This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study to Evaluate the Safety and Efficacy of Denosumab and Ibandronate in Postmenopausal Women Sub-Optimally Treated With Daily or Weekly Bisphosphonates (NCT00936897), a randomized phase 3 study. The primary outcome is Total Hip Bone Mineral Density Percent Change From Baseline at Month 12.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00936897 |
| Phase | Phase 3 |
| Condition | Postmenopausal Osteoporosis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 833 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Amgen |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled postmenopausal women with postmenopausal osteoporosis who were described as sub-optimally treated with daily or weekly bisphosphonates. The primary analysis population was all randomized subjects, with regression imputation used for missing post-baseline data. The registry record does not provide further eligibility details in the information reported for this analysis.
Intervention
One randomized group received denosumab 60 mg by subcutaneous injection every six months. The arm description identifies a pre-filled syringe. The central outcome was assessed from baseline to month 12, so the reported comparison concerns the first year of change in total hip bone mineral density.
Comparator
The comparison group received ibandronate 150 mg orally once a month as a tablet. The registry describes a randomized, open-label, parallel-group design, with the study summary specifying a 1:1 allocation. The record does not describe masking; the study is listed as having none.
Primary question
The primary question was how the groups differed in mean percent change from baseline in total hip bone mineral density at month 12. The registry reports an ANCOVA mean difference of 1.4 percentage points, with a 95% confidence interval from 1.0 to 1.8 and p < 0.001. This is a statistical comparison of the posted endpoint, not a complete account of every possible outcome.
3. Trial Design
This was a phase 3, randomized, open-label, parallel-group study. The registry lists enrollment of 833. Its study summary describes an approximately 800-subject study at about 65 sites in the United States and Europe, with 1:1 allocation. The registry status is completed. The recorded study start is 2009-07, and primary completion is recorded as 2011-11.
The two groups received denosumab 60 mg subcutaneously every six months or ibandronate 150 mg orally once a month. The reported primary endpoint was total hip bone mineral density percent change from baseline at month 12. The primary analysis population is described as all randomized subjects, using regression imputation for missing post-baseline data. The record lists three secondary outcomes: serum Type-1 C-Telopeptide percent change from baseline at month 1, femoral neck bone mineral density percent change from baseline at month 12, and lumbar spine bone mineral density percent change from baseline at month 12.
Open-label means masking was not used, as also indicated by the registry entry for masking. The record identifies randomized allocation and a parallel model but does not report further details of the randomization procedure, allocation concealment, or site-level distribution. It also does not report the protocol’s sample-size justification or whether interim analyses were planned. These omissions limit what can be concluded about trial conduct from the registry record alone; they do not alter the meaning of the endpoint estimate that is posted.
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
| Stage | Denosumab 60 mg SC Q6M | Ibandronate 150 mg PO QM |
|---|---|---|
| STARTED | 417 | 416 |
| COMPLETED | 398 | 356 |
| NOT COMPLETED | 19 | 60 |
Reasons for not completing this period:
| Reason | Denosumab 60 mg SC Q6M | Ibandronate 150 mg PO QM |
|---|---|---|
| Withdrawal by Subject | 9 | 19 |
| Adverse Event | 4 | 13 |
| Other | 3 | 9 |
| Lost to Follow-up | 1 | 10 |
| Administrative Decision | 1 | 2 |
| Protocol Violation | 1 | 1 |
| Ineligibility Determined | 0 | 3 |
| Noncompliance | 0 | 2 |
| Death | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: All randomized subjects using regression imputation for missing post baseline data.
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.
