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 Alendronate Prevents Microarchitectural Deterioration of Trabecular Bone in Early Postmenopausal Women (NCT00504166), a randomized phase 4 study. The primary outcome is Mean % Change From Baseline in Trabecular Number (Tb.N) by HR-pQCT.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00504166 |
| Phase | Phase 4 |
| Condition | Osteopenia, Osteoporosis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 53 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of California, San Francisco |
| Results posted | Yes |
2. Clinical Question
Population
Early postmenopausal women with osteopenia or osteoporosis are the stated population of interest. The registry record does not report detailed eligibility criteria, such as age limits or requirements for bone measurements. It records an enrollment of 53 and says the final statistical analysis was performed per protocol.
Intervention
The intervention was alendronate sodium, described as a 70 mg tablet taken once a week for 24 months. The registry identifies the study as phase 4. It does not report adherence, treatment discontinuation, or the extent to which participants followed the assigned regimen.
Comparator
The comparison group received placebo intended to match alendronate sodium. The trial is described as randomized, double-masked, and parallel-group. The registry does not identify which people or study personnel were masked, or explain how the randomization sequence and allocation concealment were implemented.
Primary question
The stated primary outcome is mean percent change from baseline in trabecular number, measured by HR-pQCT, with baseline and 24 months identified in the outcome timeframe. The study question is whether this bone micro-architectural measure changed during treatment and how its change compared between the alendronate and placebo groups. Group-specific results, an estimated between-group contrast, uncertainty intervals, and a statistical test are not reported in the registry record, so the comparative result cannot be assessed from the available outcome entry.
3. Trial Design
The record describes a randomized, double-masked, parallel-group phase 4 trial sponsored by the University of California, San Francisco. Participants were assigned to alendronate sodium or matching placebo. The intervention description specifies alendronate sodium 70 mg once a week for 24 months. The registry status is completed, records enrollment of 53, and gives the start as 2006-02 and primary completion as 2009-03.
Randomization is intended to make treatment groups comparable on average, including with respect to factors that are measured and factors that are not measured. In a parallel-group design, participants remain assigned to their respective groups rather than switching between the study treatments as part of the design. Masking can reduce the influence of treatment knowledge on participant behavior, clinical management, and outcome assessment. The registry identifies double masking but does not say exactly who was masked or give procedural details for either masking or randomization.
The stated population is early postmenopausal women, and the listed conditions are osteopenia and osteoporosis. The record does not provide detailed eligibility criteria, recruitment methods, the number screened, or the reasons for exclusion or withdrawal. It identifies a per-protocol final statistical analysis, but does not define the protocol-compliant population or describe how participants were handled if they did not complete assigned treatment.
The brief summary describes evaluation of bone structure using magnetic resonance imaging measurements. In contrast, the primary outcome title identifies HR-pQCT, and its description refers to high-resolution CT imaging of the distal radius and distal tibia. The record does not explain the difference between these modality descriptions. This matters when identifying exactly how the primary measure was obtained; the record does not permit a more specific reconciliation.
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 | Alendronate Sodium | Placebo |
|---|---|---|
| STARTED | 26 | 27 |
| COMPLETED | 20 | 13 |
| NOT COMPLETED | 6 | 14 |
Reasons for not completing this period:
| Reason | Alendronate Sodium | Placebo |
|---|---|---|
| Adverse Event | 1 | 4 |
| Withdrawal by Subject | 3 | 6 |
| Physician Decision | 1 | 1 |
| Lost to Follow-up | 1 | 3 |
Analysis population for the primary outcome, as defined in the registry: final statistical analysis was performed per protocol
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 | Alendronate Sodium | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 26 | 27 | 53 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 26 | 27 | 53 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Age Continuous | years | 55.8 (SD 3.9) | 55.4 (SD 3.3) | 55.6 (SD 3.6) |
| Sex: Female, Male: Female | Participants | 26 | 27 | 53 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 26 | 27 | 53 |
6. Primary Endpoint
The registry lists the primary outcome as Mean % Change From Baseline in Trabecular Number (Tb.N) by HR-pQCT, measured over Baseline, 24 months.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | Percent change |
| Endpoint classification | Continuous Endpoint |
Trabecular number (Tb.N) is described in the registry as a three-dimensional measure of mean inter-trabecular distance and as a primary micro-architectural feature measured by high-resolution CT imaging. The outcome is expressed as mean percent change from baseline. Its stated timeframe is baseline and 24 months, while the description says measurements were calculated from scans of the distal radius and distal tibia at baseline, 12, and 24 months.
