A Study of Bone Turnover Markers in Post-Menopausal Women With Osteoporosis Treated With Monthly Boniva (Ibandronate): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Bone Turnover Markers in Post-Menopausal Women With Osteoporosis Treated With Monthly Boniva (Ibandronate) (NCT00303485), a randomized phase 4 study. The primary outcome is Relative Percent Change in Serum C-terminal Telopeptide of Type 1 Collagen Concentration (sCTX) From Baseline to Day 3.

2. Clinical Question

3. Trial Design

This was a randomized, double-blind, parallel-group, placebo-controlled Phase 4 study sponsored by Hoffmann-La Roche. The registry lists an enrollment of 67 and describes the condition as postmenopausal osteoporosis. The study started in 2006-02, had primary completion in 2007-06, and is recorded as completed.

Participants were assigned to monthly ibandronate or a matching placebo. Both arms were described as receiving vitamin D and calcium supplementation: vitamin D 200 IU and elemental calcium 500 mg twice daily with meals. The arm descriptions state that the tablets and supplements were given for 6 months. The brief summary anticipated approximately 7 months on study treatment; the registry does not explain the distinction between that anticipated duration and the arm descriptions.

The primary endpoint compared the relative percent change in serum sCTX from baseline to Day 3. The registry’s primary analysis population was the ITT Population, which included randomized participants who received at least one dose of study medication. The reported endpoint summaries include 46 participants in the ibandronate arm and 16 in the placebo arm. These analysis counts differ from the arm counts listed for safety outcomes, which are 49 and 17, respectively. The registry record does not explain the differences among these denominators, so they should be understood in the context of the specific outcome being reported rather than treated as interchangeable.

The trial also listed secondary outcomes involving sCTX, bone-specific alkaline phosphatase, parathyroid hormone, laboratory abnormalities, and other sCTX thresholds or summaries. Nine secondary outcomes are recorded as posted. The registry record does not report a detailed protocol, the randomization procedure, allocation concealment, or a sample-size justification.

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: This analysis was performed on the ITT Population. The ITT Population included all randomized participants who received at least 1 dose of study medication.

5. Baseline Characteristics

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

Population: The Intent-to-Treat (ITT) Population included all randomized participants who received at least 1 dose of study medication.

6. Primary Endpoint

The registry lists the primary outcome as Relative Percent Change in Serum C-terminal Telopeptide of Type 1 Collagen Concentration (sCTX) From Baseline to Day 3, measured over Baseline (Visit 1) and Day 3.

The primary endpoint was the relative percent change in serum C-terminal Telopeptide of Type 1 Collagen, or sCTX, from baseline to Day 3. The registry describes sCTX as a biochemical marker used to detect increased bone resorption, the process by which bone is broken down within the body. The endpoint therefore measures a short-term change in a marker of bone turnover, rather than a clinical event or a direct measure of a patient’s health status.

The registry defines relative change as the difference between the sCTX value at a follow-up time point and the baseline value, divided by the baseline value, then multiplied by 100. A negative value represents a decrease from baseline under that definition. Baseline was defined using the average of two blood samples collected at screening. If one sample was missing or nonquantifiable, the available sample was used. The registry does not report how often this exception was needed.

A Day 3 measurement addresses the timing of change shortly after treatment begins, consistent with the study’s stated interest in the time to onset of sCTX suppression. It is a biomarker endpoint: its statistical result describes the observed marker values in the analyzed participants. By itself, it does not establish a change in bone strength, fracture occurrence, or other clinical outcomes. The registry record does not report such outcomes as the primary question.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a relative change from baseline, summarized by the median in each arm. A median is the middle value when observations are ordered. It is less sensitive than a mean to very large or very small observations, which can be useful when biomarker values or changes are skewed. A median summary does not describe the full distribution, so it does not show how many participants had increases, decreases, or changes near the group median.

The registry reports 95% confidence intervals around the arm medians. In general, a confidence interval communicates the uncertainty of an estimate under the method used to calculate it. It is not a range that contains a fixed proportion of individual participant values, and it does not mean that there is a 95% probability that the true value lies within the particular interval. Its interpretation depends on the statistical procedure and the assumptions supporting that procedure. The registry gives the interval limits but does not report the method used to calculate the arm-level intervals.

