Treatment With Zoledronic Acid Subsequent to Denosumab in Osteoporosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Treatment With Zoledronic Acid Subsequent to Denosumab in Osteoporosis (NCT03087851), a randomized phase 4 study. The primary outcome is Change in Lumbar Spine BMD From Baseline to 6 Months After the Zoledronic Acid Infusion..

2. Clinical Question

The trial asks whether the timing and use of zoledronic acid after denosumab are associated with different changes in lumbar spine bone mineral density (BMD). The primary endpoint is the change from baseline to 6 months after the zoledronic acid infusion. Results are reported as mean percentage change in each study group, with the posted comparisons contrasting each zoledronic acid group with an observation group.

The broader study summary asks whether bone mass can be maintained with zoledronic acid and whether the timing of the first dose after denosumab matters. The posted primary outcome addresses one part of that question: lumbar spine BMD at a specified follow-up after infusion. It does not, by itself, cover every aspect of bone health, fracture risk, or the longer-term consequences of different dosing schedules.

3. Trial Design

The registry record describes a Phase 4, randomized, parallel-group trial with no masking. It lists 61 participants with osteoporosis and reports that the study is completed. The intervention is zoledronic acid. The posted results are organized into three groups: 6-month Group, 9-months Group, and Observation Group. The outcome records list 20 participants in each zoledronic acid group and 21 in the observation group.

The registry description says zoledronic acid is administered to the 6-month group at study day 0. It describes later or conditional administration in the other groups, based on serum CTX (s-CTX), BMD change, or specified fractures, with latest administration times also stated. Some arm-description text is incomplete in the registry record, so the full dosing and follow-up rules cannot be reconstructed from the posted text alone. The exact relation of study day 0 to every participant’s denosumab dose is not reported in the registry record.

Randomization means the study assigned participants to groups by chance, but the randomization procedure, allocation concealment, and any stratification factors are not reported in the registry record. With no masking, participants and study staff were not blinded to group assignment according to the design listing. The record does not describe whether outcome assessors were masked.

The study dates listed are 2017-03-13 for start and 2020-08-01 for primary completion. The registry record does not report the original sample-size justification or the trial’s detailed statistical analysis plan. The results section includes endpoint summaries, but no reported analyses are listed. Those omissions limit how fully the design and analysis choices can be evaluated.

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:

Analysis population for the primary outcome, as defined in the registry: Change in lumbar spine BMD from baseline to 6 months after the zoledronic acid infusion.

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 Change in Lumbar Spine BMD From Baseline to 6 Months After the Zoledronic Acid Infusion., measured over baseline to 6 months after the zoledronic acid infusion.

The primary endpoint is the change in lumbar spine BMD from baseline to 6 months after zoledronic acid infusion. BMD is a continuous measurement of bone density; here, the registry expresses the change as a percentage change and summarizes it with a mean and standard error for each group. The endpoint therefore describes the average direction and size of lumbar spine BMD change over the stated interval, rather than the experience of every individual participant.

Lumbar spine BMD is used in this trial as a measure of skeletal response after zoledronic acid. The study’s stated question concerns whether bone mass can be maintained after denosumab and whether the timing of zoledronic acid matters. Measuring change from baseline makes the endpoint responsive to movement over follow-up, while comparing group means gives a way to describe differences across the assigned strategies.

This endpoint has a defined scope. It concerns lumbar spine BMD at the specified follow-up after infusion. It is not itself a fracture outcome, a measure of all skeletal sites, or a direct account of the full balance of benefits and harms. The registry record also lists other BMD, bone-turnover, cortical-porosity, and vertebral-fracture outcomes, but those address different dimensions of the study question. BMD change can help characterize the biological response, while clinical events and other measurements provide complementary evidence.

The registry record reports group means and standard errors but does not describe the measurement protocol, equipment, or rules for handling a missing baseline or follow-up measurement. Those details are not reported in the registry record.

7. Results Posted in the Registry

• 6-month Group: mean -2.10 versus -3.00 on control; difference 0.90 (95% CI -1.89 to 3.69), standardized effect d = 0.20; z-test p = 0.527.
• 9-months Group: mean -4.30 versus -3.00 on control; difference -1.30 (95% CI -4.35 to 1.75), standardized effect d = -0.26; z-test p = 0.403.

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.

Changes in BMD From Baseline to One Year After the Zoledronic Acid Infusion.

