Denosumab for Prevention of Osteoporosis in Renal Transplant Recipients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Denosumab for Prevention of Osteoporosis in Renal Transplant Recipients (NCT01377467), a randomized phase 3 study. The primary outcome is Percent Change in BMD at the Total Lumbar Spine From Baseline to Month 12.

2. Clinical Question

3. Trial Design

This was a phase 3, investigator-initiated, randomized, open-label, single-center study with a parallel-group design. The registry lists 90 enrolled participants. The primary outcome results include 46 participants assigned to denosumab and 44 assigned to control. The study status is completed. Its registry dates list a start in 2011-06 and primary completion in 2015-05.

Participants assigned to denosumab received 60 mg subcutaneously at baseline and after 6 months. The control group received no treatment. Because the study was open-label, participants and study personnel were not masked to assignment according to the registry record. Further details about random sequence generation, allocation concealment, treatment adherence, or co-interventions are not reported in the registry record.

The primary outcome was percent change in total lumbar-spine bone mineral density from baseline to month 12. The record also lists secondary assessments of bone mineral density at the total hip and femoral neck, including measures at month 6 and month 12, as well as bone-turnover markers. The stated broader secondary objectives included body height, bone mineral metabolism, fractures, allograft function, and safety outcomes.

The record describes an intention-to-treat primary efficacy analysis, with missing values replaced using last value carried forward. It reports an ANCOVA comparison of final values as the sponsor's analysis. Details of the covariates, the original sample-size justification, the planned multiplicity strategy, and any interim analyses are not reported in the registry record. Those omissions limit how fully the analysis plan can be reconstructed from the posted information.

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

Analysis population for the primary outcome, as defined in the registry: The intention-to-treat (ITT) population was used for the primary efficacy analysis, i.e. all subjects were included that have been randomized to the control group or to the denosumab group. Missing values were replaced with a last-value-carried-forward approach (LVCF).

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.

Population: Randomized patients with a functioning graft

6. Primary Endpoint

The registry lists the primary outcome as Percent Change in BMD at the Total Lumbar Spine From Baseline to Month 12, measured over Baseline and month 12.

The primary endpoint is percent change in total lumbar-spine bone mineral density from baseline to month 12. The registry says bone mineral density was measured using dual-energy X-ray absorptiometry and expressed in g/cm2 hydroxylapatite. The posted group summaries describe the mean percent change and its standard deviation. In the denosumab group, the mean change was 4.5, with a standard deviation of 3.8; in the control group, it was -0.3, with a standard deviation of 5.1.

Bone mineral density is a continuous measurement: it can take a range of values, and the analysis compares average changes between the randomized groups. In general, a continuous endpoint can capture differences in a measured quantity without reducing each participant's result to a yes-or-no event. In this trial, the registry chose lumbar-spine bone mineral density as the primary efficacy measure after one year of treatment. The record does not state the clinical threshold, if any, that would define a meaningful change in this measure.

The endpoint is not the same as fracture occurrence or overall bone health. Fractures, bone-turnover measures, and other outcomes were listed separately. The primary result therefore addresses the measured lumbar-spine density change over the stated period; it does not, by itself, establish the direction or size of effects on those other outcomes.

7. Results Posted in the Registry

• Denosumab: mean 4.50 versus -0.30 on control; difference 4.80 (95% CI 2.94 to 6.66), standardized effect d = 1.07; z-test p = <0.001.

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 Change in BMD at the Total Hip From Baseline to Month 12

• 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:
  • Denosumab: mean 2.30 versus 0.50 on control; difference 1.80 (95% CI 0.16 to 3.44), standardized effect d = 0.46; z-test p = 0.031.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Denosumab than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Percent Change in BMD at the Femoral Neck From Baseline to Month 12

• 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:
  • Denosumab: mean 1.10 versus 0.80 on control; difference 0.30 (95% CI -1.93 to 2.53), standardized effect d = 0.06; z-test p = 0.792.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Denosumab and the control. The interval gives the range of effects that remain compatible with the data.

