This study compared the histological outcomes of deproteinized bovine bone (DBB) and technically derived calcium phosphate for sinus floor augmentation. MEDLINE, PubMed, Cochrane, EMBASE, and Google Scholar databases were searched until April 2015 with the following key words: dental implants, augmentation/augmented, calcium phosphate/ceramic/tricalcium phosphate, bovine bone/Bio-Oss, deproteinized/anorganic. Randomized controlled trials (RCTs) and two-arm prospective/retrospective studies that used DBB or biphasic calcium phosphate/tricalcium phosphate (BCP/TCP) for sinus augmentation with quantitative results were included. Outcomes were the percentage of new bone formed and percentage of surface contact between the graft material and new bone (bone-to-graft contact). Four RCTs and one prospective study were included, with a total of 110 patients and 145 implants. All studies reported the percentage of new vital bone; however, large heterogeneity was present ( Q = 15.23, P = 0.004, I 2 = 73.8%). BCP/TCP was associated with a higher percentage of new bone, but the pooled results did not reach significance (pooled standardized mean difference (SMD) = 0.145, 95% confidence interval (CI) −0.488 to 0.778, P = 0.654). Only two studies reported bone-to-graft contact, and BCP/TCP was associated with significantly lower bone-to-graft contact (pooled SMD = −0.807, 95% CI −1.276 to −0.337, P = 0.001). This meta-analysis does not allow us to conclude superiority of one particular material with respect to histological outcomes.
Dental implant placement in the posterior maxilla is often difficult because the alveolar bone is primarily cancellous, bone height is limited by the maxillary sinus, and in many cases bone height does not meet the minimum requirements for implant anchorage. If bone height is inadequate, a bone graft or bone substitute can be inserted in the maxillary sinus after elevation of the Schneiderian membrane (sinus augmentation).
Autologous bone has long been considered the gold standard graft material, as it is osteoinductive and osteoconductive and promotes angiogenic ingrowth from surrounding bone, is not immunogenic, exhibits high biological viability, and typically revascularization occurs within 3–4 months. Disadvantages, however, are significant and include a second surgical site for harvesting the bone with associated morbidity and potential hospital stay, and reabsorption of the augmented bone over time. Because of these disadvantages, alternative materials have been sought.
The range of graft materials is diverse, and these can be categorized broadly as alloplasts (which include technically derived hydroxyapatite and β-tricalcium phosphate), xenografts (such as deproteinized bovine bone), and allografts (freeze-dried demineralized bone). An advantage of non-resorbable materials such as deproteinized (anorganic) bovine bone is that the volume of the graft will not change as healing occurs. While the structure of bovine bone is similar to that of human bone, its use has been questioned with respect to the transmission of infectious diseases. Technically derived tricalcium phosphate, on the other hand, is readily absorbed and will eventually be replaced by newly formed bone; however, the volume of the augmentation will decrease as a result of the rapid absorption.
Histological outcomes are commonly used as a surrogate for clinical performance, although these results should not be overestimated because if a treatment performs well the histology may be of little significance. The purpose of this study was to perform a systematic review of the literature and meta-analysis to examine the histological outcomes of the two materials most commonly used for sinus augmentation for the placement of dental implants: deproteinized bovine bone (natural calcium phosphate) and technically derived calcium phosphate. The analysis was performed with respect to the area fraction (percentage) of new vital bone formed in the grafted region and the percentage of surface contact between the graft substitute material and new bone (bone-to-graft contact).
Materials and methods
Literature search strategy and study selection
This systematic review and meta-analysis was conducted in accordance with the PRISMA guidelines. MEDLINE, PubMed, Cochrane, EMBASE, and Google Scholar databases were searched from inception until 2 April 2015 using combinations of the following search terms: dental implant/implants, augmentation/augmented, calcium phosphate/ceramic/tricalcium phosphate, bovine bone/Bio-Oss, deproteinized/anorganic. Inclusion criteria were: (1) randomized controlled trials (RCTs), two-arm prospective studies, or retrospective studies; (2) sinus floor augmented with either anorganic bovine bone (natural calcium phosphate) or technically derived biphasic calcium phosphate/tricalcium phosphate; (3) quantitative outcomes reported. Cohort studies, letters, comments, editorials, case reports, proceedings, and personal communications, as well as studies in which a quantitative outcome was not reported, were excluded. Studies were identified using the search strategy by two independent reviewers. Where there was uncertainty regarding eligibility, a third reviewer was consulted. The reference lists of relevant studies were also hand-searched.
The following information/data were extracted from studies that met the inclusion criteria: the name of the first author, year of publication, study design, number of participants in each group, the age and sex of the participants, and the outcomes.
The methodological quality of each study was assessed using the risk-of-bias assessment tool outlined in the Cochrane Handbook for Systematic Reviews of Interventions (version 5.1.0). Briefly, six domains were evaluated: random sequence generation, allocation concealment, blinding of patients and personnel, blinding of outcome assessment, incomplete outcome data, and selective reporting risk. The assessment was conducted by two reviewers, with a third consulted to resolve any disagreements.
