Histomorphometric assessment of the long-term effects of alendronate on bone quality and remodeling in patients with osteoporosis.

Treatment effects on bone quality and remodeling was assessed in postmenopausal women with osteoporosis treated with oral alendronate. One transiliac bone biopsy was obtained from 231 women at either 24 mo (n = 11) or 36 mo (n = 120) from the start of treatment with alendronate at doses of between 5 and 20 mg/d, or placebo. 64 biopsies at 24 mo (31 from the placebo group and 33 alendronate-treated patients) and 95 biopsies at 36 mo (40 from the placebo group and 55 alendronate-treated patients) provided adequate cancellous tissue, and were analyzed by histomorphometry. Mineral apposition rate was unaffected by treatment. At 24 and 36 mo, osteoid thickness, volume, and surface significantly decreased. At each of the doses studied, mineralizing surface and activation frequency significantly decreased at each time point (e.g., -92% and -87%, respectively, for the 10 mg daily dose after 2 yr). These diminutions were of the same magnitude for each dose at 24 mo, and for the two highest doses at 36 mo. A significant increase in wall thickness accompanied by a reduction in erosion depth was detected in biopsies obtained at 24 mo. These findings confirm that mineralization is normal, and trabecular bone turnover markedly decreased in patients receiving long-term dosing with alendronate. The findings also suggest that the observed increases in bone mineral density could result both from a reduction in the remodeling space due to a decreased activation frequency and a possible trend to a positive bone balance. In addition, further studies focused on a possible increase in the degree of mineralization of bone are required.

Comparative study of alendronate versus etidronate for the treatment of Paget's disease of bone.

Alendronate, an aminobisphosphonate, is much more potent than etidronate, an older bisphosphonate, in inhibiting osteoclast-mediated bone resorption, and unlike etidronate, therapeutic doses of alendronate are not associated with abnormal mineralization. In the present study, we compared the effectiveness, safety, and tolerability of 6 months of daily oral administration of alendronate (40 mg) with those of etidronate (400 mg) in 89 patients with clinically active Paget's disease. The primary efficacy end point was the percent change in serum alkaline phosphatase. Other end points included changes in urinary deoxypyridinoline excretion, pain, functional impairment scores, and radiological osteolysis. Tetracycline-labeled bone biopsies were obtained for histomorphometric analysis from a subset of 43 patients at the 6-month visit. The alendronate-treated group had significantly greater decreases in both serum alkaline phosphatase (79% vs. 44%) and urinary deoxypyridinoline (75% vs. 51%) than the etidronate-treated group (P < 0.001 in both cases). Normalization of serum alkaline phosphatase was much more frequent in alendronate-treated patients (63.4% vs. 17.0%; P < 0.001). Alendronate was well tolerated and had a safety profile similar to that of etidronate. Histomorphometry revealed decreased bone turnover and no qualitative abnormalities, including no direct negative effects on bone mineralization, with alendronate treatment. One patient receiving etidronate developed frank osteomalacia. Alendronate appears to be a highly effective treatment for Paget's disease of bone that offers an important therapeutic advance over etidronate.

[Trans-scleral cyclo-photocoagulation. Results over 6 months]. / Cyclophotocoagulation transsclérale de contact. Résultats à 6 mois.

Transscleral contact cyclophotocoagulation with ND YAG Laser continuous mode permits the induction of a focused ciliary process with a secretory surface decrease. This treatment has been used for the treatment of refractory glaucoma since 1987. We report the treatment by transscleral cyclophotocoagulation of 49 patients with terminal glaucoma. All 49 patients had a measurable visual acuity and an elevated intraocular pressure under maximal medical treatment. None could be operated by trabeculectomy. The origin of the glaucoma was neovascular (26 patients), open angle glaucoma (9 patients) secondary glaucoma (14 patients). 62.2% of the patients had an intraocular pressure < or = 25 mm after 6 months; 8% showed decrease visual acuity. We describe the complications of the treatment and compare the efficacy of treatment depending on the origin of the glaucoma: neovascular or not.