Percent Change in BMD at the Total Lumbar Spine From Baseline to Month 6

• 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:
  • Denosumab: mean 2.90 versus -1.50 on control; difference 4.40 (95% CI 2.86 to 5.94), standardized effect d = 1.19; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Denosumab than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The posted secondary outcomes add context across skeletal sites and measurement times. The total-hip and femoral-neck measures at month 12 complement the primary lumbar-spine measure, while month-6 results describe an earlier assessment. The listed bone-turnover markers provide a different kind of measurement from bone mineral density. Taken together, the secondary outcomes cover related but distinct aspects of the study's stated objectives.

The reported results do not show a uniform pattern across every site and time point: the sponsor's ANCOVA results for total hip at month 12 and lumbar spine at month 6 have p-values below 0.05, while the femoral-neck comparison at month 12 has p = 0.380 and an interval that includes zero. These are secondary analyses and should be considered alongside, not in place of, the primary lumbar-spine result. The record lists 21 outcome measures overall, while seven secondary outcomes are posted in the results information.

In general, examining many outcomes and time points creates multiple opportunities for nominally small p-values, even when no multiplicity adjustment is made. The registry record does not report a multiplicity procedure. Consequently, the secondary p-values are best read as outcome-specific, unadjusted evidence rather than as a single confirmatory claim across all secondary outcomes. The results also cannot establish that unreported secondary measures had similar findings.

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

• Percent Change in BMD at the Total Hip From Baseline to Month 12
• Percent Change in BMD at the Femoral Neck From Baseline to Month 12
• Percent Change in BMD at the Total Lumbar Spine From Baseline to Month 6
• Percent Change in BMD at the Total Hip From Baseline to Month 6
• Percent Change in BMD at the Femoral Neck From Baseline to Month 6
• Beta-CTX at Baseline and Months 3, 6 and 12
• P1NP at Baseline and Months 3, 6 and 12

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is continuous, so the central summaries are group means and standard deviations. A mean describes the average observed change in a group; a standard deviation describes how dispersed individual measurements are around that average. Neither summary alone describes every participant's result. The denosumab group mean was 4.5 with a standard deviation of 3.8, and the control group mean was -0.3 with a standard deviation of 5.1.

What does the unadjusted comparison represent?

The recalculated comparison subtracts the control mean from the denosumab mean using the posted summary statistics. It is an unadjusted estimate of the difference between group averages, not a reconstruction of a baseline-adjusted model. Its estimate is 4.8, with a 95% confidence interval from 2.935 to 6.665 and p < 0.001. In general, an unadjusted comparison uses the observed group summaries without accounting for other variables that might be included in a model.

The standardized effect size listed with the recalculation is a way to express the mean difference relative to the pooled variability. In general, standardization can help compare differences measured on different scales, but it does not change the original measurement or establish clinical importance. The standardized value for the primary comparison is 1.071. It should be treated as a statistical description of this sample, not as an independent clinical endpoint.

What is ANCOVA doing?

The registry reports ANCOVA for its primary comparison, describing the parameter as a mean difference in final values. ANCOVA is a general statistical method that compares group outcomes while adjusting for one or more covariates. Such adjustment can account for relevant differences in measured covariates and may improve precision. The registry record does not report which covariates were included, how they were selected, or other model diagnostics, so the exact adjustment cannot be reconstructed. The reported estimate is 5.059, with a 95% confidence interval from 3.137 to 6.980 and p < 0.001.

The registry describes the primary efficacy population as intention-to-treat: all participants randomized to either group were included. It also states that missing values were replaced using last value carried forward. In general, this approach fills a missing later value with the participant's last available value. It can preserve the assigned-group analysis, but it relies on an assumption that the last observed value is a reasonable stand-in for the missing value. The record does not report how many values were missing, why they were missing, or whether sensitivity analyses tested alternative missing-data assumptions.

How should confidence intervals and p-values be read?

A confidence interval expresses uncertainty around an estimated quantity under the assumptions of the model and data. In general, a narrower interval indicates greater precision, while a wider interval leaves more uncertainty about the size of the effect. The reported primary interval extends from 3.137 to 6.980. It does not mean that individual participant outcomes fall within this range, and it is not a prediction interval for future participants.

A p-value is calculated under a null hypothesis and a statistical model. In general, a small p-value indicates that data at least as incompatible with that null model would be unusual under the model's assumptions. It does not quantify the probability that a treatment effect is absent, establish clinical relevance, or correct for multiple testing unless an adjustment is made. The primary ANCOVA p-value is <0.001. The registry record does not report the full statistical analysis plan or whether any other inferential procedures were prespecified.

