Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
Fosamax (Merck Sharp & Dohme)
10 mg and 40 mg tablets
Indications: Paget's disease, osteoporosis
The bisphosphonates are effective inhibitors of bone resorption. They can therefore be used in conditions where bone resorption is increased such as Paget's disease and osteoporosis.
Several trials have reported that alendronate increases bone mineral density in postmenopausal women with osteoporosis. A randomised placebo controlled trial of 994 women found that those taking alendronate for 3 years increased their bone density and reduced vertebral fractures. In the final analysis of 881 of the women, 22 (6.2%) of the 355 in the placebo group had at least one new vertebral fracture, compared with 17 (3.2%) of the 526 women who took alendronate.1 However, the effect on non-vertebral fractures was not significant.
In osteoporosis, the recommended dose is 10 mg a day. A daily dose of 40 mg is recommended for Paget's disease. This higher dose reduces the activity of the disease as judged by significant decreases in alkaline phosphatase concentrations. Treatment is restricted to 6 months' duration.
The bioavailability of alendronate is very low (<1%) so it is important to take the drug at least 30 minutes before food. It should be taken with water as coffee and orange juice reduce the bioavailability by 60%. After absorption, the drug distributes to soft tissues, but is then either excreted or redistributed to bone. Although half of a radio labelled (intravenous) dose will be excreted within 72 hours, the terminal elimination half-life probably exceeds 10 years.
The adverse effects of alendronate are mainly gastrointestinal and include abdominal pain, oesophageal ulcers and dyspepsia. Some patients will complain of musculoskeletal pain.
Although experience is limited, alendronate appears to have little effect on bone mineralisation. Impairment of bone mineralisation has been a problem with another bisphosphonate, sodium etidronate, resulting in increased fractures.
Alendronate may have an advantage over sodium etidronate, but its exact role is uncertain. Not all patients with Paget's disease require treatment and the clinical outcomes of treatment with alendronate are not clear. The drug is not yet approved for the prevention of osteoporosis. Its use is restricted to postmenopausal women with evidence of an atraumatic fracture or a bone density measurement two or more standard deviations below the mean. It is hoped that the role of the bisphosphonates can be clarified at this year's consensus conference- 'The prevention and management of osteoporosis'.
- Liberman UA, Weiss SR, Broll J, Minne HW, Quan H, Bell NH, et al. Effect of oral alendronate on bone mineral density and the incidence of factures in postmenopausal osteoporosis. N Engl J Med 1995;333:1437-43.