tibia
Tibia
Group 2: 5 aged sheep
Vidigal et al21
Group 3: 5 aged OVX sheep Group 1: 4 OVX sheep
Gao et al22
Group 2: 4 Sham operated sheep Group 1: 18 OVX rabbits
Group 1: 18 OVX rats
Group 2: 18 sham operated rats
Implants were immersed in 4 different solutions before placement Group a: water
Group b: ZOL Group c: bFGF Group d: ZOL + bFGF Implant I: implants with a single Ti coating
Follow-up (wk)
Outcome
12
BV and BIC were higher in groups b, c, and d than group a Highest BV and BIC were observed in group d compared with groups b and c
12
Affinity index§ for implant II was higher than implant I in all groups with no significant differences between groups
16
Bone hardness and BIC were significantly high around implant II than implant I
12
All implant surfaces in group 2 showed higher BV and BIC compared with group 2
8
All bioactive ceramics were bound to bone with no significant differences between implants in groups 1 and 2
Implant II: implants with a duplex coating of HA over Ti
L3, L4, and L5
Tibia
Group 2: 18 rabbits without OVX Borsari et al23
Implant Surface Modifications
Femoral condyle
Implant I: uncoated screws
Implant II: HA-coated screws Implant I: machined surface
Implant II: aluminacoated surface Implant III: HA-coated Implant I: HA-coated
Implant II: aluminacoated Implant III: zirconia coated Implant IV: coated with biological glasses Implant V: coated with Ti-6Al-4V alloy
*Five rabbits were killed to determine the preoperative BMD. †Implants were sterilized with ultraviolet light. ‡Eight rabbits were sacrificed at 3 months to determine preoperative BMD. §(Length of bone directly opposing the implant divided by the total length of the bone-implant interface) 3 100. 1,25(OH)(2)D(3) indicates 1,25 dihydroxy vitamin D(3); alendronate-Na, alendronate-sodium; bFGF, basic fibroblast growth factor; HA-PS, hydroxyapatite coated and plasma sprayed; modSLA, modifiedetched hydrophilic titanium; NA, not available; OVX, ovariectomized; PTH, parathyroid hormone; SLA, etched titanium; SS, stainless steel.
IMPLANT DENTISTRY / VOLUME 23, NUMBER 6 2014 parietal bone and lumbar vertebrae, respectively. In the remaining studies, implants were either placed in the femoral condyle or tibia (Table 2).13–18,21–23 Implant-Related Characteristics of the Studies
Table 3 summarizes the implantrelated characteristics of the studies that
fulfilled our eligibility criteria. In these studies, the numbers of implants placed ranged between 48 and 144.13–23 In 6 studies, cylindrical implants were used.13,14,17,19,22,23 Screw-shaped implants were used in 4 studies.15,16,18,20 The lengths and diameters of implants used ranged between 3 to 30 mm and 2 to 5 mm, respectively. In 9 studies,
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osteogenic coatings were placed on Ti implants.13–16,20–23 In one study, stainless steel screws were coated with osteogenic materials.19 In all studies, rough-surfaced dental implants were used. In the study by De Benedittis et al,18 implants composed of different materials (including Ti, hydroxyapatite [HA], and zirconia) were used. In
Table 3. Implant-Related Characteristics of the Studies Included Authors Alghamdi et al13
Alghamdi et al14 Yang et al15
Implant Length (mm)
Implant Diameter (mm)
Cylindrical
5
2.85
Grit-blasted Ti implants coated with CaP or collagen type-1 coating
Cylindrical
5
2
192
Screwshaped
4
2.2
80
Screwshaped Cylindrical
12
2
10
3.8
Grit-blasted Ti implants with and without CaP coating Grit-blasted Ti implants treated with hydrofluoric acid/nitric acid solution and hydrochloric acid/ sulfuric acid solutions HA and ZOL coated Ti implants Machined, sand-blasted, or HA-coated implants
30 CaP or Collagen type-1 coated implants 30 non-coated implants 48
Qi et al16 Jung et al17
Implant Shape
No. of Implants Placed
De Benedittis et al18
48 implants with machined surface 48 oxidized implant surfaces 48 HA-coated implants 54 implants with different coatings in OVX rats
Fini et al19
54 implants with different coatings in Shamoperated rats 16 uncoated SS screws
Mardas et al20
16 HA-coated SS screws 72 discs*
Screwshaped
3
Cylindrical
30
3*
60
Screwshaped NA
10
3.8
20 implants in distilled water
Cylindrical
12
1
Cylindrical
12
3.5
Vidigal et al21
Gao et al22
Borsari et al23
20 implants 20 implants 20 implants 30 implants coating
in ZOL in bFGF in ZOL + bFGF with a single Ti
Implant Surface Characteristics
2
HA, sand-blasted, Zirconia, bioactive glass, and Tialloy coatings
4.1
SS implants with and without HA-coating
5*
30 Ti implants with a duplex coating of HA *Titanium discs were placed on induced parietal bone defects. bFGF indicates basic fibroblast growth factor; HA-PS, hydroxyapaptite coated and plasma sprayed; NA, not available; SS, stainless steel.