In general, a structural measure can characterize an aspect of bone architecture that is not captured simply by describing a diagnosis. A change from baseline expresses follow-up measurement relative to the participant's starting measurement; a group comparison can then assess whether the measured changes differed between assigned treatments. The registry identifies the outcome as continuous and specifies a mean with standard deviation as the summary form. These details describe the intended measurement and summary, not the observed result.
The registry record does not report the group means, standard deviations, numbers contributing endpoint data, or an estimated between-group difference. It also does not report uncertainty intervals or a test result. Consequently, the entry explains what was intended to be measured, but does not establish the direction, size, or precision of any treatment-group difference.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the trial question and design, but it does not provide a reported primary-outcome analysis. It names mean percent change from baseline in trabecular number by HR-pQCT, with baseline and 24 months in the outcome timeframe. However, the record gives no group-specific mean changes, standard deviations, between-group contrast, confidence interval, or p-value. Without those results, it is not possible to describe whether the measured outcome increased or decreased in either group, whether changes differed between groups, or how precisely a difference was estimated.
The distinction between a within-group change and a between-group comparison is important. A group's change from its own baseline describes what happened over follow-up within that group. The trial's comparative question is addressed by comparing the changes between the randomized groups, rather than treating change in either group alone as evidence of a treatment contrast. The registry does not report either kind of numerical endpoint result.
The primary outcome description states that the final statistical analysis was performed per protocol. This identifies the analysis population in broad terms, but the record does not define which participants qualified, report exclusions from that population, or explain how missing measurements were handled. A per-protocol analysis can describe outcomes among participants meeting specified protocol requirements; if the requirements or participant flow are not given, readers cannot determine how that population relates to all randomized participants.
The record reports an enrollment of 53, but enrollment alone does not show how many participants contributed measurements at each visit or to the final analysis. The outcome entry does not provide visit-specific denominators. Nor does the registry report an analysis among all randomized participants. The absence of these details limits assessment of attrition and the possibility that unavailable measurements affected the comparison.
The adverse-event entry separately records serious and other adverse events by group. Those counts are safety information, not a substitute for the missing efficacy outcome analysis. The listed serious-event terms do not supply the primary outcome estimate, and the record does not report enough detail to determine whether an individual event or term is attributable to treatment. The outcome findings, and the precision with which any group contrast was estimated, are not reported in the registry record.
9. Statistical Methods Explained
What does a mean change describe?
For a continuous outcome, a mean summarizes the central value of measurements in a group. Here the planned measure is percent change from baseline in trabecular number. A group mean change would describe the average relative change among the participants included in that analysis. The registry also specifies standard deviation, which describes the spread of participant measurements around the group mean. A standard deviation is not the same as a confidence interval: it characterizes variation among observations, whereas a confidence interval describes uncertainty around an estimated quantity.
The registry identifies the outcome as a continuous measure and says the parameter is a mean with standard deviation. It does not report the actual mean changes, standard deviations, or numbers of observations used in the analysis. Therefore, the summary-statistic labels alone do not reveal the observed pattern or its variability.
Why is the between-group contrast central?
In general, a randomized comparison is interpreted through a contrast between groups. A change from baseline in the alendronate group alone does not show what would have happened without alendronate; the placebo group supplies the comparison under the trial design. A difference between group changes is one way to express the comparative question for a change outcome. The registry record does not provide such a contrast, so no direction or magnitude of comparative effect can be stated.