Why can over-dispersion matter?

Over-dispersion is a general concern when observed variability exceeds what a statistical model assumes. If a model understates variability, standard errors can be too small and confidence intervals too narrow. The primary outcome is continuous and the record gives group standard deviations; it does not report an over-dispersion assessment or identify over-dispersion as an issue. The concept is therefore relevant as a general statistical consideration, not as a reported finding for this trial.

What do the planning illustrations represent?

The planning illustrations use the observed effect as a starting point and show participant counts under different fractions of that effect. Their stated assumptions are a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation. The smallest-effect scenario uses 50% of the observed effect, and it requires more participants per arm than the scenarios based on 75% or 100% of the observed effect. This is a general consequence of planning for a smaller difference when other assumptions are held fixed. These illustrations are not a record of the original trial design calculation.

The original sample-size justification, including its target effect and assumptions, is not reported in the registry record. The planning counts also do not account for details that are not listed in the stated assumptions, such as missing outcome data or any multiplicity adjustment. They are illustrations for planning, not evidence about the achieved operating characteristics of the completed study.

11. Confidence Intervals and Precision

The registry's primary ANCOVA estimate is 5.059, with a 95% confidence interval from 3.137 to 6.980. This interval describes uncertainty in the estimated mean difference under the reported analysis. Its endpoints are both above zero, while the interval still spans a range of possible magnitudes. The estimate should therefore be read together with the interval rather than as an exact value.

The unadjusted recalculation gives an estimate of 4.8 and a 95% confidence interval from 2.935 to 6.665. This interval also lies above zero. The recalculation and ANCOVA are not identical estimands: one is based directly on group summary statistics and the other is the registry's adjusted analysis of final values. Their similar direction and broadly comparable precision are descriptive; they do not remove uncertainty or replace the reported model.

In general, a confidence interval is a range produced by a procedure that, under its assumptions, would cover the target quantity at the stated rate over repeated applications. It is not a range containing a stated proportion of individual results, nor a guarantee that the true value lies within these specific limits. Precision depends on factors including variability, sample size, and model assumptions. The posted group standard deviations, 3.8 for denosumab and 5.1 for control, indicate that participant-level outcomes varied around their group means.

The registry does not provide confidence intervals for every secondary group summary, but it reports intervals for the ANCOVA comparisons. The interval for total-hip bone mineral density at month 12 runs from 0.132 to 3.659. The femoral-neck interval runs from -1.329 to 3.447, and the month-6 lumbar-spine interval runs from 2.975 to 6.178. The differences in interval placement and width illustrate that the estimates have different degrees of precision and are not interchangeable measures of one common outcome.

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 planning illustrations express counts as participants per arm, not total events. The record's stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. For each scenario, the assumed effect is a stated fraction of the observed effect. The original trial's own sample-size assumptions and justification are not reported in the registry record.

The 80% power column gives the estimated number of participants per arm that a hypothetical study would need to have an 80% chance of detecting the assumed effect under the stated model and significance level, if the assumptions hold. The 90% power column gives the corresponding planning count for a 90% chance. These are design targets for hypothetical studies, not observed outcomes of the completed trial. They do not show the probability that the trial's result is correct.

For the primary outcome, the illustration lists 14 participants per arm when planning for 100% of the observed effect, 25 when planning for 75%, and 55 when planning for 50% at the 80% power target. At the 90% target, the corresponding figures are 19, 33, and 74 participants per arm. The pattern reflects a general planning principle: smaller effects are harder to detect, so more participants are needed when the assumed effect is smaller.

These counts are not observed power. They use the observed effect as a planning reference, so they should not be treated as proof that the completed trial had adequate or inadequate power. They are conditional illustrations based on the stated assumptions, rather than a substitute for the unreported original design rationale.