36 modSLA Ti discs and 36 SLA discs HA-PS Ti implant surfaces and Ti implants coated with HA with biomimetic process HA-coated Ti implants immersed in water, ZOL, bFGF, or ZOL + bFGF
Implants with a single Ti coating or implants with HA-coating over Ti
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2 studies, calcium phosphate (CaP)– coated implants were used.13,14 Zoledronic acid (ZOL)–coated implant surfaces were used in 2 studies.16,22 Three studies assessed the effect of implants with and without a duplex coating of HA on osseointegration under OP-like conditions.19,21,23 Jung et al17 compared the efficacy of alumina-coated and HA-coated implants with machined surfaces in achieving osseointegration under OP-like conditions. In a study on rat models, efficacy of fibroblast growth factor with and without adjunct ZOL coating in increasing BV and BIC was assessed.22 In one study, Ti implants were dipped in 2 different concentrations of a hypolipidemic drug before insertion in rat tibia.15 Main Outcome of Studies
Outcomes of all studies were based on histomorphometric analyses and/or microcomputotomographic assessment of region of interest (ie, bone-implant interface at the test and control sites).13– 23 In 9 studies, BV and BIC were significantly higher around coated implants as compared with non-coated implants placed in subjects with OP-like conditions.13–20,22 In 2 studies, there was no significant difference in BIC around HA-coated and non-coated implants placed in subjects with OP-like conditions.21,23
DISCUSSION From the literature reviewed, nearly 80% of studies reported that osteogenic coatings around implant surfaces enhance bone formation, BIC, and BV under OP-like conditions. This could possibly be accredited to the increase in surface roughness of the implant caused by osteogenic coatings, which facilitate the attachment of osteoprogenitor cells to the implant surface. Studies have also reported that implant surface roughness is directly associated with the degree of primary stability achieved and long-term success rate of the implant.4,34,35 Based on these results, it is tempting to presume that rough-surfaced implants promote bone formation around implants in systemically healthy subjects and osteoporotic patients. However, it is pertinent to
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mention that all results included in the present review were derived from studies based on animal models. In these studies, OP-like conditions were established within 4 weeks to 24 months of OVX.13–23 From a clinical perspective, it is known that advancing age is a significant risk factor of osteoporosis.36 Therefore, it may be questioned whether OP-like conditions induced in the experimental studies included in the present review truly replicate a clinical scenario of osteoporosis. In addition, hyperglycemia is a common manifestation in elderly patients with osteoporosis.37 It is known that chronic hyperglycemia and aging undermine the differentiation and growth of osteoprogenitor cells.38,39 Therefore, it is hypothesized that merely using implants with osteogenic coatings in osteoporotic patients is unable to significantly enhance new bone formation. We support the experimental results by Borsari et al23 in which HA-coated implants placed in aged sheep (with and without OVX) demonstrated no significant difference in their affinity indexes. It is noteworthy that the choice of coating materials varied among the included studies. For example, results by Alghamdi et al13,14 showed that coating implant surfaces with CaP is effective in enhancing BIC and BV around implants compared with non-coated implants. An explanation in this regard may be that coating implants with CaP increases the attachment of osteoblastlike cells and mesenchymal stem cells on implant surfaces, and adsorption of proteoglycans that in turn promote osteogenic cell migration toward the implant surface.40,41 Likewise, 2 studies reported that ZOL-coated implants exhibit superior osseointegration under OP-like conditions compared with noncoated implants.16,22 It has been proposed that under OP-like conditions, ZOL coatings improve osseointegration of HA-coated implants by converting the rod-like structure of trabeculae (after estrogen deficiency) to the platelike structure thereby increasing bone mass around implants and improving implant fixation.22 However, it has also been reported that coating implant surfaces with growth factors + ZOL gives
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the highest BIC than when ZOL is used alone.22 In this regard, we find it exigent to elect a single implant coating material that would be most suitable for increasing osseointegration under OPlike conditions. Results from a recent experimental study showed that the secondary stability of implants is associated with the BIC, and the role of implant diameter in this context is insignificant.42 From the literature reviewed, we observed that implants used in the respective studies varied in diameters; however, histologic outcomes of most studies revealed significantly more BIC around coated implants compared with non-coated surfaces in animals with and without OP-like conditions. In general, outcomes of studies included in the present review are in accordance with those reported by Veltri et al.42
CONCLUSION On experimental grounds, osteogenic surface coatings on implants enhanced osseointegration under OP-like conditions; however, additional long-term prospective clinical trials are warranted to assess the role of osteogenic coatings in increasing osseointegration in humans with osteoporosis.
DISCLOSURE The authors claim to have no financial interest, either directly or indirectly, in the products or information listed in the article.
REFERENCES 1. Pinholt EM. Brånemark and ITI dental implants in the human bone-grafted maxilla: A comparative evaluation. Clin Oral Implants Res. 2003;14:584–592. 2. Schulz MC, Korn P, Stadlinger B, et al. Coating with artificial matrices from collagen and sulfated hyaluronan influences the osseointegration of dental implants. J Mater Sci Mater Med. 2014;25: 247–258. 3. Javed F, Romanos GE. The role of primary stability for successful immediate loading of dental implants. A literature review. J Dent. 2010;38:612–620. 4. Javed F, Almas K, Crespi R, et al. Implant surface morphology and primary
IMPLANT DENTISTRY / VOLUME 23, NUMBER 6 2014 stability: Is there a connection? Implant Dent. 2011;20:40–46. 5. Wang J, An Y, Li F, et al. The effects of pulsed electromagnetic field on the functions of osteoblasts on implant surfaces with different topographies. Acta Biomater. 2014;10:975–985. 6. Olivares-Navarrete R, Hyzy SL, Gittens RA, et al. Rough titanium alloys regulate osteoblast production of angiogenic factors. Spine. 2013;13:1563–1570. 7. Durual S, Pernet F, Rieder P, et al. Titanium nitride oxide coating on rough titanium stimulates the proliferation of human primary osteoblasts. Clin Oral Implants Res. 2011;22:552–559. 8. Mendonca DB, Miguez PA, Mendonca G, et al. Titanium surface topography affects collagen biosynthesis of adherent cells. Bone. 2011;49: 463–472. 9. Le Guehennec L, Soueidan A, Layrolle P, et al. Surface treatments of titanium dental implants for rapid osseointegration. Dent Mater. 2007;23:844–854. 10. Schouten C, Meijer GJ, van den Beucken JJ, et al. In vivo bone response and mechanical evaluation of electrosprayed CaP nanoparticle coatings using the iliac crest of goats as an implantation model. Acta Biomater. 2010;6:2227–2236. 11. Shibli JA, Vitussi TR, Garcia RV, et al. Implant surface analysis and microbiologic evaluation of failed implants retrieved from smokers. J Oral Implantol. 2007;33:232–238. 12. Noro A, Kaneko M, Murata I, et al. Influence of surface topography and surface physicochemistry on wettability of zirconia (tetragonal zirconia polycrystal). J Biomed Mater Res B Appl Biomater. 2013;101:355–363. 13. Alghamdi HS, Bosco R, van den Beucken JJ, et al. Osteogenicity of titanium implants coated with calcium phosphate or collagen type-I in osteoporotic rats. Biomaterials. 2013;34:3747–3757. 14. Alghamdi HS, Cuijpers VM, Wolke JG, et al. Calcium-phosphate-coated oral implants promote osseointegration in osteoporosis. J Dent Res. 2013;92:982–988. 15. Yang G, Song L, Guo C, et al. Bone responses to simvastatin-loaded porous implant surfaces in an ovariectomized model. Int J Oral Maxillofac Implants. 2012;27:369–374. 16. Qi M, Hu J, Li J, et al. Effect of zoledronate acid treatment on osseointegration and fixation of implants in autologous iliac bone grafts in ovariectomized rabbits. Bone. 2012;50:119–127. 17. Jung YC, Han CH, Lee IS, et al. Effects of ion beam-assisted deposition of hydroxyapatite on the osseointegration of endosseous implants in rabbit tibiae. Int J Oral Maxillofac Implants. 2001;16:809–818.
