EFFECT OF HYPOGONADISM AND DEFICIENT CALCIUM INTAKE ON BONE-DENSITY IN PATIENTS WITH GALACTOSEMIA

Forty children and adults with classic galactosemia had vertebral bone density determined by standard quantitative computed tomography at 3. 4 to 44.2 years of age. Compared with age- and sex-matched control sub jects, patients with galactosemia had diminished bone density (p = < 0 .001). Prepubertal patients of both sexes had bone density determinati ons below those of the control group (p = 0.008); similar findings wer e seen in postpubertal patients as well (women, p = 0.001; men, p = 0. 008). Women receiving replacement estrogen-progestin therapy for prema ture ovarian failure had abnormal bone density (136.3 +/- 17.3 mg/cm3 vs 166.0 +/- 17.5 mg/cm3 for control subjects; p = 0.002); patients wi th evidence of ovarian insufficiency not receiving replacement sex ste roids had even lower bone density (92.4 +/- 14.3 Mg/CM3 VS 160.2 +/- 2 0.2 mg/cm3 for control subjects; p < 0.001). Calcium intake for the en tire galactosemia group was 540 +/- 344 mg/day. Calcium intake correla ted positively with bone density in women given exogenous estrogen (r = 0.87; p = 0.002) and in men (r = 0.74; p = 0.009). Thus the diminish ed mineralization of bones appears to be another abnormality associate d with galactosemia. The results of our study suggest that this is lik ely secondary to abnormal levels of sex steroids in female patients, l ow calcium intake, and perhaps an intrinsic defect in the normal galac tosylation of the collagen matrix of bone caused by the enzyme defect. Strategies to improve bone formation should be considered to diminish morbidity in patients with this inborn error of metabolism.