Alternatives to HRT for reducing bone mineral loss following the menopause include lifestyle changes and certain drug therapies.

Lifestyle interventions include dietary supplementation with calcium and vitamin D and pursuit of weight-bearing exercise. There are no controlled trials to support dietary changes but the National Osteoporosis Society (NOS) recommends increasing dietary calcium or taking calcium supplements (36). Calcium-rich foods include cheese, yoghurt, milk, nuts, tinned salmon and sardines, and dark green vegetables. Weight bearing activity has been shown to improve bone mineral density in some postmenopausal women (37).  Cigarette smoking and high alcohol intake are both risk factors for osteoporosis, therefore stopping smoking and avoiding excess alcohol might also be helpful.

A number of drugs are available which are effective at reducing bone turnover and osteoporotic fractures. The bisphosphonates include alendronic acid, risedronate and etidronate, while selective oestrogen receptor modulators (SERMs) include drugs such as tamoxifen and raloxifene.

Bisphosphonates

Bisphosphonates are analogues of pyrophosphate, an inhibitor of bone mineralisation. They inhibit osteoclast function, reducing bone turnover. In addition to reducing bone turnover in patients at risk of osteoporosis, bisphosphonates also have a major role in the management of malignancy-associated hypercalcaemia and skeletal pain and other complications in patients with bone secondaries resulting from malignant disease. However, only three bisphosphonates are currently licensed in the United Kingdom for prevention or treatment of osteoporosis, i.e. the oral agents, alendronic acid, risedronate and disodium etidronate

Oral formulations of bisphosphonates are poorly absorbed and need to be taken on an empty stomach at least 30 minutes before any other food. Side effects include indigestion, constipation and oesophageal ulceration. These formulations may not be suitable for patients with renal impairment.

Alendronic acid (Fosamax) 5mg daily is used to prevent post-menopausal osteoporosis and 10mg daily (or 70mg weekly preparation) is given as a treatment dose. Side effects include oesophageal reactions, gastrointestinal disturbance, musculoskeletal pain and headaches. Alendronic acid reduced the risk of radiographic vertebral and hip fracture by 47 to 56% in postmenopausal women who had one or more existing vertebral fracture and in those with no existing vertebral fractures but who had osteoporosis. (38).

Risedronate (Actonel) is associated with a 39 % reduction in fractures over 3 years (39). The drug is used as an oral 5mg daily dose or 35mg once weekly.

Etidronate (Didronel PMO) is given in 90-day cycles with 400mg/day of etidronate for 14 days followed by 500mg of calcium (Cacit) daily for 76 days. The cycle is then repeated. A meta-analysis of 13 randomised trials on 1,267 patients showed that cyclical treatment with etidronate and calcium in postmenopausal women lowered the risk of vertebral fracture by 37 per cent at one year (40).

SERMS are agents that block the oestrogen receptor at one site (e.g. in breast tumours) and have stimulatory activity at another site (e.g. the bone). Examples of such drugs are tamoxifen and raloxifene.

Tamoxifen improves bone density and reduces fracture risk in postmenopausal women, as well as benefiting lipid profiles, but causes hot flushes and a small increase in risk of endometrial cancer.

Raloxifene has both oestrogen antagonistic and agonistic properties. Unlike tamoxifen, whose partial-agonistic properties result in side effects such as endometrial proliferation and uterine cancer, it lacks adverse effects on the postmenopausal uterus, while retaining beneficial impact on bone mineral density and lipid profile (41).

Raloxifene is now approved for the treatment and prevention of osteoporosis. In postmenopausal women with osteoporosis it has been shown that raloxifene at a dose of 60mg/day significantly decreases risk of vertebral fracture. Unfortunately, raloxifene also has anti-oestrogenic effects, resulting in hot flushes/sweats.

Raloxifene also has potential for reducing the risk of breast cancer (42). A study of tamoxifen and raloxifene (STAR) is being conducted in the USA and results should be available in 2005.

The use of SERMs can be considered in all patients who have undergone a premature menopause as a result of breast cancer treatment.