Histological Comparison of Ridge Preservation Using Mineralized FDBA Alone Versus a Combined Mineralized-Demineralized Freeze Dried Bone Allograft: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Histological Comparison of Ridge Preservation Using Mineralized FDBA Alone Versus a Combined Mineralized-Demineralized Freeze Dried Bone Allograft (NCT01924390), a randomized na study. The primary outcome is Percent New Vital Bone Formation.

2. Clinical Question

The study focused on a tissue-level outcome rather than a clinical measure of implant function. Its primary question concerns the amount of newly formed vital bone identified histologically in the healing extraction site. The registry also names percent residual graft material and percent connective tissue as secondary outcomes, but the posted secondary result is presented as a continuous measure of residual graft material; a separate connective-tissue result is not reported in the registry record.

The comparison is between two graft compositions, not between grafting and no grafting. The randomized design therefore addresses whether the observed histological measures differed between the assigned material strategies among the participants represented in the posted results. It does not, by itself, answer how either material compares with an ungrafted socket or with other approaches to ridge preservation.

3. Trial Design

The registry describes a randomized, open-label, parallel-group study with an enrollment of 44. Its status is completed. The listed study condition is tooth extraction, and the sponsor is The University of Texas Health Science Center at San Antonio. The study began in 2012-11, with primary completion in 2013-09. The phase is listed as not applicable.

Participants were assigned to socket grafting with either mineralized FDBA alone or a combination of mineralized and demineralized FDBA. The study summary describes the combination as 70% mineralized and 30% demineralized material, while the comparator used 100% mineralized FDBA. The summary says allocation was based on numbers drawn from a stack of sealed envelopes. Further details about sequence generation, envelope preparation, or safeguards against foreknowledge of assignments are not reported in the registry record.

Although the planned enrollment was 44, the posted primary outcome summaries include 21 participants in each arm. The reason that the outcome summaries include fewer participants than the enrollment figure is not reported in the registry record. The registry does not explain whether this reflects unavailable biopsies, exclusions, withdrawal, or another feature of the analysis population. The posted results therefore describe the arm-level data shown, and the relationship between those data and all enrolled participants cannot be determined from the record.

The primary outcome was the percentage of new vital bone measured histologically in a bone core biopsy at 18-20 weeks. The listed secondary outcome concerns percent residual graft material and percent connective tissue at the same timeframe. The record gives means and standard deviations by arm for the posted continuous outcomes. It does not report details of masking; the masking field is none, consistent with an open-label design. Whether laboratory assessors were masked is not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Percent New Vital Bone Formation, measured over 18-20 weeks.

The primary endpoint is percent new vital bone formation, assessed by histological evaluation of a bone core biopsy collected 18-20 weeks after grafting. In practical terms, the measure describes what proportion of the examined biopsy consists of newly formed vital bone. It is a continuous outcome, and the registry reports an arm-level mean and standard deviation for each grafting strategy.

Histology is used because the study question concerns the tissue composition of the healing extraction site. A biopsy can distinguish newly formed vital bone from other components in the sampled tissue, including remaining graft material and connective tissue. That makes the measure directly relevant to the biological comparison the study set out to make. It is not a direct measure of implant survival, function, symptoms, or long-term ridge dimensions; those outcomes are not reported in the registry record as primary measures.

The endpoint is a percentage-based summary of sampled tissue, so its interpretation depends on the biopsy and the histological assessment. The record describes evaluation of the bone core biopsy but does not report the laboratory scoring procedure, number of sections or fields assessed, reader reliability, or criteria used to classify tissue. Those details would help readers understand how consistently the tissue measure was obtained and how representative the sampled core may be of the broader extraction site.

The registry reports the endpoint at 18-20 weeks. This is the specified assessment timeframe, and the results should be interpreted as a comparison at that time rather than as evidence about the course of healing at other times.