Random allocation supports a causal comparison when assignment is maintained and outcomes are analyzed appropriately, but it does not remove the need to report the analysis population, missing data, and statistical uncertainty. The record identifies randomization but does not describe the sequence-generation or concealment methods. These implementation details are not reported in the registry record.
How should uncertainty be understood?
In general, a confidence interval gives a range of values compatible with the data and the statistical model at a stated confidence level. A narrower interval indicates greater precision for the estimated quantity; a wider interval indicates more uncertainty. A p-value, when reported, evaluates the compatibility of the data with a specified null hypothesis under the test assumptions. Neither a p-value nor an interval alone conveys the clinical importance of an effect.
No confidence interval, p-value, test statistic, or group contrast for the primary endpoint is reported in the registry record. It is therefore not possible to judge statistical compatibility with a null hypothesis or to assess the precision of a treatment comparison. The absence of a reported test should not be interpreted as evidence that the groups were the same.
What does the per-protocol label imply?
The registry says that the final statistical analysis was performed per protocol. In general, this means the analysis focuses on participants who meet specified protocol requirements, but those requirements need to be known to interpret the population. The record does not define them or provide an account of which participants were included or excluded. It does not report an intention-to-treat analysis, and no alternative analysis population is described.
When data are missing, the method used to handle them can affect the estimate and its uncertainty. In general, complete-case analysis uses only participants with the required observations; other approaches may make additional assumptions about unobserved measurements. The record does not state how missing endpoint observations were handled, whether any imputation was used, or how many measurements were available at each visit. No particular missing-data approach should be inferred.
What can sample-size planning say?
In general, sample-size planning illustrates how many participants may be needed to detect an effect under stated assumptions. The planning assumptions described for this trial use a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation, with the target effect expressed as a fraction of the observed effect. Such planning values are assumptions for a future or hypothetical design calculation. They are not observed trial results and are not observed power.
The registry record does not report the trial's own sample-size justification or the numerical planning illustrations. It also does not report the observed primary-outcome effect needed to assess planning based on that effect. The sample-size assumptions therefore cannot be used to reconstruct an endpoint estimate or to establish how informative the completed trial was.
Why can over-dispersion matter?
In general, over-dispersion means that observed variability is greater than a statistical model expects. If a model underestimates variability, its uncertainty estimates may be too small and its tests may be misleading. The stated primary endpoint is a continuous measure summarized by a mean and standard deviation; the registry does not report a model, residual diagnostics, or a concern about over-dispersion. This general concept should not be read as a finding about this trial.
10. Multiplicity, Missing Data and Analysis Populations
The record lists one outcome measure, but the outcome description includes measurements at baseline, 12, and 24 months and scans of the distal radius and distal tibia. It also says that the primary outcome is percent change from baseline over these time periods. The registry's analysis entry does not reduce this outcome to a single reported comparison. The record does not specify which visit, site, or combination of measurements was used for the primary inference, or whether other analyses were treated as secondary.
In general, testing multiple outcomes, time points, or anatomical sites can increase the chance of a false-positive finding if each is treated as a separate confirmatory test. Prespecifying a primary comparison and describing any adjustment or hierarchy helps readers understand how multiplicity was handled. The registry record does not report a multiplicity procedure, analysis hierarchy, or statistical analysis plan. It would be inappropriate to assume that an adjustment was or was not used.
The outcome entry states that final statistical analysis was performed per protocol. It does not define the analysis population, report participant flow into that population, or state whether an intention-to-treat analysis was performed. The record also does not report missing-data methods, endpoint denominators by visit or site, or sensitivity analyses. Whether measurements were unavailable, and how any missing measurements affected the estimates, is not reported in the registry record.
Interim analyses, stopping rules, and a sample-size justification are not reported in the registry record. The absence of these details does not establish that any particular procedure was used or omitted. These gaps limit assessment of the analysis plan and of the robustness of a primary finding, especially because no primary-outcome result is reported.