| Characteristic | Unit | Denosumab 60 mg SC Q6M | Ibandronate 150 mg PO QM | Total |
|---|---|---|---|---|
| Participants analysed | 417 | 416 | 833 | |
| Age Continuous | Years | 67.2 (SD 8.1) | 66.2 (SD 7.8) | 66.7 (SD 8) |
| Sex/Gender, Customized: Female | Participants | 417 | 416 | 833 |
| Sex/Gender, Customized: Male | Participants | 0 | 0 | 0 |
| Race/Ethnicity, Customized: White or Caucasian | Participants | 348 | 361 | 709 |
| Race/Ethnicity, Customized: Black or African American | Participants | 3 | 4 | 7 |
| Race/Ethnicity, Customized: Hispanic or Latino | Participants | 54 | 42 | 96 |
| Race/Ethnicity, Customized: Asian | Participants | 3 | 4 | 7 |
| Race/Ethnicity, Customized: American Indian or Alaska Native | Participants | 2 | 0 | 2 |
| Race/Ethnicity, Customized: Other | Participants | 1 | 2 | 3 |
| Race/Ethnicity, Customized: Native Hawaiian or Other Pacific Islander | Participants | 6 | 3 | 9 |
6. Primary Endpoint
The registry lists the primary outcome as Total Hip Bone Mineral Density Percent Change From Baseline at Month 12, measured over Baseline to month 12.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | Percentage Change From Baseline |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is total hip bone mineral density percent change from baseline to month 12. Bone mineral density is a quantitative measure of the mineral content of bone at a specified skeletal site. In general, measuring percent change places the follow-up measurement in relation to the participant’s baseline value, making the endpoint a measure of change over the stated period rather than a month-12 value alone.
In general clinical research, bone mineral density is used to characterize bone status and to assess how a measured value changes during a study. The total hip is the specific anatomical site named for this primary outcome; the registry also lists femoral neck and lumbar spine bone mineral density as secondary outcomes. These are distinct measures at different skeletal sites and should not be treated as interchangeable endpoints.
The registry reports the endpoint as a mean, with a 95% confidence interval for each arm. The primary analysis population is all randomized subjects, and the record states that regression imputation was used for missing post-baseline data. This matters to interpretation because the posted endpoint is not simply a summary of observed month-12 measurements: the stated approach includes imputed values for missing post-baseline data. Further details of the measurement procedure and the imputation model are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
At month 12, the posted mean percent change in total hip bone mineral density was 2.2 for the denosumab group and 0.9 for the ibandronate group. The corresponding 95% confidence intervals were 2.0 to 2.5 and 0.6 to 1.1. The registry reports an ANCOVA mean difference, denosumab relative to ibandronate, of 1.4, with a 95% confidence interval from 1.0 to 1.8 and p < 0.001.
The confidence interval describes the statistical uncertainty around the reported mean difference under the analysis used. Its range is above zero, so the posted analysis is consistent with a positive mean difference favoring the denosumab group on this endpoint. The interval also indicates that the estimate is not a single exact value: uncertainty remains about the size of the underlying difference. The registry’s p-value gives evidence against a zero-difference null hypothesis under the model and assumptions used, but it does not measure the probability that the null hypothesis is true.
The arm-specific means are descriptive estimates, while the reported net mean difference comes from the specified ANCOVA analysis. The analysis result should be interpreted as a comparison of group means for the month-12 endpoint, not as a comparison of every participant’s individual response. The record does not provide the covariates or other model details needed to reconstruct the ANCOVA result independently.
These statistics address one endpoint at one stated time point. They do not by themselves establish the size of any longer-term difference, explain outcomes for each secondary endpoint, or resolve the clinical importance of the observed statistical contrast. The registry record does not report a threshold for a clinically meaningful change in total hip bone mineral density. The result also does not describe all aspects of safety or the overall balance of outcomes. Those questions require information beyond this endpoint estimate and its confidence interval.
9. Statistical Methods Explained
The primary outcome is continuous: it is a mean percent change in total hip bone mineral density. The registry reports arm means and 95% confidence intervals, then gives the between-group result from an analysis of covariance (ANCOVA). The method and the endpoint describe different things: the endpoint defines what was measured, while ANCOVA is the statistical procedure used to compare groups.
What does the confidence interval communicate?
In general, a confidence interval gives a range of values compatible with the observed data under the statistical model and its assumptions. A 95% confidence interval is not a statement that 95% of participants had results within the interval, nor does it show the range of individual responses. It expresses uncertainty around an estimate of a population-level quantity. For the posted mean difference, the interval is 1.0 to 1.8. Its width is relevant because a point estimate alone does not convey the same information about precision.
