Increments in bone mineral density of the lumbar spine and hip and suppression of bone turnover are maintained after discontinuation of alendronate in postmenopausal women.

PURPOSE: Previously we have reported a significant increase in bone mineral density (BMD) of the spine and the hip and reductions in biochemical indices of bone turnover in postmenopausal women with osteoporosis treated with alendronate at various doses over 1 to 2 years. We have followed BMD and biochemical parameters in these patients for 1 or 2 years after discontinuation of alendronate to determine resolution of alendronate effects. PATIENTS AND METHODS: Participants received daily oral doses of placebo, 5 or 10 mg of alendronate for 2 years, or 20 or 40 mg of alendronate for 1 year followed by 1 year of placebo. No treatment was given in the third year of study. RESULTS: Lumbar spine BMD changes in the 5- and 10-mg groups (-1.4 and -0.4%) were similar to those in the placebo group (-1.2%) 1 year after discontinuation of drug and lumbar spine BMD changes in the 20- and 40-mg groups (-1.2% and 0.8%) were similar to those in the placebo group (-0.9%) 2 years after discontinuation of drug. BMD of the total hip followed the same pattern of resolution. The difference in BMD between alendronate and placebo groups at the end of alendronate treatment was maintained up to 2 years. Residual reductions in the bone resorption markers urinary deoxypyridinoline (D-Pyr) and collagen type 1 cross-linked N telopeptides and the bone formation markers serum bone-specific alkaline phosphatase and osteocalcin remained for 1 year after discontinuation of 5 and 10 mg of alendronate and for 2 years after discontinuation of 20 and 40 mg of alendronate, other than return of D-Pyr to baseline 1 year after cessation of treatment with the 5- and 10-mg doses. CONCLUSIONS: A residual decrease in bone turnover may be found up to 2 years after discontinuation of alendronate. Accelerated bone loss is not observed when treatment is discontinued. However, continuous therapy with alendronate is required to achieve a continuous gain in BMD.

Esophagitis associated with the use of alendronate.

BACKGROUND: Alendronate, an aminobisphosphonate and a selective inhibitor of osteoclast-mediated bone resorption, is used to treat osteoporosis in postmenopausal women and Paget's disease of bone. Aminobiphosphonates can irritate the upper gastrointestinal mucosa. METHODS: We describe three patients who had severe esophagitis shortly after starting to take alendronate and also analyze adverse esophageal effects reported to Merck, the manufacturer, through postmarketing surveillance. RESULTS: As of March 5, 1996, alendronate had been prescribed for an estimated 475,000 patients worldwide, and 1213 reports of adverse effects had been received. A total of 199 patients had adverse effects related to the esophagus; in 51 of these patients (26 percent), including the 3 we describe in case reports, adverse effects were categorized as serious or severe. Thirty-two patients (16 percent) were hospitalized, and two were temporarily disabled. Endoscopic findings generally indicated chemical esophagitis, with erosions or ulcerations and exudative inflammation accompanied by thickening of the esophageal wall. Bleeding was rare, and stomach or duodenal involvement unusual. In patients for whom adequate information was available, esophagitis seemed to be associated with swallowing alendronate with little or no water, lying down during or after ingestion of the tablet, lying down during or after ingestion of the tablet, continuing to take alendronate after the onset of symptoms, and having preexisting esophageal disorders. CONCLUSIONS: Alendronate can cause chemical esophagitis, including severe ulcerations, in some patients. Recommendations to reduce the risk of esophagitis include swallowing alendronate with 180 to 240 ml (6 to 8 oz) of water on arising in the morning, remaining upright for at least 30 minutes after swallowing the tablet and until the first food of the day has been ingested, and discontinuing the drug promptly if esophageal symptoms develop.

An overview of the results of clinical trials with alendronate, a promising treatment of osteoporosis in postmenopausal women.

The purpose of this overview is to provide a summary of recent data on the clinical safety and efficacy of alendronate sodium, an amino-bisphosphonate that is a potent and specific inhibitor of osteoclast mediated bone resorption, in the treatment of osteoporosis in postmenopausal women. Published data are available from two randomized, placebo-controlled, double-blind clinical trials of 2-year duration in over 470 patients with postmenopausal osteoporosis. The women studied were 4 to 5 years postmenopause, ages 42 to 76, with osteoporosis defined on the basis of low spine bone mineral density (BMD). Percent change in spine BMD was the primary endpoint; hip and total body BMD were secondary outcomes. In the Dose Ranging Study, alendronate 5 and 10 mg/day for 2 years significantly increased lumbar spine BMD by approximately 7.2%, which did not differ from patients receiving higher doses. Total hip BMD increased by 3.6 and 5.3%, respectively, with the 5 and 10 mg doses; 10 mg was significantly more effective than 5 mg. Placebo patients lost 1.2-1.4% BMD at these sites. Total body BMD also significantly increased with alendronate. In the Calcitonin Comparison Study, alendronate 10 and 20 mg/day for 2 years significantly increased spine and hip BMD; 100 IU of intranasal salmon calcitonin did not increase BMD at any site, and did not differ from placebo. Alendronate reduced bone turnover to a new steady state, as assessed by biochemical markers and was well tolerated. Preliminary reports indicate that alendronate progressively increases spine, hip, and total body bone mass for 3 years, with associated significant reductions in vertebral fractures, stature loss, and non-vertebral fractures.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of a rapid (2-h) versus a slow (24-h) infusion of alendronate in the treatment of hypercalcemia of malignancy.

Alendronate (aminohydroxybutylidene bisphosphonate) is a potent inhibitor of bone resorption but the role of the duration of intravenous infusion in its efficacy profile is unclear. In a two-centre, parallel, randomized, double-blind study, 20 patients with tumoral hypercalcemia received a single 10-mg i.v. infusion over either 2 h (group A, n = 10) or 24 h (group B, n = 10). Recurrences (n = 6) were retreated using the same regimen. Pretreatment plasma calcium (Ca) was 3.32 +/- 0.08 mM (mean +/- SEM) for all patients. Treatment A and B were associated with similar temporal profiles for onset, time to reach normocalcemia, (6 vs 5 days), nadir (day 6: 2.45 +/- 0.06 vs 2.43 +/- 0.08 mM) and time to relapse (day 21). Normocalcemia (2.15-2.55 mM) was achieved in seven (A) and nine (B) patients with other cases being partial responders (Ca: 2.65-2.76 mM). A significant decrease of urinary calcium and hydroxyproline excretion and a significant increase of PTH accompanied Ca normalization in both groups. Ca response was 50% lower on 2nd treatment with alendronate. Both treatments were well tolerated with transient mild fever being the most common adverse experience. In conclusion, whether infused over 2 or over 24 h, a single dose of 10 mg alendronate led to normalization of tumoral hypercalcemia in a large majority of cases.