3 The technologies
3.1 The bisphosphonates alendronate, etidronate and risedronate are inhibitors of bone resorption and increase BMD by altering osteoclast activation and function.
3.2 Alendronate is an oral bisphosphonate that has a UK marketing authorisation as a once-weekly preparation (70 mg) for the treatment of postmenopausal osteoporosis. It also has a marketing authorisation at a daily dose of 10 mg for the treatment of osteoporosis in postmenopausal women to prevent fractures. Non-proprietary alendronate (Teva UK) costs £4.12 for four 70 mg tablets and £8.30 for twenty-eight 10 mg tablets (excluding VAT; NHS Drug Tariff, 24 February 2008). At these prices the drug costs for 1 year are £53.56 for once-weekly (70 mg) tablets and £108.20 for daily (10 mg) tablets. Proprietary alendronate (Fosamax; Merck Sharp & Dohme) is priced at £22.80 for four 70 mg tablets and £23.12 for twenty-eight 10 mg tablets (excluding VAT; 'British national formulary' [BNF] edition 54). At these prices, the drug costs for 1 year are £296.40 for once-weekly (70 mg) tablets and £301.39 for daily (10 mg) tablets. Costs may vary in different settings because of negotiated procurement discounts.
3.3 Etidronate (Didronel; Procter & Gamble UK) is an oral bisphosphonate that has a UK marketing authorisation for the treatment of osteoporosis. The drug is administered in 90-day cycles, with each cycle consisting of etidronate (400 mg/day) for 14 days followed by calcium carbonate (1.25 g/day) for the remaining 76 days. The price per 90-day pack is £21.12 (excluding VAT; BNF 54), which equates to a yearly cost of £85.65. Costs may vary in different settings because of negotiated procurement discounts.
3.4 Risedronate (Actonel; Procter & Gamble UK) is an oral bisphosphonate that has a UK marketing authorisation at a dosage of 5 mg/day or 35 mg/week for the treatment of postmenopausal osteoporosis, to reduce the risk of vertebral fractures, and for the treatment of established postmenopausal osteoporosis, to reduce the risk of hip fractures. Prices are £19.10 for twenty-eight 5 mg tablets and £20.30 for four 35 mg tablets (excluding VAT; BNF 54), which equates to yearly costs of £248.98 for the daily treatment or £264.63 for the once-weekly treatment. Costs may vary in different settings because of negotiated procurement discounts.
3.5 Gastrointestinal side effects are common with oral bisphosphonates. In people with oesophageal abnormalities and other factors that delay oesophageal transit or emptying, risedronate should be used cautiously and alendronate is contraindicated. For full details of side effects and contraindications, see the summaries of product characteristics.
3.6 Bisphosphonates have relatively complex instructions for administration. Alendronate and risedronate must be taken with 200 ml and 120 ml of water, respectively. Before and immediately after administration patients should not eat or drink, and must remain upright for stipulated time periods. Etidronate should be taken with water at the midpoint of a 4-hour fast (that is, 2 hours after and 2 hours before food, vitamins with mineral supplements such as iron, calcium supplements, laxatives containing magnesium, or antacids containing calcium or aluminium).
3.7 Selective oestrogen receptor modulators (SERMs) are drugs with selective activity in various organ systems, acting as weak oestrogen-receptor agonists in some systems and as oestrogen antagonists in others. The aim of treatment with SERMs is to maximise the beneficial effects of oestrogen on bone and to minimise the adverse effects on the breast and endometrium.
3.8 Raloxifene (Evista; Eli Lilly) has marketing authorisation for the treatment of osteoporosis in postmenopausal women. The recommended dosage is 60 mg/day. The prices of 28- and 84-tablet packs are £17.06 and £59.59, respectively (excluding VAT; BNF 54), which equate to yearly costs of £222.39 and £258.93, respectively. Costs may vary in different settings because of negotiated procurement discounts.
3.9 Raloxifene is contraindicated in people with a history of venous thromboembolism (VTE), hepatic impairment, cholestasis, severe renal impairment, unexplained uterine bleeding or endometrial cancer. Raloxifene should not be co-administered with systemic oestrogens, and in patients with breast cancer it should not be used for osteoporosis treatment or prevention until treatment of the breast cancer, including adjuvant treatment, has been completed. Raloxifene is associated with an increased risk of venous thromboembolic events, particularly during the first 4 months of treatment, which is similar to the reported risk associated with hormone replacement therapy. For full details of side effects and contraindications, see the summary of product characteristics.
3.10 Strontium ranelate (Protelos; Servier Laboratories) is a divalent strontium salt of ranelic acid (strontium is an element with properties similar to calcium). It is thought to have a dual effect on bone metabolism, increasing bone formation and decreasing bone resorption. It has a UK marketing authorisation for the treatment of postmenopausal osteoporosis to reduce the risk of vertebral and hip fractures. The recommended dose is one 2 g sachet taken daily as a suspension in water. The price of a 28-sachet pack is £25.60 (excluding VAT; BNF 54), which equates to a yearly cost of £333.71. Costs may vary in different settings because of negotiated procurement discounts.
3.11 The absorption of strontium ranelate is reduced by food, milk and products derived from milk. It should therefore be administered between meals, ideally at bedtime and preferably at least 2 hours after eating.
3.12 The summary of product characteristics states that strontium ranelate is not recommended in patients with severe renal impairment and that it should be used with caution in patients at increased risk of VTE. Treatment with strontium ranelate should be discontinued during treatment with oral tetracycline or quinolone antibiotics. For full details of side effects, drug interactions and contraindications, see the summary of product characteristics.