Calcium Absorption in Patients With Rothmund-Thomson Syndrome: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Calcium Absorption in Patients With Rothmund-Thomson Syndrome (NCT01304407), a na na study. The primary outcome is Bone Density (Low Areal Bone Mineral Density (aBMD)).

2. Clinical Question

The study concerns bone density in people with Rothmund-Thomson Syndrome (RTS), a genetic disorder associated with skeletal abnormalities. The registry background also describes an increased risk of cancer, particularly osteosarcoma, among people with RTS. The study record focuses on characterizing a skeletal measure; it does not describe a test of cancer treatment or a comparison of therapies.

3. Trial Design

The registry describes a completed, single-group study with an enrollment of 29 and no listed phase. Baylor College of Medicine is named as sponsor. The record gives a start date of 2011-03 and a primary completion date of 2015-10. Allocation is listed as NA, and masking is listed as NONE. There is no separate control arm or randomized treatment allocation described, so the study is not a randomized comparison.

The intervention is identified as a calcium stable isotope and classified as OTHER. The arm description says subjects consumed breakfast and 180 ml of calcium-fortified orange juice with 20 mg of 46Ca stable isotope added. Immediately after breakfast, subjects received 5 mg of 42Ca intravenously. The registry outcome description gives an 8 days timeframe for the primary bone-density measure. It does not describe additional protocol details for calcium-absorption sampling or analysis.

The stated study population for the primary outcome includes 13 pediatric patients and 9 adult patients. The record says 7 patients did not have successful bone-density scans to be included in the analysis. Those counts describe the outcome population and scan exclusions; the reason for any other difference between enrollment and analyzed participants is not reported in the registry record.

The record identifies one outcome measure and lists no analyses. It provides no numeric primary outcome estimate, analysis model, inferential test, or confidence interval. Details such as how participants were recruited, the intended sample-size rationale, and any interim analyses are not reported in the registry record. The design supports description of measurements among participants, but it does not establish a between-group treatment effect.

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

Analysis population for the primary outcome, as defined in the registry: Areal bone mineral density (aBMD) z-scores of 13 pediatric patients, 9 adult patients. 7 of the patients did not have successful bone density scans to be included in the analysis.

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 Bone Density (Low Areal Bone Mineral Density (aBMD)), measured over 8 days.

The primary outcome is titled Bone Density (Low Areal Bone Mineral Density (aBMD)) and is expressed in z-scores. The registry specifies a median and inter-quartile range as the summary statistics and gives an 8 days timeframe. Its description says aBMD was assessed by DXA using a Hologic Delphi-A instrument. Scans covered the whole body, lumbar spine, and proximal femur; bone mineral content, bone area, and BMD were measured using Hologic Discovery V12.1 analysis software.

The record says adult subjects' BMD z-scores for the whole body, lumbar spine, left total hip, and left femoral neck were calculated using the Hologic Reference Database. For pediatric subjects, validated age- and sex-matched control data generated by the Body Composition Laboratory of the Children's Nutrition Research Center were used to calculate z-scores. In general, a z-score expresses a measurement relative to a reference distribution, which can make measurements interpretable against an age- and sex-relevant reference where that reference is used.

Bone density is used in this study to characterize skeletal phenotype in RTS. However, the registry record does not report the median, inter-quartile range, or any other numeric result for the primary outcome. It also does not state a threshold defining low aBMD.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the registry is limited. It names a median and inter-quartile range as the intended summary for the primary bone-density outcome, but it does not provide the resulting values, a statistical test, a model, or a confidence interval. The registry also lists no analyses. Statistical interpretation is therefore constrained to the design and outcome definitions rather than the size or precision of an estimated effect.

What does a median describe?

In general, the median is a measure of the center of a distribution. It is the value at the midpoint when observations are ordered. Unlike a mean, it is less directly influenced by unusually high or low observations. The record specifies the median for the primary outcome, but its value is not reported in the registry record. It is therefore not possible to say where the analyzed participants' central aBMD z-score fell.

What does an inter-quartile range describe?

In general, the inter-quartile range describes the spread of the middle half of observations. It complements the median by indicating how dispersed the central portion of a distribution is. It does not show every observed value or the full range. Although the registry specifies this measure of spread, the inter-quartile range itself is not reported in the registry record. The variability of the primary outcome cannot be assessed from the listed outcome definition alone.

How should the z-score be understood?