The reported between-group test was the Wilcoxon rank sum test. In general, this test compares the rank ordering of observations from two independent groups. It can be useful when outcome distributions are not well represented by a normal model. It does not automatically test a difference between medians in every situation: interpretation as a location or median difference relies on conditions about the shapes and spread of the group distributions. The registry labels the reported estimate as a difference in median, but does not give further detail on the estimation procedure or assumptions.

The registry reports a difference in median of -64.20 and a 95% confidence interval from -80.28 to -46.21. The associated p-value is p < 0.001. In general, a p-value measures how unusual data at least as incompatible with a specified null hypothesis would be if that hypothesis and the test assumptions were correct. It is not a measure of effect size, does not indicate the probability that the null is true, and does not establish that the observed difference is important to patients. The confidence interval is useful alongside the p-value because it shows the range of estimated differences compatible with the reported analysis.

The endpoint’s relative-change definition uses a participant’s baseline value as the reference. In general, percent changes can be affected by baseline values: the same absolute change can correspond to different relative changes when starting values differ. The registry defines baseline using the average of two screening blood samples, or the one available sample if the other was missing or nonquantifiable. It does not report the distribution of baseline sCTX values or how frequently the single-sample exception occurred.

The registry identifies the primary analysis population as ITT, but defines it as randomized participants who received at least one dose of study medication. This definition is narrower than the everyday use of ITT that includes every randomized participant regardless of treatment receipt. The stated analysis population is therefore important when interpreting the results. The endpoint summaries list 46 participants in the ibandronate arm and 16 in the placebo arm; the safety record lists different at-risk counts. The registry does not explain these differences, and the counts should not be inferred to represent the same analysis set.

In general, missing outcome data can affect estimates if the participants with observed measurements differ systematically from those without them. Statistical methods may address missingness in different ways, but the registry record does not report a missing-data method for this endpoint, the amount of missing data, or an analysis assessing sensitivity to missingness. The baseline rule addresses a particular missing or nonquantifiable screening sample; it does not describe how missing Day 3 measurements were handled.

The record lists nine secondary outcomes in addition to the primary endpoint. In general, when many hypotheses are tested, the chance of at least one apparently notable result can increase unless testing is controlled or interpreted with suitable caution. Methods such as a prespecified testing hierarchy or multiplicity adjustment can address that issue, but the registry record does not report whether either was used. The fact that one analysis is listed for the primary outcome does not establish how all secondary tests were handled.

The sample-size assumptions describe planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. They are not observed power and are not the trial’s original design justification. In general, planning calculations estimate how many participants might be needed under stated assumptions to detect a chosen effect. Such illustrations depend on the assumed effect and analysis model and do not show that a study was adequately planned or that its results are unbiased. The registry record does not report the original sample-size justification.

10. Analyses Reported by the Sponsor

The registry’s reported between-group result is a Wilcoxon rank sum test, with the estimate labeled as a difference in median. It reports a difference of -64.20, a 95% confidence interval from -80.28 to -46.21, and p < 0.001. That is the sponsor analysis recorded for the primary endpoint and is the relevant reported inferential comparison.

The arm summaries report median relative changes of -70.16 for ibandronate and -5.96 for placebo. These summaries help describe the observed endpoint values, while the reported test and its confidence interval address the comparison between groups. A difference between medians and a rank-based test result are related but are not interchangeable descriptions of the same statistical quantity in all circumstances.

The registry record does not report a separate recalculated estimate or test with which to compare the sponsor analysis. There is therefore no independent recalculated result to set against the sponsor’s reported comparison. The record identifies no discrepancy between the posted results and the analysis information recorded for this endpoint. Interpretation should remain tied to the sponsor’s stated test, estimate, confidence interval, and analysis population, while recognizing that important details of the method and missing-data handling are not reported in the registry record.

