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 Therapy of the Skeletal Disease of Type 2 Diabetes With Denosumab (NCT03457818), a randomized phase 2 study. The primary outcome is Change in Cortical Porosity (Ct.Po) (%) by High Resolution Peripheral Quantitative Computed Tomography (HR-pQCT) Imaging From Baseline to 6 and 12 Months..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03457818 |
| Phase | Phase 2 |
| Condition | Diabetes Mellitus, Type 2, Osteoporosis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 8 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Mishaela Rubin |
| Results posted | Yes |
2. Clinical Question
Population
The planned population was postmenopausal women with type 2 diabetes. The registry record lists type 2 diabetes and osteoporosis as the conditions. The brief summary describes a planned enrollment of 66 women, while the recorded enrollment was 8. These figures describe the plan and the recorded enrollment, respectively; they do not establish that the planned study population was achieved.
Intervention
The intervention was denosumab 60 mg/ml [Prolia], administered subcutaneously at baseline and 6 months. The brief summary describes a 12-month treatment period.
Comparator
The comparison group received placebo subcutaneously at baseline and 6 months. The trial was randomized, double-blind, and parallel-group, according to the registry record.
Primary question
The planned primary question was whether the change in cortical porosity, measured by high-resolution peripheral quantitative computed tomography, differed between the denosumab and placebo groups. The primary outcome description specifies change from baseline at 12 months, with measurements also listed at 6 months. The registry record says the study was terminated because of poor enrollment compounded by the COVID-19 pandemic and that primary outcome data were not collected. Consequently, the record does not provide an estimate of the treatment-group difference for this question.
3. Trial Design
This was a randomized, double-blind, parallel-group phase 2 trial comparing denosumab with placebo. The registry lists an enrollment of 8 and a terminated status. The brief summary describes an intended study of 66 postmenopausal women with type 2 diabetes over 12 months. The recorded enrollment and intended enrollment should be kept distinct: the record does not indicate that the intended enrollment was reached.
The treatment group was assigned denosumab 60 mg/ml [Prolia] by subcutaneous administration at baseline and 6 months. The control group was assigned placebo by the same route at baseline and 6 months. The brief summary describes the placebo as identical. The record identifies the study as double-blind but does not report further details about how masking was implemented or maintained.
The primary outcome was cortical porosity measured using high-resolution peripheral quantitative computed tomography, with assessment listed at baseline, 6 months, and 12 months. The primary outcome description identifies the 12-month change as the primary endpoint. Secondary measures included blood-test changes in serum collagen type I C-telopeptide and tartrate-resistant acid phosphatase 5b, and dual-energy X-ray absorptiometry changes at the lumbar spine, femoral neck, total hip, and radius. The listed time points varied by measure.
The registry record attributes termination to poor enrollment compounded by the COVID-19 pandemic. It states that primary outcome data were not collected. The record does not report whether all planned secondary assessments were completed or provide a detailed account of participant follow-up.
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 | Treatment Group | Control Group |
|---|---|---|
| STARTED | 4 | 4 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 4 | 4 |
Analysis population for the primary outcome, as defined in the registry: The study was terminated due to poor enrollment compounded by the COVID-19 pandemic. Data for Primary Outcome Measure was not collected.
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: Study terminated
| Characteristic | Unit | Treatment Group | Control Group | Total |
|---|---|---|---|---|
| Participants analysed | 4 | 4 | 8 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 | 0 | 0 |
| Age, Categorical: >=65 years | Participants | 4 | 4 | 8 |
| Age, Continuous | years | 69 (SD 14) | 69.5 (SD 7) | 69 (SD 10) |
| Sex: Female, Male: Female | Participants | 4 | 4 | 8 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 2 | 0 | 2 |
| Race (NIH/OMB): White | Participants | 2 | 4 | 6 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 4 | 4 | 8 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Cortical Porosity (Ct.Po) (%) by High Resolution Peripheral Quantitative Computed Tomography (HR-pQCT) Imaging From Baseline to 6 and 12 Months., measured over Baseline, 6 months and 12 months.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was change in cortical porosity, abbreviated Ct.Po, measured as a percentage using high-resolution peripheral quantitative computed tomography. The outcome description lists imaging at baseline, 6 months, and 12 months, and identifies the 12-month change as the primary outcome.
Cortical porosity describes pores within the cortical, or outer, bone structure. As general statistical and clinical context, an imaging measure of bone structure can characterize an aspect of bone quality that is not captured by bone mineral density alone. The brief summary says the study aimed to characterize denosumab’s effect on indices of bone strength and lists skeletal microarchitecture among the measures of bone quality under assessment. The registry does not state that cortical porosity is a direct measure of fracture risk, nor does it list fractures as the primary endpoint.