18. De Benedittis A, Mattioli-Belmonte M, Krajewski A, et al. In vitro and in vivo assessment of bone-implant interface: A comparative study. Int J Artif Organs. 1999;22:516–521. 19. Fini M, Giavaresi G, Greggi T, et al. Biological assessment of the bone-screw interface after insertion of uncoated and hydroxyapatite-coated pedicular screws in the osteopenic sheep. J Biomed Mater Res Part A. 2003;66:176–183. 20. Mardas N, Schwarz F, Petrie A, et al. The effect of SLActive surface in guided bone formation in osteoporotic-like conditions. Clin Oral Implants Res. 2011; 22:406–415. 21. Vidigal GM Jr, Groisman M, Gregorio LH, et al. Osseointegration of titanium alloy and HA-coated implants in healthy and ovariectomized animals: A histomorphometric study. Clin Oral Implants Res. 2009;20:1272–1277. 22. Gao Y, Luo E, Hu J, et al. Effect of combined local treatment with zoledronic acid and basic fibroblast growth factor on implant fixation in ovariectomized rats. Bone. 2009;44:225–232. 23. Borsari V, Fini M, Giavaresi G, et al. Osteointegration of titanium and hydroxyapatite rough surfaces in healthy and compromised cortical and trabecular bone: In vivo comparative study on young, aged, and estrogen-deficient sheep. J Orthop Res. 2007;25:1250–1260. 24. Torricelli P, Fini M, Giavaresi G, et al. Human osteoblast cultures from osteoporotic and healthy bone: Biochemical markers and cytokine expression in basal conditions and in response to 1,25 (OH)2D3. Artif Cells Blood Substit Immobil Biotechnol. 2002;30:219–227. 25. NIH Consensus Development Panel on osteoporosis prevention, Diagnosis, and Therapy, March 7–29, 2000: Highlights of the conference. South Med J. 2001;94:569–573. 26. Wong MM, Rao LG, Ly H, et al. In vitro study of osteoblastic cells from patients with idiopathic osteoporosis and comparison with cells from non-osteoporotic controls. Osteoporos Int. 1994;4:21–31. 27. Neidlinger-Wilke C, Stalla I, Claes L, et al. Human osteoblasts from younger normal and osteoporotic donors show differences in proliferation and TGF betarelease in response to cyclic strain. J Biomech. 1995;28:1411–1418. 28. Abraham A, Cohen A, Shane E. Premenopausal bone health: Osteoporosis in premenopausal women. Clin Obstet Gynecol. 2013;56:722–729. 29. Corina M, Vulpoi C, Branisteanu D. Relationship between bone mineral density, weight, and estrogen levels in pre and postmenopausal women. Rev Med Chir Soc Med Nat Iasi. 2012;116:946–950.
685
30. Erdogan O, Shafer DM, Taxel P, et al. A review of the association between osteoporosis and alveolar ridge augmentation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;104:738 e1–738 e13. 31. Holahan CM, Koka S, Kennel KA, et al. Effect of osteoporotic status on the survival of titanium dental implants. Int J Oral Maxillofac Implants. 2008;23: 905–910. 32. Almagro MI, Roman-Blas JA, et al. PTH [1-34] enhances bone response around titanium implants in a rabbit model of osteoporosis. Clin Oral Implants Res. 2013;24:1027–1034. 33. Heydecke G, Boudrias P, Awad MA, et al. Within-subject comparisons of maxillary fixed and removable implant prostheses: Patient satisfaction and choice of prosthesis. Clin Oral Implants Res. 2003;14:125–130. 34. Tabassum A, Meijer GJ, Wolke JG, et al. Influence of surgical technique and surface roughness on the primary stability of an implant in artificial bone with different cortical thickness: A laboratory study. Clin Oral Implants Res. 2010;21:213–220. 35. Tabassum A, Meijer GJ, Wolke JG, et al. Influence of the surgical technique and surface roughness on the primary stability of an implant in artificial bone with a density equivalent to maxillary bone: A laboratory study. Clin Oral Implants Res. 2009;20:327–332. 36. Srivastava M, Deal C. Osteoporosis in elderly: Prevention and treatment. Clin Geriatr Med. 2002;18:529–555. 37. Xia J, Zhong Y, Huang G, et al. The relationship between insulin resistance and osteoporosis in elderly male type 2 diabetes mellitus and diabetic nephropathy. Ann Endocrinol (Paris). 2012;73:546–551. 38. Zhang Y, Yang JH. Activation of the PI3K/Akt pathway by oxidative stress mediates high glucose-induced increase of adipogenic differentiation in primary rat osteoblasts. J Cell Biochem. 2013;114: 2595–2602. 39. Marie PJ, Kassem M. Extrinsic mechanisms involved in age-related defective bone formation. J Clin Endocrinol Metab. 2011;96:600–609. 40. de Jonge LT, Leeuwenburgh SC, Wolke JG, et al. Organic-inorganic surface modifications for titanium implant surfaces. Pharm Res. 2008;25:2357–2369. 41. Yang Y, Bumgardner JD, Cavin R, et al. Osteoblast precursor cell attachment on heat-treated calcium phosphate coatings. J Dent Res. 2003;82:449–453. 42. Veltri M, Gonzalez-Martin O, Belser UC. Influence of simulated bone-implant contact and implant diameter on secondary stability: A resonance frequency in vitro study. Clin Oral Implants Res. 2014;25: 889–904.
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Appendix A: List of Excluded Studies. Reason for Exclusion Is Shown in Parenthesis Xiao JR, Li DH, Chen YX, et al. Evaluation of fixation of expandable implants in the mandibles of ovariectomized sheep. J Oral Maxillofac Surg. 2013;71:682–688. (Focused question not answered) Irish J, Virdi AS, Sena K, et al. Implant placement increases bone remodeling transiently in a rat model. J Orthop Res. 2013;31:800–806. (Focused question not answered) Li CY, Zhou YM, Wang L, et al. Effect of alendronate sodium on torque-out testing on implant-bone interfaces in estrogen-deficient rabbits with alendronate systemic administration [in Chinese]. Hua Xi Kou Qiang Yi Xue Za Zhi. 2011;29:233–236. Linderbäck P, Areva S, Aspenberg P, et al. Sol-gel derived tetania coating with immobilized bisphosphonate enhances screw fixation in rat tibia. J Biomed Mater Res A. 2010;94:389–395. (Focused question not answered) Carvalho CM, Carvalho LF, Costa LJ, et al. Titanium implants: A removal torque study in osteopenic rabbits. Indian J Dent Res. 2010;21:349–352. (Focused question not answered) Li JP, Zhang WQ, Yu J, et al. The effect of experimental osteoporosis on bone healing of
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autologous iliac crest graft around implants [in Chinese]. Hua Xi Kou Qiang Yi Xue Za Zhi. 2010;28:435–438. Glösel B, Kuchler U, Watzek G, et al. Review of dental implant rat research models simulating osteoporosis or diabetes. Int J Oral Maxillofac Implants. 2010;25:516–524. (Review article) Goldhahn J, Neuhoff D, Schaeren S, et al. Osseointegration of hollow cylinder based spinal implants in normal and osteoporotic vertebrae: A sheep study. Arch Orthop Trauma Surg. 2006;126:554–561. (Focused question not answered) Cho P, Schneider GB, Krizan K, et al. Examination of the bone-implant interface in experimentally induced osteoporotic bone. Implant Dent. 2004;13:79–87. (Focused question not answered) Duarte PM, César Neto JB, Gonçalves PF, et al. Estrogen deficiency affects bone healing around titanium implants: A histometric study in rats. Implant Dent. 2003;12:340–346. (Focused question not answered) Ozawa S, Ogawa T, Iida K, et al. Ovariectomy hinders the early stage of bone-implant integration: Histomorphometric, biomechanical, and molecular analyses. Bone. 2002;30:137–143. (Focused question not answered)
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Yoshinari M, Oda Y, Inoue T, et al. Bone response to calcium phosphate-coated and bisphosphonate-immobilized titanium implants. Biomaterials. 2002;23:2879–2885. (Focused question not answered) Lugero GG, de Falco Caparbo V, Guzzo ML, et al. Histomorphometric evaluation of titanium implants in osteoporotic rabbits. Implant Dent. 2000;9:303–309. (Focused question not answered) Pan J, Shirota T, Ohno K, et al. Effect of ovariectomy on bone remodeling adjacent to hydroxyapatite-coated implants in the tibia of mature rats. J Oral Maxillofac Surg. 2000;58:877–882. (Focused question not answered) Yamazaki M, Shirota T, Tokugawa Y, et al. Bone reactions to titanium screw implants in ovariectomized animals. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1999;87:411–418. (Focused question not answered) Mori H, Manabe M, Kurachi Y, et al. Osseointegration of dental implants in rabbit bone with low mineral density. J Oral Maxillofac Surg. 1997;55:351–361; discussion 362. (Focused question not answered) Maugars Y, Berthelot JM, Delécrin J, et al. Dual-energy X-ray absorptiometry: Value in orthopedics [in French]. Rev Chir Orthop Reparatrice Appar Mot. 1995;81:326–332.
