Longitudinal Effects of Denosumab on Trabecular Bone Score and Femur Strength Index: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Longitudinal Effects of Denosumab on Trabecular Bone Score and Femur Strength Index (NCT02435147), a registered phase not stated study. The primary outcome is Proportion of Change in Mean Trabecular Bone Score.

2. Clinical Question

At a broad level, the study asks whether trabecular bone score changes over the specified follow-up period among people receiving denosumab in a real-world clinical practice setting. The listed primary outcome is a continuous measure, summarized as a mean, with standard deviation identified as its dispersion measure. The record does not state the numerical mean change, its variability, or the number of participants contributing measurements at either time point. It also does not report an effect estimate, confidence interval, or significance test.

Although the summary mentions femur strength index and fracture-related risks, those statements describe the study’s rationale and hypotheses rather than reported findings. The registry lists a secondary outcome for change in mean femur strength index, but gives no result for it. Consequently, the record supports describing the intended research question and measurement plan, not drawing a conclusion about the direction or size of any change.

3. Trial Design

The registry identifies this as a completed study sponsored by HealthEast Care System. Its listed enrollment is 86, and the study dates run from 2015-04 to a primary completion date of 2016-06. The intervention is denosumab, classified as a drug. The condition fields list osteoporosis and bone fracture.

The record does not describe a randomized comparison. Allocation is not stated, and the record does not identify a control group suitable for a like-for-like comparison. It therefore does not support interpreting the listed treatment group as one arm of a randomized efficacy comparison. Details such as recruitment procedures, eligibility criteria, treatment schedule, follow-up procedures, and the number of participants with completed measurements are not reported in the registry record.

The primary outcome is the proportion of change in mean trabecular bone score, measured at baseline and 36 months. The primary outcome description says it concerns change at 36 months following denosumab initiation. The registry also lists proportion of change in mean femur strength index as a secondary outcome. Two outcome measures are recorded, but the record reports zero analyses. No numerical outcome findings or analysis populations are described.

The study summary presents a real-world clinical practice rationale and a hypothesis about continued denosumab therapy. That framing does not establish that the study tested a causal treatment effect: the registry does not provide a randomized control comparison, nor does it detail adjustment for differences over time or between participants. The sample-size assumptions described for the planning illustration are not the trial’s own design. The registry record does not report a trial-specific sample-size justification or statistical analysis plan.

Overall, the available design information establishes the intervention, intended primary measure, measurement timeframe, and broad clinical context. It does not establish how participants were selected into treatment, how missing measurements were handled, or how the investigators conducted analyses. Those omissions limit the conclusions that can be drawn from 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

Reasons for not completing this period:

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 Proportion of Change in Mean Trabecular Bone Score, measured over Baseline and 36 months.

The primary endpoint is the proportion of change in mean trabecular bone score from baseline to 36 months following denosumab initiation. Trabecular bone score is the named continuous measure; the registry specifies a mean as the summary and standard deviation as its dispersion. The timeframe identifies the planned comparison of measurements at baseline and 36 months.

In general, a continuous endpoint can describe the magnitude and direction of change in a measured characteristic. A mean summarizes the central level of measurements, while a standard deviation describes how dispersed individual measurements are around that mean. A change measure can focus attention on how the outcome differs between the specified time points, rather than only describing its level at one time.

The registry’s description does not define the formula used to calculate “proportion of change,” clarify whether the outcome is calculated for each participant before summarizing, or specify how incomplete paired measurements would be treated. Those details are not reported in the registry record. The record also contains no numerical endpoint result, so the size, direction, and precision of change cannot be assessed from it.

The summary’s interest in trabecular bone score reflects the study’s stated rationale. That rationale does not itself demonstrate that the measure changed, or that any measured change corresponds to a change in fractures or other clinical outcomes. The registry lists a separate secondary outcome for femur strength index but does not report results for it.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry characterizes the primary outcome as continuous, with the mean as the parameter and standard deviation as the dispersion measure. These terms describe the intended form of the outcome summary. They do not reveal the observed value, the number of observations used, or the uncertainty around an estimate. No analysis results are recorded.

What does a mean describe?

In general, the mean is an average that summarizes the measured values in a group. It can be useful for describing a continuous outcome when the scientific question concerns its average level or average change. However, a mean alone does not show how individual values are distributed. The standard deviation describes spread around the mean, but it is not the same as uncertainty in the estimated mean. A confidence interval, when reported, is one way to communicate uncertainty about an estimate. The registry record does not report a confidence interval for the primary endpoint.

What is a change endpoint?

The primary measure is described as proportion of change in mean trabecular bone score, with baseline and 36 months as the measurement times. In general, change endpoints compare measurements across time. Their interpretation depends on the exact definition of change, the treatment of measurements within each participant, and the participants included in the calculation. The registry does not specify the calculation formula or whether the proportion is calculated at the participant level or from group means. These details are not reported in the registry record.

