Secondary Prevention of Osteoporosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Secondary Prevention of Osteoporosis (NCT00421343), a na phase 3 study. The primary outcome is Number Adherent With the Intervention.

2. Clinical Question

In statistical terms, this is a descriptive question about adherence within a group receiving the protocol, rather than an estimate of a difference between treatments. Without a comparator group, the record cannot establish what adherence or later functional outcomes would have been under another strategy or without the intervention. The record lists reasons for unwillingness and non-adherence as a secondary outcome, but does not give results for that outcome.

3. Trial Design

NCT00421343, titled “Secondary Prevention of Osteoporosis,” is recorded as a Phase 3, completed, single-group study sponsored by Hebrew SeniorLife. Its official title describes a window of opportunity in the acute rehabilitation setting. The recorded start is 2007-02 and primary completion is 2008-06. Enrollment is listed as 29.

The design is not a randomized comparison: allocation is listed as NA, masking as none, and the model as single group. The arm description identifies one intervention group, “Treatment for osteoporosis and falls.” It says participants received calcium, vitamin D, a weekly oral bisphosphonate, and falls-prevention measures, with no comparator group. The listed drug interventions are alendronate with cholecalciferol and calcium carbonate with cholecalciferol; falls-prevention measures are listed as behavioral.

The registry’s stated purpose is to develop and implement an evidence-based protocol for secondary prevention of osteoporotic fractures and falls, and to determine how compliance with the intervention relates to muscle strength and functional status following a fracture. The primary outcome is the number adherent with the intervention, with a timeframe of 6 months. A secondary outcome concerns reasons for unwillingness and non-adherence.

These design features shape what can be learned. A single-group study can describe implementation and adherence among the participants who received the protocol. It cannot separate changes associated with the intervention from changes that might occur over time, during rehabilitation, or for other reasons. Details such as eligibility criteria, recruitment procedures, adherence thresholds, and the protocol’s operational definitions are not reported in the registry record. Although the record labels the study Phase 3, that label does not by itself supply the missing information about outcomes or 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

Reasons for not completing this period:

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.

6. Primary Endpoint

The registry lists the primary outcome as Number Adherent With the Intervention, measured over 6 months.

The primary endpoint is titled “Number Adherent With the Intervention.” Its unit is participants, its parameter is a number, and its timeframe is 6 months. It is therefore intended to count participants classified as adherent by the study at the stated follow-up, rather than to measure a continuous change in strength or function.

Adherence is relevant to an intervention that combines medication and falls-prevention measures: implementation depends on whether participants follow the intended components. A count can describe how many participants met the study’s adherence definition, and can help characterize feasibility in the rehabilitation setting. However, the count alone does not explain why some participants were or were not adherent, how adherence was assessed, or the level of adherence required for classification. Those details are not reported in the registry record.

The registry record does not report the observed number adherent, a denominator for the reported endpoint, uncertainty intervals, or an inferential analysis. The enrollment entry of 29 is not a substitute for an outcome result. The endpoint also does not directly measure fractures, falls, muscle strength, or functional status. The stated study purpose mentions strength and functional status, but the primary endpoint listed in the record is adherence. Any conclusions about those other outcomes require their own reported definitions and results, which are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods that can be interpreted from the registry record are limited. The study is identified as single group, with allocation listed as NA and masking as none. Its intervention group received the same osteoporosis and falls-prevention protocol, and no comparator group is described. The primary endpoint is a participant count at 6 months. The record lists 0 analyses, so it does not specify a statistical analysis of the primary endpoint or provide a result from which to assess an analysis method.

What does a participant count represent?

As a general statistical concept, a count endpoint records how many participants meet a defined condition. In this study, the condition is being classified as adherent with the intervention. A count is interpretable only in relation to its denominator and the rule used to classify each participant. The registry lists enrollment of 29, but does not report the number assessed at 6 months, the number meeting the adherence definition, or how participants with incomplete follow-up were handled. The adherence definition and measurement process are also not reported in the registry record.

A count can be presented descriptively without a formal model. For inference, analysts might use methods suited to binary participant-level outcomes or count data, depending on how the endpoint is defined and what comparison is being made. That is general statistical context, not a claim about the analysis used in this study. Since this study has no comparator and no analysis result is reported, there is no basis in the registry record to identify a particular inferential procedure or to describe its assumptions as having been checked.

Why does the single-group structure matter?

General causal reasoning distinguishes observing an outcome after an intervention from estimating what would have happened under an alternative. A comparator provides information about that alternative, subject to the design and analysis. In a single-group study, outcomes can be described for participants receiving the intervention, but the record does not supply a concurrent control outcome. Changes over time may reflect the intervention, the course of recovery, or other influences. Statistical adjustment cannot create a randomized or concurrent comparison that the design did not include.

For this reason, statistical significance would not resolve the central causal limitation even if a within-group test were available. An estimate’s interpretation depends on design as well as calculation. The registry record does not report a within-group test, a comparison with an external group, or an adjusted model; none should be inferred from the study’s Phase 3 label or completed status.

