Prevention of Bone Loss After Pediatric Hematopoietic Cell Transplantation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Prevention of Bone Loss After Pediatric Hematopoietic Cell Transplantation (NCT02074631), a randomized phase 2 study. The primary outcome is Lumbar Spine Bone Mineral Content.

2. Clinical Question

This is a question about a measured bone outcome at a specified follow-up time, not about every aspect of bone health or longer-term clinical outcomes. The trial was randomized and controlled, so its intended comparison is between the assigned treatment strategies. It was open-label, meaning the registry records no masking. The record describes the study as Phase 2 and lists an enrollment of 63. The primary outcome summaries are based on smaller arm-specific participant counts; the reasons those counts differ from the enrollment figure are not reported in the registry record.

The primary comparison is expressed as the average outcome in the pamidronate group relative to the control group. The estimate is negative, indicating that the reported average in the pamidronate group was lower in this dataset. Its confidence interval is broad and covers values on either side of no difference. The posted summaries therefore do not establish a clear separation between the groups for this measure. They also do not determine whether any difference would matter clinically, since a clinically important threshold is not reported in the registry record.

3. Trial Design

The registry describes a randomized, controlled, parallel-group Phase 2 trial of pamidronate after pediatric HCT. One group received pamidronate in addition to calcium and vitamin D; the control group received calcium and vitamin D alone. The study was open-label, with masking listed as none. Enrollment was 63. The record lists the study status as completed, with a start of 2015-02 and primary completion on 2022-10-06.

The treatment schedule in the intervention description calls for pamidronate infusions approximately 100, 180, and 270 days after HCT, together with calcium and vitamin D. The control description specifies a standard recommended dose of calcium and vitamin D. The registry record does not give further details about adherence, treatment changes, or the handling of participants who did not follow the assigned schedule.

The primary outcome was average lumbar spine bone mineral content at 1 year after HCT. The outcome summaries list 29 participants in the control group and 23 in the pamidronate group. The reasons these outcome counts differ from the enrollment figure are not reported in the registry record. It also describes the primary population as participants unable to be evaluated because of declining health or failure of follow up. That wording does not clarify how the analyzed population was defined or how those unable to be evaluated were handled.

The record lists several additional bone, biochemical, and bone-turnover outcomes. It does not describe the original sample-size justification, the planned statistical model, an interim-analysis plan, or the analysis population definition. No sponsor-reported analysis results are listed in the registry record. The posted group summaries and their unadjusted comparisons therefore offer descriptive and recalculated statistical information, but do not reveal the full prespecified analysis strategy.

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: Participants unable to be evaluated due to declining health or failure of follow up.

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 Lumbar Spine Bone Mineral Content, measured over 1 year after HCT.

Lumbar spine bone mineral content (LBMC) is the amount of mineral content measured in the lumbar spine, reported in average grams in this trial. The registry identifies DXA as the measurement method and sets the assessment at 1 year after HCT. The primary comparison asks whether the average value was higher among participants assigned to pamidronate with calcium and vitamin D than among those assigned to calcium and vitamin D alone.

A continuous measurement retains more gradation than a simple category such as above or below a threshold. Comparing group averages can describe the overall separation in the measured values, while the spread among participants gives context for how much individual measurements vary. A lumbar spine measure is relevant to a study of post-transplant bone loss because it focuses on bone mineral content at a specified skeletal site. The registry record does not state a threshold for clinical importance or explain why this endpoint was selected over other bone measures.

The outcome is a measurement at a follow-up time, not a direct count of fractures, symptoms, or other clinical events. Nor does an average alone describe the experience of every participant. Its interpretation depends on the observed group values, their variability, the precision of the estimated comparison, and the completeness of outcome measurement. The registry describes the primary population in terms of inability to be evaluated due to declining health or failure of follow up, but does not explain the implications of that wording for the reported averages.

7. Results Posted in the Registry

• Pamidronate Group: mean 38.70 versus 41.40 on control; difference -2.70 (95% CI -15.00 to 9.60), standardized effect d = -0.12; z-test p = 0.667.

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.

Total Body Bone Mineral Content (TBMC; Excluding Head; Adjusted for Height, Age, Sex, Tanner Stage, and Race)

• 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 errors.
• Result:
  • Pamidronate Group: mean 1,204 versus 1,231 on control; difference -27.00 (95% CI -316.35 to 262.35), standardized effect d = -0.05; z-test p = 0.855.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Pamidronate Group and the control. The interval gives the range of effects that remain compatible with the data.