• 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:
  • 6-month Group: mean -4.80 versus -4.70 on control; difference -0.10 (95% CI -2.82 to 2.62), standardized effect d = -0.02; z-test p = 0.943.
  • 9-months Group: mean -4.10 versus -4.70 on control; difference 0.60 (95% CI -2.59 to 3.79), standardized effect d = 0.11; z-test p = 0.712.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 6-month Group and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 9-months Group and the control. The interval gives the range of effects that remain compatible with the data.

Changes in BMD From Baseline to Two Years After the Zoledronic Acid Infusion.

• 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:
  • 6-month Group: mean -4.00 versus -4.30 on control; difference 0.30 (95% CI -3.03 to 3.63), standardized effect d = 0.05; z-test p = 0.860.
  • 9-months Group: mean -4.10 versus -4.30 on control; difference 0.20 (95% CI -3.13 to 3.53), standardized effect d = 0.04; z-test p = 0.906.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 6-month Group and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 9-months Group and the control. The interval gives the range of effects that remain compatible with the data.

Changes in Cortical Porosity Measured by High-resolution Peripheral Quantitative Computed Tomography (HR-pQCT) Scan at the Radius and Tibia From Baseline to One Year After the Zoledronic Acid Infusion.

• 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:
  • 6-month Group: mean -2.50 versus -4.20 on control; difference 1.70 (95% CI -18.54 to 21.94), standardized effect d = 0.05; z-test p = 0.869.
  • 9-months Group: mean -1.60 versus -4.20 on control; difference 2.60 (95% CI -16.68 to 21.88), standardized effect d = 0.08; z-test p = 0.792.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 6-month Group and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 9-months Group and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary results follow a broadly similar pattern of uncertainty to the primary result. The reported comparisons for BMD at later follow-ups and cortical porosity have estimates that are imprecise, with intervals that include zero. This means the posted summaries do not clearly separate the zoledronic acid groups from the observation group on those measured outcomes. The secondary results therefore provide context around the primary BMD finding rather than a distinct, conclusive pattern that resolves its uncertainty.

These measures relate to the main question in different ways. BMD at later follow-ups extends the assessment of bone density beyond the primary endpoint’s follow-up. Cortical porosity, measured using high-resolution peripheral quantitative computed tomography at the radius and tibia, represents another aspect of bone structure. The registry also lists bone-turnover measures and morphometric vertebral fractures as secondary outcomes, but results for these listed outcomes are not reported in the registry record.

Secondary outcomes can help describe whether a pattern is consistent across related biological measures and clinical events. They do not automatically confirm the primary result, especially when they address different constructs, time points, or measurement methods. A result on one endpoint cannot be substituted for an unreported result on another.

The posted secondary comparisons are unadjusted recalculations, and no multiplicity strategy or hierarchy among secondary outcomes is reported. General statistical explanation: when many outcomes or comparisons are considered, chance alone can produce some seemingly notable estimates. Without a stated adjustment plan and without reported sponsor analyses, secondary findings should be treated as exploratory and interpreted cautiously. The main value of the posted secondary information is to show the scope and direction of the available measurements while making clear that several registry-listed outcomes lack posted results.

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

• Changes in BMD From Baseline to One Year After the Zoledronic Acid Infusion.
• Changes in BMD From Baseline to Two Years After the Zoledronic Acid Infusion.
• Changes in Cortical Porosity Measured by High-resolution Peripheral Quantitative Computed Tomography (HR-pQCT) Scan at the Radius and Tibia From Baseline to One Year After the Zoledronic Acid Infusion.
• Changes in p-CTX From Baseline to Six Months After the Zoledronic Acid Infusion.
• Changes in p-CTX From Baseline to 12 Months After the Zoledronic Acid Infusion.
• Morphometric Vertebral Fractures Assessed by Vertebral Fracture Assessment (VFA) One and Two Years After the Zoledronic Acid Infusion.

9. Statistical Interpretation

10. Statistical Methods Explained

The primary measure is continuous: it is a percentage change in lumbar spine BMD. The registry reports a mean for each group and a standard error (SE). A mean summarizes the central level of a continuous measure; it does not show the full spread or shape of participant-level results. An SE describes the precision of an estimated mean. General statistical explanation: a smaller SE usually indicates a more precise estimate of the mean, while an SE is not the same thing as the standard deviation of individual observations.

How to read the group summaries

The posted group summaries are -2.1 for the 6-month Group, -4.3 for the 9-months Group, and -3.0 for the Observation Group. Each is a mean change from baseline in the endpoint’s percentage-change units. The table also reports an SE for each mean: 0.9, 1.1, and 1.1, respectively. These summaries describe the observed groups and should not be interpreted as exact values for the wider population from which participants might be drawn.