7. Results Posted in the Registry

• Combination of Mineralized and Demineralized FDBA: mean 36.20 versus 24.70 on control; difference 11.50 (95% CI 2.97 to 20.03), standardized effect d = 0.82; z-test p = 0.008.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Percent Residual Graft Material and Percent Connective Tissue

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Combination of Mineralized and Demineralized FDBA: mean 18.20 versus 27.00 on control; difference -8.80 (95% CI -16.67 to -0.93), standardized effect d = -0.68; z-test p = 0.028.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Combination of Mineralized and Demineralized FDBA than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry names percent residual graft material and percent connective tissue as secondary outcomes, assessed at 18-20 weeks. The posted numerical secondary summaries concern percent residual graft material. They show a lower mean in the combination arm than in the mineralized FDBA-alone arm. This direction is consistent with a difference in tissue composition, but it is not another measure of the primary endpoint: residual graft and newly formed vital bone are distinct components of the biopsy assessment.

The secondary result can be considered alongside the primary pattern as context about the sampled tissue. It does not independently establish the mechanism behind the primary difference, and it should not be combined with the primary measure as though the outcomes were interchangeable. A separate numerical result for percent connective tissue is not reported in the registry record, despite its inclusion in the secondary outcome title.

The registry lists no reported analyses. The secondary inferential statistics are unadjusted re-calculations from the posted arm summaries, rather than a reported analysis plan with an account of how multiple outcomes were handled. General statistical principle: when several outcomes or comparisons are examined, the chance of obtaining at least one apparently strong result by chance can increase unless the analysis strategy addresses multiplicity. The record does not state whether any multiplicity adjustment or prioritization was planned.

For that reason, the secondary evidence carries less weight than a clearly prespecified and fully reported primary analysis, and it is best treated as exploratory context. This caution does not mean the observed pattern is uninformative; it means the registry record does not establish how much confirmatory emphasis it deserves. The missing separate connective-tissue result and absent account of analysis planning further limit conclusions across the secondary outcome domain.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Percent Residual Graft Material and Percent Connective Tissue

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: each participant's biopsy assessment is summarized as a percentage, and the registry reports the mean and standard deviation within each arm. A mean describes the average observed value in an arm. A standard deviation describes the spread of individual values around that average; it is not the uncertainty interval for the mean. The two standard deviations, 16.0 and 11.9, indicate that participants' biopsy results varied within both groups.

What does the difference in means represent?

The comparison expresses the mean in the combination arm relative to the mean in the mineralized FDBA-alone arm. The estimated difference is 11.5 percentage points, calculated as combination minus mineralized FDBA alone. This is an unadjusted re-calculation from the posted arm-level means. It represents a contrast between group averages, not a change experienced by every participant and not an adjusted estimate that accounts for baseline characteristics.

An unadjusted comparison can be useful when only group summaries are posted, but it cannot show whether the groups differed in relevant baseline features or whether adjustment would change the estimate. Details of baseline characteristics and an adjusted primary analysis are not reported in the registry record. The registry also does not report an analysis plan describing which model, if any, was specified before examining the results.

How should the interval be understood?

The interval from 2.972 to 20.03 gives a range of values for the mean difference that are compatible with the observed summary data under the calculation's assumptions. A confidence interval is a statistical device for expressing estimation uncertainty, not a range containing a specified proportion of individual biopsy measurements. The interval's width reflects that the estimate is not known exactly. Its lower and upper limits are both above zero, so the posted unadjusted interval is consistent with a positive mean difference under the method used.

The confidence level and exact method used to construct the posted interval are not reported in the registry record. As a result, the interval can be interpreted as an uncertainty summary, but its precise repeated-sampling coverage should not be asserted from the registry information alone.

What does the p-value contribute?

The unadjusted p-value of 0.008 summarizes the compatibility of the observed comparison with a null model in which the arm means do not differ. Smaller p-values indicate that the observed data would be less typical under that model, conditional on the assumptions of the test. A p-value does not state the probability that the null model is correct, and it does not describe the size, clinical relevance, or reproducibility of the estimated difference.

Because the p-value is an unadjusted re-calculation, it does not account for the fact that the registry also lists a secondary outcome or for any other analyses that may have been performed. The record lists no reported analyses. It does not state whether the displayed comparison was the sole planned primary test, whether other endpoints were tested, or whether multiplicity procedures were used. The primary result should therefore be read as a summary of the posted data rather than as a complete account of a prespecified analysis strategy.