11. Multiplicity, Missing Data and Analysis Populations

The primary endpoint is one of several outcomes listed in the registry. The record lists nine secondary outcomes, including changes in sCTX, bone-specific alkaline phosphatase, and parathyroid hormone, as well as sCTX thresholds and laboratory abnormalities. It reports one analysis for the primary endpoint, but does not describe a complete statistical analysis plan or explain how testing across the primary and secondary outcomes was handled.

In general, testing many outcomes can make chance findings more likely if each is interpreted without considering the number of tests. Researchers may use adjustment procedures, prespecified hierarchies, or other strategies to control how multiple comparisons are interpreted. The registry record does not report whether such an approach was used. This absence does not establish that there was no plan; it means that the details are not reported in the registry record. The primary comparison can be described as posted, but secondary findings should not be treated as confirmatory without information about their prespecification and multiplicity handling.

The primary analysis population is described as randomized participants who received at least one dose. The registry record does not report the number of participants with missing Day 3 measurements, the reasons for missingness, or a method used to account for missing outcome data. It also does not report a sensitivity analysis showing whether alternative missing-data assumptions would change the interpretation.

The baseline definition allows use of one screening sample if the other of the two samples was missing or nonquantifiable. This rule concerns construction of baseline; it does not explain how missing follow-up measurements were handled. The registry lists 46 participants in the ibandronate primary endpoint summary and 16 in the placebo summary, while the safety record lists 49 and 17 at risk. The record does not explain these differences. They should not be reconciled by assumption or interpreted as a direct account of missingness.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: angina unstable (5.9%), hypertension (5.9%), dizziness (2.0%).

The safety record lists 49 participants at risk in the ibandronate group and 17 in the placebo group. Serious adverse events affected 1 participant in the ibandronate group and 2 in the placebo group. Other adverse events affected 28 and 10 participants, respectively. These are counts in the safety record, not estimates adjusted for duration of observation or other differences between participants. The registry does not provide enough detail to infer comparative risk from the counts alone.

The record lists Angina Unstable and Hypertension at 5.9% each, and Dizziness at 2.0%, among the top serious adverse event terms. It does not specify an arm attribution for these percentages in the listed terms, so they should not be assigned to a treatment group. Deaths are not reported in the registry record.

Safety counts can be affected by the number of people assessed, follow-up time, event definitions, and how events are collected and coded. The registry does not provide those details for interpreting these figures. In particular, the safety at-risk counts differ from the primary endpoint analysis counts, and the record does not explain why. The serious and other adverse event figures are descriptive registry entries; they do not by themselves establish whether an observed event was caused by study treatment or provide a complete comparison of safety.

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

The posted primary results show a more negative median relative change in sCTX from baseline to Day 3 in the ibandronate group than in the placebo group. The reported between-group analysis gives a difference in median of -64.20, with a 95% confidence interval from -80.28 to -46.21 and p < 0.001. These values describe the biomarker endpoint and the statistical comparison reported in the registry.

The result does not establish that every participant experienced a decrease, nor does it quantify the range of individual responses. Group medians summarize the center of the observed distributions, and confidence intervals describe uncertainty about estimates rather than the spread of individual participant outcomes. The registry does not provide individual-level measurements or enough distributional detail to assess how responses varied within each arm.

The endpoint is a biochemical marker of bone resorption measured at Day 3. A change in this marker is not itself a clinical outcome. The result does not establish an effect on fractures, symptoms, quality of life, or other outcomes not reported as the primary endpoint. It also does not establish how the marker behaves over longer follow-up from this particular comparison.

The reported p-value is evidence against the null hypothesis used for the Wilcoxon rank sum test, under the method’s assumptions. It is not the probability that there is no difference, and it does not determine whether the result is clinically meaningful. The confidence interval gives information about the estimated difference and its uncertainty, but it does not address all sources of uncertainty, such as missing data, deviations from the planned analysis, or limitations in how well the enrolled participants represent other populations.

Interpretation should also account for what the registry does not describe. The detailed statistical plan, missing-data methods, multiplicity handling, and reasons for differences among analysis denominators are not reported in the registry record. The posted data support a description of the Day 3 sCTX results and the sponsor’s reported statistical comparison, but they do not answer every question about the trial’s conduct or the clinical implications of a biomarker change.

