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 Transiliac Crest Bone Histology and Histomorphometry Study in Postmenopausal Women With Low Bone Mass or Osteoporosis Previously Treated With Denosumab (NCT00887965), a na phase 2 study. The primary outcome is Number of Participants With Normal/Abnormal Bone Histology.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00887965 |
| Phase | Phase 2 |
| Condition | Low Bone Mass, Low Bone Mineral Density, Osteoporosis |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 15 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Amgen |
| Results posted | Yes |
2. Clinical Question
Population
Postmenopausal women with low bone mass or osteoporosis who had previously received denosumab and met the study’s eligibility criteria. Eligible participants had completed specified prior studies, with an additional eligibility route for participants in an off-treatment imaging study. The primary endpoint population was all enrolled patients who had at least one evaluable biopsy; the number meeting that definition is not reported in the registry record.
Intervention
There was no newly assigned drug intervention. Participants with previous denosumab exposure underwent a transiliac crest bone biopsy following standard labeling procedures with tetracycline or a tetracycline derivative. The study concerned bone findings after prior denosumab treatment.
Comparator
No concurrent comparator group is described. This was a single-group study, and allocation is listed as not applicable. The prior denosumab group is not a randomized comparison with an untreated or alternative-treatment group.
Primary question
The study aimed to characterize bone histology after discontinuation of denosumab in this population. Its primary endpoint counted participants classified as having normal or abnormal bone histology from biopsy samples assessed at a central histomorphometric facility, 25-34 days post-Day 1. The registry record describes the classifications but does not report the resulting counts.
3. Trial Design
This was a Phase 2, single-group study with enrollment of 15. The registry lists allocation as not applicable and masking as none. Participants had previously received denosumab; the listed study procedure was a transiliac crest bone biopsy, performed with tetracycline or a tetracycline derivative according to standard labeling procedures. The study was designed to characterize histologic findings after treatment discontinuation, not to estimate a randomized treatment contrast.
Eligibility was tied to earlier studies of denosumab or to participation in an off-treatment imaging study. The brief description identifies participants who completed specified previous studies, including a condition relating to enrollment in another study. These eligibility details indicate a selected group with prior study participation. The registry record does not report how long each participant had received denosumab, the interval between stopping treatment and biopsy, or whether those features varied across participants.
The primary outcome was assessed from biopsy samples at a central histomorphometric facility within the stated timeframe of 25-34 days post-Day 1. The record also lists bone histomorphometry outcomes including cancellous bone volume, trabecular number, trabecular separation, trabecular thickness, cortical width, surface density, the osteoblast-osteoid interface, and osteoid surface. It lists 27 outcome measures overall, but no analyses are reported in the registry record.
Because there is no concurrent comparator and no random allocation, the design supports descriptive characterization of the observed biopsy findings. It does not, by itself, separate effects of discontinuing denosumab from other differences between participants or from changes that may occur over time. The registry record does not report a protocol-level statistical analysis plan, a sample-size justification, or details of interim analyses.
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 | Previous Denosumab |
|---|---|
| STARTED | 15 |
| COMPLETED | 15 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: All enrolled patients who had at least one evaluable biopsy
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 | Previous Denosumab |
|---|---|---|
| Participants analysed | 15 | |
| Age Continuous | Years | 62.1 (SD 5.9) |
| Sex: Female, Male: Female | Participants | 15 |
| Sex: Female, Male: Male | Participants | 0 |
| Ethnic group: White or Caucasian | Participants | 15 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Normal/Abnormal Bone Histology, measured over 25-34 days post-Day 1.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants classified as having normal or abnormal bone histology based on biopsy samples assessed at a central histomorphometric facility. The assessment timeframe is 25-34 days post-Day 1. The endpoint description defines normal histology by normal lamellar bone, normal mineralization, or osteoid, described as young bone that has not undergone calcification. It defines abnormal histology by osteomalacia, marrow fibrosis, a clinically significant marrow abnormality, or woven bone.
A participant count is a descriptive measure of how many people fall into each category under the stated classification. It can communicate the frequency of biopsy classifications in the assessed study group, but interpretation depends on knowing how many participants had evaluable biopsies and how missing or uninterpretable samples were handled. The endpoint population is described as all enrolled patients who had at least one evaluable biopsy; the number in that population is not reported in the registry record.
