The aim of this study was to compare the values of bone-implant contact (BIC) and removal torque (RTQ) reported in different animal studies for titanium–zirconium (TiZr) and titanium (Ti) dental implants. This review has been registered at PROSPERO under number CRD42016047745. We undertook an electronic search for data published up until November 2017 using the PubMed/Medline, Embase, and The Cochrane Library databases. Eligibility criteria included in vivo studies, comparisons between Ti and TiZr implants in the same study, and studies published in English that evaluated BIC and RTQ. After inclusion criteria, 8 studies were assessed for eligibility. Of the 8 studies, 7 analyzed BIC outcome and 3 analyzed RTQ outcome. Among such studies, 6 studies were considered for meta-analysis of quantitative for BIC and 2 studies for RTQ. There was no significant difference for BIC analysis (P = .89; random ration [RR]: −0.21; 95% confidence interval [CI]: −3.14 to 2.72). The heterogeneity of the primary outcome studies was considered low (7.19; P = .21; I2 : 30%). However, the RTQ analysis showed different results favoring the TiZr dental implants (P = .001; RR: 23.62; 95%CI: 9.15 to 38.10). Low heterogeneity was observed for RTQ (χ2: 1.25; P = .26; I2 : 20%). Within the limitations of this study, there was no difference between TiZr and Ti alloys implants in terms of BIC. However, TiZr implants had higher RTQ than Ti alloys.
The use of dental implants in oral rehabilitation to replace lost teeth (unitary or total) has improved patient quality of life.1 Currently, studies show high long-term survival rates for dental implants.2
Since the introduction of the osseointegration concept, several studies have tried to develop new materials to manufacture implants. Surface treatments have been developed to accelerate the osseointegration process, increasing the success of rehabilitation using dental implants.3,4 Two methods can be used to evaluate the quality of osseointegration in a quantitative manner: (1) bone-to-implant contact (BIC) that assesses the percentage of the bone formation (mature bone) in direct contact with the implant surface and (2) removal torque (RTQ) that calculates the torsional strength required to remove an inserted implant.5
Titanium (Ti) alloy is the main material used for manufacturing dental implants due to its excellent mechanical properties and biocompatibility.6,7 Currently, continuous technological developments offer new materials—such as zirconium (Zr)5 and titanium–zirconium alloy (TiZr)—as alternatives to titanium.8
Due to its aesthetic features, zirconia implants were developed for use especially in the anterior region; specifically, the anterior region has a thin gum and bone tissue, which may reveal the grayish color of the titanium implant.9 A recent systematic review reported that zirconia implants yield no difference related to degree of osseointegration for BIC: Ti (range: 24%–83%) and Zr (range: 27%–71%), while RTQ: Ti (range: 42–72 Ncm) and Zr (range: 12–92 Ncm). Thus, modified-surface zirconia may be a potential candidate for successful implant material.5
The TiZr alloy (Roxolid, Institut Straumann AG, Basel, Switzerland) originated from mixing an alloy of Ti with 13%–15% of Zr. This alloy has increased mechanical resistance than titanium alloys, with similar biocompatibility in the bone tissue.8 Because of this feature, TiZr alloy is recommended when manufacturing small diameter implants, mainly in regions with high occlusal overload.11,10 Furthermore, TiZr is compatible with the surface treatment applied to the titanium alloys. However, to date, there is limited literature on the BIC and RTQ of TiZr alloy implants.
Thus, this systematic review and meta-analysis has evaluated the performance of TiZr dental implants compared to Ti implants. The study used the following null hypotheses: (1) TiZr implants and Ti implants do not differentially affect the BIC rate, and (2) TiZr implants and Ti implants do not differentially affect RTQ values.
Materials and Methods
This systematic review was based on the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) checklist structure12 and in accordance with models proposed in published reports.13,14 Moreover, the methods for this systematic review were registered with PROSPERO CRD42016047745.