Why can variation and over-dispersion matter?

For a continuous measure, the standard deviation is one way to describe observed variation. General statistical principle: if the variability is larger than a model assumes, standard errors and intervals based on that model may be too small, giving an overly precise impression. Conversely, methods that account for greater variability can widen uncertainty. The registry does not report a formal assessment of distributional assumptions, outliers, or over-dispersion, nor does it identify the exact procedure used for the re-calculated comparison. The displayed standard deviations help readers see that measurements are not identical, but they do not establish whether a particular model was adequate.

General statistical principle: randomized allocation can support a fair comparison because it aims to make treatment groups comparable on average, including for factors that are not measured. Randomization does not guarantee exact balance in a particular trial, especially when the analyzed groups are limited in size. The registry gives the assignment approach in broad terms but does not report enough detail to evaluate sequence generation or concealment, and it does not give baseline characteristics for assessing the realized balance.

General statistical principle: an analysis based on participants with observed outcomes can be biased if outcome availability is related to the outcome itself or to the assigned group. The record posts outcome summaries for 21 participants per arm, but does not explain missing outcomes, participant flow, exclusions, or the analysis population. It is therefore not possible to determine from the registry record whether the summaries represent all randomized participants or a subset selected after allocation.

The trial was open-label according to the registry. Lack of masking can affect behavior or assessment in some settings, while histological scoring may involve judgment. Whether the biopsy readers were unaware of group assignment is not reported in the registry record. The registry does not report reader training, reproducibility, or other quality-control procedures. These missing details limit assessment of measurement reliability, but do not by themselves show that the measurements were biased.

11. Confidence Intervals and Precision

The primary difference in means is 11.5 percentage points, with an interval from 2.972 to 20.03. The limits convey that the estimated difference is uncertain: the data are compatible with a range of possible mean differences rather than one exact value. Because the interval excludes zero, it is consistent with a positive difference under the calculation used. The interval does not establish the size of an effect in a future sample or indicate how much individual participants' biopsy values overlap.

Precision is also informed by the number of participants represented in each arm and by the spread of their measurements. The posted primary summaries include 21 participants per arm. The standard deviations are 16.0 for mineralized FDBA alone and 11.9 for the combination. Those within-arm spreads are substantial relative to the group means, so individuals may have values quite different from their arm average. The registry does not provide individual observations, which prevents assessment of the distribution's shape or potential influential values.

The exact confidence level and interval construction method are not reported in the registry record. The numerical limits should therefore be treated as the posted interval without attaching an unreported confidence level or method. Nor does the interval incorporate uncertainty about outcome availability, assessment procedures, or analysis choices that are not described in the record.

Precision is not the same as practical importance. The interval quantifies statistical uncertainty in the estimated group contrast under the calculation's assumptions; it does not define a clinically important threshold. Such a threshold is not reported in the registry record. The result also applies to the specified biopsy assessment at 18-20 weeks, and it does not quantify later outcomes or effects in populations not described by this study.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations expressed as participants per arm, not total event counts. They use the observed effect as a reference and show the number of participants per arm associated with 80% power or 90% power for different fractions of that observed effect. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect equal to the stated fraction of the observed effect. The original trial's own sample-size justification and design assumptions are not reported in the registry record.

The 80% power column describes an illustrative design that would have an 80% chance of detecting the specified effect at the stated significance level if the assumptions and effect were correct. The 90% power column describes the corresponding illustration for a 90% chance. These are planning probabilities for hypothetical study designs, not probabilities that the observed result is true. They are not observed power.