The planned analysis was a one-way ANCOVA with treatment group as a fixed effect and baseline cortical porosity as a continuous covariate. Such an analysis would compare groups while accounting statistically for baseline values. That is a description of the planned approach, not a result: the registry record states that the primary outcome data were not collected. It therefore reports no treatment contrast, estimate of change, confidence interval, or test result for this endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central statistical fact is that the primary outcome was not collected. The registry record therefore cannot answer whether cortical porosity changed differently between the denosumab and placebo groups. No primary-outcome estimate, confidence interval, or p-value is reported. This is not evidence that the groups were the same; it is an absence of primary-outcome data for evaluating the planned comparison.
The trial was terminated because of poor enrollment compounded by the COVID-19 pandemic. The record lists enrollment of 8, compared with the brief summary’s planned enrollment of 66. With the primary endpoint unavailable, the trial’s planned ANCOVA cannot yield a treatment comparison from the posted record. The registry does not report whether any primary-outcome observations were obtained but omitted from analysis; it specifically states that primary outcome data were not collected.
Secondary outcomes were listed for blood markers and bone mineral density at specified skeletal sites and time points. The record lists 4 outcome measures and 0 analyses. It does not provide secondary-outcome estimates or tests. Therefore, the presence of secondary measures in the study description should not be mistaken for reported evidence about changes in those measures.
The safety entries are descriptive counts, not a basis for a precise comparative safety conclusion. The registry lists 4 at risk for serious adverse events in each group, with 0 affected in the treatment group and 1 in the control group. For other adverse events, it lists 4 at risk in each group, with 1 affected in each. Deaths are recorded as 0 in both groups. The registry record does not provide enough information to establish whether the groups differed in safety, and sparse counts do not support strong comparative interpretation.
As general statistical context, estimates are most informative when accompanied by measures of uncertainty, such as confidence intervals. A confidence interval expresses the range of values compatible with the observed data under the statistical model; it does not repair the absence of outcome data. No such interval is reported for the primary endpoint. The record supports a description of the intended question, design, termination, and posted safety counts, but not an estimate of the primary treatment effect.
9. Statistical Methods Explained
What analysis was planned?
The primary outcome description specifies a one-way ANCOVA. It identifies treatment group, treated versus placebo, as a fixed effect and baseline cortical porosity as a continuous covariate. The stated primary analysis population is intention-to-treat. These details describe the registered analysis plan; the record also states that primary outcome data were not collected, so no result from that analysis is reported.
As general statistical context, ANCOVA is a regression-based method for comparing outcome values between groups while adjusting for a baseline measurement. The treatment term represents the comparison of interest, while the baseline covariate accounts for the relationship between starting values and later outcome values. This adjustment can improve precision when baseline and follow-up measurements are related, and it can account for chance differences in baseline values. It does not compensate for missing outcome measurements or create an estimate when the outcome was not collected.
What does the intention-to-treat description mean?
As general context, an intention-to-treat analysis aims to analyze participants according to their randomized assignment, regardless of whether they followed the assigned intervention exactly. It is commonly used to preserve the comparison created by randomization. The registry names intention-to-treat as the primary analysis approach, but does not describe the operational definition of the analysis population, how participants with missing measurements would be handled, or whether any departures from the intended approach occurred. Those details are not reported in the registry record.
Randomization assigns participants to groups using a chance-based procedure. In general, randomization is intended to reduce systematic differences between groups at assignment, while double-blinding is intended to limit the influence of knowledge about assignment on care, assessment, or reporting. The registry identifies the trial as randomized and double-blind, but does not report the randomization sequence method, concealment procedure, or details of masking.
What would an estimate and confidence interval tell readers?
As general explanation, an estimated treatment contrast describes the observed difference between groups for the outcome and time point specified by the analysis. A confidence interval communicates uncertainty around that estimate under the model’s assumptions. A narrow interval indicates greater statistical precision than a wide interval, while neither interval alone establishes clinical importance. A p-value, when reported, describes compatibility between the data and a statistical null hypothesis under the analysis assumptions; it does not measure the probability that a treatment works.
For this trial’s primary endpoint, the registry reports no estimate, confidence interval, or p-value because the primary outcome data were not collected. Readers should not infer an effect size or precision from the planned design, the enrollment figure, or the fact that an analysis method was specified.
How should repeated measurements be understood?
