Oral alendronate induces progressive increases in bone mass of the spine, hip, and total body over 3 years in postmenopausal women with osteoporosis.

To determine the effects of long-term daily oral alendronate sodium (ALN) on bone mass in postmenopausal women with osteoporosis, 19 centers enrolled 516 postmenopausal women aged 45-80 years with spine bone mineral density (BMD) at least 2.5 SD below the mean for young premenopausal women in a 3-year, double-blind, placebo-controlled study. Subjects were randomly allocated to one of four treatment groups: placebo; alendronate, 5 or 10 mg/day for 3 years; or alendronate, 20 mg/day for 2 years followed by 5 mg/day for the 3rd year. All patients received 500 mg/day of supplemental calcium to ensure adequate calcium intake. BMD was measured by dual-energy X-ray absorptiometry at several skeletal sites. Nonsignificant mean decreases in BMD of the spine, femoral neck, and trochanter of 0.6, 0.7, and 0.4%, respectively, occurred in the placebo group at 3 years. Relative to placebo-treated patients, spine BMD increased by 5.4%, 7.4%, and 8.4% in the 5, 10, and 20/5 mg ALN groups, respectively. Increases at the femoral neck were 3.5%, 5.5%, and 4.3%, and those at the trochanter were 5.1%, 7.2%, and 7.2%, respectively. Thus, efficacy of 10 and 20/5 mg ALN was similar, whereas the 5 mg dose was less effective. BMD continued to increase over the entire 3-year study duration in the ALN-treated groups and, compared with the other dosage groups, 10 mg ALN produced the largest gains in BMD during the 3rd year. Changes in biochemical markers of bone turnover and mineral homeostasis confirmed the effect of ALN to decrease bone turnover to a new steady-state level. The safety and tolerability of ALN were comparable with those of placebo. In summary, 10 mg daily oral ALN given for 3 years significantly and progressively increases bone mass and is a generally well-tolerated treatment for osteoporosis in postmenopausal women.

Interleukin-6 in synovial fluid and serum of patients with rheumatoid arthritis and other inflammatory arthritides.

Interleukin-6 (IL-6), also called 26-kd protein, hybridoma plasmacytoma growth factor, beta 2-interferon, or B cell stimulatory factor 2, is a recently described human cytokine with multiple growth and differentiation activities. Using a very sensitive bioassay based on the growth factor activity of this protein for B cell hybridomas, we found that IL-6 activity was significantly elevated in synovial fluid from patients with rheumatoid arthritis (RA) or other inflammatory arthritides, as compared with that in a group of patients with osteoarthritis. Moreover, IL-6 was detected in about one-third of the serum samples from patients with RA. In the latter group, we found a significant correlation between serum IL-6 activity and serum levels of C-reactive protein, alpha 1-acid glycoprotein, alpha 1-antitrypsin, fibrinogen, and haptoglobin, which indicates that IL-6 is related to disease activity in patients with RA.

Hypertrophic osteoarthropathy related to end stage cholestatic cirrhosis: reversal after liver transplantation.

A case is reported of hypertrophic osteoarthropathy with recovery after a liver graft in a young man with end stage cholestatic cirrhosis related to non-Wilsonian copper overload. To our knowledge this is the first case in the literature illustrating the curative role of liver grafting on hypertrophic osteoarthropathy associated with chronic cholestatic liver disease.

Articular chondrocalcinosis in seropositive rheumatoid arthritis. Comparison with a control group.

The prevalence of articular chondrocalcinosis was studied in a group of 100 patients with seropositive rheumatoid arthritis (RA). Articular chondrocalcinosis was observed less frequently (3%) than in a control group (19%) of 221 age and sex matched patients with low back pain or extraarticular rheumatism. This difference is statistically significant (p less than 0.001). Articular chondrocalcinosis occurred in the older patients with RA, and was observed in those with the shortest duration of the disease.

The effect of low dosage glucocorticoids on bone mass in rheumatoid arthritis: a cross-sectional and a longitudinal study using single photon absorptiometry.

The cross-sectional study of patients with RA receiving LDGC, compared with those on NSAID alone (or patients with AS) showed that LDGC significantly affects bone mass at midshaft and even more so at the distal radius. The loss of bone seems to be brisk but continuous on the long run, at least at the distal scanning site, and thus increases the C/T ratio, especially in aged men. The loss of bone mass in the LDGC group correlates with the duration of the disease as well as with carpal destruction (especially at mid shaft radius), with both parameters being correlated with one another. At equal carpal destruction, LDGC still affects bone mass. Whether receiving NSAID alone or LDGC in addition, patients with RA, as compared with controls, are more liable to lose bone when they grow older. In a longitudinal study, premenopausal women were unaffected by the administration of LDGC at both scanning sites. In contrast, postmenopausal women receiving LDGC lost at least twice as much bone as did normal women after the menopause. Men of all ages on LDGC lost bone at a rate equal to that of normal women after the menopause. Men with RA or with AS on NSAID alone did not significantly lose bone. It is concluded that LDGC may be given to premenopausal women without harm to their bone mass. After the menopause, hormonal replacement therapy, if not contra-indicated, should be given in association with LDGC. Men fortunately have a higher peak bone mass and therefore can afford to lose bone during a decade before they attain the same situation as women at the time of their menopause. If treatment is then continued for another two decades, their bone mass might behave as does that of postmenopausal women if bone loss is continuous over such long periods of time. This latter assumption has yet to be verified.

Dissociation of parathyroid hormone bioactivity and immunoreactivity in pseudohypoparathyroidism type I.

Circulating levels of parathyroid hormone (PTH) in six patients with pseudohypoparathyroidism type I (PSPI) have been measured by two immunoassays and by cytochemical bioassay and compared with measurements in normal subjects and patients with clinically defined hyper- and hypoparathyroidism. In all PSPI patients, the levels of immunoreactive PTH were in the hyperparathyroid range, whereas the bioactive levels were either in the normal or close to the normal range. In one patient from whom the dihydrotachysterol therapy was withdrawn, both immunoreactive and bioactive PTH concentrations increased. The finding that the PTH measured by RIA in these PSPI patients may have reduced biological activity may explain some of the clinical findings of hypoparathyroidism in this syndrome.