The eligible studies criteria used were the following characteristics: (1) in vivo studies, (2) comparisons between Ti and TiZr implants in the same study, and (3) studies published in English. Exclusion criteria were: (1) in vitro studies, (2) case reports, (3) computer simulations, (4) data repeated in another article, and (5) reviews.
The PICO approach—population, intervention, comparison, outcomes—was used to address the question: Do TiZr alloy implants have similar BIC and RTQ when compared with the titanium alloy implants? In this study, population was dental implants placed in the bone tissue, intervention was TiZr alloy implants placed in the bone tissue, and comparison was made with Ti alloy implant placed in the bone tissue. The primary outcome evaluated was the BIC, with the RT as a secondary outcome.
The selection of articles was done individually by 2 of the authors (R.S.C. and H.F.F.O.) who retrieved studies that evaluated the BIC and RTQ rates of TiZr alloy implants installed in the bone tissue compared to Ti alloys implants. Electronic searches were conducted at selected databases PubMed/Medline, Embase, and Cochrane Library for articles published until 10 November 2017 according to the eligibility criteria. The keywords used in this study were: “titanium zirconium,” “TiZr,” “Roxolid,” “dental implants,” “titanium,” “zirconium,” “titanium-zirconium,” and “Roxolid implant.” The terms have been grouped in the following ways: (1) Roxolid implant and dental, (2) titanium-zirconium and dental implant, (3) TiZr and dental implant, (4) titanium zirconium OR TiZr OR Roxolid, and (5) dental implants and titanium and zirconium and titanium–zirconium.
In addition, the two authors (R.S.C. and H.F.F.O.) conducted manual searches of the following journals for articles published up to November 2017: Clinical Oral Implants Research, Clinical Implant Dentistry and Related Research, International Journal of Oral and Maxillofacial Surgery, International Journal of Oral and Maxillofacial Implants, Journal of Oral and Maxillofacial Surgery, Journal of Clinical Periodontology, Journal of Oral Rehabilitation and Journal of Periodontology.
One of the authors (R.S.C.) collected relevant information from the articles, and a second author (H.F.F.O.) checked all collected information. A careful analysis was performed to check for disagreements among authors, and a third author (F.R.V.) discussed all disagreements between the investigators until consensus was obtained.
The meta-analysis was based on the inverse variance method. The effects of BIC and RTQ were the continuous outcome measures evaluated for mean difference (MD) and the corresponding 95% confidence intervals (CI) by random ratio (RR). The MD values were considered significant when P < .05. The I2 statistic was used to express the percentage of the total variation across studies due to heterogeneity, and I2 values above 75% (range 0–100) were considered high, indicating significant heterogeneity.15,16 In addition, in case of statistically significant (P < .10) for heterogeneity, a random-effects model was used to assess the significance of treatment effects. Where no statistically significant heterogeneity was found, analysis was performed using a fixed-effects model.17,18 In addition, a funnel plot (plot of effect size vs standard error) was drawn. Asymmetry of the funnel plot may indicate possible publication bias and other biases.17 Review Manager (RevMan version 5.3, The Nordic Cochrane Centre, The Cochrane Collaboration, London, UK) was used for the meta-analysis and to create the forest and funnel plots.
Two investigators (R.S.C, and H.F.F.O,) assessed the methodological quality of studies to show their quality according to levels of evidence as proposed by the methodological index for nonrandomized studies (MINORS) and based on different components to evaluate the included studies: a clearly state aim, inclusion of consecutive samples, prospective data collection, endpoints appropriate to the aim of the study, unbiased assessment of the study endpoint, follow-up period appropriate to the aim of the study, loss of sample up less than 5%, an adequate control group, contemporary groups, baseline equivalence of groups, and adequate statistical analysis. The items were scored 0 (not reported), 1 (reported but inadequate), or 2 (reported and adequate). The global ideal score was 24 for comparative studies.19
Additional analysis was performed, and a Kappa score was used to calculate the interreader agreement during the inclusion process for publication-evaluated databases.
