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 Enhancing Osteoporosis Therapy: Can We Open the Anabolic Window? (NCT01166958), a randomized phase 4 study. The primary outcome is Serum Markers of Skeletal Turnover (Serum CTX).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01166958 |
| Phase | Phase 4 |
| Condition | Osteoporosis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 26 |
| Arms in the primary outcome | 2 |
| Lead sponsor | University of Wisconsin, Madison |
| Results posted | Yes |
2. Clinical Question
The trial explored a proposed sequence of osteoporosis therapies: teriparatide followed by raloxifene in monthly cycles. Its scientific question was whether this approach could alter the pattern of skeletal turnover described by the investigators as the “anabolic window,” the period after starting teriparatide when bone formation exceeds resorption. The registry record reports serum CTX as the primary outcome and bone mineral density at several skeletal sites as secondary outcomes.
Population
People with osteoporosis enrolled in a pilot study. The registry record reports an enrollment of 26. Further eligibility criteria and participant characteristics are not reported in the registry record.
Intervention
Monthly cycles of teriparatide followed by raloxifene. The registry record does not give further details about cycle duration or the timing of each medicine within a cycle.
Comparator
Daily teriparatide, identified in the registry record as Forteo. The trial was randomized, parallel-group, and unmasked.
Primary question
How did the reported overall serum CTX average and range compare between the daily-teriparatide group and the group assigned to monthly cycles of teriparatide followed by raloxifene?
This is a question about a biomarker of skeletal turnover, not a direct comparison of fractures, symptoms, or quality of life. The registry describes the study as a pilot intended to obtain preliminary data for future work. The posted outcome summaries can describe what was recorded in these groups, but they do not by themselves establish whether the proposed sequence changes bone formation and resorption in the intended way. The registry record does not report a formal statistical comparison, an estimate of uncertainty for the between-group contrast, or an analysis of clinical outcomes.
3. Trial Design
The registry record identifies this as a phase 4, randomized, parallel-group study with no masking. It lists University of Wisconsin, Madison as the sponsor and osteoporosis as the condition. The study status is completed. Its recorded start was 2010-09, and primary completion was 2012-11. Enrollment was 26.
The two groups were daily teriparatide and monthly cycles of teriparatide followed by raloxifene. The outcome summaries list 13 participants in each group. The registry record does not report the randomization method, how allocation was concealed, the treatment doses, or the detailed schedule of the monthly cycles. It also does not report whether treatment adherence was measured or how deviations from assigned treatment were handled.
The primary outcome was serum CTX, measured at baseline and at the 1, 1.5, 2, 2.5, 3, 4, 5, and 6 month visits. The posted primary outcome is described as an overall average and range across all time points. Three secondary outcomes concern average bone mineral density at the spine, proximal femur (hip), and one-third radius, each at baseline, 3 months, and 6 months.
The study is described in its summary as a pilot project intended to generate preliminary data. That context matters: a pilot can explore feasibility and produce estimates for later research, but the registry record does not specify a formal feasibility objective or a design intended to establish a definitive treatment effect. The statistical plan, target enrollment rationale, and whether any interim analyses occurred are not reported in the registry record.
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 | Daily Teriparatide (Forteo) | Monthly Cycles of Teriparatide Followed by Raloxifene |
|---|---|---|
| STARTED | 13 | 13 |
| COMPLETED | 12 | 13 |
| NOT COMPLETED | 1 | 0 |
Reasons for not completing this period:
| Reason | Daily Teriparatide (Forteo) | Monthly Cycles of Teriparatide Followed by Raloxifene |
|---|---|---|
| Withdrawal by Subject | 1 | 0 |
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 | Daily Teriparatide (Forteo) | Monthly Cycles of Teriparatide Followed by Raloxifene | Total |
|---|---|---|---|---|
| Participants analysed | 13 | 13 | 26 | |
| Age, Continuous | years | 67.7 (61.2 to 83.1) | 66.2 (56.0 to 78.8) | 67.0 (56.0 to 83.1) |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 4 | 7 | 11 |
| Age, Categorical: >=65 years | Participants | 9 | 6 | 15 |
| Sex: Female, Male: Female | Participants | 13 | 13 | 26 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 13 | 13 | 26 |
6. Primary Endpoint
The registry lists the primary outcome as Serum Markers of Skeletal Turnover (Serum CTX), measured over These were measured at the baseline and 1, 1.5, 2, 2.5, 3, 4, 5 and 6 month visits..