The trial is listed as randomized and parallel group. In a parallel-group design, participants are assigned to a group and the groups are compared over follow-up. Randomization can reduce systematic differences at baseline on average, but it does not guarantee identical groups, especially in a study of this size. The method used to generate or conceal the allocation is not reported in the registry record. The study is listed as having no masking, so expectations or care decisions could potentially be influenced by knowledge of assignment; whether outcome assessment was masked is not reported.

How to read the comparisons

The displayed comparisons use the Observation Group as the reference and report mean differences. The 6-month Group estimate is 0.9, calculated from the posted group means; the 9-months Group estimate is -1.3. Positive and negative signs indicate the direction of the comparison as presented, not whether a result is favorable. Interpretation should keep the outcome’s coding and the study question in view.

The intervals shown alongside those differences express uncertainty around the estimated contrasts. General statistical explanation: an interval is a range of values compatible with the data under the method used to construct it. An interval spanning zero includes the possibility of no between-group difference. Its width is informative: a wide interval indicates that the estimate is not sharply determined. The confidence level and the interval-construction method are not reported in the registry record, so the intervals should be treated as the simple recalculated intervals shown with the posted comparison summaries.

The unadjusted p-values for the primary comparisons are 0.527 and 0.403. General statistical explanation: a p-value summarizes how inconsistent data are with a specified no-difference model under the assumptions of the test. It does not give the probability that the no-difference model is true, and it does not measure the size or importance of an effect. These p-values are unadjusted recalculations from posted summary statistics; the registry record does not list a reported analysis for the endpoint.

Why variability matters

Standard errors and intervals help show how much uncertainty accompanies an estimate. General statistical explanation: more variability among individual measurements, or fewer informative observations, tends to make estimates less precise. For continuous outcomes, an appropriate analysis also depends on the distribution of the observations and on whether measurements are available for the participants assigned to each group. Participant-level data and diagnostics are not available in the registry record, so those features cannot be assessed.

The comparison calculations include pooled standard deviations and standardized effect summaries, but these do not replace the original outcome scale. Standardization can help describe an effect relative to variability, while the mean difference remains in the endpoint’s units and is easier to relate to the reported BMD changes. No prespecified threshold for a clinically meaningful difference is reported in the registry record.

There are several outcomes and group contrasts in the record. General statistical explanation: examining multiple outcomes or comparisons can increase the chance of seeing an apparently notable result by chance if no adjustment or prespecified hierarchy is used. The registry record does not report a multiplicity strategy, a primary analysis model, or planned adjustments for baseline covariates. The posted comparisons are therefore best regarded as descriptive, unadjusted contrasts rather than as a fully documented confirmatory analysis.

The analysis population, handling of missing values, and treatment of participants who did not follow assigned dosing are not reported in the registry record. Those choices matter because they determine which observations contribute to the estimates and how the randomized assignment is represented in the analysis. The figures on this page should consequently be interpreted as summaries of what is posted, with those methodological details remaining unknown.

11. Confidence Intervals and Precision

Precision is best assessed by looking at the estimated differences together with their intervals, rather than by considering the group means or p-values alone. For the 6-month Group compared with the Observation Group, the estimated mean difference is 0.9 and the interval runs from -1.886 to 3.686. For the 9-months Group compared with the Observation Group, the estimated mean difference is -1.3 and the interval runs from -4.349 to 1.749.

Both intervals include zero. This means the recalculated results do not rule out no difference between either zoledronic acid group and the observation group. At the same time, the intervals extend to values on both sides of zero, so they also allow for differences in either direction. The point estimates alone should not be treated as settled estimates of the true group differences.

The ranges are broad enough to show that the data do not pin down the size of either contrast closely. A broad interval is not proof that there is no effect; it indicates uncertainty about the value and direction of the effect. Whether any value within an interval would matter clinically cannot be determined from these results alone, because a threshold for a meaningful difference is not reported in the registry record.

The intervals are simple unadjusted recalculations based on posted summary statistics. The registry record does not report a confidence level or the interval method used in an official analysis, and it lists no reported analyses. Thus, these intervals describe the calculations rather than a sponsor-reported inferential analysis. Their interpretation should also be considered alongside the relatively small number of participants represented in each group and the unreported details about missing data and analysis populations.

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 table and curve are planning illustrations based on the observed effect, not the trial’s original design calculation. For these continuous-outcome comparisons, the figures are participants per arm, not total events. The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. The original trial’s sample-size assumptions and justification are not reported in the registry record.