Repeated measurements also raise questions about whether the same participants contribute data at each time point. If follow-up is incomplete, a complete-case analysis can differ from an analysis that uses other assumptions or methods for missing measurements. The record does not describe the amount or pattern of missing data, or the method used to handle it. It is therefore not possible to determine which participants contributed to the endpoint or how incomplete observations affected an estimate.

Why does a comparison matter?

In general, measurements before and after treatment describe change over time, but a change alone does not isolate the effect of treatment. A comparator can help distinguish treatment-associated change from other influences, depending on how the comparison is designed and analyzed. The registry explicitly does not describe a randomized comparison; allocation is not stated, and the arms are not a like-for-like control comparison. It does not report an adjusted analysis that could address differences between groups. Causal interpretation is consequently limited by the record’s design information and missing analysis results.

What does over-dispersion mean?

In general, over-dispersion refers to observed variability that is greater than a statistical model assumes. When relevant, ignoring it can make uncertainty appear smaller than it is. The listed primary outcome is continuous and summarized using a mean and standard deviation; the registry does not report a count model or indicate that over-dispersion was assessed. This is a general statistical concept, not a method that can be attributed to this study.

How should significance and precision be assessed?

In general, a p-value addresses how compatible observed data are with a specified statistical null model, under the assumptions of the analysis. It does not measure the probability that a hypothesis is true or the size or importance of an effect. A confidence interval gives a range of values compatible with the data and analysis assumptions and communicates precision. Neither a p-value nor a confidence interval is reported for the endpoint in the registry record. Without an estimate and its uncertainty, the primary outcome cannot be assessed for statistical evidence or precision.

The registry lists two outcome measures and zero analyses. It does not report which outcomes were analyzed, any analysis model, covariate adjustment, subgroup analysis, interim analysis, or multiplicity procedure. These methods are not reported in the registry record and should not be inferred from the endpoint listings.

What are the sample-size calculations for?

The described sample-size assumptions are a planning illustration, not the trial’s own design. The illustration is based on an observed effect and assumes a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated target effect is a fraction of the observed effect. Such calculations can illustrate the scale of a future study under chosen assumptions; they do not show the power achieved by this completed study. The registry record does not report a trial-specific sample-size justification, and the outcome analysis needed to evaluate the observed effect is absent.

In general, a planning calculation is sensitive to its assumptions about effect size, variability, allocation, and analysis. If those assumptions do not match a future study, the resulting sample-size illustration may not fit that study. Because the record does not provide the primary endpoint estimate or its variability, the planning illustration cannot be independently interpreted in relation to the reported trial results. It should not be read as a substitute for an outcome analysis.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Denosumab")
n   <- c(75)
m   <- c(0.00238)
sp  <- c(0.0422)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Denosumab  75  0.002  0.042  -0.007  0.012

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures: the primary outcome of proportion of change in mean trabecular bone score and a secondary outcome of proportion of change in mean femur strength index. It reports zero analyses. No results are given for either outcome, and no testing strategy is described.

When several outcomes or hypotheses are tested, general statistical practice may consider multiplicity: repeated testing can increase the chance of at least one apparently notable finding under a set of null hypotheses. Approaches to address this depend on the study question and analysis plan. The registry record does not report a multiplicity adjustment, a hierarchy for testing outcomes, or whether any adjustment was planned. No such approach should be assumed.

The record does not describe missing outcome data, the number of participants with measurements at baseline or 36 months, or methods for handling incomplete follow-up. In general, missing data can affect both the number of observations available and the interpretation of an estimate, particularly if missingness is related to participant characteristics or outcomes. The relevant pattern and handling method are not reported in the registry record, so the direction or extent of any impact cannot be assessed.

Analysis populations are also not specified. The registry does not state whether analyses included all enrolled participants, only those receiving treatment, or only those with measurements at both time points. It does not report exclusions or protocol deviations. These omissions prevent readers from identifying who contributed to any endpoint estimate; no estimate is reported in any case.

12. 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.

The registry safety entry for the denosumab group lists 75 participants at risk and zero serious adverse events. This is the serious-adverse-event information recorded in the registry, not a complete description of all adverse events or a comparison with another treatment group.

A zero count in this entry means that no serious adverse events are recorded for the listed group in this safety summary. It does not establish that no adverse events of any kind occurred, nor does it establish that serious events could not occur. The record does not report the safety observation period, the event definitions used, or the process for collecting events. It also does not explain how the participants at risk relate to the enrollment or to the primary-outcome analysis population.

Because the registry does not describe a like-for-like control comparison, the safety figures cannot be used to estimate a relative difference between treatments. The registry record does not report comparative safety analyses or additional context for interpreting the listed count. These figures should be read narrowly as the recorded serious-adverse-event entry, not as evidence of overall safety.

