Licensed Indication
Alendronate is indicated for the:

• ‘treatment of osteoporosis in post-menopausal women to prevent fractures.’

• ‘prevention of osteoporosis in those post-menopausal women considered at risk of developing the disease.’

• ‘treatment of glucocorticoid-induced osteoporosis and prevention of bone loss in men and women considered at risk of developing the disease.’¹

'Risk factors often associated with the development of osteoporosis include thin body build, family history of osteoporosis, early menopause, moderately low bone mass and long-term glucocorticoid therapy, especially with high doses (³ 15mg/day).'¹

Background information
Osteoporosis is a disease characterised by low bone mass and deterioration of bone microarchitecture leading to increased fragility and a consequent increase in fracture risk.²

Risk factors for osteoporosis include; a family history, smoking, the menopause (natural, premature or surgical), low body mass index, physical inactivity, long-term corticosteroid use (³ 7.5mg prednisolone for ³ 6 months), and a diet low in calcium or vitamin D.^2,3 Bone mineral density (BMD) is an important determinant of fracture risk, but other factors also contribute to the risk, eg liability to falls and types of fall.⁴

The clinical significance of osteoporosis lies in the fractures that arise. Common fractures include vertebral compression fractures and fractures of the distal radius and the proximal femur. Fractures at the spine and forearm are associated with significant morbidity, but hip fractures are associated with a significant increase in mortality, particularly in the elderly.

Current treatment options
The primary aim in treating osteoporosis is to prevent fractures. Both lifestyle modification and drug therapy are important in the prevention and treatment of osteoporosis. Advisable lifestyle measures include undertaking regular weight-bearing exercise, smoking cessation, and avoidance of excessive alcohol intake. Adequate calcium intake and adequate vitamin D status should be ensured.

Drug therapy options for osteoporosis include:

• hormone replacement therapy (HRT), or alternatives such as raloxifene or tibolone. HRT prevents further bone loss in women with osteoporosis⁴ and remains the intervention of choice in postmenopausal women.
• salmon calcitonin, as an analgesic, and to reduce bone loss and the rate of new vertebral fractures.⁴ It is licensed for short-term use only.
• bisphosphonates, eg etidronate, alendronate, risedronate, which inhibit bone resorption.

Dosage and administration
The recommended dose of alendronate for:

• treatment of osteoporosis is 10mg daily
• prevention of osteoporosis is 5mg daily
• glucocorticoid-induced osteoporosis is 5mg daily except for women not receiving HRT where 10mg daily is recommended.¹

Alendronate should be swallowed whole with a full glass of plain water, while in an upright position. Patients should not lie down for at least 30 minutes after taking the tablet to reduce the potential for oesophageal irritation.

The bioavailablility of alendronate is considerably reduced if taken with food. Alendronate should be taken at least 30 minutes before the first food, beverage or medication of the day.

Clinical Efficacy
Trials of up to 3 years duration, in over 4,000 postmenopausal women with confirmed osteoporosis have established that alendronate 10mg daily significantly (p < 0.05) increases the bone mineral density (BMD) of the spine, femoral neck, trochanter and total body compared to placebo. In active comparator studies alendronate demonstrated greater increases in BMD at the spine than salmon calcitonin 100IU daily and similar increases to HRT. Combination treatment with alendronate plus HRT demonstrated greater increases in BMD than either treatment alone.^5-10

In the Fracture Intervention Trial (n = 6459), alendronate 10mg daily, for up to 4 years, significantly reduced the incidence of vertebral fractures compared to placebo, in osteoporotic postmenopausal women, with or without a vertebral fracture at baseline (NNT 14, 59 respectively). Clinical fractures were only significantly (p = 0.004) reduced in patients who had a vertebral fracture at baseline.^11,12

Two studies (n = 447 & 1609) have evaluated the efficacy of alendronate in preventing bone loss in postmenopausal women. In both studies, up to 4 years treatment with alendronate 5mg daily significantly (p < 0.001) increased BMD at the spine, femoral neck and trochanter, compared to significant decreases in the placebo group. Further long-term data are awaited.^13-15

Combined data from two, 1 year, studies (n = 560) evaluated use of alendronate 5mg or 10mg daily in the management of glucocorticoid-induced osteoporosis in men and women receiving ³ 7.5mg prednisolone or equivalent per day. Both doses demonstrated similar efficacy and significantly (p < 0.001) increased BMD at the lumbar spine, femoral neck and trochanter compared to placebo. In a subgroup of women not receiving HRT, the higher dose was more effective.¹⁶

Adverse Effects
The clinical tolerability of alendronate in the studies to-date has been comparable to placebo. Alendronate can cause local irritation of the gastrointestinal mucosa, which can be severe, and should be used with caution in patients with upper gastrointestinal problems including severe oesophageal reactions. The potential for oesophageal irritation can be reduced by patients taking each dose with plenty of water and remaining in an upright position for at least 30 minutes after each dose. Alendronate is estimated to have a half-life of 10 years in the skeleton. The long-term side effects of alendronate are not known.

Costs
At current prices one years' treatment costs:

• £301 for alendronate 5mg or 10mg daily
• £163 for etidronate (Didronel PMO®)
• £284 for risedronate 5mg daily.

There is insufficient evidence to judge the relative cost-effectiveness of alendronate compared with HRT or other bisphosphonates.

Summary
Alendronate is a bisphosphonate that is licensed for the prevention and treatment of osteoporosis in postmenopausal women and for the prevention and treatment of glucocorticoid-induced osteoporosis in both men and women.

In a large trial alendronate 10mg daily significantly reduced the incidence of vertebral fractures compared to placebo, in postmenopausal women with osteoporosis with or without a vertebral fracture at baseline.

In placebo controlled studies for the prevention of bone loss in postmenopausal women, alendronate 5mg daily significantly increased BMD at the spine and hip.

In studies for the management of glucocorticoid-induced osteoporosis, alendronate 5mg or 10mg daily significantly increased BMD at the lumbar spine, femoral neck and trochanter compared to placebo in men and women receiving ³ 7.5mg prednisolone or equivalent per day.

The most common adverse events with alendronate are related to the upper gastrointestinal tract. Severe oesophageal reactions have been reported.

Alendronate is an alternative treatment option for the management of postmenopausal and glucocorticoid-induced osteoporosis. However, it is important that patients follow the strict administration instructions.

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© MTRAC, Department of Medicines Management