Klinefelter's syndrome and bone mineral density: is osteoporosis a constant feature?

OBJECTIVES: Data on bone mineral density (BMD) in Klinefelter syndrome (KS) are scarce and contradictory. The aim of the present study was to investigate BMD in patients with KS and in healthy controls with special attention to gonadal status. MATERIAL AND METHODS: We investigated 26 patients with KS (30±9 yr) who had never been treated with testosterone. Thirty-nine age-matched healthy males served as controls. We assessed BMD by performing dual energy X-ray absorptiometry and measured serum hormone levels, including total testosterone (T), free testosterone, estradiol (E2), leptin. The estrogen to androgen ratio (E2/T) was used as an indirect measure for aromatase activity. RESULTS: No difference was found in BMD at femoral neck (1.06 ± 0.16 vs 1.04 ± 0.14 g/cm²), or at lumbar spine (1.00 ± 0.09 vs 1.03 ± 0.11) between patients and controls. Two patients and one control were classified as osteoporotic (T-score ≤ -2.5). Compared with controls, patients had lower levels of T and free testosterone, similar E2 levels, and increased E2/T (P < 0.05). In KS patients, leptin was significantly higher and correlated positively with E2/T (r = 0.484, P = 0.02). E2/T correlated with femoral neck BMD (r = 0.566, p = 0.02), T and free T correlated with lumbar spine BMD (r = 0.433, P = 0.05 and r = 0.534, P = 0.05). CONCLUSION: Osteoporosis is not a constant feature in young patients with KS, even without testosterone substitution. The aromatisation of T into E2, related to adiposity, may contribute to the achievement and maintenance of normal BMD in some KS patients.

Treatment of rheumatoid arthritis with methotrexate: a prospective open longterm study of 191 cases.

One hundred and ninety-one patients with severe rheumatoid arthritis (RA) were included in a prospective open longterm study of the safety, efficacy and maintenance of methotrexate (MTX) treatment. The mean duration of MTX treatment was 19 +/- 13.2 (3-58) months; the mean weekly dose of MTX was 10.2 +/- 0.2 mg. Analysis of the 191 patients in an intent-to-treat manner showed a significant improvement of all the clinical variables and a decrease of erythrocyte sedimentation rate with a steroid sparing effect. The probability of continuing MTX therapy for up to 2 years was 65% and for up to 5 years was 46%. Adverse effects of MTX occurred in 37.1% of the patients, but only 15.7% discontinued MTX permanently.

Clinical significance of anti-RNP and anti-Sm autoantibodies as determined by immunoblotting and immunoprecipitation in sera from patients with connective tissue diseases.

Antibodies to Sm and RNP antigens have been detected by immunoblotting and immunoprecipitation of small nuclear ribonucleoproteins in 168 sera from patients with connective tissue diseases previously characterized by immunodiffusion. Anti-RNP and anti-Sm antibodies immunoprecipitated U1 and U1-U6 snRNA respectively. By immunoblotting anti-Sm reacted with B-B' and D polypeptides and we have distinguished two types of anti-RNP sera: 1) 'full spectrum' anti-RNP sera reacted with the 68 kD, A, C and B-B' polypeptides; 2) 'partially reactive' anti-RNP sera reacted with various combinations of these polypeptides but not the four of them. A strong specificity of anti-Sm antibodies for systemic lupus erythematosus (SLE) was found with all three methods but immunoblotting was more sensitive and detected anti-Sm in 76% of SLE sera. Sera containing a high titer of 'full spectrum' anti-RNP without anti-Sm activity were only detected in mixed connective tissue disease (MCTD) whereas anti-68 kD antibodies alone seemed to be less specific. This strong association between 'full spectrum' anti-RNP antibodies and MCTD supports the hypothesis that MCTD is a distinct clinical entity associated with a specific serologic marker.