Total Bone Mineral Density (BMD), Cortical BMD, Trabecular BMD, and Estimated Bone Strength Measured by pQCT

• 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:
  • Pamidronate Group: mean 0.76 versus 0.83 on control; difference -0.07 (95% CI -0.18 to 0.04), standardized effect d = -0.35; z-test p = 0.216.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Pamidronate Group and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists secondary measures spanning total body bone mineral content, bone mineral density and estimated bone strength, cytokines, and markers of bone formation and resorption. These outcomes address related biological and measurement domains, but they do not all measure the same construct as the primary lumbar spine endpoint. Together they can provide a broader descriptive picture of bone-related outcomes after HCT, while remaining secondary to the primary question.

For the posted secondary comparisons with numerical summaries, the estimated contrasts are negative, consistent in direction with the primary point estimate. Their confidence intervals are broad and include no difference. That broad pattern offers no precise evidence of separation between groups across those measures. It also does not establish that every listed secondary measure followed the same pattern: the registry record does not provide a numerical result for each outcome in the outcome list.

Secondary results generally carry less weight than the primary endpoint because they are not the main trial question and because multiple outcomes create multiple opportunities for apparently notable results by chance. The registry record does not report a prespecified hierarchy, multiplicity adjustment, or detailed statistical plan for the secondary outcomes. Their unadjusted p-values, where available in the posted summaries, should therefore be treated cautiously rather than as independent confirmatory tests.

These outcomes may be useful for generating hypotheses or for understanding which biological domains deserve further study. They cannot, however, repair imprecision in the primary result or replace it with a more favorable interpretation. A consistent direction across measures can be descriptively interesting, but formal conclusions require the planned analysis strategy, adequate precision, and appropriate consideration of the number and relationship of outcomes.

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

• Total Body Bone Mineral Content (TBMC; Excluding Head; Adjusted for Height, Age, Sex, Tanner Stage, and Race)
• Total Bone Mineral Density (BMD), Cortical BMD, Trabecular BMD, and Estimated Bone Strength Measured by pQCT
• Cytokine Levels (Interleukin IL-6, IL-7, and TNF-α)
• Receptor Activator of the Nuclear Factor-κB Ligand [RANKL], Osteoprotegerin [OPG]
• Marker of Bone Resorption (Carboxy-terminal Collagen Crosslinks [CTX]
• Markers of Bone Formation (Procollagen Type 1 N-terminal Propeptide [P1NP])
• Ratio of Receptor Activator of the Nuclear Factor-κB Ligand [RANKL] and Osteoprotegerin [OPG]
• Marker of Bone Resorption Deoxypyridinoline [DPD])

9. Statistical Interpretation

10. Statistical Methods Explained

What does a difference in means describe?

The primary outcome is continuous, so the reported comparison is a difference between group averages. The estimate is defined as the pamidronate group mean minus the control group mean. A negative value therefore indicates that the reported average is lower in the pamidronate group; a positive value would indicate a higher average. The posted estimate is -2.7 grams. This is a description of the observed contrast, not an adjusted causal estimate that accounts for other characteristics of participants.

A group average condenses many individual values into one summary. It can be useful for comparing groups, but it does not show the full distribution of measurements, whether there were unusually high or low values, or how outcomes varied across participant subgroups. The registry provides standard deviations for the primary measure, which describe spread among observed values. The difference in means and the standard deviations answer related but distinct questions: the first describes separation between averages, while the latter describes variation within each group.

How should the confidence interval be read?

A confidence interval gives a range of values compatible with the observed data under the assumptions of the statistical method. It conveys precision as well as direction. For the primary mean difference, the interval is -15.0 to 9.595 grams. Because this range includes zero, it includes no average difference as one value compatible with the data. It also includes negative and positive values, so the data do not pin down the direction with precision. The interval should not be read as a guarantee that the true difference lies within those limits, nor as a range of individual participant outcomes.

The interval is broad in relation to the point estimate, which means the estimate is uncertain. A point estimate alone can make an observed contrast look more settled than it is. Reading the estimate and interval together keeps the observed direction in view while acknowledging that materially different underlying contrasts remain compatible with the summary. The registry does not report a threshold for a clinically important difference, so the interval cannot be classified against such a threshold.

What does an unadjusted p-value tell the reader?

The primary unadjusted p-value is 0.667. A p-value measures how unusual data at least as discrepant as those observed would be under a specified null model and its assumptions. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of a difference. A comparatively large p-value does not prove that the groups have identical outcomes. It indicates that this unadjusted comparison does not provide strong evidence against a null of no difference.

