Genetic susceptibility and late bone outcomes in childhood acute lymphoblastic leukemia survivors
An erratum to this article was published (J Bone Miner Res, 5 Aug 2024 ↗)
Authors' conclusion
In conclusion, a PGS, in combination with clinical risk factors, could be used as a tool to risk stratify cALL survivors for treatment-related bone morbidity.
Study context
- Population
- Childhood acute lymphoblastic leukemia survivors from the PETALE study; median age 21 yr, 51% female51% female
- Participants
- 214 survivors
- Exposure
- Polygenic scores (PGS) for heel quantitative US speed of sound above vs below the mean
- Outcome
- BMD Z-scores (LS-BMD, FN-BMD, TB-BMD by DXA) and vertebral fracture risk
Methodological detailspolygenic score, multivariate adjustment for clinical risk factors, sex and prognostic risk-stratified analyses
- Polygenic score
- Multivariate adjustment for clinical risk factors
- Sex and prognostic risk-stratified analyses
Main finding
As reported in the abstract
Association of gSOS with BMD Z-scores (univariate)
Per 1 SD increase in gSOS: LS-BMD increase
0.16 SD
95% CI 0.005–0.31
gSOS above the mean: higher LS-BMD
0.31 SD
95% CI 0.008–0.61
gSOS above the mean: higher TB-BMD
0.36 SD
95% CI 0.06–0.67
gSOS above the mean: higher FN-BMD
0.43 SD
95% CI 0.13–0.72
Observational data: associations, not effects.
Further findings
Models combining gSOS with clinical risk factors
- Variance of bone mineral density (BMD) phenotypes explained, up to
- 16%
- AUC for vertebral fractures (VF) in subgroup analyses
- 0.77
Clinical risk factors for lower BMD Z-scores
- Cranial radiation, high cumulative glucocorticoid doses, high risk group and male sex were significant risk factors
Original publication
Genetic susceptibility and late bone outcomes in childhood acute lymphoblastic leukemia survivors. J Bone Miner Res. Published 4 January 2024. doi:10.
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