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Significance of Osteogenic Surface Coatings on Implants to Enhance Osseointegration Under Osteoporotic-like Conditions Fawad Javed, BDS, PhD,* Fahim Vohra, BDS, MClinDent,† Sohail Zafar, BDS, MSc, PhD,‡ and Khalid Almas, BDS, MSc§
t is well acknowledged that the quality and quantity of host bone, presence of sufficient primary stability at the time of implant placement and formation of a direct bone-to-implant contact (BIC) are critical parameters that govern the overall success and survival of implants.1–4 However, implant surface characteristics (including surface topography, energy, chemistry, and roughness) also play significant roles in enhancing osseointegration and BIC. Studies have reported that increasing surface roughness of implants favors osteoblastic proliferation, collagen synthesis, and expression of integrins in the extracellular matrix, thereby improving the mechanisms associated with osseointegration.5–12 In this regard, some studies placed localized organic and inorganic osteogenic coatings on implant surfaces in an attempt to
I
*Assistant Professor, Engineer Abdullah Bugshan Research Chair for Growth Factors and Bone Regeneration, 3D Imaging and Biomechanical Laboratory, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia. †Assistant Professor, Department of Prosthetic Dental Sciences, College of Dentistry, King Saud University, Riyadh, Saudi Arabia. ‡Assistant Professor, Department of Dental Biomaterials, College of Dentistry, Taibah University, Madinah, Saudi Arabia. §Professor, Division of Periodontology, College of Dentistry, University of Dammam, Dammam, Saudi Arabia.
Reprint requests and correspondence to: Fawad Javed, BDS, PhD, Engineer Abdullah Bagshan Research Chair for Growth Factors and Bone Regeneration, 3D Imaging and Biomechanical Laboratory, College of Applied Medical Sciences, King Saud University, PO Box 60169, Riyadh 11545, Saudi Arabia, Phone: +966 50 968 6328, Fax: +96614678639, E-mail: [email protected] ISSN 1056-6163/14/02306-679 Implant Dentistry Volume 23 Number 6 Copyright © 2014 by Lippincott Williams & Wilkins DOI: 10.1097/ID.0000000000000161
Purpose: The aim was to assess the significance of osteogenic surface coatings on implants to enhance osseointegration under osteoporoticlike (OP-like) conditions. Methods: To address the focused question “Do osteogenic surface coatings on implants enhance osseointegration under OP-like conditions?” PubMed/MEDLINE and Google-Scholar databases were searched from 1995 up to and including February 2014 using various keywords. Unpublished data, letters to the editor, review articles, and articles published in languages other than English were excluded. Results: Of the 28 studies identified, 11 experimental studies were included. These studies were performed on bilaterally ovariectomized animals. In all studies, implant surface roughness was increased by various osteogenetic surface coat-
ings including alumina, hydroxyapatite, calcium phosphate, and zoledronic acid. Nine studies reported that compared with noncoated surfaces, osteogenic coatings on implant surfaces increases bone volume and bone-to-implant contact (BIC) under OP-like conditions. In 2 studies, there was no difference in BIC around hydroxyapatite-coated implants placed in animals with and without OP-like conditions. Conclusion: Osteogenic coatings on implant surfaces enhanced osseointegration in animals with OP-like conditions. However, additional clinical studies are warranted to assess the role of osteogenic coatings in increasing osseointegration in patients with osteoporosis. (Implant Dent 2014;23:679–686) Key Words: bone-to-implant contact, coating, implant surface, osseointegration and osteoporosis
improve implant surface activity and osteopromotive activity.13–23 Osteoporosis is a metabolic disease of bone characterized by low bone mineral density (BMD) and reduced bone mass due to impaired bone metabolism and imbalanced osteoblastic and osteoclastic activities.24,25 In osteoporotic bone, osteoblasts demonstrate impaired proliferative, synthetic, and reactive
ability to cellular mediators.24,26,27 Underlying causes of osteoporosis include premenopausal and postmenopausal estrogen deficiency, excessive glucocorticoid intake, eating disorders such as anorexia nervosa and celiac disease.28,29 Although the bone quality and strength are compromised in osteoporotic patients (compared with healthy individuals) because of low BMD and
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osteoregenerative capacity of osteoporotic bone, osteoporosis is not considered a contraindication for implant placement.30,31 Because optimal bone volume (BV) and BIC are critical in establishing implant stability in bones with low BMD, and that implant surface topography influences the mechanisms of osseointegration, it is hypothesized that implant surfaces with osteogenic coatings increase osteoblastic activity thereby enhancing BV and BIC under osteoporotic-like (OP-like) conditions as compared with implants with noncoated surfaces.13,14,32,33 The aim of this study was to review the significance of osteogenic coatings on implant surfaces in enhancing osseointegration under OP-like conditions.