The posted comparisons are unadjusted recalculations based on the summary statistics. There are no sponsor-reported analyses listed in the registry record. Without the original statistical plan or participant-level data, the calculations cannot establish whether they match the study's planned model, covariate adjustments, handling of missing observations, or other analytic decisions. The registry record does not report these details.

Why does variation matter?

Variation among participants affects how precisely a group contrast can be estimated. When measurements differ substantially within groups, it can be harder to distinguish a group-level contrast from ordinary participant-to-participant variation. The primary standard deviations are 22.8 grams in the control group and 22.2 grams in the pamidronate group, while the reported group sizes are 29 and 23. These are the observed summary quantities; they do not reveal whether the measurements follow a particular distribution or whether any assumptions were checked.

The calculations include a pooled standard deviation of 22.54 and a standardized mean difference of -0.120. A standardized effect expresses a mean difference relative to a measure of variability, allowing outcomes on different scales to be compared in broad terms. It does not replace the outcome in its original unit, and it does not provide a clinical interpretation by itself. The standardized value remains an estimate based on a small set of outcome summaries and should be read with the uncertainty in mind.

Why can over-dispersion matter in other kinds of outcomes?

General statistical explanation: for count outcomes, over-dispersion means that observed variation exceeds what a simple model assumes. If a model does not allow for that extra variation, uncertainty can be understated and statistical evidence can appear stronger than it is. The posted primary outcome is continuous, not a count outcome, and the registry record does not state that over-dispersion methods were used. This concept is therefore general background, not a description of the trial's reported analysis.

What can the secondary comparisons add?

The registry lists additional outcomes involving total body bone mineral content, bone mineral density and estimated bone strength, cytokines, and markers related to bone formation and resorption. These measures examine related but distinct aspects of bone status and biology. They can provide context for the primary measure, but they are not interchangeable with lumbar spine bone mineral content. Differences in measurement scale, outcome definition, and the available participant counts also mean that their estimates should not be treated as direct replications of the primary comparison.

For the posted secondary summaries, the comparisons are likewise unadjusted recalculations, and no reported sponsor analyses are listed. A series of outcomes creates a multiplicity issue: when many comparisons are considered, chance findings become more likely across the set if each is interpreted as a standalone test. Statistical methods can address this issue, but the registry record does not report a multiplicity procedure or a hierarchy for secondary outcomes. Accordingly, secondary p-values and estimates are exploratory in interpretation unless a fuller analysis plan establishes otherwise.

These methods explain how to read the numerical summaries, not how the trial's original analysis was designed. The original statistical model, covariate strategy, missing-data method, analysis population, and interim-analysis plan are not reported in the registry record. The recalculated comparisons therefore provide a transparent, unadjusted reading of the posted group summaries, with uncertainty that should remain central to interpretation.

11. Confidence Intervals and Precision

The primary estimate is -2.7 grams, with a confidence interval from -15.0 to 9.595 grams. This interval is wide enough to include a range of possible group differences in both directions. It includes zero, so the summary does not resolve whether the underlying average is lower, higher, or essentially similar between groups. The point estimate gives the direction of the observed contrast, but the interval shows that the direction and magnitude are uncertain.

Precision depends in part on the amount of information available and the variability of the outcome. The primary outcome counts are 29 in the control group and 23 in the pamidronate group, and the reported standard deviations are 22.8 and 22.2 grams. The registry record does not report a planned precision target or a clinically important difference against which the interval could be assessed. Thus, the interval can describe statistical uncertainty, but it cannot by itself determine whether the range is clinically meaningful.

The secondary comparisons also have intervals that span values on either side of no difference. For total body bone mineral content, the mean difference is -27.0 grams with an interval from -316.3 to 262.3 grams. For the pQCT bone measure family, the reported mean difference is -0.069 g/cm2 with an interval from -0.178 to 0.040 g/cm2. These intervals likewise convey uncertainty; neither should be read as proving no difference simply because the range includes zero.

Confidence intervals describe uncertainty about group-level estimates under statistical assumptions. They do not show the range of outcomes among individual participants, and they do not account automatically for missing data, multiplicity, or unreported design features. The registry does not provide enough information to assess those issues fully.

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 figures are participants per arm for each listed effect assumption, not total events. They are illustrations derived from the observed effect, rather than the trial's original sample-size plan. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set to the stated fraction of the observed effect. The registry record does not report the original design assumptions or sample-size justification.