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

The registry record establishes that a completed study examined denosumab in relation to trabecular bone score, with baseline and 36 months identified as the primary outcome measurement times. It also records a secondary outcome concerning femur strength index and provides a study summary describing hypotheses about bone-health measures and risks. These details identify the research question; they do not answer it.

No primary or secondary outcome results are reported, and the record lists zero analyses. There is no numerical estimate of change, no measure of precision, and no reported statistical test. Consequently, the record does not show whether trabecular bone score or femur strength index increased, decreased, or remained similar. It also does not report fracture findings.

The record does not describe a randomized comparison, does not state allocation, and does not identify a like-for-like control group. Even if before-and-after measurements had been reported, a change over time alone would not establish that treatment caused the change. The record also lacks information about analyzed participants, missing measurements, and the statistical methods used.

The serious-adverse-event entry records zero events among 75 at risk in the denosumab group. That entry does not address all adverse events, provide a comparative estimate, or establish the absence of risk. The safety collection details are not reported in the registry record.

The planning illustration is not the study’s own design and is not observed power. It cannot be interpreted as evidence that the trial did or did not detect an effect. Overall, the registry record describes the intended endpoint and study context but does not support a conclusion about efficacy, clinical importance, or comparative safety.

14. Why This Trial Matters Statistically

This study is statistically notable as a registry record with a clearly identified continuous primary outcome and a stated measurement timeframe, but without reported analysis results. That distinction matters: registering an outcome and its timing makes the intended question visible, while a result and its uncertainty are necessary for evaluating what the study found. Here, the record does not include an estimate of change in trabecular bone score, a confidence interval, or a statistical test.

The record also illustrates why design information is essential to interpretation. A real-world clinical practice setting can make a research question relevant to routine care, but the registry does not describe a randomized comparison or a like-for-like control. Allocation is not stated. Without reported methods for choosing or comparing participants, a change over time cannot be separated from other possible influences on measurements.

Outcome and analysis transparency are also important. The registry lists a secondary outcome and describes hypotheses about additional bone-health risks, yet does not provide results for those measures. It reports zero analyses, and does not specify multiplicity handling, missing-data methods, or analysis populations. Readers therefore cannot assess whether results were complete, how uncertainty was estimated, or how the listed outcomes were treated analytically.

Finally, the distinction between planning and observation is important. The stated sample-size illustration is explicitly not the trial’s own design and should not be confused with the evidence generated by the study. The record can support a precise description of what was intended and what was recorded, but not a claim about the magnitude, precision, or clinical meaning of any treatment effect.

15. 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 most immediate limitation is that the registry record contains no outcome results and lists zero analyses. It therefore does not report the primary endpoint estimate, variability, confidence interval, or statistical test. The secondary outcome also has no reported result. No inference about the direction, magnitude, or precision of change is possible from the record.

The record does not describe a randomized comparison, and allocation is not stated. It does not identify a like-for-like control group or describe adjustment for potential differences between participants. Any causal interpretation would require design and analysis information that is not reported in the registry record.

Important details about participants and follow-up are absent. Although enrollment is listed as 86, the record does not report the number contributing to the primary outcome, participant characteristics, reasons for non-completion, or the extent and handling of missing measurements. The listed timeframe does not establish that measurements were available for every participant at both time points.

The registry does not report the calculation method for the proportion of change, the statistical model, analysis populations, covariate adjustment, or multiplicity procedures. It does not provide a trial-specific sample-size justification. The planning illustration is not the study’s own design and cannot replace the absent results.

Safety information is limited to the serious-adverse-event entry. The record does not describe event collection, the observation period, or broader adverse events. These omissions restrict interpretation of both the outcome and safety information to the narrow details recorded.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Longitudinal Effects of Denosumab on Trabecular Bone Score and Femur Strength Index — NCT02435147.
• Registry record last updated 2018-10-29; status last verified 2018-10.
• Results first posted 2018-10-29.
• 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.

19. Record Summary

The registry identifies a completed denosumab study sponsored by HealthEast Care System, with enrollment of 86. The listed study dates are 2015-04 and 2016-06 for start and primary completion. The conditions are osteoporosis and bone fracture.

The primary outcome is proportion of change in mean trabecular bone score from baseline to 36 months. The secondary outcome concerns proportion of change in mean femur strength index. The study summary describes hypotheses about these measures and bone-health risks in post-menopausal women with osteoporosis. The registry does not describe a randomized comparison, and allocation is not stated.

The record lists zero analyses and reports no outcome estimates. It does not report analysis populations, missing-data methods, or a statistical plan. The safety entry records zero serious adverse events among 75 at risk in the denosumab group. These registry entries describe the recorded design and safety information but do not establish an outcome effect or comparative safety.