MATERIALS
AND
METHODS
Focused Question
The addressed focused question was “Do osteogenic coatings around implant surfaces enhance osseointegration under OP-like conditions?” Eligibility Criteria
The following eligibility criteria were entailed: (1) original studies; (2) clinical and experimental studies; (3) intervention: role of modifications in Titanium (Ti) implant surfaces in enhancing osseointegration in OP-like conditions; (4) articles published only in English language. Letters to the Editor, commentaries, case reports, review articles, and unpublished articles were excluded. Search Strategy
To address the focused question, PubMed/MEDLINE (National Library of Medicine, Bethesda, MD) and GoogleScholar databases were searched from 1995 up to and including February 2014 using different combinations of the following key words: “bone,” “implant surface,” “osseointegration,” “osteoporosis,” and “ovariectomy” (Fig. 1). Titles and abstracts of studies that fulfilled the eligibility criteria were screened by the authors and checked for agreement. Full texts of studies judged by title and abstract to be relevant were read and independently assessed against the selection protocol. After this, reference lists of original and review studies that were found to be pertinent in the
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Fig. 1. A schematic presentation of the literature search strategy used in this study. PubMed/ MEDLINE and Google-Scholar databases were searched from 1995 up to and including February 2014 using various key words. Letters to the editor, reviews, case reports, unpublished studies, and articles published in languages other than English were excluded. Disagreements among the authors regarding study selection were resolved through discussion.
previous step were handsearched and checked for agreement through discussion among the authors. The initial search yielded 28 studies. Seventeen studies, which did not fulfill our eligibility criteria, were excluded (Appendix A). In total, 11 studies were included and processed for data extraction.
RESULTS General Characteristics of the Studies
The general characteristics of the studies that were included in the present
systematic review are summarized in Table 1. All studies were experimental and were performed at University settings.13–23 Rats, rabbits, and sheep were used in 5, 4, and 2 studies, respectively.13–23 In these studies, the mean ages of rats, rabbits, and sheep ranged between 3 to 10 months, 6 to 15 months, and 2 to 7, years, respectively.13–23 In all studies, the animals underwent bilateral ovariectomy (OVX) for the induction of OP-like conditions (Table 2).13–23 The follow-up period after implant placement ranged between 1 and 16 weeks. In studies by Fini et al19 and Mardas et al,20 implants were placed in the
Table 1. General Characteristics of Studies That Fulfilled Our Eligibility Criteria Authors 13
Alghamdi et al Alghamdi et al14 Yang et al15 Qi et al16 Jung et al17 De Benedittis et al18 Fini et al19 Mardas et al20 Vidigal et al21 Gao et al22 Borsari et al23
Study Design
Subjects
Mean Age (mo)
Experimental Experimental Experimental Experimental Experimental Experimental Experimental Experimental Experimental Experimental Experimental
15 rats 24 rats 48 rats 56 rabbits 36 rabbits 36 rats 8 sheep 36 rabbits 20 rabbits 40 rats 15 sheep
3 3 NA NA 15 10 48 6 12 NA Young sheep: 24 Aged sheep: 108 Aged OVX sheep: 84
NA indicates not available; OVX, ovariectomized.
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Table 2. Study Grouping and Implant-Related Characteristics of Studies That Fulfilled Our Eligibility Criteria Authors Alghamdi et al13
Study Groups Group 1: 15 OVX rats
Implants Placed in Femoral condyle
Group 2: 15 rats without OVX Alghamdi et al14
Yang et al15
Qi et al16
Group 1: 13 OVX rats
Group 2: 11 rats without OVX Group 1: 64 OVX rats with simvastatin treatment Group 2: 32 OVX rats without simvastatin treatment
Group 1: 40*‡ OVX rabbits
Femoral condyle
Tibia
Tibia
Group 2: 16*‡ without OVX
Jung et al17
De Benedittis et al18
Group 1: 12 OVX rabbits treated with alendronate-Na tablets Group 2: no treatment in 12 OVX rabbits Group 3: Sham surgery (controls) Group 1: 10 OVX rabbits
Group 2: 10 rabbits without OVX
Implant Surface Modifications Implant I: CaP coated
Implant II: collagen type1 coated Implant III: non-coated Group a: 13 CaP coated and 13 non-coated
Group b: 11 CaP coated and 11 non-coated Group 1a: implants† coated with 10−7 mol/L simvastatin Group 1b: implants† coated with 10−6 mol/L simvastatin Group 2: implants without simvastatin coating Group 1a: OVX alone
Follow-up (wk) 12
BV and BIC were higher around implants I and II than implant III
8
BV and BIC were higher around CaP coated implants in both groups
1, 2, 4, and 12
In groups 1a and 1b, BV increased after 1 wk In group 2, BV increased after 2 wk
12
Group 1b: local ZOL
Parietal bones
Tibia
Group 1c: systemic ZOL Group 1d: local + systemic ZOL Group 2: Sham surgery (controls) In each group, one modSLA and one SLA titanium dome was placed
In each group, implants with 3 types of surfaces were placed
Outcome
At all time points, BV and BIC were higher in groups 1a and 1b than group 2 BV and BIC were higher in groups 1b, 1c, and 1d Highest increase in BV and BIC occurring in group 1d compared with group 2
4 and 16
modSLA Ti surface increased BIC and new bone formation in all groups compared with SLA surfaces
16
No difference in BIC among the implants placed in groups 1 and 2
a) Ti implant b) HA-PS implant c) Implant coated with HA with biomimetic process (continued on next page)
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Table 2. (Continued) Authors Fini et al
Study Groups 19
Mardas et al20
40 OVX rats
Group 1: 5 young sheep
Implants Placed in Tibia
Tibia
Group 2: 5 aged sheep
Vidigal et al21
Group 3: 5 aged OVX sheep Group 1: 4 OVX sheep
Gao et al22
Group 2: 4 Sham operated sheep Group 1: 18 OVX rabbits
Group 1: 18 OVX rats
Group 2: 18 sham operated rats
Implants were immersed in 4 different solutions before placement Group a: water
Group b: ZOL Group c: bFGF Group d: ZOL + bFGF Implant I: implants with a single Ti coating
Follow-up (wk)
Outcome
12
BV and BIC were higher in groups b, c, and d than group a Highest BV and BIC were observed in group d compared with groups b and c
12
Affinity index§ for implant II was higher than implant I in all groups with no significant differences between groups
16
Bone hardness and BIC were significantly high around implant II than implant I
12
All implant surfaces in group 2 showed higher BV and BIC compared with group 2
8
All bioactive ceramics were bound to bone with no significant differences between implants in groups 1 and 2
Implant II: implants with a duplex coating of HA over Ti
L3, L4, and L5
Tibia
Group 2: 18 rabbits without OVX Borsari et al23
Implant Surface Modifications
Femoral condyle
Implant I: uncoated screws
Implant II: HA-coated screws Implant I: machined surface
Implant II: aluminacoated surface Implant III: HA-coated Implant I: HA-coated
Implant II: aluminacoated Implant III: zirconia coated Implant IV: coated with biological glasses Implant V: coated with Ti-6Al-4V alloy
*Five rabbits were killed to determine the preoperative BMD. †Implants were sterilized with ultraviolet light. ‡Eight rabbits were sacrificed at 3 months to determine preoperative BMD. §(Length of bone directly opposing the implant divided by the total length of the bone-implant interface) 3 100. 1,25(OH)(2)D(3) indicates 1,25 dihydroxy vitamin D(3); alendronate-Na, alendronate-sodium; bFGF, basic fibroblast growth factor; HA-PS, hydroxyapatite coated and plasma sprayed; modSLA, modifiedetched hydrophilic titanium; NA, not available; OVX, ovariectomized; PTH, parathyroid hormone; SLA, etched titanium; SS, stainless steel.
