Study Evaluating Changes In Bone Mineral Density (BMD), And Safety Of Rhbmp-2/CPM In Subjects With Decreased BMD: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study Evaluating Changes In Bone Mineral Density (BMD), And Safety Of Rhbmp-2/CPM In Subjects With Decreased BMD (NCT00752557), a randomized phase 2 study. The primary outcome is Change From Baseline in Bone Mineral Density (BMD) Measured by Dual-Energy X-ray Absorptiometry (DXA).

2. Clinical Question

3. Trial Design

This was a Phase 2, multicenter, randomized, active-controlled, parallel-group, dose-finding and safety study. The registry lists double masking and an enrollment of 50. The study status is completed; the recorded start date is 2008-12-03 and the primary completion date is 2015-04-24.

Participants were assigned to one of three groups: rhBMP-2/CPM 1.0 mg/mL, rhBMP-2/CPM 2.0 mg/mL, or oral bisphosphonate therapy as standard of care. All groups received bisphosphonates, calcium, and vitamin D. The two injection groups therefore differed from the control group by the addition of a local rhBMP-2/CPM injection; the two active groups also differed from one another by the listed concentration.

The parallel-group structure means participants were assigned to a treatment group rather than being described as switching between treatments. Random assignment is intended, in general, to reduce systematic differences between groups at the start of a trial. The registry does not report details of the randomization procedure, how masking was maintained, or which people were masked.

The primary endpoint is change from baseline in BMD measured by DXA, with a stated timeframe of baseline and 12 months post dose. The stated aim was to assess local changes in BMD after rhBMP-2/CPM against changes with systemic osteoporosis therapy alone. The record also lists secondary outcome topics including volumetric density, injectability questionnaire responses, serum biomarkers of bone turnover, and areal BMD for the contralateral total hip. The protocol details, eligibility criteria, and allocation ratios 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.

Before assignment: Treatment assignments were stratified by previous osteoporosis (OP) therapy regardless of rhBMP-2/CPM treatment assignment; bisphosphonate, calcium, vitamin D were provided to all participants as background concomitant OP therapy.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: As-treated population included randomly assigned participants who received at least 1 dose of rhBMP-2/CPM or comparator agent. Participants were grouped as per the treatment they received (not to the treatment they were randomly assigned). Here, overall number of participants analyzed = participants evaluable for this outcome measure.

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: The as-treated population included randomly assigned participants who received at least 1 dose of rhBMP-2/CPM or comparator agent. Participants in the as-treated population are grouped according to the treatment they received (not the treatment to which they were randomly assigned).

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Bone Mineral Density (BMD) Measured by Dual-Energy X-ray Absorptiometry (DXA), measured over Baseline, 12 months post dose.

The primary endpoint is change from baseline in bone mineral density measured by dual-energy X-ray absorptiometry (DXA), expressed in gram per centimeter squared (g/cm^2). The registry gives the measurement timeframe as baseline and 12 months post dose and describes the summary measure as a mean with standard deviation.

BMD is a derived measure: the registry defines it as bone mineral content divided by the total area of the region scanned. In general, DXA provides a way to quantify bone mineral content over a scanned area, making BMD a useful measure for tracking changes in bone density. A change from baseline focuses on how the measurement differs from a participant’s starting value, while the comparison between groups addresses whether those changes differ across the assigned treatment approaches.

The stated purpose was to evaluate local changes in BMD after rhBMP-2/CPM. The record notes that bone mineral content might instead serve as the primary measure if changes in the total area surrounding the proximal femur were observed. Whether that alternative was used is not reported in the registry record. Nor are the group means, standard deviations, changes, or a between-group estimate reported, so the endpoint’s numerical result and precision cannot be described.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean change describe?

The primary endpoint is a continuous measurement, summarized in the registry as a mean and standard deviation. In general, a mean change describes the average difference between a participant’s follow-up measurement and baseline measurement within a group. Comparing group mean changes can describe the average contrast between treatment approaches. That contrast is most informative when accompanied by its uncertainty, because the point estimate alone does not show how precisely the data determine the size of the difference.

The standard deviation describes how spread out individual measurements are around the group mean. It is not the same as a confidence interval: the standard deviation describes variation among measurements, while a confidence interval describes uncertainty around an estimated quantity. The registry does not report the primary endpoint means, standard deviations, or a confidence interval.

Why does the measurement schedule matter?

The stated timeframe is baseline and 12 months post dose. In general, a change-from-baseline analysis compares a follow-up value with the starting value, while an analysis of follow-up measurements may account for baseline values in another way. These approaches can produce different estimates and rely on different modeling choices. The registry record does not report which specific method was used for the primary comparison, or whether additional measurements contributed to that analysis.

The endpoint description also allows for bone mineral content to replace BMD if changes in the total area surrounding the proximal femur are observed. This distinction is relevant because BMD is calculated using both bone mineral content and scanned area. The record does not state whether the alternative measure was used.

What can randomization and masking contribute?

