The Relationship Between Irisin and Bone Health in Individuals With Spinal Cord Injury: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Relationship Between Irisin and Bone Health in Individuals With Spinal Cord Injury (NCT05319522), a non-randomized na study. The primary outcome is Irisin-Trabecular vBMD Correlation.

2. Clinical Question

The broader study description also raises questions about muscle fiber type, irisin concentrations, and whether exercise can increase circulating irisin. The listed behavioral intervention is acute exercise. The primary endpoint, however, is a correlation between a blood measure and a bone measure, not a comparison of exercise against a control intervention.

The registry record describes a total enrollment of 11. It does not report the numerical correlation estimates, their uncertainty, or the significance tests for the primary endpoint. Consequently, the stated question can be described, but the posted primary results cannot establish the direction, magnitude, or precision of either within-group association.

3. Trial Design

This is a completed, nonrandomized, parallel study sponsored by the VA Office of Research and Development. The registry lists the study as starting on 2023-05-05, with primary completion on 2025-04-30. It records enrollment of 11 and lists spinal cord injury as the condition. The phase is listed as NA, which is consistent with a study not presented as a phase-based therapeutic trial.

There are two groups: Individuals with SCI and Controls (No SCI). The first includes male and female Veterans and non-Veterans with traumatic spinal cord injury. The control group includes male and female Veterans described as age- and sex-matched to participants with spinal cord injury. Because allocation is nonrandomized, differences between groups could reflect characteristics other than spinal cord injury. The registry's description does not establish that the groups are otherwise exchangeable.

Both groups are described as completing a baseline blood draw, muscle biopsy, and bone imaging using DXA and HR-pQCT. Both also complete an arm ergometer high-intensity interval exercise bout, with blood draws before and after it. This is a behavioral intervention and does not imply that participants were assigned randomly to different exercise conditions. Masking is listed as none.

The primary outcome is a Pearson correlation coefficient for the relationship between circulating irisin and trabecular volumetric bone mineral density at the distal tibia (4% site), measured at baseline while at rest. The correlation analyses are described as separate within-group analyses. They were intended to determine whether the association was significant within each group, not whether the correlations differed between groups.

The registry record does not report a protocol-level sample-size justification, a recruitment target by group, or a detailed statistical analysis plan. It also does not report whether any interim analyses were planned. These details should not be inferred from the total enrollment or the study's completion status.

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:

Analysis population for the primary outcome, as defined in the registry: The correlations were analyzed separately for the Individuals with SCI group and the Controls group. Analyses were intended to determine if the correlation between the trabecular vBMD and irisin was significant in each group, not to compare the correlations between groups. Given the sample size of the Controls group (n=3), the results should be interpreted with caution.

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 Irisin-Trabecular vBMD Correlation, measured over Baseline; at rest.

The primary endpoint is the Pearson correlation coefficient between circulating irisin concentration and trabecular volumetric bone mineral density at the distal tibia (4% site). Measurements are described as baseline and at rest, and the analysis is conducted separately for participants with spinal cord injury and controls without spinal cord injury.

A correlation coefficient describes the direction and strength of a linear association between two measured variables. It does not establish that one variable causes a change in the other. In this study, the endpoint can indicate whether participants with higher irisin measurements tend also to have higher or lower trabecular bone density measurements within a group. It does not, by itself, test whether spinal cord injury causes a difference in bone density or whether exercise changes bone health.

Using a continuous measurement of bone density can preserve information about variation across participants rather than reducing the outcome to a simple category. The distal tibia site and the use of volumetric bone mineral density specify which bone measurement is being related to irisin. The endpoint is therefore relevant to the stated association question, while remaining distinct from a fracture outcome.

The registry record does not report the observed correlation coefficients, confidence intervals, or significance test results. The endpoint definition is available, but the numerical primary result and its precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The listed primary measure is the Pearson correlation coefficient. In general, Pearson correlation quantifies the direction and strength of a linear relationship between two continuous measurements. A positive value indicates that larger values of one measure tend to occur with larger values of the other; a negative value indicates that larger values of one tend to occur with smaller values of the other. A value near zero can indicate little linear association, although it does not rule out a nonlinear relationship. These are general properties of the method, not findings from this study.

What does a correlation test assess?

In general, a significance test for correlation evaluates how compatible the observed data are with a null hypothesis of no linear association in the population, under the assumptions of the test. A p-value is not the probability that the null hypothesis is true, and it does not quantify the size or importance of an association. The estimate itself and its confidence interval are important for judging magnitude and precision. The registry record does not report the primary coefficients, confidence intervals, or p-values.

Correlation is not a causal method. Even a clear association between irisin and trabecular bone density would not show that irisin changes bone density, that bone density changes irisin, or that another factor does not influence both. The baseline, at-rest timing gives the endpoint a specific observational interpretation. It does not establish temporal ordering between the two measures or the effect of an intervention.

Why are the groups analyzed separately?

The registry describes separate correlation analyses for the spinal cord injury group and the control group. This estimates the association within each group. It does not directly test whether the two correlations differ. In general, comparing whether one result crosses a significance threshold and the other does not is not equivalent to testing the difference between the underlying associations. A direct comparison would require an analysis designed for that question. The registry states that the analyses were intended to assess significance within each group, not compare correlations between groups.