The baseline search recovered 4664 titles and abstracts, including 1823 from PubMed/MEDLINE, 2739 from Embase, and 102 from the Cochrane Library. Of the articles retrieved using the initial search strategy, 13 articles were selected, and the full texts were read. After reading the full text for these studies, 5 studies were excluded and 8 studies were included in this systematic review. Of 8 studies, 7 analyzed the BIC outcome and 3 analyzed the RTQ outcome (Figure 1). Exclusion criteria are detailed in Table 1.
The interinvestigator agreement (Kappa) was calculated by evaluating the selected titles and abstracts. The values derived for the articles selected from PubMed/MEDLINE (kappa = 0.95), Embase (kappa = 0.93), and the Cochrane Library (kappa = 1.00), suggesting a high level of agreement between investigators.
The studies included in this systematic review focused the behavior of Ti and TiZr implants in animal models: Two studies used dog models,20,21 3 used mini pig models22–24 and 3 used rabbit models.25–27 The follow-up periods of the studies ranged from 3–16 weeks. The average age and weight of the animals included in this review varied from 9–74 months and 3–80 kg. Regarding the implants used, 195 were Ti alloy and 188 were TiZr alloy (383 total). Furthermore, 81 implants were used to analyze RQT (41 TiZr and 40 Ti), and 302 were used to analyze BIC (147 TiZr and 155 Ti).
The methodological quality of included studies evaluated by MINORS. Among in the selected studies in an overall ideal score of 24 possible points,19 four obtained 20 points,20,21,26,27 and the other four studies obtained 21 points,23 22 points,24 23 points,25 and 24 points.22 Thus, the included studies obtained good methodological quality. However, not all studies reported calculating sample size20,23,24,26,27 and performed blind evaluation of objective end points20,23,26,27 (Table 2).
Five of the eight studies were randomized controlled trials.20,22–24,26 Three studies realized Split Mouth format,22,23,25 and no complications were observed in any animals during the study period. The diameter and length of the implants varied from 3.3–4.8 mm and 6–8 mm, respectively. Descriptions of the main results of each included study were reported for BIC (Table 3) and RTQ (Table 4).
Six studies20–24,26 were considered for quantitative analysis for BIC and two studies for RTQ.22,27 A meta-analysis was performed to verify if Ti and TiZr showed similar results compared to BIC. A fixed-effect model found no statistically significant difference between Ti and TiZr for BIC (P = .89; RR: −0.21; 95% CI: −3.14 to 2.72; Figure 2). The heterogeneity of the primary outcome studies was considered low (7.19; P = .21; I2 : 30%; Figure 2). A subgroup analyzes according to type of animals were performed. No significant difference between Ti and TiZr for BIC for dogs (P = .51; RR: 1.53; 95% CI: −3.05 to 6.10), mini pigs (P = .29; RR: −2.29; 95% CI: −6.49 to 1.91) and rabbits (P = .56; RR: 2.70; 95% CI: −6.46 to 11.86; Figure 3).
However, the meta-analysis found that TiZr was favorable to Ti for RTQ (P = .001; RR: 23.62; 95% CI: 9.15 to 38.10; Figure 4). Low heterogeneity was observed for RTQ (χ2: 1.25; P = 0.26; I2 : 20%; Figure 4). Furthermore, the funnel plot showed clear symmetry for the BIC and RTQ analysis, indicating possible absence of publication bias (Figures 5 and 6).
