We have performed a 2-year prospective double-masked study to determine whether the bisphosphonate pamidronate can prevent bone loss in postmenopausal women and its optimal dosage regimen. One hundred and twenty-one such women (mean +/- SD age 57.6 +/- 3.4 years; mean +/- SD time since menopause 7.5 +/- 3.5 years) were randomized to receive either oral pamidronate (300 mg/day) for 4 weeks every 4 months (group A), oral pamidronate (150 mg/day) for 4 weeks every 2 months (group B) or identical placebo capsules (group C). Bone mineral density (BMD) measurements at the lumbar spine and proximal femur were performed at baseline and at 6-month intervals for 2 years using dual-energy X-ray absorptiometry. BMD at the lumbar spine (L2-4) increased significantly in groups A and B after 2 years of treatment (mean +/- SD 2.8 +/- 2.1% and 3.0 +/- 2.9% respectively, both p < 0.001) but decreased in the placebo group (-1.6 +/- 3.1%, p < 0.01). Identical results were seen for BMD at the femoral neck, which increased significantly in groups A and B after 2 years of treatment (1.2 +/- 2.3% and 1.3 +/- 2.9% respectively, both p < 0.05) but decreased in the placebo group (-1.9 +/- 3.9%, p < 0.05). There were significant differences over 2 years between the groups at all anatomical sites (lumbar spine, femoral neck and trochanteric region, all p < 0.001; Ward's triangle, p < 0.01). However, there were no significant differences between groups A and B, suggesting that the two treatment regimens were equally effective in conserving BMD. There were, however, marked differences in tolerability between the two treatment regimens: 13 women (34%) in group A withdrew from the study because of side-effects, but only 5 women (12%) in group B, which was comparable with placebo. These data demonstrate that intermittent oral pamidronate will prevent bone loss from the lumbar spine and proximal femur of postmenopausal women, and that the more frequent but lower dose regimen is well tolerated.
[Show abstract][Hide abstract] ABSTRACT: Bisphosphonates have emerged as a valuable treatment for postmenopausal osteoporosis. Bisphosphonate treatment is usually accompanied by a 3-6% gain in bone mineral density (BMD) during the first year of treatment and by a decrease in bone turnover. Despite low bone turnover, BMD continues to increase slowly beyond the first year of treatment. There is evidence that bisphosphonates not only increase bone volume but also enhance secondary mineralization. The present study was conducted to address this issue and to compare the effects of continuous and intermittent bisphosphonate therapy on static and dynamic parameters of bone structure, formation, and resorption and on mineral properties of bone. Sixty dogs were ovariohysterectomized (OHX) and 10 animals were sham-operated (Sham). Four months after surgery, OHX dogs were divided in six groups (n = 10 each). They received for 1 year ibandronate daily (5 out of 7 days) at a dose of 0, 0.8, 1.2, 4.1, and 14 microg/kg/day or intermittently (65 microg/kg/day, 2 weeks on, 11 weeks off). Sham dogs received vehicle daily. At month 4, there was a significant decrease in bone volume in OHX animals (p < 0.05). Doses of ibandronate >/= 4.1 microg/kg/day stopped or completely reversed bone loss. Bone turnover (activation frequency) was significantly depressed in OHX dogs given ibandronate at the dose of 14 microg/kg/day. This was accompanied by significantly higher crystal size, a higher mineral-to-matrix ratio, and a more uniformly mineralized bone matrix than in control dogs. This finding lends support to the hypothesis that an increase in secondary mineralization plays a role in gain in BMD associated with bisphosphonate treatment. Moreover, intermittent and continuous therapies had a similar effect on bone volume. However, intermittent therapy was more sparing on bone turnover and bone mineral properties. Intermittent therapy could therefore represent an attractive alternative approach to continuous therapy.
Journal of Bone and Mineral Research 11/1999; 14(10):1768-78. DOI:10.1359/jbmr.19188.8.131.528 · 6.83 Impact Factor
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