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Full Range |
| Unit | ng/mL |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is serum CTX, reported in ng/mL. The registry describes CTX as a serum marker of skeletal turnover and states that measurements were made at baseline and at the 1, 1.5, 2, 2.5, 3, 4, 5, and 6 month visits. The posted result is an overall average and range from all time points for each group, rather than a separate reported estimate at each visit.
As a general clinical measurement concept, a biomarker can provide information about a biological process without directly measuring a patient-centered outcome. CTX is used as a marker of bone resorption and skeletal turnover. In this trial, it therefore relates to the investigators’ interest in how formation and resorption might change during the treatment sequence. It is not itself a measure of bone density, fracture occurrence, symptoms, or quality of life.
Reporting an average gives a compact description of the observed measurements, while a range conveys the span from the lowest to highest reported values. A range is not a confidence interval: it describes observed spread, not the precision of an estimated group mean or the uncertainty in a comparison between groups. The registry does not report a confidence interval or a time-specific comparison for this endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary outcome reports an overall serum CTX average of 0.989 ng/mL in the daily-teriparatide group, with a full range from 0.599 to 1.404. For the group assigned to monthly cycles of teriparatide followed by raloxifene, the reported average is 0.544 ng/mL, with a full range from 0.433 to 0.584. These summaries combine measurements across the scheduled visits rather than presenting the course at each visit.
The values describe the observed summaries for the two groups. They do not, on their own, establish the size or precision of a treatment contrast. The registry record does not report a formal between-group estimate, confidence interval, or p-value for serum CTX. A reader should therefore distinguish the descriptive difference between the displayed group summaries from an inferential result based on a specified statistical model. No numerical contrast or significance calculation is made.
The listed ranges show observed variation across measurements, but the registry record does not make clear whether each participant contributed the same number of measurements or how missing measurements, if any, were handled in forming the overall averages. The range also cannot serve as a substitute for a confidence interval. It does not show how precisely the group averages estimate an underlying value, nor does it quantify uncertainty in a comparison.
The study summary presents a biological rationale: treatment that stimulates formation may also stimulate resorption, and the investigators proposed that sequential therapy could open an “anabolic window.” The endpoint is relevant to that rationale because CTX is a marker of skeletal turnover. However, the overall average and range do not show whether changes occurred at particular visits, whether formation and resorption were uncoupled, or whether the hypothesized window was achieved. The registry does not report the corresponding time-specific CTX results or a formal analysis addressing those questions.
The registry lists bone mineral density at the spine, proximal femur, and one-third radius as secondary outcomes, measured at baseline, 3 months, and 6 months. These outcomes could describe a different aspect of skeletal response from a turnover marker. Their numerical results and analyses are not reported in the registry record. The record lists three secondary outcomes, but does not provide a full statistical account of their results.
Safety summaries list no serious adverse events and no other adverse events in either group in the posted counts. Those observations describe what was recorded in this study; they do not establish that adverse events cannot occur or characterize risks with high precision. The death counts are not reported in the registry record.
Overall, the reported data support a descriptive account of the serum CTX summaries and safety counts in this pilot. They do not provide a formal estimate of comparative effectiveness, an uncertainty interval, or an account of clinical outcomes. The registry does not report the analysis plan, missing-data methods, or population used for any inferential analysis, so those aspects cannot be evaluated from the record.
9. Statistical Methods Explained
Randomization is intended to assign participants to groups by chance, which can help make groups comparable on average. This trial is identified as randomized, but the registry record does not describe how the random sequence was generated, how assignments were concealed before enrollment, or whether any stratification was used. Without those details, the randomization label alone does not allow a reader to assess every feature of allocation.