The 80% power column gives the estimated participants per arm for a future study to have an 80% chance of detecting the chosen effect under the listed planning assumptions, if that effect and the assumptions are correct. The 90% power column gives the corresponding planning target for a 90% chance. These are prospective design quantities, not evidence about the chance that the current trial detected an effect. The table’s rows for 100%, 75%, and 50% of the observed effect show how the planning target changes when the effect to detect is varied.

Smaller effects are harder to distinguish from random variation, so the planning tables require more participants per arm when the assumed effect is reduced. The displayed figures can help illustrate the scale of a future study under the stated assumptions, but they should not be interpreted as a recommendation or as a reconstruction of the trial’s actual planning process.

This is not observed power. The original sample-size rationale, target effect, and analysis plan are not reported in the registry record. The illustrated estimates use the observed effects, which are uncertain estimates themselves, and the actual design or analysis may have used different assumptions.

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 = 0.900; pooled standard deviation σ = 4.574.
2. n = 2 × (1.96 + 0.842)² × 4.574² / 0.900² = 405.5, rounded up to 406 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 <- 0.9                      # observed difference in means
sigma <- 4.57417499917493                     # 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(3087851)
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 = 406 (80% power), 543 (90% power)
 75% of observed effect: n per arm = 721 (80% power), 966 (90% power)
 50% of observed effect: n per arm = 1,622 (80% power), 2,172 (90% power)
power.t.test: 406.5 
Simulated power at n = 406 per arm: 0.797 (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 multiple outcomes, including the primary lumbar spine BMD measure and secondary measures of BMD, cortical porosity, bone turnover, and vertebral fractures. It does not report how the trial planned to address multiplicity across outcomes, time points, or group comparisons. No hierarchy for testing secondary outcomes, family-wise error control, or other multiplicity procedure is reported in the registry record.

This matters because each additional comparison creates another opportunity for a result to appear notable by chance. General statistical explanation: prespecifying a primary question and a method for handling multiple tests helps readers distinguish confirmatory evidence from exploratory patterns. Here, the primary outcome is identified in the registry, but a detailed analysis plan and any multiplicity procedure are not reported. The displayed secondary comparisons are unadjusted recalculations and should not be treated as confirmatory evidence.

Missing-data methods are also not reported in the registry record. It does not state how missing baseline or follow-up measurements were handled, whether imputation was used, or how participants with incomplete data contributed to each outcome. The participant counts shown with the posted outcomes do not establish whether all randomized participants were analyzed or whether the analysis followed an intention-to-treat, per-protocol, or other approach. The analysis populations are not reported in the registry record.

The record also does not report how adherence, protocol deviations, or changes in treatment were handled analytically. The arm descriptions include conditional dosing rules, but no statistical method is given for incorporating those events into the analysis. Interim analyses and stopping rules are not reported in the registry record.

These gaps do not invalidate the posted summaries, but they limit the strength of conclusions that can be drawn from them. Without a documented analysis plan, readers cannot assess whether the displayed comparisons match a prespecified model, how incomplete observations may have affected estimates, or whether the multiplicity of outcomes was accounted for. The calculations on this page should therefore be read as descriptive and unadjusted summaries of the posted results.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cancer (19.0%).

The registry reports serious adverse events in 0 of 20 participants in the 6-month Group, 1 of 20 in the 9-months Group, and 4 of 21 in the Observation Group. It reports no deaths in any of the three groups. The figures describe counts of participants recorded as affected among those at risk; they do not establish that an event was caused by a particular treatment or strategy.

The record lists Cancer as the top serious-event term, with 19.0%. It does not clarify in the posted summary how that term relates to individual groups, whether the percentage refers to participants or events, or the event-coding context. The serious-event counts are therefore more directly interpretable than that term percentage, but neither summary provides detailed event narratives.

Other adverse events are reported for 18 of 20 participants in each zoledronic acid group and 20 of 21 in the Observation Group. These are counts, not estimates adjusted for exposure time or other differences between groups. The registry record does not provide enough detail to compare event severity, duration, timing, or attribution. Safety counts should be read as descriptive reporting, not as proof of a causal difference.

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

The posted results describe mean changes in lumbar spine BMD and other measures across the assigned groups. At the primary follow-up, the group means are negative, and the unadjusted between-group estimates are uncertain: each comparison interval includes zero and extends in both directions. The results therefore do not precisely establish the size or direction of a difference between either zoledronic acid group and the Observation Group on the primary endpoint.

This finding should not be translated into a claim that the strategies are identical. A lack of a clearly separated estimate is different from evidence of equivalence. To establish equivalence or non-inferiority, a study generally needs a prespecified margin and a corresponding design and analysis; such a margin is not reported in the registry record. Nor do the results prove that a particular timing strategy is beneficial or harmful.