The rows for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect ask how planning changes when the effect one aims to detect becomes smaller relative to the one observed. Smaller effects need more participants to detect with the same planned power, under the stated assumptions. The figures should not be read as a recommendation for a future study without considering whether the assumed effect, endpoint, analysis method, and participant population are appropriate. The registry record does not report the original design rationale, and the planning illustration is based on the observed effect, which may itself be uncertain.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 11.500; pooled standard deviation σ = 14.100.
2. n = 2 × (1.96 + 0.842)² × 14.100² / 11.500² = 23.6, rounded up to 24 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 11.5                      # observed difference in means
sigma <- 14.0998226939207                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1924390)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 24 (80% power), 32 (90% power)
 75% of observed effect: n per arm = 42 (80% power), 57 (90% power)
 50% of observed effect: n per arm = 95 (80% power), 127 (90% power)
power.t.test: 24.6 
Simulated power at n = 24 per arm: 0.791 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry record does not report whether the investigators planned an adjustment for testing multiple outcomes or comparisons. It lists one primary outcome and a secondary outcome covering residual graft material and connective tissue, but does not describe a hierarchy of tests, an overall error-rate strategy, or a statistical analysis plan. The primary comparison is therefore presented as an unadjusted re-calculation, and the secondary comparison should be interpreted cautiously. The record also does not report whether any additional analyses were conducted but not posted.

Missing-data handling is not described. The enrollment was 44, whereas the posted primary outcome summaries include 21 participants in each arm. The registry does not report participant flow by reason, the number with unavailable biopsies, withdrawals, exclusions after randomization, or whether any values were imputed. Without that information, readers cannot determine whether the displayed outcome summaries include all randomized participants or how missing observations might affect the comparison.

The analysis population is not identified. The registry does not say whether the analysis followed assigned groups regardless of treatment received, included only participants who completed the biopsy assessment, or used another definition. It also does not report adherence to assigned graft material, crossovers, or protocol deviations. These omissions limit evaluation of whether the randomized comparison was preserved in the analysis.

Baseline characteristics, covariate adjustment, and model diagnostics are not reported in the registry record. Nor are details of the histological assessment process, including reader masking and reliability. These omissions do not establish that the analyses were inappropriate, but they prevent a complete assessment of bias, precision, and reproducibility.

General statistical principle: prespecified analysis choices help distinguish planned tests from analyses selected after results are known. When the plan, missing-data rules, and multiplicity approach are unavailable, statistical findings are harder to interpret as confirmatory. The posted summaries remain descriptive evidence, but their place within the study's original analysis strategy is not reported in the registry record.

15. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The registry lists 21 participants at risk for serious adverse events in each arm and reports zero affected participants in each. It also lists 21 participants at risk for other adverse events in each arm and reports zero affected participants in each. No serious adverse-event terms are listed.

These figures describe what is recorded for the posted safety categories and participants at risk. They should not be read as proof that no adverse events occurred outside the categories, time period, or reporting process captured in the registry. The record does not provide additional detail about adverse-event definitions, collection methods, severity grading, or duration of follow-up for safety reporting.

Deaths are not reported in the registry record. A missing death value is not equivalent to a report of zero deaths. The safety figures also do not compare risks with a level of precision that can be evaluated from these counts alone, and they do not establish broader safety conclusions beyond the participants and events represented in the record.

16. What the Result Does, and Does Not, Mean

The posted primary summaries describe a higher mean percentage of new vital bone in the combination arm than in the mineralized FDBA-alone arm at 18-20 weeks. The unadjusted mean difference is 11.5 percentage points, with an interval from 2.972 to 20.03 and an unadjusted p-value of 0.008. These results characterize the observed biopsy measurements in the participants included in the registry summaries.

They do not establish that every participant in the combination arm had more new vital bone than every participant in the comparator arm. The standard deviations indicate variation within both groups, and group averages do not describe each person's result. Nor do these statistics alone establish a clinically important difference: a threshold for clinical importance is not reported in the registry record.

The result is specific to the comparison between mineralized FDBA alone and the stated mineralized-demineralized combination. There is no ungrafted comparison arm, so the study does not estimate the effect of either material relative to no grafting. The endpoint is histological tissue composition at the specified assessment timeframe; the registry does not report primary results on implant survival, function, or longer-term outcomes.

The unadjusted comparison is based on posted arm-level summaries, and the record does not report the trial's analysis plan, participant flow, handling of missing outcomes, or whether the result was adjusted for other variables. It also does not report the confidence level or exact method for the interval. Those gaps limit how fully the estimate can be evaluated and reproduced.