The primary outcome was listed at baseline, 6 months, and 12 months, with the 12-month change designated as primary. Secondary blood-marker measurements were listed at baseline, 3, 6, and 12 months. Secondary bone-density measurements were listed at baseline, 6 and 12 months. As general context, repeated measurements can describe how an outcome changes over time, but they also require a clear specification of which time point or overall pattern is the main comparison. The registry identifies the primary 12-month change but does not report a model for jointly analyzing repeated measurements or a result for any of the listed time points.
What assumptions and additional methods are described?
ANCOVA relies on model assumptions, including an appropriate relationship between baseline and outcome and suitable behavior of model residuals. General statistical practice may include assessing assumptions and selecting an appropriate model, but the registry record does not report diagnostic procedures or whether assumptions were evaluated. It also does not report interim analyses, a sample-size justification, or a detailed statistical analysis plan beyond the primary ANCOVA description.
The record lists no analyses and does not report primary outcome data. Accordingly, questions about model fit, outliers, covariate handling, and robustness cannot be resolved from the registered results. The stated model is useful for understanding what the investigators planned to estimate, but it is not evidence that the model was fitted or that its assumptions were checked.
As general context, over-dispersion occurs when observed variability exceeds what a statistical model assumes. It can make standard errors too small if not addressed in a setting where it is present. The registry does not report a count-based primary model or identify over-dispersion as a concern; the primary measure is an imaging-derived percentage analyzed using ANCOVA. This general concept should not be read as a claim that over-dispersion occurred in this trial.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies one primary endpoint, with the 12-month change in cortical porosity described as the primary outcome. It also lists secondary blood-marker and bone-density outcomes at multiple time points and sites. Considering multiple outcomes or time points can increase the chance of finding a nominally notable result by chance if many statistical tests are conducted. As general statistical context, investigators may address this by prespecifying a testing hierarchy, adjusting significance thresholds, or treating secondary analyses as exploratory. The registry record does not report a multiplicity adjustment or a testing hierarchy.
The record lists 4 outcome measures and 0 analyses. It does not provide results for the secondary measures, so there are no posted outcome tests for which to interpret multiplicity. The primary outcome data were not collected, and no primary effect estimate is available.
The primary analysis description names an intention-to-treat approach, but detailed handling of missing data is not reported in the registry record. In general, missing-data methods depend on why observations are missing and on assumptions about the unobserved values. Here, the registry says primary outcome data were not collected, rather than describing a particular pattern of missing measurements or a method used to impute them. It does not report whether secondary data were collected, the extent of missingness for those measures, or any sensitivity analysis.
The study was terminated because of poor enrollment compounded by the COVID-19 pandemic. The record does not report whether the termination decision followed a prespecified rule or whether any interim analysis informed it. Such details are not reported in the registry record.
11. 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 |
|---|---|---|---|
| Treatment Group | 0 | 4 | 0.0% |
| Control Group | 1 | 4 | 25.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Treatment Group | 0 of 4 |
| Control Group | 0 of 4 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Treatment Group | 1 of 4 |
| Control Group | 1 of 4 |
Most frequent serious adverse event terms
| Event term | Organ system | Treatment Group | Control Group |
|---|---|---|---|
| urinary tract infection | Renal and urinary disorders | 0 of 4 | 1 of 4 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Treatment Group | Control Group |
|---|---|---|---|
| rash | Skin and subcutaneous tissue disorders | 1 of 4 | 0 of 4 |
| vaginal yeast infection | Reproductive system and breast disorders | 0 of 4 | 1 of 4 |
| back pain | Musculoskeletal and connective tissue disorders | 0 of 4 | 1 of 4 |
Serious events with the highest arm-level rate: urinary tract infection (25.0%).
The registry lists serious adverse events and other adverse events separately. For serious adverse events, 4 were at risk in each group; the treatment group had 0 affected and the control group had 1 affected. For other adverse events, 4 were at risk in each group; 1 was affected in each group. Deaths are recorded as 0 in both groups. These are the posted group counts and should be read as descriptive safety information.
The registry lists urinary tract infection as a top serious adverse event term at 25.0%. The denominator and the basis for that percentage are not reported in the registry record, so the percentage should not be used to infer a group-specific rate. The record also does not provide event-level timing, severity details beyond the serious-event classification, or information about relatedness to treatment.
As general statistical context, small safety counts are imprecise: a difference in the observed counts does not by itself establish a difference in underlying risk. These entries do not provide a robust comparative safety assessment. They should not be taken as evidence that an adverse event was caused by an intervention or that no other events occurred outside the posted record.
12. What the Result Does, and Does Not, Mean
The registry record documents a randomized, double-blind comparison of denosumab and placebo, with cortical porosity selected as the primary endpoint. It also documents termination because of poor enrollment compounded by the COVID-19 pandemic and states that primary outcome data were not collected. The primary treatment comparison therefore has no reported result in the registry.