The endpoint is a measure of average lumbar spine BMD change at a defined follow-up, not a direct measure of fractures or every aspect of osteoporosis. The broader secondary outcomes could add useful context, but several registry-listed results are not reported, and the posted secondary comparisons remain imprecise. The adverse-event summaries are counts and do not, on their own, establish causation or comparative safety.

Interpretation is further limited by missing information about the original sample-size rationale, analysis populations, missing data, multiplicity, and the detailed statistical plan. The posted comparisons are simple unadjusted recalculations from summary statistics rather than reported sponsor analyses. These limitations mean the numerical estimates should be viewed as a description of the available registry results, not as a complete account of the trial’s analysis or a basis for treatment decisions.

General statistical point: an estimate, its uncertainty, the outcome’s clinical relevance, and the quality of the underlying reporting all matter. Here, the estimates are visible, but the intervals show considerable uncertainty and several design and analysis details remain unknown. The most defensible conclusion is that the posted record does not precisely resolve the comparative primary BMD question.

17. Why This Trial Matters Statistically

This trial is statistically useful because it frames a practical timing question as a randomized comparison and reports a continuous primary outcome with group-level means and standard errors. The three-group structure makes clear that the question is not simply whether zoledronic acid was administered, but how approaches involving different timing or conditional administration compare with an observation strategy. The primary endpoint also gives a defined measurement and follow-up for those comparisons.

The record illustrates why point estimates should not be read in isolation. The estimated contrasts differ in direction, while their intervals include zero and are broad. That combination communicates uncertainty more fully than a binary reading of the p-values would. The result is not a definitive separation of the study groups, but neither does it establish that the groups are equivalent.

The trial also highlights the importance of transparent reporting. Information on the analysis plan, missing-data handling, multiplicity, allocation procedures, and analysis populations would help readers judge how robust the estimates are. Without those details, even a randomized design and clear outcome definition cannot answer every question about the validity and scope of the posted comparisons.

Finally, the planning illustrations help distinguish what can be learned from this trial’s observed estimates from what a future study might require under stated assumptions. They are not a report of the original design rationale. Their dependence on the observed effect emphasizes that planning involves uncertainty about the effect worth detecting, not simply reusing an estimate from a small study.

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 posted evidence comes from 61 enrolled participants, distributed across groups with outcome counts of 20, 20, and 21. The estimates consequently represent a limited amount of information, and the primary comparison intervals are broad. The registry record does not report the original sample-size calculation, so it is not possible to determine what effect the trial was designed to detect or whether that design target was achieved.

The arm descriptions are not complete: parts of the 9-months and Observation group descriptions end mid-sentence. Although the record outlines some dosing triggers and latest administration times, it does not provide a fully readable account of every treatment rule. The exact relationship between study day 0 and the prior denosumab dose is not reported in the registry record.

Important analysis details are also absent. The randomization procedure, allocation concealment, outcome-assessor masking, analysis populations, missing-data methods, and handling of protocol deviations are not reported. The statistical analysis plan, multiplicity strategy, and interim-analysis plans are likewise not reported in the registry record. The reported analyses list is empty, so the comparisons are unadjusted recalculations from summary statistics rather than posted sponsor analyses.

Only some of the registry-listed secondary outcomes have results shown. Results for the listed bone-turnover and morphometric vertebral-fracture outcomes are not reported in the registry record. The available summaries also do not provide participant-level data, event narratives, or enough detail to assess measurement distributions and model assumptions. These limitations constrain both the precision of the comparison and the range of conclusions that can be drawn from it.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Treatment With Zoledronic Acid Subsequent to Denosumab in Osteoporosis — NCT03087851.
• Registry record last updated 2021-02-21; status last verified 2021-02.
• Results first posted 2021-01-14.
• 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

NCT03087851 is a completed, randomized, open-label, parallel-group Phase 4 trial of zoledronic acid after denosumab in participants with osteoporosis. The registry reports enrollment of 61 and three groups: 6-month Group, 9-months Group, and Observation Group.

The primary outcome is mean change in lumbar spine BMD from baseline to 6 months after zoledronic acid infusion. The posted group means and recalculated comparisons show substantial uncertainty, with both comparison intervals including zero. The registry also lists secondary outcomes, but results are not posted for all listed measures.

The registry record does not report the original sample-size justification, detailed analysis plan, multiplicity method, missing-data approach, or analysis populations. The comparisons on this page are unadjusted recalculations from the posted summary statistics and should be interpreted with those reporting limitations in mind.