How should uncertainty be understood?

In general, a confidence interval expresses uncertainty about an estimated quantity under a specified statistical method. A narrow interval indicates greater precision than a wide interval on the same scale, while both its limits and the endpoint definition matter. For a count, uncertainty is often considered relative to a denominator or a model for the underlying event probability. The record does not report a primary estimate, denominator at follow-up, confidence interval, or model. As a result, precision cannot be assessed from the registry information.

In general, a p-value measures how compatible data are with a null hypothesis under an assumed model. It does not measure the probability that the null hypothesis is true, and it does not establish clinical importance or causality. The registry record lists 0 analyses and reports no p-value for the primary outcome. It is therefore not appropriate to characterize the result as statistically significant or non-significant.

What do the planning assumptions describe?

The planning description refers to a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect and distinguishes total events for time-to-event planning from participants per arm for other planning. These are planning conventions, not observed trial outcomes. The present study is recorded as single group and has no comparator group, so the two-arm allocation assumption does not describe its enrolled design. Sample-size illustrations are planning scenarios, never observed power. The registry record does not report the values needed to interpret an observed primary effect or a trial-specific sample-size justification.

Over-dispersion is a general concern when observed variability in count data exceeds what a chosen model assumes. If a model ignores such extra variability, uncertainty can be understated. Whether over-dispersion is relevant depends on the outcome definition, repeated observations, and analysis model. The registry record does not describe a count model, repeated measurements for the primary endpoint, or a dispersion estimate, so no conclusion about over-dispersion in this study is possible.

Overall, the registry record supports a design-level reading: this was an uncontrolled, single-group implementation study with a participant-count adherence endpoint. The outcome definition, analysis procedures, uncertainty estimates, and primary result are not reported in the registry record. General methods can explain what would be needed for stronger statistical interpretation, but they cannot fill those reporting gaps.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Osteoporosis Medication")
n      <- c(29)
events <- c(29)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Osteoporosis Medication  29  29  100.0  88.1  100.0  88.3  100.0  88.4  99.9

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 2 outcome measures: the primary outcome is the number adherent with the intervention, and the secondary outcome concerns reasons for unwillingness and non-adherence. It lists 0 analyses. It does not report which outcomes were analyzed, whether any outcome was prioritized beyond its primary label, or whether statistical adjustment for multiple outcomes or multiple tests was planned or used. A multiplicity procedure is therefore not reported in the registry record.

As a general principle, examining multiple outcomes or analyses can increase the chance of a seemingly notable result arising by chance. Prespecifying a primary outcome and describing any multiplicity strategy helps readers interpret results. Here, the primary outcome is named, but no analysis result is reported. The number of outcome measures alone does not reveal how many tests were conducted, and the record’s analysis count does not provide evidence about tests that may or may not have occurred outside the registry entry.

Missing-data handling is also not reported in the registry record. There is no account of participants with missing 6-month adherence assessments, withdrawals, exclusions, or how incomplete observations were treated. The number assessed for the primary endpoint and the denominator used for any adherence calculation are not reported. An analysis population, such as an intention-to-treat or per-protocol set, is not identified.

These omissions matter because the interpretation of an adherence count depends on who was assessed and how missing status was classified. They also limit assessment of possible bias if follow-up differed by adherence or other participant characteristics. The registry record does not describe imputation, sensitivity analyses, or other methods for evaluating missing outcomes. No conclusions about the impact of missing data or multiplicity can be drawn from the posted information.

12. 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

Serious events with the highest arm-level rate: death (3.4%).

The registry’s serious adverse event summary for the osteoporosis medication group lists 29 at risk and 1 affected. Its other adverse event fields list 29 at risk and 0 affected. The deaths field is null. The serious adverse event term list includes death at 3.4%. These entries should be read as registry-reported fields, not as a complete narrative of event timing, severity assessment, or clinical context.

The record does not explain the definitions used for serious and other adverse events, whether events were assessed as related to the intervention, or the observation period for these safety summaries. It also does not clarify the relationship between the serious-event count and the listed death term. The death entry should therefore be reported as it appears rather than reconciled through an assumption about the underlying records. No additional death count can be inferred from the null deaths field.

These figures are descriptive and arise from a single-group study. Without a comparator, they cannot show whether event frequency differed from what would have occurred under another treatment or without the intervention. The registry record does not provide enough detail to evaluate comparative safety, timing, or causality. The posted fields should not be interpreted as establishing that the intervention caused an event, or that an event did not occur beyond what is specifically recorded.

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

The record documents a completed, single-group study designed around a protocol for secondary prevention of osteoporotic fractures and falls in an acute rehabilitation setting. It describes a combined intervention and identifies adherence at 6 months as the primary outcome. It also lists reasons for unwillingness and non-adherence as a secondary outcome. These details clarify the study’s focus on implementation and compliance.