Bone biopsy can provide tissue-level information that is not captured by a clinical diagnosis alone. Histomorphometric measures can characterize bone structure and features related to formation and mineralization. The endpoint is therefore relevant to the study’s aim of describing bone histology after prior denosumab treatment. The registry record does not report the primary endpoint counts, so it does not establish how many biopsies were classified as normal or abnormal.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the study question and the rules used to classify biopsy findings, but it does not report the primary endpoint results. There are no posted counts of participants with normal or abnormal bone histology in the record. Consequently, the direction or frequency of the observed histologic findings cannot be summarized, and no estimate of precision for those findings can be assessed from the record.
The primary endpoint is a count, not a comparative effect estimate. In a single-group study, such a count describes the participants whose biopsies were evaluated and classified. Without a concurrent comparator, it does not establish what the findings would have been without prior denosumab exposure or under another treatment strategy. Nor does the study design alone establish that any finding was caused by treatment discontinuation. Such causal conclusions require a comparison that addresses alternative explanations.
The listed histology definitions distinguish normal patterns from specified abnormal findings. Those definitions clarify what the investigators intended to classify, but they do not reveal how often each feature occurred. The record also identifies several secondary histomorphometry outcomes, including measures of trabecular structure, cortical width, and osteoid. Their listing indicates planned or recorded outcome domains, not evidence of a particular result. Results for those measures are not reported in the registry record.
The adverse-event information is also limited to registry counts. The record lists 0 participants with serious adverse events among 15 at risk, and 15 participants with other adverse events among 15 at risk. These counts should be read within the registry’s categories and reporting framework; the record does not list serious adverse-event terms, and the death count is not reported in the registry record. The other adverse-event count does not identify event types, severity, timing, or whether events were considered related to the biopsy or prior treatment.
In general, a confidence interval describes the statistical uncertainty around an estimate, with wider intervals indicating less precision. No primary endpoint estimate or interval is reported in the registry record, so precision cannot be judged. The absence of reported analyses also means there is no registry-reported inferential test to interpret. The record supports describing the design and endpoint definitions, but not drawing a conclusion about the distribution of biopsy findings or the effect of stopping denosumab.
9. Statistical Methods Explained
The central statistical feature of this study is its single-group structure. The registry lists allocation as not applicable and masking as none. There is no randomized treatment contrast. In a single-group design, descriptive results can characterize what was observed among assessed participants, but they do not provide the same causal comparison as a randomized study with a concurrent control group. Differences from an external or historical group, if considered, would require careful attention to differences in eligibility, assessment, timing, and other factors; such a comparison is not reported in the registry record.
What does the primary count represent?
The endpoint is a count of participants assigned to normal or abnormal bone histology categories. The category definitions are based on features assessed in biopsy samples at a central histomorphometric facility. Counts are useful for describing the observed classification, but they must be interpreted together with the number of evaluable biopsies and the handling of missing or inadequate samples. The stated primary population includes enrolled patients with at least one evaluable biopsy. The number of participants in that analysis population and the count in each histology category are not reported in the registry record.
A count and a proportion answer different descriptive questions. A count states how many participants met a category; a proportion relates that count to a defined denominator. The registry record names a participant-count endpoint but does not provide outcome results or an endpoint denominator. No proportion should therefore be inferred from the enrollment figure or from the adverse-event figures, which refer to separate safety categories.
Why does the absence of a comparator matter?
Without a concurrent comparator, the study cannot directly estimate a difference in histology between participants who discontinued denosumab and participants who did not receive it or continued it. Its stated purpose is to characterize findings after discontinuation. General statistical interpretation distinguishes description from causal inference: the biopsy observations can describe the assessed participants, while a causal claim about the treatment or its discontinuation requires an appropriate comparison and assumptions that address other explanations. The registry record does not report such a comparison.
What can be said about statistical testing?
The registry record lists 27 outcome measures and 0 analyses. It does not report statistical tests, model specifications, effect estimates, confidence intervals, or a detailed analysis plan. A p-value, if available, would address compatibility of data with a specified statistical model and null hypothesis; it would not by itself establish clinical importance or causation. Since no inferential analysis is reported, there is no registry-reported p-value to interpret.
In general, a confidence interval communicates uncertainty around an estimate. Its width depends on features such as the amount of information in the data and the variability of the outcome. It can help distinguish a precise estimate from one that remains uncertain. Here, the registry record does not provide the primary estimate or a confidence interval, so the precision of the endpoint findings cannot be evaluated. No unadjusted recalculation is reported.
How should planning calculations be read?
