Bone mineral density in children and adults with classic galactosemia

Low bone mineral density (BMD) is a well-recognized complication of classic galactosemia (CG), but the timing and potential modifiers remain poorly understood. Here we analyzed clinically obtained dual energy x-ray absorptiometry (DEXA) age- and sex-normed Z-scores from 66 children and adults with CG, comparing these with each other and normative data to reveal patterns and test candidate modifiers. The overall prevalence of Z-scores less than -2.0 was 25% for males and 44% for females. BMD Z-scores were not associated with age at the time of DEXA, severity of neonatal symptoms, developmental outcomes, predicted galactose-1-P uridylyltransferase (GALT) activity, or gal-1P levels. Age at which females requiring pubertal induction initiated hormone replacement therapy (HRT) showed an apparent inverse relationship with later DEXA Z-scores. Similarly, women with CG experiencing premature ovarian insufficiency (POI) and receiving inadequate estrogen replacement showed apparently lower DEXA Z-scores than women receiving adequate HRT or women not experiencing POI. While some of these relationships appeared strong, larger data sets will be required to confirm significance of specific tests. Finally, both male and female patients who took non-hormonal medication for osteoporosis reported no unexpected complications, and those with follow-up DEXA scans showed improved scores. Combined, these results suggest that hypogonadism is a major and modifiable factor contributing to low BMD in CG. However, males and also females without clear evidence of POI remain at risk and should have routine BMD screening. Further research is needed to elucidate the non-hormonal etiologies for low BMD in CG.