Aims: Several studies show a deficit in cortical bone in adults with Klinefelter syndrome (KS). A correlation between the adult cortical bone deficit and impaired bone accumulation during childhood or adolescence remains unclear. Therefore, we evaluated the cortical bone by automated digital X-ray radiogrammetry in KS children and adolescents and evaluated potential associations with hormonal, radiographic, and anthropometric factors implicated in bone mineral accumulation in childhood and adolescence.
Methods: Automated bone age readings at the left hand and wrist by the BoneXpert method, performed between 2011 and 2021, together with anthropometric measurements were retrieved from 50 KS adolescents (aged between 3.6 and 19 years), none of them treated with testosterone substitution. Bone health index (BHI) by the BoneXpert method and digit 2 and digit 4 lengths by an inbuild measurement program were calculated from the left-hand X-ray. Results of lumbar spine bone mineral density (LS BMD) and routine hormonal measurements of LH, FSH testosterone, estradiol, 25 OH vitamin D and PTH were available in respectively 30/50 and 22/50 patients.
Results: Mean (SD) chronological age (CA) was 12.0 (3.79) and 52% were prepubertal. Mean (SD) height Z-score was 0.68 (1.20). Bone ages (BA) ranged between 3.3 and 19.0 years, showing a median advancement of + 1.2 years. While mean (SD) bone age Z-score (0.07 (1.14)) was not significantly advanced, mean BHI Z-score (-0.56 (0.99)) was significantly decreased (P< 0001). Five patients (10%) had a BHI Z-score below -2. Mean (SD) LS BMD was 0.84 (0.19). All 30 studied patients had a normal BMD Z-score. Of the 14 patients having a Tanner G2 or more, 11 presented with an elevated FSH value, whereas only 4 showed a decreased testosterone value. Twelve (52%) of the 23 investigated patients had a serum 25-OH vitamin D level below 20µg/l. KS males with a BHI Z-score below 1 (n=13) were significantly older (mean age 14.69 vs 11.07) and had significantly lower mean serum 25 OH vitamin D concentrations (11.70 vs 26.19 µg/l) in comparison with those of normal BHI scores (P<0.001). BHI Z-score did not correlate significantly with serum LH, FSH, testosterone, estradiol, and the Z-scores of bone age, LS BMD and D2/D4. In six patients BHI and LS BMD Z-scores differed with >2 SDS.
Conclusion: Cortical bone accumulation at the appendicular skeleton assessed by DXR is only slightly reduced in KS children and teenagers. Older age and lower circulating 25-OH vitamin D were clinical at-risk conditions for a lower BHI. BHI Z-scores, which were unrelated to the D2/D4 ratios and the LS BMD Z-scores, cannot be used in clinical practice to predict the LS BMD Z-score.