IMPLANT DENTISTRY / VOLUME 23, NUMBER 6 2014 parietal bone and lumbar vertebrae, respectively. In the remaining studies, implants were either placed in the femoral condyle or tibia (Table 2).13–18,21–23 Implant-Related Characteristics of the Studies
Table 3 summarizes the implantrelated characteristics of the studies that
fulfilled our eligibility criteria. In these studies, the numbers of implants placed ranged between 48 and 144.13–23 In 6 studies, cylindrical implants were used.13,14,17,19,22,23 Screw-shaped implants were used in 4 studies.15,16,18,20 The lengths and diameters of implants used ranged between 3 to 30 mm and 2 to 5 mm, respectively. In 9 studies,
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osteogenic coatings were placed on Ti implants.13–16,20–23 In one study, stainless steel screws were coated with osteogenic materials.19 In all studies, rough-surfaced dental implants were used. In the study by De Benedittis et al,18 implants composed of different materials (including Ti, hydroxyapatite [HA], and zirconia) were used. In
Table 3. Implant-Related Characteristics of the Studies Included Authors Alghamdi et al13
Alghamdi et al14 Yang et al15
Implant Length (mm)
Implant Diameter (mm)
Cylindrical
5
2.85
Grit-blasted Ti implants coated with CaP or collagen type-1 coating
Cylindrical
5
2
192
Screwshaped
4
2.2
80
Screwshaped Cylindrical
12
2
10
3.8
Grit-blasted Ti implants with and without CaP coating Grit-blasted Ti implants treated with hydrofluoric acid/nitric acid solution and hydrochloric acid/ sulfuric acid solutions HA and ZOL coated Ti implants Machined, sand-blasted, or HA-coated implants
30 CaP or Collagen type-1 coated implants 30 non-coated implants 48
Qi et al16 Jung et al17
Implant Shape
No. of Implants Placed
De Benedittis et al18
48 implants with machined surface 48 oxidized implant surfaces 48 HA-coated implants 54 implants with different coatings in OVX rats
Fini et al19
54 implants with different coatings in Shamoperated rats 16 uncoated SS screws
Mardas et al20
16 HA-coated SS screws 72 discs*
Screwshaped
3
Cylindrical
30
3*
60
Screwshaped NA
10
3.8
20 implants in distilled water
Cylindrical
12
1
Cylindrical
12
3.5
Vidigal et al21
Gao et al22
Borsari et al23
20 implants 20 implants 20 implants 30 implants coating
in ZOL in bFGF in ZOL + bFGF with a single Ti
Implant Surface Characteristics
2
HA, sand-blasted, Zirconia, bioactive glass, and Tialloy coatings
4.1
SS implants with and without HA-coating
5*
30 Ti implants with a duplex coating of HA *Titanium discs were placed on induced parietal bone defects. bFGF indicates basic fibroblast growth factor; HA-PS, hydroxyapaptite coated and plasma sprayed; NA, not available; SS, stainless steel.
36 modSLA Ti discs and 36 SLA discs HA-PS Ti implant surfaces and Ti implants coated with HA with biomimetic process HA-coated Ti implants immersed in water, ZOL, bFGF, or ZOL + bFGF
Implants with a single Ti coating or implants with HA-coating over Ti
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2 studies, calcium phosphate (CaP)– coated implants were used.13,14 Zoledronic acid (ZOL)–coated implant surfaces were used in 2 studies.16,22 Three studies assessed the effect of implants with and without a duplex coating of HA on osseointegration under OP-like conditions.19,21,23 Jung et al17 compared the efficacy of alumina-coated and HA-coated implants with machined surfaces in achieving osseointegration under OP-like conditions. In a study on rat models, efficacy of fibroblast growth factor with and without adjunct ZOL coating in increasing BV and BIC was assessed.22 In one study, Ti implants were dipped in 2 different concentrations of a hypolipidemic drug before insertion in rat tibia.15 Main Outcome of Studies
Outcomes of all studies were based on histomorphometric analyses and/or microcomputotomographic assessment of region of interest (ie, bone-implant interface at the test and control sites).13– 23 In 9 studies, BV and BIC were significantly higher around coated implants as compared with non-coated implants placed in subjects with OP-like conditions.13–20,22 In 2 studies, there was no significant difference in BIC around HA-coated and non-coated implants placed in subjects with OP-like conditions.21,23
DISCUSSION From the literature reviewed, nearly 80% of studies reported that osteogenic coatings around implant surfaces enhance bone formation, BIC, and BV under OP-like conditions. This could possibly be accredited to the increase in surface roughness of the implant caused by osteogenic coatings, which facilitate the attachment of osteoprogenitor cells to the implant surface. Studies have also reported that implant surface roughness is directly associated with the degree of primary stability achieved and long-term success rate of the implant.4,34,35 Based on these results, it is tempting to presume that rough-surfaced implants promote bone formation around implants in systemically healthy subjects and osteoporotic patients. However, it is pertinent to
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mention that all results included in the present review were derived from studies based on animal models. In these studies, OP-like conditions were established within 4 weeks to 24 months of OVX.13–23 From a clinical perspective, it is known that advancing age is a significant risk factor of osteoporosis.36 Therefore, it may be questioned whether OP-like conditions induced in the experimental studies included in the present review truly replicate a clinical scenario of osteoporosis. In addition, hyperglycemia is a common manifestation in elderly patients with osteoporosis.37 It is known that chronic hyperglycemia and aging undermine the differentiation and growth of osteoprogenitor cells.38,39 Therefore, it is hypothesized that merely using implants with osteogenic coatings in osteoporotic patients is unable to significantly enhance new bone formation. We support the experimental results by Borsari et al23 in which HA-coated implants placed in aged sheep (with and without OVX) demonstrated no significant difference in their affinity indexes. It is noteworthy that the choice of coating materials varied among the included studies. For example, results by Alghamdi et al13,14 showed that coating implant surfaces with CaP is effective in enhancing BIC and BV around implants compared with non-coated implants. An explanation in this regard may be that coating implants with CaP increases the attachment of osteoblastlike cells and mesenchymal stem cells on implant surfaces, and adsorption of proteoglycans that in turn promote osteogenic cell migration toward the implant surface.40,41 Likewise, 2 studies reported that ZOL-coated implants exhibit superior osseointegration under OP-like conditions compared with noncoated implants.16,22 It has been proposed that under OP-like conditions, ZOL coatings improve osseointegration of HA-coated implants by converting the rod-like structure of trabeculae (after estrogen deficiency) to the platelike structure thereby increasing bone mass around implants and improving implant fixation.22 However, it has also been reported that coating implant surfaces with growth factors + ZOL gives
ET AL
the highest BIC than when ZOL is used alone.22 In this regard, we find it exigent to elect a single implant coating material that would be most suitable for increasing osseointegration under OPlike conditions. Results from a recent experimental study showed that the secondary stability of implants is associated with the BIC, and the role of implant diameter in this context is insignificant.42 From the literature reviewed, we observed that implants used in the respective studies varied in diameters; however, histologic outcomes of most studies revealed significantly more BIC around coated implants compared with non-coated surfaces in animals with and without OP-like conditions. In general, outcomes of studies included in the present review are in accordance with those reported by Veltri et al.42
CONCLUSION On experimental grounds, osteogenic surface coatings on implants enhanced osseointegration under OP-like conditions; however, additional long-term prospective clinical trials are warranted to assess the role of osteogenic coatings in increasing osseointegration in humans with osteoporosis.