The group structure also affects interpretation. Allocation is nonrandomized, and the groups differ in spinal cord injury status. Age and sex matching is described for controls, but the registry record does not report the matching procedure, whether matching was individual or group-based, or whether the analysis accounted for matching. These details should not be assumed. More generally, matching can help align selected characteristics, but it does not automatically control all potential confounding.

What does precision mean in this setting?

In general, a confidence interval gives a range of values compatible with the observed data and the method's assumptions. A narrow interval indicates greater statistical precision than a wide interval, but precision is not the same as absence of bias. A small study may yield an imprecise estimate even when a statistical test is performed correctly. The total enrollment is 11, while the group-specific numbers contributing to the primary correlation are not reported in the registry record. The primary estimates and their confidence intervals are also not reported, so their precision cannot be evaluated.

For correlation analyses, the amount and pattern of variation in both measures matter. An unusual observation can have substantial influence, particularly when the analysis includes few participants. A linear summary may also fail to represent a curved or otherwise more complex relationship. The registry record does not report diagnostic plots, influence checks, transformations, or other model checks for the primary analysis. That absence does not establish that such checks were not performed; their status is not reported in the registry record.

How should the exercise measurements be distinguished?

The arm ergometer bout and blood draws before and after it create a repeated-measure setting for circulating irisin. In general, repeated measurements from the same participant are related and should not be treated as independent observations. An analysis of change or of measurements over time should account for that within-participant relationship. The registry description does not report the statistical method used for the exercise-related measurements, the numerical results, or whether the analysis adjusted for other variables. The primary endpoint is instead the resting baseline correlation with bone density.

Over-dispersion is a general concern for count outcomes when their variability is greater than expected under a simple count model. It is not a description of the primary endpoint here, which is a correlation between continuous measurements. The endpoint's key concerns are the linearity and stability of the association, the sample contributing to the estimate, and uncertainty around the coefficient.

What can be learned from the planning assumptions?

The planning illustration is described as a calculation from an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. In general, such calculations translate an assumed effect and selected design assumptions into a planning sample size. They depend on the effect size and the statistical model; changing those assumptions changes the planning result. The illustrations are not a record of the trial's original sample-size justification and are not observed power. Numerical outputs and the effect value used are not reported in the registry record.

The record lists 7 outcome measures and 12 analyses. Those counts indicate that the study has multiple reported outcome and analysis entries, but they do not reveal which tests were designated as confirmatory, how outcomes were prioritized beyond the primary endpoint, or whether multiplicity adjustments were applied. The statistical analysis plan and these specific decisions are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 7 outcome measures and 12 analyses. When several outcomes or analyses are considered, the chance of at least one apparently notable result can increase if each is interpreted as an isolated test. In general, multiplicity procedures can control error rates across a defined family of tests, but they can also affect the interpretation and precision of individual estimates. The record does not report whether an adjustment was planned or used, which analyses were considered part of a family, or which results were intended as confirmatory. Those details are not reported in the registry record.

The primary endpoint is described as two separate within-group correlation analyses. The record states that the analyses were intended to assess whether each group's correlation was significant, not to compare the correlations. It does not report the primary coefficients or test results, so their relation to the other analyses cannot be assessed.

The registry entry does not report how missing measurements were handled, whether all enrolled participants contributed to every analysis, or whether any exclusions occurred. The number contributing to each primary correlation and the analysis population definitions are not reported in the registry record. It is therefore not possible to determine whether the endpoint results represent all enrolled participants or a subset with complete measurements.

In general, missingness can matter when the probability of a measurement being unavailable is related to participant characteristics or outcomes. Complete-case analyses can be biased under some missing-data patterns, while other approaches rely on their own assumptions. No method should be attributed to this study without a report of it. The registry record also does not report a prespecified missing-data strategy, sensitivity analyses for missing data, or reasons for any missing measurements.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: bone fracture (12.5%), high blood pressure (12.5%).

The registry lists serious adverse events for the Individuals With SCI group among 8 participants at risk: 2 participants were recorded as having a serious adverse event. For Controls (No SCI), 0 serious adverse events were recorded among 3 participants at risk. The registry lists 0 other adverse events in each group and 0 deaths in each group.

The top serious event terms are Bone Fracture and High blood pressure, each listed as 12.5%. These are registry event summaries. They do not, on their own, show whether an event was caused by study participation or by the exercise bout. The record does not report a causal assessment in the information, so the event counts should not be interpreted as proof of causation or proof that no risk exists.

These small group counts provide limited descriptive safety information. A zero count does not establish that an event cannot occur; it indicates that no event was recorded in the stated at-risk group during the registry's reporting. The registry record does not report additional detail about event timing, severity beyond the serious classification, relatedness, or the observation period used for these counts.

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

The study addresses an association question involving circulating irisin and a specified bone-density measure in people with spinal cord injury and controls. Its design also includes muscle biopsy, bone imaging, and blood collection around an acute arm ergometer exercise bout. These features make the study relevant to describing relationships among muscle-related measures, irisin, and bone health, as well as to exploring an acute exercise question.