This absence of a primary result does not show that denosumab changed cortical porosity, that it did not change cortical porosity, or that the groups were equivalent. Equivalence would require a suitable design, prespecified criteria, and outcome data that support a sufficiently precise comparison. None of those conclusions can be drawn from the missing primary endpoint.
The intended study population, treatment schedule, and secondary outcomes describe what the investigators planned to study. They are not substitutes for observed outcome results. Similarly, the recorded enrollment of 8 and the planned enrollment of 66 do not establish a treatment effect or its precision. The registry lists no analyses and does not report secondary outcome results.
The posted adverse-event counts provide limited descriptive information. They do not support a firm comparison of safety between groups, particularly because the counts are sparse and details about event timing and relatedness are not reported.
As general statistical context, a study can be informative even when it does not resolve its primary question: its record can show what was planned, what was enrolled, why it ended, and which data were unavailable. For this trial, the main interpretive conclusion is about the limits of the evidence in the registry, not about the effect of denosumab on bone measures.
13. Why This Trial Matters Statistically
This trial matters statistically because its record clearly separates a planned analysis from an analyzable primary outcome. A registered ANCOVA can explain how investigators intended to compare treatment groups, but a specified method cannot yield an estimate without the endpoint data. The registry states that cortical porosity data were not collected, making the absence of a treatment estimate central to interpreting the study.
The gap between the planned enrollment of 66 and recorded enrollment of 8 also illustrates why design intentions and completed evidence must be distinguished. The record attributes termination to poor enrollment compounded by the COVID-19 pandemic. It does not report a sample-size justification, so the planned enrollment should not be treated as proof that the study had a particular level of power or precision.
As general statistical context, study size and outcome availability affect how precisely a treatment contrast can be estimated. A planning calculation is not observed power, and a planned analysis is not a result. Sample-size illustrations are useful for considering future designs only when their assumptions and target effects are clear; they cannot recover information that was never collected.
The registry also lists multiple secondary measures and time points while reporting no analyses. This emphasizes the importance of prespecifying which outcome is primary, how multiplicity will be handled, and how missing data will be addressed. The record specifies the primary endpoint and a primary analysis model, but does not report those additional methods. The trial is therefore a useful example of why a registry entry should be read as both a record of plans and a record of what results are actually available.
14. 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 principal limitation is that the registry record states that primary outcome data were not collected. There is therefore no posted result for the planned primary comparison of cortical porosity at 12 months. Without that outcome, the effect estimate and its uncertainty cannot be evaluated.
Enrollment was recorded as 8, while the brief summary described a planned enrollment of 66. The registry attributes termination to poor enrollment compounded by the COVID-19 pandemic. The record does not provide further details about recruitment, the timing or circumstances of termination, or the number of participants who completed each assessment.
The registry lists several secondary outcomes, but it reports 0 analyses and no secondary results. It is not reported in the registry record which secondary measurements were collected, how much data were missing for those measures, or how any missing observations were handled. The stated intention-to-treat approach is not accompanied by a detailed definition of the analysis population.
Additional statistical details are also absent. The record does not report a sample-size justification, an interim-analysis plan, a multiplicity procedure, or model diagnostics. It does not state how randomization was generated or concealed, or how masking was maintained. These omissions limit assessment of the planned methods and their implementation.
Safety information is limited to posted counts and a listed serious adverse-event term. The registry does not report event timing, treatment relatedness, or the denominator underlying the listed 25.0% term. Sparse safety counts should therefore be interpreted descriptively, not as a precise comparison between groups.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Therapy of the Skeletal Disease of Type 2 Diabetes With Denosumab — NCT03457818.
- Registry record last updated 2024-07-03; status last verified 2024-06.
- Results first posted 2021-05-11.
- 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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18. Record Summary
The registry describes a randomized, double-blind, parallel-group phase 2 trial comparing subcutaneous denosumab with placebo in postmenopausal women with type 2 diabetes. The brief summary planned treatment over 12 months and enrollment of 66; the recorded enrollment is 8.
The primary endpoint was change in cortical porosity measured by high-resolution peripheral quantitative computed tomography. The planned primary analysis was a one-way ANCOVA with treatment group and baseline cortical porosity. The registry states that the trial was terminated because of poor enrollment compounded by the COVID-19 pandemic and that primary outcome data were not collected. It lists 0 analyses and does not report secondary outcome results.
Posted safety counts include serious adverse events, other adverse events, and deaths by group. The record does not support an estimate of the primary treatment effect or a precise comparative safety conclusion.