The parallel-group design means the registry lists separate treatment groups rather than a planned sequence in which every participant receives each strategy. The two listed groups were daily teriparatide and monthly cycles of teriparatide followed by raloxifene. The registry record says masking was none. In an unmasked study, participants and study personnel are not described as blinded to assignment. The record does not indicate whether anyone involved in measuring or analyzing outcomes was masked.
The primary outcome is a continuous measurement: serum CTX in ng/mL. The registry reports the parameter as a mean and the spread as a full range. A mean is a measure of the center of a set of values, while the range gives its minimum-to-maximum span. These summaries answer descriptive questions about recorded measurements. They do not give the uncertainty around a group mean or around a contrast between groups. A confidence interval would address uncertainty in an estimate under a statistical model; none is reported for this outcome.
The registry says that the primary outcome summary is an overall average and range across all time points. Repeated measurements from the same participant are generally related, so they are not equivalent to observations from unrelated people. As a general statistical point, an analysis of repeated measurements may need to account for that within-participant correlation. The record does not say whether the summaries were calculated by first combining visits within each participant, pooling all visit measurements, or using another procedure. It also does not report a longitudinal model or a visit-specific treatment comparison.
For a comparison of group means, an analysis might estimate a difference and its uncertainty, with a method chosen to suit the design and data. The registry record does not report such an estimate, standard error, confidence interval, or test for the primary outcome. The posted group averages can be read descriptively, but a reader should not treat them as a substitute for the sponsor’s prespecified analysis. No formal analysis results are listed in the registry record.
The full range deserves particular care. As a general statistical concept, a range is sensitive to the lowest and highest observations and ordinarily becomes wider as more observations are included. It does not describe the precision of a mean in the way a confidence interval is intended to do. The record’s use of “full range” indicates a descriptive spread measure, not an interval estimate for a treatment effect. The reported ranges should therefore not be interpreted as bounds on the likely treatment contrast.
Missingness can affect both descriptive summaries and comparisons. For instance, if some visits are not observed, an overall average may reflect a different set of measurements across participants or groups. That is a general concern, not a claim that this trial had missing data. The registry does not report the number of missing CTX measurements, reasons for missingness, imputation procedures, or sensitivity analyses. It also does not specify whether the reported summaries include all randomized participants or only participants with available outcome measurements.
The trial’s enrollment was 26, and the posted outcome summaries list 13 participants in each group. These are descriptive group counts, not a statement about the number included at every visit or in a particular analysis. The registry record does not report participant flow, exclusions after randomization, treatment discontinuations, or the analysis population. It is therefore not possible to determine from the record whether an intention-to-treat, per-protocol, or other population was used.
The sample-size rationale and statistical plan are not reported in the registry record. The record does not state a target effect, assumed variability, power, or a planned significance threshold for the original design. A sample-size calculation based on an observed effect, if displayed as a planning illustration, would be a hypothetical design exercise rather than evidence of the study’s observed power. The registry record does not report numerical planning illustrations for this trial in the registry record, so no such values can be interpreted.
Multiplicity arises when several outcomes, visits, or comparisons are examined. As a general statistical principle, testing many hypotheses can increase the chance of at least one apparently positive result unless the analysis plan accounts for that process. This trial lists a primary outcome and secondary bone-density outcomes at multiple sites and visits, but the registry record does not report how multiplicity was addressed, if at all. It also does not identify a hierarchy or adjustment procedure.
Over-dispersion is a general issue for some count outcomes when observed variability exceeds the assumptions of a simple count model. It is not the central issue for the continuous CTX summary. More relevant uncertainties are the repeated-measure structure, the handling of missing values, and the absence of a reported model and interval estimate. The registry does not give enough methodological detail to resolve them.
