General Information

Fosamax (alendronate sodium) is a bisphosphonate.

Fosamax is specifically indicated for the following:

• Treatment and prevention of osteoporosis in postmenopausal women
• Treatment to increase bone mass in men with osteoporosis
• Treatment of glucocorticoid-induced osteoporosis
• Treatment of Paget's disease of bone

Fosamax is supplied as tablets and an oral solution. The recommended dosing is as follows:

Treatment of osteoporosis in postmenopausal women and in men:

• 10 mg daily or 70 mg (tablet or oral solution) once weekly.

Prevention of osteoporosis in postmenopausal women:

• 5 mg daily or 35 mg once weekly.

Glucocorticoid-induced osteoporosis:

• 5 mg daily; or 10 mg daily in postmenopausal women not receiving estrogen.

Paget's disease:

• 40 mg daily for six months.

Instruct patients to: 

• Swallow tablets whole with 6-8 ounces plain water at least 30 minutes before the first food, drink, or medication of the day.
• Swallow oral solution followed by at least 2 ounces of water.
• Not lie down for at least 30 minutes after taking Fosamax and until after food.

Mechanism of Action

Animal studies have indicated the following mode of action. At the cellular level, alendronate shows preferential localization to sites of bone resorption, specifically under osteoclasts. The osteoclasts adhere normally to the bone surface but lack the ruffled border that is indicative of active resorption. Alendronate does not interfere with osteoclast recruitment or attachment, but it does inhibit osteoclast activity. in mice on the localization of radioactive [ 3H]alendronate in bone showed about 10-fold higher uptake on osteoclast surfaces than on osteoblast surfaces. Bones examined 6 and 49 days after [ 3H]alendronate administration in rats and mice, respectively, showed that normal bone was formed on top of the alendronate, which was incorporated inside the matrix. While incorporated in bone matrix, alendronate is not pharmacologically active. Thus, alendronate must be continuously administered to suppress osteoclasts on newly formed resorption surfaces. Histomorphometry in baboons and rats showed that alendronate treatment reduces bone turnover (i.e., the number of sites at which bone is remodeled). In addition, bone formation exceeds bone resorption at these remodeling sites, leading to progressive gains in bone mass.

Side Effects

Adverse effects associated with the use of Fosamax may include, but are not limited to, the following:

• abdominal pain
• acid regurgitation
• constipation
• diarrhea
• dyspepsia
• musculoskeletal pain
• nausea

Clinical Trial Results

Osteoporosis Treatment

The FDA clearance of Fosamax to treat osteoporosis is based on efficacy data from five clinical trials involving 1,827 postmenopausal women with osteoporosis in 16 countries who were followed for at least two years.

In clinical trials, Fosamax significantly increased bone mineral density (closely related to bone strength) at the spine (8.2%), hip (7.2%), and other sites. While the studies were not designed to detect fracture risk, further analysis supports that Fosamax reduced the number of women with new spinal fractures by nearly half (48%), reduced the total number of new spinal fractures by 63%, and reduced overall height loss by 35%. Women treated with Fosamax lost an average of 3 mm in height, compared with women on placebo who lost an average of 4.6 mm in height.

Osteoporosis Prevention in Postmenopausal Women

Prevention of bone loss was demonstrated in two double-blind, placebo-controlled studies of postmenopausal women 40-60 years of age. One thousand six hundred nine patients (Fosamax 5 mg/day; n=498) who were at least six months postmenopausal were entered into a two-year study without regard to their baseline BMD. In the other study, 447 patients (Fosamax 5 mg/day; n=88), who were between six months and three years post-menopause, were treated for up to three years. In the placebo-treated patients BMD losses of approximately 1% per year were seen at the spine, hip (femoral neck and trochanter) and total body. In contrast, Fosamax 5 mg/day prevented bone loss in the majority of patients and induced significant increases in mean bone mass at each of these sites. In addition, Fosamax 5 mg/day reduced the rate of bone loss at the forearm by approximately half relative to placebo. Fosamax 5 mg/day was similarly effective in this population regardless of age, time since menopause, race and baseline rate of bone turnover.

Treatment to Increase Bone Mass in Men with Osteoporosis

he efficacy of Fosamax in men with hypogonadal or idiopathic osteoporosis was demonstrated in two clinical studies.

Daily Dosing

A two-year, double-blind, placebo-controlled, multicenter study of Fosamax 10 mg once daily enrolled a total of 241 men between the ages of 31 and 87 (mean, 63). All patients in the trial had either a BMD T-score less than or equal to -2 at the femoral neck and less than or equal to -1 at the lumbar spine, or a baseline osteoporotic fracture and a BMD T-score less than or equal to -1 at the femoral neck. At two years, the mean increases relative to placebo in BMD in men receiving Fosamax 10 mg/day were significant at the following sites: lumbar spine, 5.3%; femoral neck, 2.6%; trochanter, 3.1%; and total body, 1.6%. Treatment with Fosamax also reduced height loss (Fosamax, -0.6 mm vs. placebo, -2.4 mm).

