Statistical analysis
SECONDARY
The primary efficacy endpoint was changes in BMD at the TH, FN and LS at 18 months compared to baseline. The sample size was based on a difference between the control group and treatment groups of a change in BMD of 3% (clinically significant) at the hip with an SD of 3%. Assuming a 10% non-compliance rate, 28 patients in each arm will provide 95% power to detect a change in the primary outcome at the 5% significance level. To make allowance for the unknown distribution of the primary outcome, we increased the sample size by a further 15% to 32 per group. Further accounting for a drop-out rate of 10% consistent with previous trials, 35 patients were recruited in each group for a total study population of 105. The secondary end points included changes in BTMs and HSA parameters.Statistical analyses were done according to the statistical analysis plan using R Core Team Version 4.0 [Changes in BTMs as secondary efficacy endpoints were analysed using repeated measures ANCOVA adjusted for baseline based on the intention to treat (ITT) and per protocol (PP) population. Bonferroni test was used for group comparisons. Data for the BTMs were logarithmic transformed to achieve normal distribution. Additional secondary outcome measures included changes in the HSA parameters at 18 months compared to baseline. Differences in HSA were tested by ANCOVA with Bonferroni test (adjustment for multiple comparisons) as for the primary outcome. A Further exploratory analyses were performed including multivariate models correcting for co-variates including age, BMI, baseline serum vitamin K