The outcome summaries do not include a reported inferential analysis. In general, descriptive statistics and inferential statistics answer different questions: description characterizes observed data, while inference uses a model or design-based method to quantify uncertainty about a broader contrast. With only the descriptive values and ranges, the strength and precision of any between-group conclusion cannot be assessed. The sponsor’s own analysis would take precedence if it were reported; the registry record does not provide such an analysis for the primary outcome.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists serum CTX as the primary outcome and bone mineral density at the spine, proximal femur, and one-third radius as secondary outcomes. Each secondary outcome is specified at baseline, 3 months, and 6 months. Considering multiple outcomes and visits raises the general issue of multiplicity: if many comparisons are tested, the chance of a chance finding can increase. The registry record does not report a multiplicity adjustment, a testing hierarchy, or which secondary comparisons, if any, were considered confirmatory.
Missing-data handling is also not reported in the registry record. It does not state whether all scheduled measurements were available, how missing visits were treated, or whether any imputation or sensitivity analysis was performed. Because the primary result is described as an overall average and range across time points, the method used to combine available observations would affect how that summary should be understood. The record does not give enough detail to determine that method.
The posted outcome counts list 13 participants in each group, but the registry does not report whether those counts represent the analysis population for every endpoint or visit. It does not describe participant flow after randomization or identify an intention-to-treat, per-protocol, or other analysis population. The registry also reports no analysis entries. Consequently, the record does not establish how the analysis handled participants who did not complete treatment or lacked an outcome measurement.
These are reporting gaps, not evidence that missing data, exclusions, or multiple testing necessarily affected the results. They limit the ability to assess the reliability and scope of any comparative interpretation. The registry record does not report an analysis plan that would resolve these questions.
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 |
|---|---|---|---|
| Daily Teriparatide (Forteo) | 0 | 13 | 0.0% |
| Monthly Cycles of Teriparatide Followed by Raloxifene | 0 | 13 | 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 |
|---|---|
| Daily Teriparatide (Forteo) | 0 of 13 |
| Monthly Cycles of Teriparatide Followed by Raloxifene | 0 of 13 |
The posted safety counts list zero serious adverse events in the daily-teriparatide group and zero in the group assigned to monthly cycles of teriparatide followed by raloxifene. The same counts list zero other adverse events in each group. Each group’s safety entry lists 13 participants at risk for serious adverse events and 13 at risk for other adverse events.
These are observed counts in this study, not proof that the treatments carry no risk. A zero count can occur in a study even when an event remains possible, and a small study cannot characterize uncommon events precisely. The registry record does not give event-specific follow-up time, additional details about how events were collected, or a separate narrative of safety monitoring. Death counts are not reported in the registry record.
The safety entries should be read alongside the study’s pilot context and not as a comprehensive estimate of safety in a broader population. The counts describe recorded events among the listed groups; they do not support medical advice or a conclusion that one treatment strategy is safer than the other.
12. What the Result Does, and Does Not, Mean
The main result is a descriptive summary of serum CTX across the listed visits. The daily-teriparatide group had a reported overall average of 0.989 ng/mL, with a full range from 0.599 to 1.404. The monthly-cycles group had a reported overall average of 0.544 ng/mL, with a full range from 0.433 to 0.584. The registry does not report a formal between-group estimate or uncertainty interval, so these values should not be converted into a claim about a statistically established treatment effect.
The result does not show how CTX changed at each visit. A single average across visits can conceal different patterns over time, including increases, decreases, or fluctuating values. The registry record does not report visit-specific values or a longitudinal comparison. It is therefore not possible to judge from the reported overall summaries whether the proposed “anabolic window” occurred or how long any such period lasted.
The biomarker result also does not directly establish changes in bone mineral density or clinical outcomes. The registry names bone mineral density at the spine, proximal femur, and one-third radius as secondary outcomes, but their numerical findings are not reported in the registry record. Fracture outcomes, symptoms, and quality of life are not listed as results in the record.
The observed safety counts were zero for serious and other adverse events in both groups. This records no events in the posted counts; it does not establish that events cannot occur, nor does it provide a precise comparison of safety between strategies. The death counts are not reported in the registry record.