The primary endpoint does not measure fractures. It is a correlation between irisin and trabecular volumetric bone mineral density at the distal tibia (4% site). A correlation can describe how two measurements vary together, but it cannot establish a causal pathway. Nor does an association within each group establish that the relationship differs by spinal cord injury status. The registry explicitly says that comparing the correlations between groups was not the analysis objective.

The numerical primary results are not reported in the registry record. Therefore, the available information does not establish whether the correlations were positive or negative, whether either was statistically significant, or how precisely either was estimated. The same limitation applies to the exercise-related irisin results: the stated study aim and measurement schedule do not show whether irisin changed after exercise.

The total enrollment of 11 and nonrandomized allocation also constrain what can be concluded. Group differences may reflect characteristics other than spinal cord injury, and estimates from a small sample can be uncertain. The record does not report the group-specific primary analysis sample sizes, missing-data handling, or enough numerical outcome information to assess the stability of estimates.

Thus, the registry record identifies a focused observational primary question and describes related measurements, but it does not report the numerical evidence needed to characterize the primary association. The study should not be read as proving a treatment effect, a causal relationship, or an effect on fracture risk based solely on the information recorded.

13. Why This Trial Matters Statistically

Clinical research often asks whether a biological measure is associated with a health-related measurement before stronger causal claims can be considered. This study makes that distinction important: its primary endpoint is an association between circulating irisin and trabecular bone density, while its broader description also concerns muscle fiber type and an acute exercise bout. Keeping these questions separate helps avoid treating an observational correlation as evidence of an intervention effect.

The registry also specifies that the correlations are assessed separately in the spinal cord injury and control groups, rather than compared directly between them. That distinction is statistically consequential. Two separate within-group tests do not automatically answer whether the association differs across groups. Clear definition of the estimand—the quantity an analysis is intended to estimate—helps readers understand what a result can support.

The design illustrates common challenges in small, nonrandomized research: group differences may have explanations beyond the condition of interest, estimates may be imprecise, and individual observations may have influence. Detailed reporting of estimates and confidence intervals would be particularly useful for judging the strength and uncertainty of associations. Those primary numerical results are not reported in the registry record.

Finally, the study has multiple outcome measures and analyses. Statistical interpretation depends not just on the number of tests, but on which questions were planned, how outcomes were prioritized, and how multiplicity was addressed. Those details are not reported in the registry record. The entry therefore highlights why transparent analysis plans, complete outcome reporting, and careful distinction between association, group comparison, and intervention effect matter in clinical biostatistics.

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 limitation for interpreting the posted endpoint is that the registry record describes the analysis but does not report the numerical correlation coefficients, confidence intervals, or significance tests. Without those results, neither the direction nor the magnitude or precision of the association can be assessed. The group-specific numbers contributing to the primary analyses are also not reported in the registry record.

Enrollment is 11, which limits the amount of information available for estimating associations, particularly when analyses are conducted separately by group. The registry record does not report a sample-size justification for the primary correlation analysis. The separate planning illustration is based on an observed effect and specified assumptions, but it is not the study's design rationale and is not observed power.

The nonrandomized design means that the groups cannot be interpreted as randomized counterparts. Controls are described as age- and sex-matched, but the matching procedure and its treatment in the analysis are not reported in the registry record. Other group differences may remain. The absence of masking is also recorded, although the record does not detail whether it affected measurement or analysis.

The registry does not report missing-data methods, analysis population definitions, model diagnostics, adjustment for potential confounding, or multiplicity procedures. It lists 7 outcome measures and 12 analyses, but does not specify how those analyses were prioritized or whether the statistical plan changed. These reporting gaps limit assessment of the robustness and selectivity of the findings.

Finally, the primary endpoint concerns a bone-density measurement, not fracture occurrence, and its baseline correlation does not establish causality. Numerical findings for the exercise-related blood draws are also not reported in the registry record, so the study's stated interest in an exercise-based increase in irisin cannot be evaluated from the registry information.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: The Relationship Between Irisin and Bone Health in Individuals With Spinal Cord Injury — NCT05319522.
• Registry record last updated 2026-09-01; status last verified 2026-08.
• Results first posted 2026-09-01.
• 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

NCT05319522 is a completed, nonrandomized, parallel study sponsored by the VA Office of Research and Development. The registry lists enrollment of 11, a start date of 2023-05-05, and primary completion on 2025-04-30. Masking is listed as none, and the phase is NA.

The study includes participants with traumatic spinal cord injury and controls without spinal cord injury. Both groups are described as completing baseline blood collection, muscle biopsy, DXA and HR-pQCT bone imaging, and an arm ergometer high-intensity interval exercise bout with blood draws before and after. The primary endpoint is the baseline, at-rest Pearson correlation between circulating irisin and trabecular volumetric bone mineral density at the distal tibia (4% site), analyzed separately by group.

The registry record lists 7 outcome measures and 12 analyses. It reports adverse-event counts, but the numerical primary correlation results, their precision, and the exercise-related irisin results are not reported in the registry record.