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 |
|---|---|---|---|
| Alendronate Sodium | 3 | 26 | 11.5% |
| Placebo | 4 | 27 | 14.8% |
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 |
|---|---|
| Alendronate Sodium | 16 of 26 |
| Placebo | 19 of 27 |
Most frequent serious adverse event terms
| Event term | Organ system | Alendronate Sodium | Placebo |
|---|---|---|---|
| significant bone mineral loss | Endocrine disorders | 0 of 26 | 2 of 27 |
| Malignant melanoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 26 | 0 of 27 |
| Diverticulitis | Gastrointestinal disorders | 1 of 26 | 0 of 27 |
| Anxiety attack | Psychiatric disorders | 1 of 26 | 0 of 27 |
| Difficulty swallowing | Gastrointestinal disorders | 0 of 26 | 1 of 27 |
| Vitamin D overdose | Injury, poisoning and procedural complications | 0 of 26 | 1 of 27 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Alendronate Sodium | Placebo |
|---|---|---|---|
| Abnormal white cell count | Blood and lymphatic system disorders | 5 of 26 | 6 of 27 |
| high monocyte level | Blood and lymphatic system disorders | 1 of 26 | 2 of 27 |
| High cholesterol | Metabolism and nutrition disorders | 2 of 26 | 1 of 27 |
| nausea | Gastrointestinal disorders | 1 of 26 | 1 of 27 |
| Broken tooth | Injury, poisoning and procedural complications | 1 of 26 | 0 of 27 |
| Hyperthyroidism | Endocrine disorders | 1 of 26 | 0 of 27 |
| mildly unpleasant feeling in the stomach | Gastrointestinal disorders | 0 of 26 | 1 of 27 |
| High calcium level | Metabolism and nutrition disorders | 0 of 26 | 1 of 27 |
| Low neutrophil count | Blood and lymphatic system disorders | 0 of 26 | 1 of 27 |
| osteoarthritis of the hip | Musculoskeletal and connective tissue disorders | 1 of 26 | 0 of 27 |
Serious events with the highest arm-level rate: significant bone mineral loss (7.4%), malignant melanoma (3.8%), diverticulitis (3.8%), anxiety attack (3.8%), difficulty swallowing (3.7%).
The registry reports serious adverse events for 3 participants in the Alendronate Sodium group, with 26 at risk, and for 4 participants in the Placebo group, with 27 at risk. It reports other adverse events for 16 participants in the Alendronate Sodium group and 19 in the Placebo group, with the same respective at-risk counts. These are registry counts; the record does not provide a detailed account of event timing, duration, severity beyond the serious classification, or participant-level overlap between categories.
The registry lists significant bone mineral loss at 7.4%, malignant melanoma at 3.8%, diverticulitis at 3.8%, anxiety attack at 3.8%, difficulty swallowing at 3.7%, and vitamin D overdose at 3.7% among the top serious terms. The record does not identify a treatment group for each listed term or give a term-specific count alongside each percentage. The listed percentages should not be treated as rates for a particular arm without that information.
Deaths are not reported in the registry record. These safety entries are descriptive and do not by themselves establish that an event was caused by a study treatment or that the groups differed in safety. The record does not report a statistical comparison of adverse events.
12. What the Result Does, and Does Not, Mean
The registry record describes a trial designed to compare weekly alendronate with matching placebo in early postmenopausal women, using trabecular number as the stated primary outcome. It provides treatment descriptions, the general design, and an outcome definition. It does not provide the primary endpoint results. Consequently, the record cannot support a conclusion about whether the groups differed in trabecular-number change or about the size and precision of any such difference.
Even a reported group difference would need to be interpreted in relation to its uncertainty, analysis population, measurement methods, and the trial's planned comparisons. Here, the record lacks the group estimates, standard deviations, denominators, confidence interval, and statistical test. It is also unclear from the registry whether the primary comparison concerned a particular scan site or visit, given the outcome description's multiple sites and time points.
The reported adverse-event counts provide a limited descriptive view of safety events. They do not establish causation, and the serious-term percentages are not assigned to a treatment group in the record. The registry does not report deaths. These data should not be used to infer a complete benefit-risk balance.