Accordingly, the data support a description of a difference in the posted group means, not a broad conclusion about all settings, patients, or later outcomes. The result should be considered together with the uncertainty interval, individual variation, secondary outcome reporting, and missing methodological details. It should not be interpreted as treatment advice or as proof of a particular mechanism.

17. Why This Trial Matters Statistically

This trial illustrates how a randomized comparison can be framed around a quantitative tissue outcome. Rather than relying only on a broad clinical description of healing, the primary endpoint measures the proportion of a biopsy classified as new vital bone. The mean difference makes the comparison explicit, while the standard deviations and interval remind readers that the observed estimate is not exact and that participants vary.

It also demonstrates why an effect estimate and a p-value answer different questions. The difference of 11.5 percentage points describes the estimated contrast between group means; the unadjusted p-value of 0.008 describes compatibility with a null model under the calculation's assumptions. Neither statistic alone explains clinical importance, and neither substitutes for transparent reporting of how the comparison was planned and analyzed.

The record highlights the value of reporting participant flow and analysis populations. Enrollment was 44, while the primary summaries include 21 participants per arm, and the reason for that difference is not described. Without those details, readers cannot establish whether outcome availability was balanced or how the analysis relates to random assignment.

Finally, the registry lists a secondary tissue-composition outcome, but its reporting does not fully resolve all components named in the outcome title. This makes multiplicity and selective reporting important interpretive questions. A clear analysis plan, complete outcome reporting, and details of assessment procedures would strengthen confidence in how the estimates should be used. These are statistical reporting considerations, not claims that the posted findings are invalid.

18. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several limitations specific to this trial constrain interpretation. The enrollment is listed as 44, while the posted outcome summaries contain 21 participants in each arm. The registry does not explain the difference, report participant flow, or state how missing outcome data were handled. Consequently, the extent to which the available biopsy summaries represent all randomized participants is not clear.

The study is described as open-label, and masking of histological assessors is not reported in the registry record. Since the primary endpoint depends on histological classification, details about reader masking, scoring criteria, repeatability, and laboratory procedures would help readers assess measurement reliability. Those details are not available in the record.

The registry reports the primary means, standard deviations, and an unadjusted comparison, but does not report a statistical analysis plan, adjusted analysis, or model-assumption checks. The exact interval method and confidence level are also not reported. There are no reported analyses listed, so the registry does not establish whether the displayed comparisons were the investigators' prespecified analyses.

The secondary outcome title includes both residual graft material and connective tissue, but a separate connective-tissue result is not reported in the registry record. The record also does not state how multiple outcomes were handled. These omissions limit a comprehensive reading of the tissue-composition results.

The endpoint is a biopsy measure at 18-20 weeks. The registry does not report longer-term primary results, implant outcomes, or a comparison with no grafting. The results therefore address a narrow histological comparison at the specified timeframe, and should not be extended to unstudied outcomes or strategies.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Histological Comparison of Ridge Preservation Using Mineralized FDBA Alone Versus a Combined Mineralized-Demineralized Freeze Dried Bone Allograft — NCT01924390.
• Registry record last updated 2014-10-06; status last verified 2014-10.
• Results first posted 2014-10-06.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

22. Record Summary

This completed, randomized, open-label, parallel-group study compared socket grafting with mineralized FDBA alone against a combination of mineralized and demineralized FDBA after tooth extraction. The registry lists an enrollment of 44 and reports primary outcome summaries for 21 participants per arm.

The primary endpoint was percent new vital bone formation in a biopsy at 18-20 weeks. The posted means were 24.7 for mineralized FDBA alone and 36.2 for the combination. The unadjusted difference was 11.5, with an interval from 2.972 to 20.03 and an unadjusted p-value of 0.008. Secondary results concern residual graft material; a separate connective-tissue result is not reported in the registry record.

Important details about participant flow, missing data, analysis populations, the statistical analysis plan, histological assessment procedures, and multiplicity are not reported in the registry record. The results describe the posted histological summaries and do not establish effects on outcomes that were not reported.