DISCLOSURE The authors claim to have no financial interest, either directly or indirectly, in the products or information listed in the article.
REFERENCES 1. Pinholt EM. Brånemark and ITI dental implants in the human bone-grafted maxilla: A comparative evaluation. Clin Oral Implants Res. 2003;14:584–592. 2. Schulz MC, Korn P, Stadlinger B, et al. Coating with artificial matrices from collagen and sulfated hyaluronan influences the osseointegration of dental implants. J Mater Sci Mater Med. 2014;25: 247–258. 3. Javed F, Romanos GE. The role of primary stability for successful immediate loading of dental implants. A literature review. J Dent. 2010;38:612–620. 4. Javed F, Almas K, Crespi R, et al. Implant surface morphology and primary
IMPLANT DENTISTRY / VOLUME 23, NUMBER 6 2014 stability: Is there a connection? Implant Dent. 2011;20:40–46. 5. Wang J, An Y, Li F, et al. The effects of pulsed electromagnetic field on the functions of osteoblasts on implant surfaces with different topographies. Acta Biomater. 2014;10:975–985. 6. Olivares-Navarrete R, Hyzy SL, Gittens RA, et al. Rough titanium alloys regulate osteoblast production of angiogenic factors. Spine. 2013;13:1563–1570. 7. Durual S, Pernet F, Rieder P, et al. Titanium nitride oxide coating on rough titanium stimulates the proliferation of human primary osteoblasts. Clin Oral Implants Res. 2011;22:552–559. 8. Mendonca DB, Miguez PA, Mendonca G, et al. Titanium surface topography affects collagen biosynthesis of adherent cells. Bone. 2011;49: 463–472. 9. Le Guehennec L, Soueidan A, Layrolle P, et al. Surface treatments of titanium dental implants for rapid osseointegration. Dent Mater. 2007;23:844–854. 10. Schouten C, Meijer GJ, van den Beucken JJ, et al. In vivo bone response and mechanical evaluation of electrosprayed CaP nanoparticle coatings using the iliac crest of goats as an implantation model. Acta Biomater. 2010;6:2227–2236. 11. Shibli JA, Vitussi TR, Garcia RV, et al. Implant surface analysis and microbiologic evaluation of failed implants retrieved from smokers. J Oral Implantol. 2007;33:232–238. 12. Noro A, Kaneko M, Murata I, et al. Influence of surface topography and surface physicochemistry on wettability of zirconia (tetragonal zirconia polycrystal). J Biomed Mater Res B Appl Biomater. 2013;101:355–363. 13. Alghamdi HS, Bosco R, van den Beucken JJ, et al. Osteogenicity of titanium implants coated with calcium phosphate or collagen type-I in osteoporotic rats. Biomaterials. 2013;34:3747–3757. 14. Alghamdi HS, Cuijpers VM, Wolke JG, et al. Calcium-phosphate-coated oral implants promote osseointegration in osteoporosis. J Dent Res. 2013;92:982–988. 15. Yang G, Song L, Guo C, et al. Bone responses to simvastatin-loaded porous implant surfaces in an ovariectomized model. Int J Oral Maxillofac Implants. 2012;27:369–374. 16. Qi M, Hu J, Li J, et al. Effect of zoledronate acid treatment on osseointegration and fixation of implants in autologous iliac bone grafts in ovariectomized rabbits. Bone. 2012;50:119–127. 17. Jung YC, Han CH, Lee IS, et al. Effects of ion beam-assisted deposition of hydroxyapatite on the osseointegration of endosseous implants in rabbit tibiae. Int J Oral Maxillofac Implants. 2001;16:809–818.
18. De Benedittis A, Mattioli-Belmonte M, Krajewski A, et al. In vitro and in vivo assessment of bone-implant interface: A comparative study. Int J Artif Organs. 1999;22:516–521. 19. Fini M, Giavaresi G, Greggi T, et al. Biological assessment of the bone-screw interface after insertion of uncoated and hydroxyapatite-coated pedicular screws in the osteopenic sheep. J Biomed Mater Res Part A. 2003;66:176–183. 20. Mardas N, Schwarz F, Petrie A, et al. The effect of SLActive surface in guided bone formation in osteoporotic-like conditions. Clin Oral Implants Res. 2011; 22:406–415. 21. Vidigal GM Jr, Groisman M, Gregorio LH, et al. Osseointegration of titanium alloy and HA-coated implants in healthy and ovariectomized animals: A histomorphometric study. Clin Oral Implants Res. 2009;20:1272–1277. 22. Gao Y, Luo E, Hu J, et al. Effect of combined local treatment with zoledronic acid and basic fibroblast growth factor on implant fixation in ovariectomized rats. Bone. 2009;44:225–232. 23. Borsari V, Fini M, Giavaresi G, et al. Osteointegration of titanium and hydroxyapatite rough surfaces in healthy and compromised cortical and trabecular bone: In vivo comparative study on young, aged, and estrogen-deficient sheep. J Orthop Res. 2007;25:1250–1260. 24. Torricelli P, Fini M, Giavaresi G, et al. Human osteoblast cultures from osteoporotic and healthy bone: Biochemical markers and cytokine expression in basal conditions and in response to 1,25 (OH)2D3. Artif Cells Blood Substit Immobil Biotechnol. 2002;30:219–227. 25. NIH Consensus Development Panel on osteoporosis prevention, Diagnosis, and Therapy, March 7–29, 2000: Highlights of the conference. South Med J. 2001;94:569–573. 26. Wong MM, Rao LG, Ly H, et al. In vitro study of osteoblastic cells from patients with idiopathic osteoporosis and comparison with cells from non-osteoporotic controls. Osteoporos Int. 1994;4:21–31. 27. Neidlinger-Wilke C, Stalla I, Claes L, et al. Human osteoblasts from younger normal and osteoporotic donors show differences in proliferation and TGF betarelease in response to cyclic strain. J Biomech. 1995;28:1411–1418. 28. Abraham A, Cohen A, Shane E. Premenopausal bone health: Osteoporosis in premenopausal women. Clin Obstet Gynecol. 2013;56:722–729. 29. Corina M, Vulpoi C, Branisteanu D. Relationship between bone mineral density, weight, and estrogen levels in pre and postmenopausal women. Rev Med Chir Soc Med Nat Iasi. 2012;116:946–950.