Outcome measures and data analysis
The primary outcomes of the analysis were the area fraction (percentage) of new vital bone formed in the grafted region and the percentage of surface contact between the graft substitute material and new bone (bone-to-graft contact). The standardized mean difference (SMD) with 95% confidence interval (CI) was used as the measure of effect size; an SMD greater than zero would indicate that patients treated with technically derived biphasic calcium phosphate/tricalcium phosphate had a greater percentage of new vital bone or greater bone-to-graft contact than those treated with deproteinized/anorganic bovine bone. A two-sided P -value of <0.05 was considered to indicate statistical significance.
Heterogeneity among the studies was assessed by Cochran Q statistic and I 2 statistic. The Q statistic was defined as the weighted sum of the squared deviations of the estimates of all studies, and a value of P < 0.10 was considered to indicate statistically significant heterogeneity. The I 2 statistic indicates the percentage of the observed between-study variability due to heterogeneity; a value >50% indicates significant (large or extreme) heterogeneity. If heterogeneity existed between studies (a Q statistic with P < 0.1, or an I 2 statistic >50%), a random-effects model of analysis (DerSimonian–Laird method) was to be performed. Otherwise, a fixed-effects model was to be used (Mantel–Haenszel method). The leave-one-out approach was used to assess the sensitivity of the meta-analysis. All statistical analyses were performed using the statistical software Comprehensive Meta-Analysis, version 2.0 (Biostat, Englewood, NJ, USA).
Literature search and study characteristics
A flow diagram of the study selection procedure is shown in Fig. 1 . A total of 390 articles were identified in the database search, and 238 remained after duplicates were removed. Of these 238 articles, 229 were found not to be relevant and were excluded. The full texts of nine articles were assessed; four were excluded, two for not reporting the outcome of interest and two because they were updates of a previous trial. Thus, five studies were included in the qualitative synthesis and meta-analysis.
A summary of the basic characteristics and outcomes of the five studies included in the meta-analysis is shown in Table 1 . Of the five studies, four were RCTs. and one was a prospective study. The number of patients in the studies ranged from 11 to 30 (total in all studies = 110). The number of implants in the biphasic calcium phosphate/tricalcium phosphate group ranged from 10 to 24 (total = 73) and in the deproteinized/anorganic bovine bone group from 11 to 23 (total = 72). Three studies reported the patient age range; overall, the patients ranged in age from 18 to 79 years. Two studies reported the sex distribution, and 43–45% of the patients were male.
|First author (publication year)||Study design||Intervention||Number of patients||Number of implants||Age (years)||Male (%)||Proportion of new vital bone (%)||Bone-to-graft contact (%)|
|Lindgren (2012)||RCT||BCP||11||24||Mean 67, range 50–79||45%||41.4 (9.8)||37.8 (10.9)|
|Deproteinized bovine bone||23||41.6 (14)||44.4 (12.1)|
|Schmitt (2013)||RCT||BCP||30||14||Range 38–79||43%||30.28 (2.16)||NR|
|Anorganic bovine bone||15||24.9 (5.67)|
|Froum (2008)||RCT||BCP||12||10||NR||NR||28.4 (23.8)||NR|
|Anorganic bovine bone matrix||11||22.3 (6.4)|
|Simunek (2008)||Prospective||TCP||20 (10 in each group)||–||NR||NR||21.4 (8.1)||NR|
|Deproteinized bovine bone||–||34.2 (13.1)|
|Cordaro (2008)||RCT||BCP||37||25||Range 18–70||NR||21.6 (10.0)||34.0 (14.0)|
|Anorganic bovine bone||23||19.8 (7.9)||48.2 (12.9)|
Percentage of new vital bone and bone-to-graft contact
All five studies reported the percentage of new vital bone. Large heterogeneity was found across studies ( Q = 15.23, P = 0.004, I 2 = 73.8%), therefore a random-effects model of analysis was used. Although patients treated with biphasic calcium phosphate/tricalcium phosphate had a higher percentage of new vital bone than those treated with deproteinized/anorganic bovine bone, the pooled results did not reach statistical significance (pooled SMD = 0.145, 95% CI −0.488 to 0.778, P = 0.654) ( Fig. 2 A) .
Two studies reported the results of bone-to-graft contact. No significant heterogeneity was noted ( Q = 1.25, P = 0.263, I 2 = 20.0%), therefore a fixed-effects model of analysis was used. The pooled results indicated significantly lower bone-to-graft contact in the biphasic calcium phosphate/tricalcium phosphate group than in the deproteinized/anorganic bovine bone group (pooled SMD = −0.807, 95% CI −1.276 to −0.337, P = 0.001) ( Fig. 2 B).
The sensitivity analysis using the leave-one-out approach for the percentage of new vital bone showed that the direction of the association changed when the study of Schmitt et al. was removed; however, the results were not statistically significant (pooled SMD = −0.092, 95% CI −0.636 to 0.451, P = 0.739) ( Fig. 3 ). A sensitivity analysis for bone-to-graft contact was not performed since only two studies were included.