The 80% power column gives the estimated number of participants per arm that the illustration would require to have an 80% chance of detecting the specified effect under those assumptions, if that effect were the true effect and the model assumptions held. The 90% power column gives the corresponding number per arm for a 90% chance. Power is a feature of a hypothetical design under specified assumptions; it is not a measure of the probability that the observed trial result is true.

Each planning row uses a different fraction of the observed effect. The observed effect is the reference point, and the smaller fractions represent smaller effects to detect. Smaller effects are harder to distinguish from random variation, so the planning illustration requires more participants per arm as the assumed effect becomes smaller. The figures are not recommendations for this trial, and they do not establish what sample size would be appropriate for a future study without a justified target effect, outcome variability, and design choices.

These calculations are not observed power. They are prospective planning illustrations based on the observed effect and the stated assumptions, and should not be used to explain the trial's result as a simple consequence of being underpowered. The precision of the posted estimates is better assessed directly from their confidence intervals and the available outcome data.

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 = -2.700; pooled standard deviation σ = 22.538.
2. n = 2 × (1.96 + 0.842)² × 22.538² / -2.700² = 1,093.8, rounded up to 1,094 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 <- -2.7                      # observed difference in means
sigma <- 22.5379679651915                     # 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(2074631)
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 = 1,094 (80% power), 1,465 (90% power)
 75% of observed effect: n per arm = 1,945 (80% power), 2,604 (90% power)
 50% of observed effect: n per arm = 4,376 (80% power), 5,858 (90% power)
power.t.test: 1094.8 
Simulated power at n = 1,094 per arm: 0.801 (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 lists a primary endpoint and multiple secondary outcomes, but it does not report how the study planned to address multiplicity. When several outcomes are tested, the chance of at least one apparently unusual result can increase if every comparison is treated as a separate confirmatory test. Researchers may address this through a prespecified hierarchy, adjusted significance thresholds, or other strategies. Which approach, if any, was used in this trial is not reported in the registry record.

No sponsor-reported analyses are listed for the posted outcomes. The unadjusted comparisons are recalculated from summary statistics and do not show whether the original investigators used covariate adjustment, a particular model, or a planned testing hierarchy. The original statistical analysis plan, any interim analyses, and the original sample-size justification are not reported in the registry record.

The registry describes the primary population as participants unable to be evaluated because of declining health or failure of follow up. It does not clarify how this description relates to the reported outcome summaries, how many participants lacked an outcome, or why outcome counts differ from enrollment. The primary group counts are 29 and 23; the registry does not identify an intention-to-treat, per-protocol, or other analysis population. It also does not report whether missing measurements were imputed, excluded, or handled by another method.

Those omissions matter because missing outcomes can affect both the size and the comparability of the analyzed groups, particularly if inability to complete follow up is related to health status or outcome values. This is a general statistical concern, not a claim that missingness biased these results. Without reasons for missingness, participant flow, and the analysis method, the direction or size of any potential effect cannot be determined. The confidence intervals and unadjusted comparisons should therefore be understood as summaries of the posted information rather than a complete account of the trial's analytic process.

15. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent non-serious adverse event terms

The registry reports zero serious adverse events among the 32 control participants at risk and zero among the 31 pamidronate participants at risk. It lists zero deaths in each group. These are event counts in the registry record; they do not establish that no other adverse experiences occurred or that the treatments had no safety risks.

For other adverse events, the registry reports 9 affected participants among 32 at risk in the control group and 19 affected participants among 31 at risk in the pamidronate group. These figures count participants affected, rather than the total number of individual events. The record does not provide event terms in the serious-event list, since no top serious-event terms are listed, and it does not give further information about event severity, timing, attribution, or the definitions used.

The groups and follow-up counts should be read as recorded, without treating the raw counts as a formal comparative safety analysis. No rates or adjusted comparisons are reported. The difference in counts alone cannot establish whether treatment caused an event or whether groups differed in risk, especially without fuller definitions and event-level details.

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

The primary posted data describe average lumbar spine bone mineral content at 1 year after HCT. The observed average was lower in the pamidronate group than in the control group, but the estimated difference is imprecise and its confidence interval includes both negative and positive values. The unadjusted comparison does not provide strong statistical evidence of a group difference. It also does not establish that the groups are equivalent or that a meaningful difference is absent.

The result is limited to the measured outcome, the specified follow-up time, and the participants represented in the posted outcome summaries. It does not directly establish effects on fractures, symptoms, later bone outcomes, or every biological measure listed in the registry. Nor does the average describe each participant's experience. The registry does not give a threshold for clinical importance, so the clinical meaning of the numerical range cannot be determined from the record alone.