In general, an interval that excludes zero for a difference is consistent with evidence of a nonzero difference under the stated model. Here, the reported interval runs from 1.0 to 1.8, and the corresponding p-value is p < 0.001. These are related ways of presenting evidence against a zero-difference hypothesis, but neither determines whether the size of the difference is clinically important. The registry record does not provide a clinical-importance threshold for this endpoint.
What does ANCOVA contribute?
In general, ANCOVA compares outcome means while incorporating one or more covariates into a statistical model. Covariate adjustment can account for measured characteristics included in that model and can affect the estimated contrast and its precision. The registry identifies the method as ANCOVA and labels the estimate a mean difference (net). However, the covariates, model specification, and details of any adjustment are not reported in the registry record. It is therefore not possible to reproduce the sponsor’s adjusted analysis from the posted summary statistics alone.
The posted arm means are 2.2 for denosumab and 0.9 for ibandronate. The reported ANCOVA contrast is 1.4, with its own confidence interval. Because the contrast comes from the named model, it should be described using that reported result rather than replaced with a newly calculated comparison of the displayed arm means. The record does not provide enough information to calculate a separate adjusted estimate.
What does the p-value say?
In general, a p-value describes how unusual data at least as incompatible with a specified null hypothesis would be if that null hypothesis and the model assumptions were correct. It is not the probability that the observed result occurred by chance, and it is not the probability that one treatment is superior. The registry reports p < 0.001 for the primary ANCOVA comparison. This conveys strong statistical evidence against the zero-difference null under the analysis used, but it does not quantify clinical importance or account automatically for multiple testing.
How should missing outcomes be considered?
The registry states that the primary analysis included all randomized subjects and used regression imputation for missing post-baseline data. In general, regression imputation uses a model to estimate missing values from available information. Its implications depend on the predictors, model form, assumptions about why data are missing, and how uncertainty from imputation is handled. Those details are not reported in the registry record. The posted estimate therefore needs to be read as an analysis that incorporates the stated imputation approach, not as a complete-case summary of observed values only.
The registry does not report the sample-size justification, interim analysis plan, or adjustment for multiple comparisons. The three listed secondary outcomes add other time points and skeletal sites, but the record does not state how inference across these outcomes was controlled. Accordingly, the p-value for the primary endpoint should be interpreted as the result reported for that comparison, without assuming an unreported multiplicity procedure or analysis plan.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| ANCOVA | Mean Difference (Net) 1.4 | 1.0 to 1.8 | < 0.001 |
The registry reports the sponsor’s primary comparison as an ANCOVA mean difference (net) of 1.4, with a 95% confidence interval from 1.0 to 1.8 and p < 0.001. The arm-level means and confidence intervals are also posted, but they are descriptive summaries and do not contain the model details needed to reproduce an ANCOVA estimate. The registry record does not report a separate unadjusted recalculation of the two-arm contrast.
No discrepancy is flagged between the reported result and a recalculated result in the registry record. The sponsor’s ANCOVA result is therefore the available inferential comparison to interpret. Its adjusted nature should not be assumed to represent a particular covariate set, because those details are not reported in the registry record. The reported estimate and its confidence interval quantify the comparison under the sponsor’s stated method; they do not establish the clinical importance of the difference or answer questions about outcomes beyond the posted endpoint.
11. Multiplicity, Missing Data and Analysis Populations
The registry lists one primary endpoint and three secondary outcomes. The primary endpoint is total hip bone mineral density percent change from baseline at month 12. The secondary outcomes are serum Type-1 C-Telopeptide percent change at month 1 and femoral neck and lumbar spine bone mineral density percent change at month 12. The record also lists four outcome measures and four analyses. It does not report how the overall number of statistical comparisons was handled.
Multiplicity arises when several hypotheses or endpoints are tested: as the number of tests increases, the chance of at least one apparently notable result can increase under a collection of null hypotheses. In general, a prespecified testing hierarchy or an adjustment procedure can address this issue. Neither a multiplicity adjustment nor a testing hierarchy is reported in the registry record. The p-value for the primary endpoint should therefore be read as the result for that reported analysis, without assuming that it has been adjusted for the secondary outcomes or other analyses.
The record specifies that the primary analysis population was all randomized subjects and that regression imputation was used for missing post-baseline data. This describes the broad population and missing-data approach, but it does not give the imputation model, predictors, assumptions, or sensitivity analyses. Those details are not reported in the registry record. The number of participants contributing observed measurements at each time point is also not stated in the primary endpoint description, beyond the posted arm counts.