Weekly Dosing

A one-year, double-blind, placebo-controlled, multicenter study of once weekly Fosamax 70 mg enrolled a total of 167 men between the ages of 38 and 91 (mean, 66). Patients in the study had either a BMD T-score less than or equal to -2 at the femoral neck and less than or equal to -1 at the lumbar spine, or a BMD T-score less than or equal to -2 at the lumbar spine and less than or equal to -1 at the femoral neck, or a baseline osteoporotic fracture and a BMD T-score less than or equal to -1 at the femoral neck. At one year, the mean increases relative to placebo in BMD in men receiving Fosamax 70 mg once weekly were significant at the following sites: lumbar spine, 2.8%; femoral neck, 1.9%; trochanter, 2.0%; and total body, 1.2%. These increases in BMD were similar to those seen at one year in the 10 mg once daily study. In both studies, BMD responses were similar regardless of age (greater than or equal to 65 years vs. less than 65 years), gonadal function (baseline testosterone less than 9 ng/dL vs. greater than or equal to 9 ng/dL), or baseline BMD (femoral neck and lumbar spine T-score less than or equal to -2.5 vs. greater than -2.5).

Treatment of Glucocorticoid-Induced Osteoporosis

The efficacy of Fosamax 5 and 10 mg once daily in men and women receiving glucocorticoids (at least 7.5 mg/day of prednisone or equivalent) was demonstrated in two, one-year, double-blind, randomized, placebo-controlled, multicenter studies of virtually identical design, one performed in the 21 United States and the other in 15 different countries (Multinational [which also included Fosamax 2.5 mg/day]). These studies enrolled 232 and 328 patients, respectively, between the ages of 17 and 83 with a variety of glucocorticoid-requiring diseases. Patients received supplemental calcium and vitamin D. After one year, significant increases relative to placebo in BMD were seen in the combined studies at each of these sites in patients who received Fosamax 5 mg/day. In the placebo-treated patients, a significant decrease in BMD occurred at the femoral neck (-1.2%), and smaller decreases were seen at the lumbar spine and trochanter. Total body BMD was maintained with Fosamax 5 mg/day. The increases in BMD with Fosamax 10 mg/day were similar to those with Fosamax 5 mg/day in all patients except for postmenopausal women not receiving estrogen therapy. In these women, the increases (relative to placebo) with Fosamax 10 mg/day were greater than those with Fosamax 5 mg/day at the lumbar spine (4.1% vs. 1.6%) and trochanter (2.8% vs. 1.7%), but not at other sites. Of the original 560 patients in these studies, 208 patients who remained on at least 7.5 mg/day of prednisone or equivalent continued into a one-year double-blind extension. After two years of treatment, spine BMD increased by 3.7% and 5.0% relative to placebo with Fosamax 5 and 10 mg/day, respectively. Significant increases in BMD (relative to placebo) were also observed at the femoral neck, trochanter, and total body. After one year, 2.3% of patients treated with Fosamax 5 or 10 mg/day (pooled) vs. 3.7% of those treated with placebo experienced a new vertebral fracture (not significant). However, in the population studied for two years, treatment with Fosamax (pooled dosage groups: 5 or 10 mg for two years or 2.5 mg for one year followed by 10 mg for one year) significantly reduced the incidence of patients with a new vertebral fracture (Fosamax 0.7% vs. placebo 6.8%).

Treatment of Paget's Disease of Bone

The efficacy of Fosamax 40 mg once daily for six months was demonstrated in two double-blind clinical studies of male and female patients with moderate to severe Paget’s disease (alkaline phosphatase at least twice the upper limit of normal): a placebo-controlled, multinational study and a U.S. comparative study with etidronate disodium 400 mg/day. At six months the suppression in alkaline phosphatase in patients treated with Fosamax was significantly greater than that achieved with etidronate and contrasted with the complete lack of response in placebo-treated patients. Response (defined as either normalization of serum alkaline phosphatase or decrease from baseline greater than or equal to 60%) occurred in approximately 85% of patients treated with Fosamax in the combined studies vs. 30% in the etidronate group and 0% in the placebo group. Fosamax was similarly effective regardless of age, gender, race, prior use of other bisphosphonates, or baseline alkaline phosphatase within the range studied (at least twice the upper limit of normal). Bone histology was evaluated in 33 patients with Paget’s disease treated with Fosamax 40 mg/day for 6 months. As in patients treated for osteoporosis, Fosamax did not impair mineralization, and the expected decrease in the rate of bone turnover was observed. Normal lamellar bone was produced during treatment with Fosamax, even where preexisting bone was woven and disorganized. Overall, bone histology data support the conclusion that bone formed during treatment with Fosamax is of normal quality.