The trial's completed status and its enrollment figure do not fill in the missing outcome analysis. Likewise, the per-protocol label does not disclose how participant inclusion, treatment adherence, or missing measurements affected the endpoint comparison. A reader can identify the question the study set out to address, but cannot determine from the registry record whether the primary outcome favored either group, whether a difference was statistically compatible with no difference, or whether any estimate was sufficiently precise.
These limitations concern what can be concluded from the registry entry, rather than proving that an analysis was never conducted elsewhere. An outcome analysis is not reported in the registry record. No treatment recommendation follows from the information reported there.
13. Why This Trial Matters Statistically
This trial is statistically relevant because it makes a structural bone measure, rather than a clinical event, the stated primary outcome. Continuous measures can capture graded changes, but their interpretation depends on a clear measurement definition, a specified comparison, and adequate reporting of variability and uncertainty. The registry identifies the measure as mean percent change in trabecular number and specifies a mean and standard deviation as the summary form, yet reports no endpoint estimates.
The record also illustrates why an outcome definition must align with the analysis. It describes scans at the distal radius and distal tibia, and measurements at baseline, 12, and 24 months, while the stated outcome timeframe names baseline and 24 months. The record does not indicate how these sites and visits were combined or selected for the primary comparison. This makes it difficult to know what a single primary result would represent.
Another important statistical issue is analysis population. The registry identifies a per-protocol analysis but does not define its membership or report how it relates to the randomized population. Readers also lack information on missing measurements and participant flow. These details matter because the estimated contrast may depend on which participants contribute data and how absent observations are treated.
Finally, the entry separates a stated endpoint and study design from reported results. Randomization and masking describe design features, but they do not substitute for a numerical effect estimate and its uncertainty. For this record, the design can be described, but the primary statistical finding cannot be evaluated because the endpoint analysis is not reported in the registry record.
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.
A key limitation is the absence of reported primary-outcome results. The registry gives the outcome definition and analysis population label, but no group-level changes, standard deviations, between-group estimate, confidence interval, p-value, or endpoint denominators. Without these, the effect's direction, magnitude, and precision cannot be assessed.
The measurement descriptions are not fully aligned. The brief summary refers to magnetic resonance imaging measurements, while the endpoint title says HR-pQCT and the outcome description refers to high-resolution CT imaging. The record does not explain this difference. It also describes scans at the distal radius and distal tibia and measurements at baseline, 12, and 24 months, whereas the primary outcome timeframe names baseline and 24 months. The primary analysis's exact site and visit specification is not reported in the registry record.
Although the trial is described as randomized and double-masked, details of sequence generation, allocation concealment, and the people masked are not reported. Detailed inclusion criteria and participant flow are also not reported. The analysis is described as per protocol, but the protocol-compliant population is not defined. Missing-data handling, adherence, discontinuation, and reasons for unavailable measurements are not reported in the registry record.
The registry does not state how multiple sites or time points were addressed statistically, nor does it report a statistical analysis plan, interim analyses, or the trial's sample-size justification. These omissions limit evaluation of the intended inferential framework. The safety record gives group counts and serious-event terms, but lacks term-specific group attribution and does not report deaths. These limitations restrict interpretation of both the efficacy question and the descriptive safety information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Alendronate Prevents Microarchitectural Deterioration of Trabecular Bone in Early Postmenopausal Women — NCT00504166.
- Registry record last updated 2013-08-14; status last verified 2013-07.
- Results first posted 2011-08-10.
- 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 completed, randomized, double-masked, parallel-group phase 4 trial sponsored by the University of California, San Francisco. It records enrollment of 53, with a start of 2006-02 and primary completion of 2009-03. The study compared alendronate sodium 70 mg once a week for 24 months with matching placebo in early postmenopausal women.
The stated primary outcome is mean percent change from baseline in trabecular number by HR-pQCT. The record says the final statistical analysis was performed per protocol, but does not report primary-outcome estimates or a statistical comparison. It also does not report the analysis population definition or missing-data methods. Serious and other adverse-event counts are listed by group; deaths are not reported in the registry record.