In this systematic review, the first hypothesis was accepted since there was no difference between the BIC values for TiZr alloy implants compared with Ti alloy implants. BIC is a quantitative parameter that verifies by histomorphometric measure the percentage of mature bone5 and is evaluated by stability and the healing bone tissue.28 As noted in the results, BIC rate was similar for both alloys, independent of surface treatment applied to the tested implants.24,27
One possible reason for finding no difference between the two alloys is that the surface treatment for Ti implants was the same used for TiZr, without change of its biocompatibility.29,30 Both titanium and zirconium are transition metals in the same group of the periodic table and have similar chemical properties.18,24 Some studies have indicated that surface treatments carried out on the implants may contribute to increased surface roughness, favoring a greater contact area of the bone/implant.22,31
A second reason that may have favored BIC is bone remodeling around the surface of the implant. Through histological analysis, it was observed that the cells responsible for bone tissue formation were present at similar levels in both Ti and TiZr implants.30 Thus, even with the additional bone conductivity of the TiZr alloy, it was not affected and showed similarity to Ti implants.
The second hypothesis was rejected because the TiZr implants showed significantly higher RTQ values than did the Ti implants. RTQ calculates the interaction strength between the bone surface.32 The TiZr alloy was higher than Ti, likely because the physical and chemical properties of the titanium material were improved through combination with other metals.33,34 The TiZr alloy has been used previously as a biocompatible material,35,30 and it has a tensile strength 2.5 to 3 times greater than that of Ti alloy or even Zr.36 Moreover, the presence of Zr in the implant increases its corrosion resistance in biological fluids, decreasing the release to the tissues and possibly contributing to the increase in the amount of RTQ.37,38
It should be noted that the mandible presented higher removal torque values when compared with the tibia/femur—independent of alloy evaluated—and it may have another characteristic that might be influenced for larger torque values for that region, regardless of the animal model used.22,26,39
The TiZr alloy was developed especially for smaller diameter implants because the combination of Zr with Ti increases fatigue resistance35 since the smaller diameter titanium implants mainly have high failure rates in the posterior regions.36 Thus, for implants in the posterior regions, it may be desirable to choose TiZr alloy implants since studies have shown a success rate greater than 95% and approximately 100% survival.41,42 Müller et al43 conducted a 5-year follow-up study comparing 3.3-mm diameter TiZr implant with Ti grade IV in mandibular implant-based removable overdentures. The authors reported a success rate of 95.8% for TiZr alloy implants and 92.6% for Ti grade IV implants. In addition, the bone level changes at 5 years showed no difference (TiZr: −0.60 ± 0.69 mm; Ti Grade IV: −0.61 ± 0.83 mm; P = .96). Another clinical study44 compared 3.3-mm TiZr alloy implants with 4.1-mm Ti alloy implants in terms of marginal bone level and clinical parameters. After 1 year, the authors reported a success rate of 100% for both groups, with no significant difference for marginal bone loss reported (Ti: −0.40, ± 0.53 and TiZr: −0.41 ± 0.66). Thus, the use of narrow diameter TiZr implants can be considered a favorable alternative of treatment.45,46
As observed by previous studies,35,36 the TiZr alloy demonstrates higher mechanical resistance and can be indicated for implant placement, especially in the posterior region. However, these results should be interpreted with caution because this study did not include any clinical studies that compared the influence of alloy (Ti vs TiZr).39 However, the analysis of BIC and RTQ rates is considered of great importance clinically.5
Regarding the quality of included studies, an adaptation of the MINORS scale was used. It was possible to detect that all selected studies were of good methodological quality with a MINORS score range 20 to 24 (maximum of 24). However, we recommend further long-term randomized controlled clinical trials to assess the impact of data according to the behavior of different alloys.
The current meta-analysis of 8 animal models suggests that there is no difference between TiZr and Ti alloys implants in terms of BIC. However, TiZr had higher RTQ values than did Ti alloys implants.
methodological index for nonrandomized studies
ovariectomies (submitted to a hypocalcic diet)
SHAM operations (not submitted to a hypocalcic diet)
titanium machined collar surface
titanium modified acid-etched collar surface
titanium alloyed with zirconium modified acid-etched collar surface
The authors report no conflicts of interest.