More broadly, this was a pilot study intended to generate preliminary data. The registry record does not report the statistical plan, missing-data methods, analysis population, or a formal comparative analysis. Those omissions prevent a full assessment of uncertainty and potential bias. The results can be read as recorded descriptive observations in the trial groups, but they do not establish whether the sequential regimen is effective, ineffective, superior, or equivalent. They do not provide a basis for treatment decisions.
13. Why This Trial Matters Statistically
This trial is statistically interesting because its question concerns a biological process that may change over time, while the primary result is reported as an overall average and range across visits. Repeated measurements can contain information about the timing and shape of a response. Compressing measurements across visits into one summary makes a simpler description, but it cannot show the trajectory that motivated the proposed “anabolic window.”
The contrast between a biomarker and a clinical outcome is also important. Serum CTX is a marker of skeletal turnover, while bone mineral density is a different measurement and fractures or symptoms would be more direct clinical outcomes. The registry identifies bone-density outcomes but does not report their numerical results. The distinction helps define what the posted CTX summaries can and cannot address.
The pilot designation sets a further interpretive boundary. A pilot may provide preliminary estimates and reveal issues relevant to later research, but the registry record does not report a design rationale or a formal inferential analysis. Without a confidence interval or an explicit treatment contrast, the apparent separation between the group summaries cannot be evaluated in terms of precision. The ranges describe observed spread, not uncertainty in the contrast.
Finally, the record illustrates why analysis details matter. Randomization is reported, but methods for allocation, missing data, repeated measurements, multiplicity, and analysis populations are not. These details help determine what a comparison estimates and how robustly it can be interpreted. Their absence does not invalidate the descriptive values, but it narrows the conclusions that can be drawn from them.
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 primary result is summarized across all time points, and the registry does not report the underlying visit-specific values. This limits interpretation of changes over time and prevents direct evaluation of the proposed period in which formation may exceed resorption. The record does not explain precisely how measurements across visits were combined into the reported average and range.
The registry does not report a formal comparison for the primary endpoint, a confidence interval, or a p-value. Thus, the precision of the apparent between-group difference cannot be assessed from the posted outcome summaries. The full ranges are descriptive and are not uncertainty intervals for a treatment effect.
Additional analysis details are absent: the randomization procedure, allocation concealment, analysis population, missing-data approach, multiplicity handling, and statistical model are not reported in the registry record. It also does not report participant flow, treatment adherence, or whether any participants discontinued. These omissions make it difficult to assess how closely the reported summaries represent the randomized groups over the study period.
The registry identifies three secondary bone-density outcomes, but numerical results for them are not reported. The record also does not provide results for fractures or other clinical outcomes. Safety counts show no events in the posted categories, but these observations from a pilot do not precisely characterize uncommon harms; death counts are not reported.
Finally, the study is described as a pilot, and the registry does not report a sample-size justification or a prospective statistical plan. The record therefore does not establish that it was designed to detect a particular effect or to provide definitive evidence about the treatment strategies.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Enhancing Osteoporosis Therapy: Can We Open the Anabolic Window? — NCT01166958.
- Registry record last updated 2014-09-22; status last verified 2014-09.
- Results first posted 2014-09-22.
- 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
This completed phase 4 study was randomized, parallel-group, and unmasked. It enrolled 26 and compared daily teriparatide with monthly cycles of teriparatide followed by raloxifene in people with osteoporosis. University of Wisconsin, Madison is listed as the sponsor. The recorded start was 2010-09, and primary completion was 2012-11.
The primary outcome was serum CTX, measured from baseline through the 6 month visit schedule and reported as an overall average and full range. The posted summaries list an average of 0.989 ng/mL for daily teriparatide and 0.544 ng/mL for monthly cycles, with their respective ranges. The registry does not report a formal statistical comparison or uncertainty interval. Three secondary outcomes concern bone mineral density at the spine, proximal femur, and one-third radius; numerical results are not reported in the registry record.
The posted safety counts list no serious or other adverse events in either group. Death counts, missing-data methods, analysis populations, and the statistical plan are not reported in the registry record.