In general, random assignment aims to make treatment groups comparable with respect to factors measured and unmeasured at the outset. It does not guarantee that groups will be identical, especially in a study with limited enrollment. Masking can reduce the influence of expectations on treatment delivery, participant reporting, or outcome assessment, depending on who is masked and how the process is implemented. The registry lists randomized allocation and double masking, but does not describe the specific procedures or identify the masked parties.

The stated primary population is as-treated, grouping participants according to treatment received. In general, this approach answers a question about outcomes among participants classified by the treatment they received, but it can be affected by differences associated with receiving that treatment. An analysis by randomized assignment instead retains participants in their original groups. The registry does not report an assignment-based primary analysis, crossover information, or the number of participants analyzed per group.

How should planning illustrations be read?

The stated sample-size illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes the effect to detect as a stated fraction of the observed effect. Such an illustration is a planning calculation, not evidence about the result and not the trial’s original sample-size justification. It is not observed power. The registry does not report the original sample-size rationale, and the primary outcome is not reduced to one comparison in the posted analysis.

In general, a sample-size calculation estimates the number of participants needed to detect a chosen effect under specified assumptions. Changing the target effect or assumptions changes the planning result. Where the calculation is based on an observed effect, the illustration depends on that estimate and should not be interpreted as a prospective design target. The stated convention is participants per arm for 80% power for non-time-to-event outcomes; no specific calculated sample-size result is reported in the registry record.

Why are confidence intervals and model details important?

In general, a confidence interval presents a range of estimates compatible with the data and the method used, under its assumptions. It helps readers distinguish a relatively precise estimate from one that leaves substantial uncertainty. A p-value, if reported, addresses compatibility with a specified null hypothesis under a statistical model; it does not measure the size or clinical importance of an effect. Neither a p-value nor a confidence interval for the primary endpoint is reported in the registry record.

Model choice can affect estimates and their uncertainty. For continuous outcomes, analyses may account for baseline measurements, repeated observations, or other design features. The registry does not report the model, covariates, handling of outliers, or diagnostics. These omissions prevent a detailed assessment of the analysis assumptions. They also mean that the endpoint definition alone should not be mistaken for a complete statistical analysis plan.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcome topics and a primary BMD outcome with a stated baseline and 12-month timeframe. It does not report a multiplicity strategy, such as whether or how statistical testing across multiple outcomes, groups, or time points was controlled. In general, when many hypotheses are tested, the chance of at least one apparently unusual result can increase. A prespecified testing strategy can clarify which comparisons are confirmatory and how to interpret other findings. No such strategy is reported in the registry record.

Missing-data methods are also not reported. The record does not state how missing baseline or follow-up measurements were handled, whether participants who lacked a measurement were excluded, or whether any imputation or sensitivity analysis was conducted. In general, missingness can affect an estimate if participants with missing data differ systematically from those with observed data. Without the extent and handling of missing observations, the potential effect on the endpoint result cannot be evaluated.

The primary population is described as as-treated and includes randomly assigned participants who received at least one dose of rhBMP-2/CPM or comparator agent, grouped according to treatment received. This is not the same description as an analysis by randomized assignment. The registry does not report a separate intention-to-treat analysis, deviations from assigned treatment, or endpoint-specific analysis counts. It also does not give group-level counts for participants contributing primary outcome data.

These reporting gaps do not establish that the analyses were not performed; they mean the relevant methods and results are not reported in the registry record. The available information is therefore insufficient to assess how multiplicity, missing measurements, or analysis-population choices affected the primary outcome estimate.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: osteonecrosis (14.3%), myocardial infarction (7.1%), cystitis (7.1%), oesophagitis (7.1%), nuclear magnetic resonance imaging abnormal (7.1%).

The registry lists serious adverse events and other adverse events separately by treatment group. For standard-of-care control, 3 of 17 participants at risk were affected by serious adverse events, and 13 of 17 were affected by other adverse events. For rhBMP-2/CPM 1.0 mg/mL, the corresponding figures are 7 of 15 and 15 of 15. For rhBMP-2/CPM 2.0 mg/mL, they are 7 of 14 and 12 of 14. These are descriptive participant counts; they are not event rates adjusted for follow-up time.

The registry also lists serious-event terms with percentages: Osteonecrosis, 14.3%; Myocardial Infarction, 7.1%; Cystitis, 7.1%; Oesophagitis, 7.1%; Nuclear magnetic resonance imaging abnormal, 7.1%; and Bone infarction, 7.1%. The record does not identify the treatment group for each listed term in this summary, so the terms should not be assigned to a particular group on this basis. Death counts are not reported in the registry record.

In general, adverse-event counts describe what was recorded among participants at risk; they do not by themselves establish causation. The record does not provide comparative statistical estimates, event timing, or detailed attribution information. The counts should therefore be read as descriptive safety information rather than as proof of a treatment-related effect or a reliable difference between groups.