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 = 4.800; pooled standard deviation σ = 4.483.
2. n = 2 × (1.96 + 0.842)² × 4.483² / 4.800² = 13.7, rounded up to 14 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 <- 4.8                      # observed difference in means
sigma <- 4.48257991867102                     # 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(1377467)
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 = 14 (80% power), 19 (90% power)
 75% of observed effect: n per arm = 25 (80% power), 33 (90% power)
 50% of observed effect: n per arm = 55 (80% power), 74 (90% power)
power.t.test: 14.7 
Simulated power at n = 14 per arm: 0.780 (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. Analyses Reported by the Sponsor

The registry reports the sponsor's primary analysis as ANCOVA, with a mean difference in final values of 5.059, a 95% confidence interval from 3.137 to 6.980, and p < 0.001. The simple recalculation from the posted group means is 4.8, with a 95% confidence interval from 2.935 to 6.665 and an unadjusted p-value of <0.001.

The recalculation is an unadjusted comparison of the arm-level summaries. The ANCOVA is the trial's reported analysis and may account for covariates, although the registry record does not state which covariates were used. The estimates are similar in direction and size, but the ANCOVA result remains the appropriate description of the sponsor's own analysis. The recalculation is useful as a transparent comparison derived from the posted summary statistics; it should not be substituted for the reported model.

The registry also reports ANCOVA analyses for selected secondary outcomes. Those estimates likewise remain the sponsor-reported analyses for those outcomes. Where a simple recalculation is available, it is a separate unadjusted check and should be interpreted with that distinction in mind.

15. Multiplicity, Missing Data and Analysis Populations

The primary efficacy population is described as intention-to-treat, including all randomized participants assigned to either group. The record says missing primary values were replaced using last value carried forward. It does not report the number of participants with missing values, the reasons for missingness, or the timing and extent of missing outcome data. Without those details, readers cannot assess how much the primary estimate depends on the imputation procedure.

Last value carried forward is a specific missing-data rule, not a guarantee that the imputed value matches what would have been observed. In general, its suitability depends on the data process and assumptions about change after the last measurement. The registry record does not report sensitivity analyses using alternative assumptions or methods, so robustness to missing-data choices cannot be assessed from the posted information.

The record lists multiple outcome measures and assessments at different times. It does not report whether the study used a prespecified hierarchy, adjusted p-values, or another strategy to address multiplicity. In general, when many hypotheses are tested, the chance of at least one apparently notable result can increase. This is why secondary results, especially those without a reported multiplicity strategy, warrant more cautious interpretation than a single prespecified primary analysis.

The record also does not report the full statistical analysis plan, covariates used in the ANCOVA, interim analyses, or the trial's original sample-size justification. The primary outcome is identified, but the available record does not establish all analytic decisions made before results were examined. These missing details constrain assessment of prespecification and analytic flexibility; they do not, by themselves, show that any particular analysis was inappropriate.

16. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: urinary tract infection (23.9%), enteritis (15.9%), lymphocele (13.6%), transplant pyelonephritis (11.4%), cmv viremia (11.4%).

The adverse-event results list 31 of 46 participants in the denosumab group and 29 of 44 in the control group as affected by serious adverse events. For other adverse events, the registry lists 45 of 46 participants in the denosumab group and 44 of 44 in the control group as affected. These are participant counts, not a measure of event duration, severity beyond the serious classification, or causal relationship to treatment.

The registry lists urinary tract infection at 23.9%, enteritis at 15.9%, lymphocele at 13.6%, transplant pyelonephritis at 11.4%, CMV viremia at 11.4%, and functional decline of transplant function at 8.7% among the most frequent serious adverse-event terms. The posted terms are not separated by treatment group in this list, so they do not support a direct group comparison for each specific event.

Deaths are not reported in the registry record. The counts should be read as descriptive safety information from this trial, not as proof that an event was caused by or unrelated to denosumab. The record does not provide additional detail in these results about event timing, recurrence, or individual-level overlap among event categories.

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

The primary result describes a difference between randomized groups in mean percent change in lumbar-spine bone mineral density from baseline to month 12. The registry's ANCOVA estimate is 5.059, with a 95% confidence interval from 3.137 to 6.980 and p < 0.001. The posted group means are 4.5 for denosumab and -0.3 for control. These statistics describe the outcome measured in this trial, under the reported analysis and its assumptions.

The result does not, by itself, show how the observed difference translates into fractures, symptoms, allograft function, or other outcomes. Those are distinct questions. Although the registry lists some related secondary objectives and results, they should not be inferred from the primary endpoint. The record also does not state a threshold for a clinically meaningful change in bone mineral density.