In general, a z-score indicates a measurement's position relative to a reference distribution, using the reference distribution's center and spread. The registry describes different references for adults and pediatric participants: the Hologic Reference Database for adult subjects and validated age- and sex-matched pediatric control data for pediatric subjects. This reference-based approach can aid interpretation of bone-density values across ages. The record does not provide the reference values, the individual z-scores, or numeric group summaries, so no further quantitative interpretation is possible.

What does the single-group design permit?

In general, a single-group study can describe measurements in its participants, while a comparison of outcomes between assigned groups requires a comparator and a design that supports that contrast. This study is listed as single-group, with allocation NA and no masking. The calcium-isotope procedure is described, but no control group is identified. Thus, the record does not provide a randomized between-group estimate. A reference database used to calculate z-scores is not the same thing as a concurrently enrolled control arm.

What is a confidence interval, and is one reported?

In general, a confidence interval conveys uncertainty around an estimated quantity, under the assumptions of the method used to calculate it. Its width reflects how precisely the quantity is estimated, as well as the chosen method. No confidence interval for the primary bone-density outcome is reported in the registry record. The record also does not provide a standard error or other numeric uncertainty estimate. Precision of the primary outcome therefore cannot be evaluated from the registry entry.

What do the sample-size assumptions mean?

In general, a sample-size planning illustration asks how many participants might be needed under specified assumptions to detect a chosen effect with a chosen power and significance level. Such an illustration is a planning calculation, not evidence that the observed study had that power and not a result of the trial. The registry describes planning assumptions based on a fraction of an observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. It also distinguishes participant counts per arm from total event counts for time-to-event calculations. Because no numeric planning results or observed effect estimate are stated in the registry record, no planning count or effect magnitude can be interpreted. These assumptions do not establish what the original design team used.

What does over-dispersion mean in general?

In general, over-dispersion occurs when observed variation is greater than a statistical model assumes. If it is ignored, uncertainty can be understated and inferential results can be too optimistic. The registry record does not report a count model, an over-dispersion assessment, or a model for the primary outcome. This concept is therefore general background rather than a description of an analysis used in this study.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure and no analyses. It does not report a multiplicity strategy, such as an adjustment for testing multiple outcomes or multiple comparisons. Because the record does not list inferential tests or numeric results, it is not possible to assess how multiplicity was handled in an analysis. The statistical plan, including any prespecified hierarchy among outcomes, is not reported in the registry record.

For the primary bone-density outcome, the registry says 7 patients did not have successful scans to be included in the analysis. It describes 13 pediatric patients and 9 adult patients as the aBMD z-score population. The record does not state why scans were unsuccessful, whether missingness was related to participant characteristics or measured bone density, or whether any missing-data method was used. It also does not report sensitivity analyses addressing missing scans.

The registry does not describe an intention-to-treat population, a per-protocol population, or other analysis-population rules. The scan population is the only analysis population described for the primary outcome. It is not reported whether all enrolled participants completed the isotope procedure, whether all participants contributed measurements within the stated timeframe, or how incomplete measurements were handled.

In general, missing outcome data can affect interpretation when the people with available measurements differ from those without them. The direction and extent of any such effect depend on information about the missingness and the analysis approach. Neither is detailed in the registry record. The available information therefore identifies scan exclusions but does not establish how those exclusions may have influenced the reported outcome.

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.

The registry's adverse-event entry lists 29 RTS patients at risk. It records 0 affected by serious adverse events, 0 affected by other adverse events, and 0 deaths. No serious adverse-event terms are listed. These are the counts reported in the registry record; they should be read as event reporting for the recorded group, not as a comparison with another group.

The record does not provide event definitions, a detailed safety-collection period, severity grades, or a breakdown by event type. The primary outcome timeframe is 8 days, but the registry does not establish that this is the safety follow-up period. Nor does the record explain whether all 29 participants received the described procedure or were followed for the same duration for safety reporting.

In general, a count of zero recorded events does not by itself quantify the probability of an event or establish that an intervention has no risk. Interpretation depends on how events were defined, monitored, and reported, and on the amount and duration of observation. With no comparator and no further safety detail in the registry record, these counts are descriptive only.

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

This study record is useful for understanding how investigators described bone-density assessment in people with RTS. It specifies DXA measurement sites, the approach to calculating adult and pediatric z-scores, the summary statistics named for the outcome, and the calcium stable-isotope procedure. It also identifies a scan population and notes that some patients did not have successful scans for inclusion.

