Bone mineral density and quantitative ultrasound parameters in patients with Klinefelter's syndrome after long-term testosterone substitution

Klinefelter's syndrome (KS) is a common sex chromosomal disorder associated with androgen deficiency and osteoporosis. Only few bone mineral density ( BMD) and no quantitative ultrasound (QUS) data are available ill these pati ents after long-term testosterone replacement therapy. We examined in a cro ss-sectional study 52 chromatin-positive KS patients aged 39.1 +/- 12.4 yea rs (mean +/- SD). Patients had been treated with oral or parenteral androge ns for 9.2 +/- 8.2 years (range 1-32 years). Areal BMD and bone mineral app arent density (BMAD, i.e., estimated volumetric BMD) at the lumbar spine, t otal hip and femoral neck were determined by dual-energy X-ray absorptiomet ry. BMD T-scores in the patient group were calculated based on three differ ent North American reference databases. The QUS parameters broadband ultras ound attenuation (BUA) and speed of sound (SOS) were measured at the calcan eus using an ultrasound imaging device (UBIS 3000) and were compared with Q US results in a sex-, age- and height-matched control group. QUS T-scores w ere calculated based on the results of QUS measurements in 50 normal Dutch men between the ages of 20 and 30 years. QUS and BMD results in the KS pati ent group were compared. Overall, based on the three reference databases, 4 6% and 63% of the KS patients had a T-score between -1 and -2.5 and a furth er 10% and 14% had a T-score less than or equal to -2.5 at the total hip an d/or lumbar spine, as measured by areal BMD or BMAD, respectively. Thirty-n ine percent of the KS patients had a T-score between -2.5 and -1, while 2% had a T-score less than or equal to -2.5 for BUA and/or SOS. BUA (77.7 +/- 15.0 dB/MHz) and SOS (1518.8 +/- 36.5 m/s) were significantly lower in the KS patients than in age- and height-matched controls (87.1 +/- 17.8 dB/MHz, p<0.005, and 1536.5 <plus/minus> 42.5 m/s, p<0.05). Correlation coefficien ts between the QUS parameters and areal BMD (0.28 to 0.37) or BMAD (0.27 to 0.46) were modest. ROC analysis showed that discrimination of a BMD or BMA D T-score <less than or equal to>-2.5 with either BUA or SOS was not statis tically significant. Although a limitation of our study is that direct comparison of BMD and QUS T-scores is not possible because in the control group in which QUS paramet ers were determined no BMD measurements were performed, we conclude that de spite long-term testosterone replacement therapy, a considerable percentage of patients with KS had a BMD T-score <-1 or even <less than or equal to> -2.5, based on different North American reference databases. This percentag e was even higher for BMAD. QUS parameters were also low in the KS patient group when compared with Dutch control subjects. QUS parameters cannot be u sed to predict BMD or BMAD in KS patients.