<div>To the Editor,</div><div>We saw with interest the paper by Gur et al reporting the effect of
Trikafta (elexacaftor/ivacaftor/tezacaftor) on bone density in young
adults with cystic fibrosis.  This is an area of significant need in
terms of research, and we are glad that it is being considered. However,
we would like to raise a number of questions regarding the findings.</div><div>The small size of the study (8 patients had 2 DEXA scans) we acknowledge
is not unusual in a pilot study, although it is difficult to draw any
conclusions from such a small group.</div><div>The lack of information regarding the control group is of significant
concern. No demographic or DEXA data is offered for the control group.</div><div>An increase in bone density over 2 years in an 18yr old would be normal.
It is unclear whether the control group are age-matched, which would
have a big impact on these findings. It is unclear whether genotype
matching with the controls could have been achieved; it seems probable
that as patients not receiving Trikafta the control group represent
non-eligible genotypes which would also have impact on disease
trajectory.   A number of other features could be matched: weight and
height at time of entering the study, diabetes status, lung function,
pubertal stage, vitamin D status.  These all have a significant impact
and are not mentioned within the study design or discussion.  The only
place corticosteroids are mentioned are in the case of participant 4,
who had a reduction in bone mineral density despite Trikafta.</div><div>The DEXA scans are 2 years apart, but Trikafta was given for only 3
months of this.  It seems likely that most of the improvement in bone
density happened prior to the commencement of Trikafta given the
timeframes. The effect of both growth and weight gain within this
timeframe should not be overlooked.</div><div>We are hopeful that CTFR modulation does have a positive impact of bone
health, but we have concerns about this study design being used to
support the hypothesis.</div><div>Yours sincerely</div><div>Elizabeth Clarke, Rheumatologist, Greater Glasgow and Clyde</div><div>Fiona Moore, Cystic Fibrosis Specialist Dietician, Greater Glasgow and
Clyde</div><div>Andy Gallagher, Endocrinologist, Greater Glasgow and Clyde</div><div>Stephen Thomson, Respiratory Consultant, Greater Glasgow and Clyde</div>