The record does not report the numeric primary outcome results. It therefore does not show the median or inter-quartile range of aBMD z-scores, and it does not quantify how low or variable the measurements were. It also does not report a numeric calcium-absorption result. No conclusion about the degree of calcium absorption or its relationship with bone density can be drawn from the registry entry alone.

The design is single-group and does not identify a comparator arm. As a result, the described measurements do not establish a causal effect of an intervention relative to a control condition. The reference databases used to calculate z-scores support measurement interpretation, but they are not described as trial participants assigned to a comparison group.

The registry background explains why skeletal phenotype is of interest in RTS, including the condition's association with skeletal abnormalities and cancer risk. That background is not an outcome of this study. The record does not report cancer incidence, osteosarcoma outcomes, or whether any measured bone-density value predicts those outcomes. It also does not provide evidence about the effect of a therapy on cancer or bone health.

The appropriate reading is therefore narrow: the record documents a study design and measurement method, along with limited participant and safety counts, but does not report the numeric primary findings needed to assess the observed bone-density distribution. The absence of those results in the registry record is not evidence for a particular outcome.

13. Why This Trial Matters Statistically

The study illustrates several issues that matter when interpreting clinical measurements in a rare condition. RTS is described as involving skeletal abnormalities, and the study sought to characterize bone density using age- and sex-referenced z-scores. The use of specified adult and pediatric reference sources is important because the interpretation of a measurement depends on the population against which it is compared. The registry identifies those sources but does not report the resulting values.

It also highlights the distinction between a measurement protocol and a reported result. The isotope procedure and DXA methods are described in detail, but numeric primary outcome results are absent from the registry record. Without those results, readers cannot evaluate the central value, spread, or precision of the measured bone-density outcome. A clear description of how a measurement was made does not substitute for reporting what was observed.

The scan exclusions are another statistically relevant feature. The outcome population includes pediatric and adult patients, while the record says 7 patients lacked successful scans for inclusion. Missing measurements can affect representativeness, and the registry does not give enough information to assess that possibility. Transparent reporting of reasons for missingness and the analysis population would help readers understand the limits of the observed data.

Finally, the single-group design sets a boundary on inference. It can describe participants' measurements, but it does not supply a randomized control contrast. Recognizing that boundary helps distinguish a descriptive study of skeletal phenotype from a comparative test of an intervention. The registry record's value lies in the methods and population information it documents; its missing numeric findings limit statistical conclusions.

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 no numeric aBMD results are reported in the registry record. Although the outcome is specified as a median and inter-quartile range of z-scores, neither statistic is given. No confidence interval, test result, or model estimate is listed. This prevents assessment of the outcome's magnitude and precision.

The study is single-group, with allocation listed as NA and masking listed as NONE. No control group is described, so the record does not support a randomized between-group treatment comparison. The adult and pediatric reference sources used to derive z-scores are not trial arms and do not create a concurrent control comparison.

The outcome population is described as 13 pediatric patients and 9 adult patients, and 7 patients did not have successful bone-density scans for inclusion. Reasons for failed scans, characteristics of excluded participants, and any approach to missing data are not reported in the registry record. The record also does not describe an analysis population beyond the scan-based outcome population.

The registry gives an 8 days timeframe for the primary outcome, but does not provide detailed measurement timing beyond the described methods. Additional protocol information, including recruitment procedures, sample-size justification, interim analyses, statistical model, and analysis plan, is not reported in the registry record. No numeric calcium-absorption findings are listed, despite the isotope procedure description. These gaps limit interpretation of both the primary outcome and the broader measurement aims.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Calcium Absorption in Patients With Rothmund-Thomson Syndrome — NCT01304407.
• Registry record last updated 2020-07-23; status last verified 2020-07.
• Results first posted 2020-07-08.
• 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

NCT01304407 is a completed, single-group study sponsored by Baylor College of Medicine, with enrollment of 29. The registry gives a start date of 2011-03 and a primary completion date of 2015-10. The study concerns calcium absorption and bone density in people with Rothmund-Thomson Syndrome.

The intervention description specifies oral 46Ca stable isotope with breakfast and calcium-fortified orange juice, followed immediately by intravenous 42Ca. The primary outcome is aBMD z-score, summarized by median and inter-quartile range, with an 8 days timeframe. DXA measurement and reference methods are described. The bone-density analysis population is described as 13 pediatric patients and 9 adult patients; 7 patients did not have successful scans for inclusion.

Numeric primary outcome and calcium-absorption results are not reported in the registry record. The record lists 0 serious adverse events, 0 other adverse events, and 0 deaths among 29 patients at risk. No comparator group or registered analyses are described.