Random allocation supports a comparative trial design, but interpretation still depends on how randomization was implemented, how participants were followed, and how missing observations were handled. The registry record does not report those analytic details or the original statistical plan. The trial was open-label, and the record does not describe whether outcome assessors were masked. These uncertainties limit what can be concluded from the posted summary statistics.

Accordingly, the figures are best read as an uncertain observed comparison, not as a declaration that pamidronate does or does not alter bone mineral content. They do not provide a definitive account of benefit, absence of benefit, equivalence, or safety. Stronger conclusions would require transparent reporting of the planned and performed analyses, the participant flow and missing outcomes, and estimates with adequate precision relative to a clinically meaningful threshold.

17. Why This Trial Matters Statistically

This trial is statistically informative because it illustrates the distinction between an observed point estimate and the strength of evidence it provides. The primary mean difference has a direction, but its confidence interval is broad and includes values on both sides of no difference. That combination is a reminder that a numerical contrast should not be interpreted without its precision.

It also illustrates why a non-small p-value is not evidence of equivalence. The unadjusted p-value is 0.667, but the registry record does not report an equivalence design or a prespecified margin. The appropriate reading is uncertainty about the group difference, not proof that the groups are the same. The confidence interval makes this uncertainty more visible than a single p-value alone.

The record also demonstrates the value of distinguishing a trial's enrolled population from the participants contributing to an outcome summary. Enrollment is 63, while the primary outcome group counts are 29 and 23. The reasons are not reported in the registry record, so the counts cannot be reconciled from the posted information. Transparent participant flow and missing-data reporting are essential for assessing how representative the analyzed results may be.

Finally, multiple secondary outcomes broaden the scientific questions but complicate interpretation. Without a reported multiplicity strategy or full analysis plan, secondary comparisons carry less confirmatory weight. In combination, these features make careful reporting of estimates, intervals, analysis populations, and statistical plans central to evaluating a randomized clinical trial.

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.

The registry record does not explain why the primary outcome counts are 29 in the control group and 23 in the pamidronate group when enrollment is 63. It also does not provide a participant-flow account, reasons for missing measurements, or the number unable to complete the 1-year assessment. The primary population description refers to participants unable to be evaluated because of declining health or failure of follow up, but does not clarify how that wording relates to the reported means.

The record does not state the original sample-size justification, planned statistical model, analysis population, covariate adjustments, missing-data strategy, interim-analysis plan, or multiplicity procedure. No sponsor-reported analyses are listed. As a result, the posted unadjusted recalculations cannot be checked against a prespecified analytic approach, and it is not possible to determine whether their assumptions match the original analysis.

The trial was open-label. The registry does not report whether outcome assessors were masked, how DXA measurements were standardized, or whether measurement reliability was assessed. It also does not describe adherence to the infusion schedule or treatment changes. These details may matter when interpreting a measured endpoint, but their absence does not establish that measurement or treatment implementation was inadequate.

The record does not provide a clinically important threshold for lumbar spine bone mineral content, detailed event definitions, or full numerical results for every listed secondary outcome. Thus, statistical uncertainty cannot be translated into a definitive clinical judgment, and the safety counts cannot support a complete comparative safety assessment. These are limitations of what the registry record reports, not proof that the underlying trial did not collect the information.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Prevention of Bone Loss After Pediatric Hematopoietic Cell Transplantation — NCT02074631.
• Registry record last updated 2024-02-20; status last verified 2024-01.
• Results first posted 2024-02-20.
• 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

NCT02074631 is a completed, randomized, open-label, parallel-group Phase 2 study of pamidronate with calcium and vitamin D versus calcium and vitamin D alone after pediatric HCT. Enrollment was 63. The registry lists a start of 2015-02 and primary completion on 2022-10-06.

The primary outcome was average lumbar spine bone mineral content in grams at 1 year after HCT. The posted means were 41.4 in the control group and 38.7 in the pamidronate group, with an unadjusted mean difference of -2.7 grams and a confidence interval from -15.0 to 9.595 grams. The interval is broad and includes no difference.

The record lists additional bone and biological outcomes, but does not report sponsor analyses, the original statistical plan, missing-data methods, or multiplicity handling. Serious adverse events and deaths are recorded as zero in both groups; other adverse-event counts are also listed. The posted information supports cautious interpretation of uncertain group comparisons, not definitive conclusions about clinical effects.