14. Why This Trial Matters Statistically

This study is statistically informative because it focuses on when a change in a biomarker is observed, rather than only on a later summary of treatment response. The primary endpoint is measured at Day 3, matching the trial’s stated interest in the onset of sCTX suppression. The time point gives the comparison a clear, short-term interpretation: it concerns relative change from the defined baseline to an early follow-up assessment.

The analysis also illustrates why an endpoint’s scale and summary matter. The outcome is a relative percent change, and the registry reports medians with confidence intervals. The sponsor’s between-group comparison uses a Wilcoxon rank sum test, a rank-based method. Those choices make it important to distinguish the median summaries from the test’s general comparison of ranked observations, and to avoid treating the reported result as a comparison of means or as a direct clinical outcome.

The registry’s analysis and safety denominators also demonstrate the value of checking which participants contribute to each result. The primary endpoint summaries and safety counts do not use identical listed counts, and the registry does not explain why. That difference does not invalidate either record, but it limits attempts to connect endpoint results, safety findings, and participant flow without further reporting.

Finally, the trial lists multiple secondary biomarker and laboratory outcomes. A statistically clear primary result does not remove the need to understand how secondary comparisons were planned and interpreted. The registry record does not report the multiplicity strategy or full analysis plan. The study therefore offers a useful example of reading an early biomarker comparison carefully while separating statistical evidence, endpoint meaning, and clinical conclusions.

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 registry record does not report the full protocol or detailed eligibility criteria, so the population’s characteristics and the extent to which it represents other groups cannot be assessed from these entries. Baseline characteristics are not included in the registry record for this record. The enrollment entry is 67, while the primary endpoint and safety records list different numbers of participants by analysis. The record does not explain the denominators or provide a participant flow account that would clarify them.

The primary endpoint is a short-term biomarker measurement at Day 3. The record does not report a primary clinical outcome such as fracture occurrence, and a biomarker comparison cannot be treated as a direct measure of such outcomes. Although secondary outcomes include marker measurements over time, the registry information does not supply their numerical results in this record’s primary comparison.

Important statistical details are not reported in the registry record, including the method for calculating the arm-level confidence intervals, the detailed analysis plan, the handling of missing Day 3 values, and whether sensitivity analyses were conducted. The registry also does not describe how multiplicity across secondary endpoints was managed. These omissions limit assessment of the robustness and confirmatory status of findings beyond the reported primary comparison.

The brief summary anticipates approximately 7 months on study treatment, while the arm descriptions state treatment for 6 months. The registry record does not explain this difference. It also does not report the original sample-size justification; planning illustrations based on an observed effect cannot substitute for that information. Safety details are limited as well: the record gives event counts and selected serious adverse event terms, but does not provide enough context to infer causality or compare risks with adjustment for exposure or other factors.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Bone Turnover Markers in Post-Menopausal Women With Osteoporosis Treated With Monthly Boniva (Ibandronate) — NCT00303485.
• Registry record last updated 2016-05-02; status last verified 2016-03.
• Results first posted 2016-05-02.
• 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

This completed Phase 4 randomized, double-blind, parallel-group study compared once-monthly ibandronate with matching placebo in postmenopausal women with osteoporosis. Both arms were described as receiving vitamin D and calcium supplementation. Enrollment was 67; the study started in 2006-02 and reached primary completion in 2007-06.

The primary endpoint was relative percent change in serum sCTX from baseline to Day 3. The registry reports median changes of -70.16 for ibandronate and -5.96 for placebo, with a Wilcoxon rank sum comparison reporting a difference in median of -64.20, a 95% confidence interval from -80.28 to -46.21, and p < 0.001. The endpoint is a biomarker outcome, and the registry record does not report a clinical outcome as the primary question.

The record lists nine secondary outcomes, but does not report the statistical plan, missing-data handling, or multiplicity approach. It also does not explain the differences between primary endpoint and safety denominators. These omissions limit interpretation beyond the reported primary comparison.