Bone Mineral Density and Quantitative Ultrasound Parameters in Patients with Klinefelter's Syndrome after Long-Term Testosterone Substitution

Abstract

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 in these patients after long-term testosterone replacement therapy. We examined in a cross-sectional study 52 chromatin-positive KS patients aged 39.1 +/- 12.4 years (mean +/- SD). Patients had been treated with oral or parenteral androgens for 9.2 +/- 8.2 years (range 1-32 years). Areal BMD and bone mineral apparent density (BMAD, i.e., estimated volumetric BMD) at the lumbar spine, total hip and femoral neck were determined by dual-energy X-ray absorptiometry. BMD T-scores in the patient group were calculated based on three different North American reference databases. The QUS parameters broadband ultrasound attenuation (BUA) and speed of sound (SOS) were measured at the calcaneus using an ultrasound imaging device (UBIS 3000) and were compared with QUS results in a sex-, age- and height-matched control group. QUS T-scores were 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 patient group were compared. Overall, based on the three reference databases, 46% and 63% of the KS patients had a T-score between -1 and -2.5 and a further 10% and 14% had a T-score < or = -2.5 at the total hip and/or lumbar spine, as measured by areal BMD or BMAD, respectively. Thirty-nine percent of the KS patients had a T-score between -2.5 and -1, while 2% had a T-score < or = -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 +/- 42.5 m/s, p < 0.05). Correlation coefficients 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 BMAD T-score < or = -2.5 with either BUA or SOS was not statistically 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 parameters were determined no BMD measurements were performed, we conclude that despite long-term testosterone replacement therapy, a considerable percentage of patients with KS had a BMD T-score < -1 or even < or = -2.5, based on different North American reference databases. This percentage 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 used to predict BMD or BMAD in KS patients.

Quantitative ultrasound and peripheral bone densitometry in patients with genetic disorders

“…1993). In some studies involving subjects with genetic disorders performed by densitometric measurements (Kao et al 1992;Sepulveda 1995;Angelopoulou et al 1999;Angelopoulou et al 2000;van der Bergh et al 2001;Sakamidis at al. 2002;Baptista et al 2004), significant differences in comparison with controls were usually shown.…”

“…In cross-sectional studies (Lippuner et al 2000;Wüster et al 2001;Drozdzowska 2003), this method proved an ability to discriminate between healthy people and individuals with different types of low-trauma fractures. Recently, in some studies, QUS measurements were used to establish skeletal status in subjects with genetic disorders (Aspray et al 1998;van der Bergh 2001;Pluskiewicz et al 2003).…”

Low Testosterone—An Important Predictor of Low Mineral Bone Density in Young Men—Our Own Experience and a Review of Literature

“…This observation together with reports that delayed testosterone therapy in men with Klinefelter syndrome diminishes the gain in BMD may indicate that the adolescents with delayed puberty, IHH, Kallmann syndrome and Klinefelter syndrome may benefit from early assessment of BMD and early treatment of hypogonadism to achieve expected peak bone mineral density [81,82].…”

Adequacy of androgen replacement influences bone density response to testosterone in androgen-deficient men

“…The pharmacokinetic limitations of the available injectable testosterone esters dictate that stable blood testosterone concentrations in the physiological range are achieved with injections at the rate of 100 mg per week, ideally with actual 100 mg injections each week (34,44,45). In practice, however, many patients do not accept regular weekly injections and this regimen is often relaxed to 200 mg every 2 weeks, although such regimens still often encounter significant non-adherence to a regular schedule (15). Maintaining the same weekly dosing at longer (3 or more weeks) inter-injection intervals leads to increasingly extreme fluctuations in blood testosterone levels and, consequentially, in mood and behavioural swings.…”