The registry record does not report whether interim analyses were planned or conducted, or how any interim testing would have affected inference. It also does not report a statistical analysis plan or the sample-size justification. Without those details, the posted primary p-value and confidence interval can be interpreted as reported, but the full prespecification and multiplicity context cannot be assessed from the registry entry.
12. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Ibandronate 150 mg PO QM | 22 | 410 | 5.4% |
| Denosumab 60 mg SC Q6M | 39 | 411 | 9.5% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Ibandronate 150 mg PO QM | 31 of 410 |
| Denosumab 60 mg SC Q6M | 42 of 411 |
Most frequent serious adverse event terms
| Event term | Organ system | Ibandronate 150 mg PO QM | Denosumab 60 mg SC Q6M |
|---|---|---|---|
| Cardiac failure congestive | Cardiac disorders | 0 of 410 | 3 of 411 |
| Chest pain | General disorders | 0 of 410 | 3 of 411 |
| Atrial fibrillation | Cardiac disorders | 0 of 410 | 2 of 411 |
| Bradycardia | Cardiac disorders | 0 of 410 | 2 of 411 |
| Sick sinus syndrome | Cardiac disorders | 0 of 410 | 2 of 411 |
| Diverticulitis | Infections and infestations | 0 of 410 | 2 of 411 |
| Gastroenteritis | Infections and infestations | 1 of 410 | 1 of 411 |
| Thoracic vertebral fracture | Injury, poisoning and procedural complications | 1 of 410 | 1 of 411 |
| Breast cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 410 | 1 of 411 |
| Colon cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 410 | 1 of 411 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Ibandronate 150 mg PO QM | Denosumab 60 mg SC Q6M |
|---|---|---|---|
| Arthralgia | Musculoskeletal and connective tissue disorders | 23 of 410 | 25 of 411 |
| Upper respiratory tract infection | Infections and infestations | 9 of 410 | 21 of 411 |
Serious events with the highest arm-level rate: cardiac failure congestive (0.7%), chest pain (0.7%), atrial fibrillation (0.5%), bradycardia (0.5%), sick sinus syndrome (0.5%).
The registry lists serious adverse events among 22 of 410 participants at risk in the ibandronate group and 39 of 411 at risk in the denosumab group. For other adverse events, it lists 31 of 410 and 42 of 411, respectively. These are posted counts and denominators; they should be read as recorded event summaries rather than as a causal comparison between treatments. Death counts are not reported in the registry record.
The serious adverse event terms with posted percentages include cardiac failure congestive and chest pain at 0.7% each, and atrial fibrillation, bradycardia, sick sinus syndrome, and diverticulitis at 0.5% each. These figures describe the terms listed in the record. They do not, on their own, show whether an event was caused by study treatment, how event severity was assessed, or whether the groups differed statistically in risk. The registry record does not report a comparative statistical analysis for these safety figures.
In general, adverse-event counts depend on how events are defined, collected, and coded, as well as on the population at risk and the observation period. The posted figures should therefore be interpreted within the limits of the registry’s reporting. They do not replace a full review of event timing, duration, seriousness, and clinical context.
13. What the Result Does, and Does Not, Mean
The primary result describes a difference between randomized groups in mean total hip bone mineral density percent change from baseline at month 12. The registry reports a mean difference of 1.4 for denosumab relative to ibandronate, with a 95% confidence interval from 1.0 to 1.8 and p < 0.001. The estimate is statistically distinguishable from zero under the reported ANCOVA analysis. The interval communicates uncertainty about the size of that group-level difference.
This result does not mean that every participant experienced a change equal to the group mean, or that individual responses were uniform. It does not establish a particular long-term outcome: the primary endpoint is defined at month 12, and no later primary endpoint result is described in this comparison. It also does not establish that the observed difference is clinically meaningful, because a clinical-importance threshold is not reported in the registry record.
The posted result is limited to one measured outcome. It does not by itself determine how the groups compare on the listed secondary outcomes, other health outcomes, or the full range of safety considerations. Nor does the p-value represent the probability that the null hypothesis is true. The estimate should be understood as an analysis result generated under the stated method and missing-data approach, not as a guarantee that the same result would occur in another population or study.