12. What the Result Does, and Does Not, Mean

The available record establishes the study question, treatment groups, endpoint definition, and selected safety counts. It does not report the numerical primary BMD result. Without group estimates and a between-group comparison, the size and direction of any observed change cannot be described, and its statistical precision cannot be assessed. No conclusion about the primary endpoint can be drawn from the endpoint definition alone.

The design is relevant to a specific comparison: local rhBMP-2/CPM added to standard oral osteoporosis therapy versus standard therapy alone, with two listed injection concentrations. The primary measurement concerns BMD change from baseline at 12 months post dose. The record’s description of an as-treated population should also be kept in view when interpreting any eventual comparison, because participants are grouped by the treatment received rather than the treatment randomly assigned.

The safety counts indicate that serious and other adverse events were recorded in all three groups. They do not, on their own, show whether the treatments caused events or whether differences between groups are statistically distinguishable. The listed serious-event terms and percentages add descriptive information, but the registry summary does not link those terms to a particular group.

In general, a trial’s results need to be interpreted alongside the estimate, its uncertainty, the analysis population, missing-data handling, and the analysis plan. Several of these details are not reported in the registry record. The study’s completed status does not substitute for outcome estimates, and the sample-size illustration is a planning aid rather than evidence of efficacy or observed power. The available record supports a description of the trial’s structure and reported safety counts, but not a determination of the primary outcome’s magnitude or precision.

13. Why This Trial Matters Statistically

This study illustrates why a clearly described endpoint is only one part of evaluating a clinical trial statistically. The registry specifies a continuous primary measure, its units, the planned measurement schedule, and a mean with standard deviation as the summary. Those details define what was intended to be measured, but they do not reveal the result. A treatment comparison still requires group estimates and an uncertainty measure.

The three-group design also raises interpretive questions that depend on the analysis plan. Two groups received different listed concentrations of rhBMP-2/CPM, while the control group received standard therapy. The registry record does not report the planned contrasts, allocation ratios, or how multiple comparisons were to be handled. Without those details and the outcome estimates, it is not possible to identify which comparison was intended to carry the strongest inferential weight.

The described as-treated population demonstrates why analysis-population definitions matter. Random assignment and analysis according to treatment received answer different statistical questions when actual treatment does not match assignment. The record gives the as-treated definition but not the relevant participant flow or an assignment-based result. Missing-data methods and the primary outcome analysis method are likewise not reported.

Finally, the safety information shows how participant counts can be informative but incomplete. Counts help describe what was recorded in each group, yet they do not supply timing, attribution, or a comparative estimate. Together, these features make the record a useful example of separating design information, outcome definitions, descriptive safety data, and inferential evidence. The distinction is important whenever a registry entry contains trial structure without a reportable primary estimate.

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 interpreting the primary outcome is that the registry record does not report its numerical results. Group-specific BMD changes, standard deviations, between-group estimates, confidence intervals, and p-values are not reported. The record therefore does not support an assessment of the magnitude or precision of the primary comparison.

The primary outcome description allows bone mineral content to replace BMD if changes in the total area surrounding the proximal femur were observed, but whether this occurred is not reported. The stated primary population is as-treated, while the registry does not provide endpoint-specific participant counts, the number analyzed in each group, or a separate analysis by randomized assignment. Details about missing measurements, exclusions, and treatment deviations are also not reported.

The registry does not describe the allocation procedure, masking procedures, analysis model, covariate adjustment, multiplicity plan, or original sample-size justification. These omissions limit assessment of the validity and reproducibility of the planned comparison. Although the study is described as dose-finding and safety focused, the record does not state decision rules for dose selection.

Safety interpretation is limited by the absence of event timing and detailed attribution information in the summary. The listed serious-event terms are not linked to particular treatment groups there, and death counts are not reported in the registry record. The reported participant counts are descriptive and do not provide a time-adjusted comparison. These limitations concern what the registry record documents; they do not establish what analyses or procedures may have been conducted outside that record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study Evaluating Changes In Bone Mineral Density (BMD), And Safety Of Rhbmp-2/CPM In Subjects With Decreased BMD — NCT00752557.
• Registry record last updated 2020-03-20; status last verified 2020-03.
• Results first posted 2020-03-20.
• 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.

18. Record Summary

NCT00752557 is a completed Phase 2, multicenter, randomized, double-masked, active-controlled, parallel-group study with an enrollment of 50. It evaluated rhBMP-2/CPM at 1.0 mg/mL and 2.0 mg/mL, each alongside oral bisphosphonates, calcium, and vitamin D, against standard oral therapy alone.

The primary endpoint was change from baseline in DXA-measured BMD, with measurement at baseline and 12 months post dose. The primary numerical comparison and its uncertainty are not reported in the registry record. The endpoint population is described as as-treated, with participants grouped according to treatment received.

Serious and other adverse-event participant counts are listed for all three groups, along with selected serious-event terms and percentages. The record does not provide enough detail to attribute the listed terms to a particular group or to interpret the counts as causal comparisons.