685
30. Erdogan O, Shafer DM, Taxel P, et al. A review of the association between osteoporosis and alveolar ridge augmentation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;104:738 e1–738 e13. 31. Holahan CM, Koka S, Kennel KA, et al. Effect of osteoporotic status on the survival of titanium dental implants. Int J Oral Maxillofac Implants. 2008;23: 905–910. 32. Almagro MI, Roman-Blas JA, et al. PTH [1-34] enhances bone response around titanium implants in a rabbit model of osteoporosis. Clin Oral Implants Res. 2013;24:1027–1034. 33. Heydecke G, Boudrias P, Awad MA, et al. Within-subject comparisons of maxillary fixed and removable implant prostheses: Patient satisfaction and choice of prosthesis. Clin Oral Implants Res. 2003;14:125–130. 34. Tabassum A, Meijer GJ, Wolke JG, et al. Influence of surgical technique and surface roughness on the primary stability of an implant in artificial bone with different cortical thickness: A laboratory study. Clin Oral Implants Res. 2010;21:213–220. 35. Tabassum A, Meijer GJ, Wolke JG, et al. Influence of the surgical technique and surface roughness on the primary stability of an implant in artificial bone with a density equivalent to maxillary bone: A laboratory study. Clin Oral Implants Res. 2009;20:327–332. 36. Srivastava M, Deal C. Osteoporosis in elderly: Prevention and treatment. Clin Geriatr Med. 2002;18:529–555. 37. Xia J, Zhong Y, Huang G, et al. The relationship between insulin resistance and osteoporosis in elderly male type 2 diabetes mellitus and diabetic nephropathy. Ann Endocrinol (Paris). 2012;73:546–551. 38. Zhang Y, Yang JH. Activation of the PI3K/Akt pathway by oxidative stress mediates high glucose-induced increase of adipogenic differentiation in primary rat osteoblasts. J Cell Biochem. 2013;114: 2595–2602. 39. Marie PJ, Kassem M. Extrinsic mechanisms involved in age-related defective bone formation. J Clin Endocrinol Metab. 2011;96:600–609. 40. de Jonge LT, Leeuwenburgh SC, Wolke JG, et al. Organic-inorganic surface modifications for titanium implant surfaces. Pharm Res. 2008;25:2357–2369. 41. Yang Y, Bumgardner JD, Cavin R, et al. Osteoblast precursor cell attachment on heat-treated calcium phosphate coatings. J Dent Res. 2003;82:449–453. 42. Veltri M, Gonzalez-Martin O, Belser UC. Influence of simulated bone-implant contact and implant diameter on secondary stability: A resonance frequency in vitro study. Clin Oral Implants Res. 2014;25: 889–904.
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OSTEOGENIC SURFACE COATINGS
Appendix A: List of Excluded Studies. Reason for Exclusion Is Shown in Parenthesis Xiao JR, Li DH, Chen YX, et al. Evaluation of fixation of expandable implants in the mandibles of ovariectomized sheep. J Oral Maxillofac Surg. 2013;71:682–688. (Focused question not answered) Irish J, Virdi AS, Sena K, et al. Implant placement increases bone remodeling transiently in a rat model. J Orthop Res. 2013;31:800–806. (Focused question not answered) Li CY, Zhou YM, Wang L, et al. Effect of alendronate sodium on torque-out testing on implant-bone interfaces in estrogen-deficient rabbits with alendronate systemic administration [in Chinese]. Hua Xi Kou Qiang Yi Xue Za Zhi. 2011;29:233–236. Linderbäck P, Areva S, Aspenberg P, et al. Sol-gel derived tetania coating with immobilized bisphosphonate enhances screw fixation in rat tibia. J Biomed Mater Res A. 2010;94:389–395. (Focused question not answered) Carvalho CM, Carvalho LF, Costa LJ, et al. Titanium implants: A removal torque study in osteopenic rabbits. Indian J Dent Res. 2010;21:349–352. (Focused question not answered) Li JP, Zhang WQ, Yu J, et al. The effect of experimental osteoporosis on bone healing of
ON IMPLANTS
JAVED
autologous iliac crest graft around implants [in Chinese]. Hua Xi Kou Qiang Yi Xue Za Zhi. 2010;28:435–438. Glösel B, Kuchler U, Watzek G, et al. Review of dental implant rat research models simulating osteoporosis or diabetes. Int J Oral Maxillofac Implants. 2010;25:516–524. (Review article) Goldhahn J, Neuhoff D, Schaeren S, et al. Osseointegration of hollow cylinder based spinal implants in normal and osteoporotic vertebrae: A sheep study. Arch Orthop Trauma Surg. 2006;126:554–561. (Focused question not answered) Cho P, Schneider GB, Krizan K, et al. Examination of the bone-implant interface in experimentally induced osteoporotic bone. Implant Dent. 2004;13:79–87. (Focused question not answered) Duarte PM, César Neto JB, Gonçalves PF, et al. Estrogen deficiency affects bone healing around titanium implants: A histometric study in rats. Implant Dent. 2003;12:340–346. (Focused question not answered) Ozawa S, Ogawa T, Iida K, et al. Ovariectomy hinders the early stage of bone-implant integration: Histomorphometric, biomechanical, and molecular analyses. Bone. 2002;30:137–143. (Focused question not answered)
ET AL
Yoshinari M, Oda Y, Inoue T, et al. Bone response to calcium phosphate-coated and bisphosphonate-immobilized titanium implants. Biomaterials. 2002;23:2879–2885. (Focused question not answered) Lugero GG, de Falco Caparbo V, Guzzo ML, et al. Histomorphometric evaluation of titanium implants in osteoporotic rabbits. Implant Dent. 2000;9:303–309. (Focused question not answered) Pan J, Shirota T, Ohno K, et al. Effect of ovariectomy on bone remodeling adjacent to hydroxyapatite-coated implants in the tibia of mature rats. J Oral Maxillofac Surg. 2000;58:877–882. (Focused question not answered) Yamazaki M, Shirota T, Tokugawa Y, et al. Bone reactions to titanium screw implants in ovariectomized animals. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1999;87:411–418. (Focused question not answered) Mori H, Manabe M, Kurachi Y, et al. Osseointegration of dental implants in rabbit bone with low mineral density. J Oral Maxillofac Surg. 1997;55:351–361; discussion 362. (Focused question not answered) Maugars Y, Berthelot JM, Delécrin J, et al. Dual-energy X-ray absorptiometry: Value in orthopedics [in French]. Rev Chir Orthop Reparatrice Appar Mot. 1995;81:326–332.