The stated planning assumptions describe an illustration using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is defined as a stated fraction of the observed effect. These are planning assumptions, not a description of the actual single-group design. A two-arm, equal-allocation framework does not match a study with no comparator. The record does not report a trial-specific sample-size justification, and a planning calculation is not observed power. Observed power is not a substitute for examining an effect estimate and its uncertainty.
More generally, sample-size planning depends on a specified outcome, target effect, variability or event assumptions, allocation, and statistical procedure. If an assumed effect is based on an observed effect, the planning result depends on that reference estimate and should not be mistaken for an observed result in the current study. The registry record does not report a primary endpoint result from which to assess such an effect in this study.
Why might over-dispersion matter in other count analyses?
As a general statistical point, over-dispersion occurs when count data vary more than a model assumes. If ignored, standard errors can be too small and uncertainty can be understated. The registry record does not report a count model or an analysis of over-dispersion for this study. This concept therefore explains a general issue in count-data analysis; it is not a finding about the biopsy endpoint in this record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 27 outcome measures, including the primary histology count and secondary bone histomorphometry measures. It reports 0 analyses. A multiplicity strategy—such as adjusting for multiple hypothesis tests, specifying a hierarchy of outcomes, or identifying a limited confirmatory family—is not reported in the registry record. Without reported tests and a stated analysis plan, the consequences of testing multiple outcomes cannot be evaluated.
Multiplicity is a general concern when several outcomes or comparisons are tested: the chance of at least one apparently unusual result can increase across a set of tests. This issue is most directly relevant to inferential claims based on multiple tests. The registry record does not provide such analyses, so no adjustment can be assessed and no claim about statistical significance across outcomes is supported.
The primary analysis population is described as all enrolled patients who had at least one evaluable biopsy. The number meeting that definition, the number with missing or unevaluable biopsies, and the reasons for missingness are not reported in the registry record. The record does not explain how missing endpoint data were handled, whether any imputation was used, or whether analyses included participants outside the stated evaluable-biopsy population.
These omissions matter because missingness can affect the interpretation of a descriptive count if the participants with evaluable samples differ from those without them. The record does not provide enough information to assess that possibility. It also does not report sensitivity analyses addressing missing data or a detailed analysis population for the secondary histomorphometry outcomes. The enrollment figure should not be treated as the number with an evaluable primary endpoint.
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 |
|---|---|---|---|
| Previous Denosumab | 0 | 15 | 0.0% |
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 |
|---|---|
| Previous Denosumab | 15 of 15 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Previous Denosumab |
|---|---|---|
| Procedural pain | Injury, poisoning and procedural complications | 12 of 15 |
| Post procedural haematoma | Injury, poisoning and procedural complications | 6 of 15 |
| Nausea | Gastrointestinal disorders | 2 of 15 |
| Hot flush | Vascular disorders | 2 of 15 |
| Dyspepsia | Gastrointestinal disorders | 1 of 15 |
| Vomiting | Gastrointestinal disorders | 1 of 15 |
| Myalgia | Musculoskeletal and connective tissue disorders | 1 of 15 |
| Hypoaesthesia | Nervous system disorders | 1 of 15 |
| Hypertension | Vascular disorders | 1 of 15 |
The registry record lists 15 participants at risk and 0 affected for serious adverse events in the Previous Denosumab group. It lists 15 participants at risk and 15 affected for other adverse events. These are category-specific registry counts; they do not describe the number or nature of individual events.
No serious adverse-event terms are listed. The death count is not reported in the registry record, so it should not be read as a reported zero. The other adverse-event count does not indicate which events occurred, how severe they were, when they occurred, or whether they were considered related to the biopsy or previous denosumab exposure. The record also does not provide event-level descriptions or a comparison group.
Safety counts describe what was recorded under the registry categories, not a causal assessment. In particular, the other-adverse-event figure should not be interpreted as evidence about a specific type of harm or as a comparison with another treatment. The absence of listed serious-event terms does not provide detail about events outside that category.
12. What the Result Does, and Does Not, Mean
The study addresses a focused descriptive question: what bone histology was observed in postmenopausal women with low bone mass or osteoporosis who had previously received denosumab and underwent biopsy after discontinuation. Its central contribution, as specified in the registry, is the use of tissue assessment and a defined classification of normal and abnormal histology. The secondary outcome list also identifies structural and surface-based histomorphometry domains.
However, the registry record does not report the primary endpoint counts or results for the secondary histomorphometry measures. It therefore does not establish the frequency of normal or abnormal histology in the assessed group, nor how precise any such estimate would be. The registry description alone cannot support a conclusion about whether histology changed, whether discontinuation caused a finding, or whether the observations apply to people outside the selected study population.