The record does not report the primary adherence count, an analysis, or estimates of muscle strength or functional status. It therefore does not quantify whether participants adhered, how outcomes changed, or how precise an estimate might be. The record’s enrollment of 29 is a design characteristic, not a result. No treatment effect can be calculated or inferred from enrollment alone.

Because there was no comparator group, the study cannot provide a controlled estimate of what would have happened under an alternative approach. Even a reported change within the group would not, by itself, separate intervention effects from recovery, time, or other factors. The registry record also does not provide the outcome definitions and missing-data procedures needed to judge how adherence or follow-up outcomes were measured.

The safety fields record serious and other adverse event information, including a serious event count and a listed death term, but do not include sufficient detail to assess timing, attribution, or comparative risk. These entries can be described as registry reports, not as proof of causation.

In short, the available record supports understanding of the trial’s intent, intervention, design, and selected outcome. It does not support a conclusion that the protocol improved strength or function, prevented fractures or falls, or produced a particular level of adherence. Those conclusions require reported outcome data and an analysis appropriate to the question. The absence of results in the registry record should not be treated as evidence that the intervention had no effect.

14. Why This Trial Matters Statistically

This study is statistically instructive because it separates implementation questions from comparative-effectiveness questions. Adherence is a meaningful implementation outcome for a protocol involving medication and falls-prevention measures. A single-group design can document the experience of participants offered that protocol, provided the outcome and follow-up are clearly defined. The registry record identifies adherence as its primary endpoint and states a 6-month timeframe, making the measurement goal visible.

At the same time, the design determines the limits of inference. With no comparator group, the study cannot estimate a controlled difference between the protocol and an alternative. This is not a flaw that can be repaired by a different p-value or confidence interval: causal interpretation depends on how the comparison was created, not only on the calculation applied afterward. A completed Phase 3 designation does not replace information about a comparator or analysis.

Reporting is also central to statistical usefulness. A participant count needs a definition, a denominator, and a clear account of follow-up. The registry record does not report the observed adherence result, the operational adherence rule, or missing-data handling. It lists 2 outcome measures but 0 analyses. Without results and methods, readers cannot evaluate precision, potential bias, or the relationship between implementation and the study’s stated interests in strength and functional status.

The record also illustrates why planning calculations must be kept distinct from trial findings. The described planning assumptions concern equal allocation between two arms, while this study is recorded as single group. Such illustrations can be used to explore hypothetical future designs, but they are not observed power and do not establish what this study found. A transparent distinction between design, planning, and observed results is essential when interpreting clinical research.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The principal limitation for interpretation is the single-group design with no comparator. Outcomes among participants receiving the protocol cannot establish what would have occurred under another strategy. This applies to adherence as well as to the stated interests in muscle strength and functional status following a fracture. The record does not report those latter outcome results.

The primary outcome is named as the number adherent at 6 months, but the registry record does not state the adherence threshold, assessment method, denominator at follow-up, or observed count. It also does not describe eligibility criteria, baseline participant characteristics, follow-up completeness, or handling of missing assessments. Those gaps make it difficult to judge representativeness and the meaning of any potential adherence estimate.

The registry lists a secondary outcome on reasons for unwillingness and non-adherence but provides no results. It also lists 2 outcome measures and 0 analyses, with no statistical plan or analysis population reported. Multiplicity procedures and missing-data methods are not reported in the registry record. The record therefore does not allow evaluation of analytical choices or selective reporting.

Safety information is limited to summary fields. Definitions, event timing, attribution, and details that would clarify the listed death term are not reported in the registry record. The serious and other event fields cannot establish comparative risks in the absence of a control group.

Finally, the planning assumptions described in the registry do not match the single-group structure because they include equal allocation between two arms. They are planning illustrations, not a description of the enrolled design or observed power. These limitations mean the record is useful for understanding the intended intervention and study structure, but not for estimating its clinical effect or precision.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Secondary Prevention of Osteoporosis — NCT00421343.
• Registry record last updated 2020-02-05; status last verified 2020-01.
• Results first posted 2011-06-10.
• 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.

19. Record Summary

NCT00421343 is a completed Phase 3, single-group study sponsored by Hebrew SeniorLife, with enrollment listed as 29. The recorded start is 2007-02 and primary completion is 2008-06. Allocation is NA, masking is none, and the arm description states there was no comparator group.

The intervention combined calcium, vitamin D, a weekly oral bisphosphonate, and falls-prevention measures. The primary outcome was the number adherent with the intervention at 6 months. A secondary outcome concerned reasons for unwillingness and non-adherence. The stated purpose also included relating compliance to muscle strength and functional status following a fracture.

The registry record lists 2 outcome measures and 0 analyses, and does not report a primary outcome result, statistical analysis, or comparative treatment effect. Serious adverse event fields list 1 affected among 29 at risk; other adverse event fields list 0 affected among 29 at risk. The serious-event term list includes death at 3.4%, while the deaths field is null. Further safety context is not reported in the registry record.