In general, statistical evidence about a group average does not imply that every participant experienced a similar change. The standard deviations show variation around the mean, and the confidence interval describes uncertainty in the estimated group difference rather than the range of individual outcomes. The result also pertains to the study's open-label, single-center design and to its recorded population and treatment comparison.

The trial's safety figures provide descriptive counts, but do not establish causal attribution for individual events. The registry record does not report deaths, and the listed serious-event terms are not presented as a comparative analysis by group. Overall, the posted findings support an interpretation limited to the measured outcomes and reported analyses; they do not settle broader clinical questions that were not directly answered by those results.

18. Why This Trial Matters Statistically

This trial illustrates several statistical features that matter when reading randomized studies. First, the primary outcome is a continuous measure, so group means and standard deviations are central to understanding the observed data. The mean difference summarizes average separation, while the confidence interval shows uncertainty about its magnitude. Reporting both helps avoid reducing the result to a p-value alone.

Second, the registry contains both an adjusted sponsor analysis and enough group summaries for a simple unadjusted recalculation. The two approaches answer related but not identical statistical questions. Comparing them can help readers understand the role of adjustment, but the unadjusted calculation cannot reveal which covariates were included in the ANCOVA or reproduce its full model.

Third, the record makes the missing-data rule visible: the primary efficacy population was intention-to-treat, with last value carried forward for missing values. That information is important because inclusion of randomized participants and handling of missing outcomes affect how an estimate is interpreted. At the same time, the absence of missingness details and sensitivity analyses leaves uncertainty about the impact of that choice.

Finally, multiple secondary outcomes and time points create interpretive challenges. The record does not report a multiplicity strategy, so secondary p-values should not be treated as if they were a single prespecified test. The planning illustrations also show how sample-size needs depend on the effect assumed in advance, while making clear that those calculations are not a record of the original design. Together, these features show why estimates, intervals, analysis choices, and reporting gaps all matter alongside statistical significance.

19. 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.

The study was open-label and single-center, according to the registry record. Those design features are relevant when considering the setting and conduct of the trial, but the record does not provide enough detail to determine how they affected measurement or care. Randomization is reported, yet the method of sequence generation and allocation concealment is not reported in the registry record.

The primary analysis used last value carried forward for missing values. The registry does not report missing-value counts, reasons for missingness, or sensitivity analyses, limiting assessment of how dependent the result is on this approach. The ANCOVA is reported, but the covariates and model details are not. Thus, the adjusted estimate cannot be fully reproduced from the information in the record.

The original sample-size justification, planned effect size, interim analyses, and multiplicity strategy are not reported in the registry record. The planning illustrations based on the observed effect do not fill those gaps. The registry lists 21 outcome measures overall, but only seven secondary outcomes are posted in the results information. This incomplete outcome reporting limits the ability to assess the full pattern across all registered measures.

The primary endpoint is bone mineral density, not a clinical event such as fracture. The record does not state a threshold for a clinically meaningful difference. It also does not provide a comparative analysis of the listed serious adverse-event terms by group. These limits mean that the posted results are most directly informative about the reported bone-density measurements and the stated safety counts, rather than broader outcomes or unreported analyses.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Denosumab for Prevention of Osteoporosis in Renal Transplant Recipients — NCT01377467.
• Registry record last updated 2016-05-26; status last verified 2016-04.
• Results first posted 2016-04-26.
• 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.

23. Record Summary

This completed phase 3 randomized, open-label, single-center study compared denosumab with no treatment in renal transplant recipients. The denosumab regimen was 60 mg subcutaneously at baseline and after 6 months. The registry lists 90 enrolled participants, with 46 in the denosumab group and 44 in control for the primary outcome.

The primary outcome was percent change in total lumbar-spine bone mineral density from baseline to month 12. The registry reports an ANCOVA mean difference of 5.059, with a 95% confidence interval from 3.137 to 6.980 and p < 0.001. The primary efficacy analysis was intention-to-treat with last value carried forward for missing values.

The record also posts selected secondary bone-density and safety results. Important details, including the original sample-size justification, multiplicity strategy, missing-data counts, and ANCOVA covariates, are not reported in the registry record. Interpretation is therefore bounded by the outcomes and analyses that are posted.