The single-group design is important to that interpretation. It can describe biopsies from participants with prior denosumab exposure, but it does not include a concurrent group with a different exposure against which to compare the findings. General causal reasoning requires a suitable comparison to distinguish a treatment-related effect from other influences. The registry record does not report such a comparison.
The safety counts are also limited: serious adverse events are recorded as affecting 0 participants among 15 at risk, while other adverse events are recorded as affecting 15 among 15 at risk. Event descriptions and the death count are not reported in the registry record. Those categories cannot, by themselves, identify specific harms or establish attribution.
Accordingly, the record is informative about the study’s population, biopsy procedure, outcome definitions, and design, but it does not provide the outcome evidence needed to characterize the actual histologic findings. It should not be read as demonstrating benefit, lack of benefit, or harm from stopping denosumab.
13. Why This Trial Matters Statistically
This study illustrates why statistical interpretation begins with the design and endpoint, rather than with an isolated count. A single-group biopsy study can provide a structured description of tissue findings in a selected population. That is a meaningful descriptive purpose, particularly when the outcome depends on central assessment and specific histologic definitions. The design nevertheless has a narrower inferential reach than a randomized comparison.
The endpoint definition makes clear that normal and abnormal histology are not simply broad clinical labels: the record identifies particular tissue features used for classification. Understanding those criteria helps readers distinguish the measured outcome from broader claims about bone health or clinical outcomes. The listed secondary measures further show that the study considered multiple aspects of bone structure and surface characteristics.
The study also demonstrates the importance of complete outcome reporting. The registry record provides the endpoint definition and the eligible analysis population but does not report the primary counts or secondary outcome results. Without those results, readers cannot judge the observed distribution or its precision. Design details alone cannot substitute for the outcome data.
Finally, the record emphasizes the need to keep planning assumptions separate from the actual study. The stated sample-size framework assumes two arms with equal allocation, while this trial is listed as single-group with no comparator. That planning framework should not be mistaken for the design or as evidence of observed power. More generally, statistical summaries are interpretable only when their assumptions and the study structure align.
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 main limitation for interpretation is that the registry record does not report the primary endpoint results or the secondary histomorphometry results. As a result, neither the observed histology distribution nor its statistical precision can be assessed. Although the primary endpoint population is defined by the presence of at least one evaluable biopsy, the number of evaluable biopsies and the handling of unevaluable or missing samples are not reported.
The single-group design has no concurrent comparator. It therefore describes findings among participants with previous denosumab exposure but cannot isolate the effect of discontinuation from other factors. The registry record also does not report duration of prior treatment, the interval since discontinuation, or other participant-level characteristics that might help readers understand variation in the findings.
The population was selected through eligibility connected to prior studies and an off-treatment imaging study. The record does not provide enough information to assess how representative these participants are of the broader population of postmenopausal women with low bone mass or osteoporosis. Generalization beyond this selected group should therefore be cautious.
Statistical analysis details are limited. The registry lists 27 outcome measures and 0 analyses, but does not report a detailed analysis plan, multiplicity handling, confidence intervals, or methods for missing data. The stated two-arm sample-size planning assumptions also do not match the single-group study design. For safety, serious adverse-event terms and the death count are not reported, and the other adverse-event count is not accompanied by event descriptions or attribution information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Transiliac Crest Bone Histology and Histomorphometry Study in Postmenopausal Women With Low Bone Mass or Osteoporosis Previously Treated With Denosumab — NCT00887965.
- Registry record last updated 2013-11-15; status last verified 2013-10.
- Results first posted 2013-10-17.
- 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
NCT00887965 is a completed Phase 2, single-group study with enrollment of 15. It enrolled postmenopausal women with low bone mass or osteoporosis who had previously received denosumab. The listed procedure was a transiliac crest bone biopsy using tetracycline or a tetracycline derivative. Allocation was not applicable, and masking was none.
The primary endpoint was the number of participants with normal or abnormal bone histology, assessed from biopsy samples at a central histomorphometric facility 25-34 days post-Day 1. The record defines the histology categories and lists secondary bone histomorphometry outcomes. It lists 27 outcome measures and 0 analyses. Primary and secondary endpoint results are not reported in the registry record.
The safety record lists 0 participants with serious adverse events among 15 at risk and 15 participants with other adverse events among 15 at risk. Serious-event terms and the death count are not reported in the registry record. No concurrent comparator is described.