In general, randomized comparisons can support an assessment of differences between assigned groups, while open-label conduct may matter for outcomes and processes that could be influenced by awareness of assignment. The endpoint is a quantitative bone mineral density measure, but the registry’s information alone does not resolve every possible source of bias or uncertainty. The most defensible interpretation is therefore specific: the posted analysis found a positive mean contrast on total hip bone mineral density percent change at month 12, with the reported uncertainty and limitations.
14. Why This Trial Matters Statistically
This study illustrates how a clinical trial result combines an endpoint definition, an analysis population, a statistical model, and an estimate of uncertainty. The primary outcome is a continuous measure of change, so the central comparison is between group means rather than event counts or time-to-event outcomes. The ANCOVA result gives a model-based mean contrast, while the arm-specific means describe each group separately.
The registry also makes the stated missing-data approach important to interpretation: all randomized subjects were included in the primary analysis, with regression imputation for missing post-baseline data. In general, imputation methods can influence estimates when outcomes are missing, so the model and assumptions matter. Here, the registry identifies the approach but does not report its implementation details. That distinction helps readers separate what is known about the analysis from what remains unclear.
The open-label, randomized design provides useful context for interpreting the comparison, as do the reported confidence interval and p-value. The interval presents precision information that a point estimate alone cannot provide, while the p-value addresses evidence against a specified null under the model. Neither substitutes for clinical judgment about importance, and neither answers questions about outcomes not reported in the primary comparison.
Finally, the record lists multiple outcomes but does not describe a multiplicity strategy. This is a reminder that a statistically strong primary result and a set of secondary tests do not automatically share the same inferential status. Reading the result in relation to its endpoint, time point, analysis method, and reporting limits is central to sound statistical interpretation.
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 gives the primary endpoint, arm summaries, and ANCOVA result, but it does not report the ANCOVA covariates or full model specification. As a result, readers cannot reconstruct the adjusted estimate from the posted summary statistics or determine how particular baseline variables entered the model. The record identifies regression imputation for missing post-baseline data but does not describe the imputation model, assumptions, or sensitivity analyses.
The study is listed as open-label, with no masking. The record does not report further details about allocation concealment, the randomization procedure, or how endpoint measurements were collected. The primary endpoint is an objective quantitative measure, but no assumptions should be made about procedures or safeguards that the registry does not describe.
The record lists three secondary outcomes as well as the primary endpoint, but does not report a multiplicity adjustment or testing hierarchy. It also does not report interim analyses, a statistical analysis plan, or the trial’s sample-size justification. These omissions limit assessment of the full inferential framework and of how the analyses were planned.
Safety summaries include serious and other adverse-event counts and selected serious-event terms, but deaths are not reported in the registry record. The listed safety figures do not provide a comparative inferential analysis or establish causal attribution. More generally, registry summaries do not provide all the detail needed to assess event timing, duration, or the clinical context of individual events. These limitations narrow interpretation to the outcomes and methods explicitly described.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: A Study to Evaluate the Safety and Efficacy of Denosumab and Ibandronate in Postmenopausal Women Sub-Optimally Treated With Daily or Weekly Bisphosphonates — NCT00936897.
- Registry record last updated 2013-02-11; status last verified 2013-02.
- Results first posted 2012-11-29.
- 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.
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19. Record Summary
NCT00936897 is a completed phase 3 randomized, open-label, parallel-group study of denosumab and ibandronate in postmenopausal women sub-optimally treated with daily or weekly bisphosphonates. Enrollment is listed as 833. The study summary describes sites in the United States and Europe, approximately 65 sites, and 1:1 allocation. The recorded study start is 2009-07 and primary completion is 2011-11.
The primary outcome was total hip bone mineral density percent change from baseline at month 12. The registry reports an ANCOVA mean difference of 1.4, with a 95% confidence interval from 1.0 to 1.8 and p < 0.001. The primary analysis population was all randomized subjects, using regression imputation for missing post-baseline data. Multiplicity handling, detailed model specifications, and the imputation model are not reported in the registry record.