Osteoporosis
Summary
Fractures resulting from osteoporosis are widely recognised as a major cause of morbidity and mortality in the elderly population. It has been estimated that approximately 310,000 osteoporotic fractures occur annually in the UK, with a consequent cost to the health service of £1.7 billion.Fractures resulting from osteoporosis are widely recognised as a major cause of morbidity and mortality in the elderly population. It has been estimated that approximately 310,000 osteoporotic fractures occur annually in the UK, with a consequent cost to the health service of £1.7 billion. Over the past two decades major advances have been made in the management of this disease and a number of pharmacological agents have been approved for the reduction of fracture risk in postmenopausal women with osteoporosis. These drugs include the bisphosphonates (alendronate and risedronate), raloxifene, teriparatide and, most recently, strontium ranelate.
In clinical practice, the choice of treatment depends on several factors. Although available interventions appear to be similar in terms of the extent by which they reduce the risk of vertebral fracture, not all of them have been shown to reduce fracture risk at non-vertebral sites, particularly the hip. This is particularly important since a fragility fracture is an independent risk factor for further fractures at any site. Evidence for a reduction in both vertebral and hip fractures in postmenopausal women with osteoporosis is currently available only for alendronate, risedronate and strontium ranelate; hormone replacement therapy (HRT) has been shown to reduce clinical vertebral and hip fractures, albeit in healthy postmenopausal women. In contrast, the reduction in fracture risk with the selective oestrogen receptor modulator (SERM), raloxifene, has only been demonstrated at vertebral sites, and whilst teriparatide was shown to reduce both vertebral and non-vertebral fractures, specific evidence for hip fracture reduction is not yet available.
Safety and tolerability are major considerations in selecting any treatment, particularly because intervention with these agents is long term, does not produce symptomatic improvement and may be associated with side-effects. The introduction of once-weekly dosing regimens for alendronate and risedronate has proved to be very popular with patients and has improved continuance and compliance, although the dosing instructions may be difficult to follow for some, particularly the frail elderly. Strontium ranelate is taken as granules dissolved in water at bedtime; it has been shown to be well tolerated in clinical trials and, as with the bisphosphonates, serious adverse effects are rare. Raloxifene is taken as a once-daily dose with no specific dosing instructions and is also well tolerated. Although raloxifene may exacerbate vasomotor menopausal symptoms in some patients, the significant protection it offers against breast cancer, which is maintained for up to 8 years of treatment, is an important benefit for some women. The risk–benefit balance of HRT is complex but generally unfavourable for the majority, with the exception of women with menopausal symptoms; nevertheless, the increase in absolute risk of stroke, breast cancer and possibly coronary heart disease is small and should not preclude HRT use in women who express an informed preference for this treatment. Finally, treatment with teriparatide was not shown to be associated with serious adverse effects in clinical trials, but the requirement for daily subcutaneous injections may be a disadvantage for some.
Cost-effectiveness of treatment is an increasingly important consideration and is the basis on which the National Institute for Health and Clinical Excellence (NICE) have produced their recent guidance (2005) on the secondary prevention of osteoporotic fractures. The costs of alendronate, risedronate, raloxifene and strontium ranelate are broadly similar (around £300 per year), although the recent introduction of generic alendronate should reduce the price of this drug in the future. In contrast, teriparatide is significantly more expensive (approximately £3,500 per year), although it is prescribed only for a maximum of 18 months in contrast to the other interventions, for which treatment periods are longer and may even be lifelong.
Since most of the clinical trials of osteoporosis therapy were conducted in women who also received calcium and vitamin D supplements, these supplements should also be used as an adjunct to therapy unless there is evidence of a good dietary calcium intake and an adequate vitamin D status. In addition, appropriate levels of physical activity should be encouraged, with an assessment of the risk of falls and appropriate advice offered where indicated. Physiotherapy has a major role to play in the management of pain given the reduced mobility and lack of confidence in individuals with osteoporotic fractures. A 6–8-week course of calcitonin often proves effective in the acute management of pain following vertebral fracture.
A number of other approaches to osteoporosis treatment are currently in development.
These include the use of intravenous bisphosphonates with dosing intervals from once every 3 months to once yearly, subcutaneous injections of an antibody to the osteoclastogenic cytokine, RANKL (receptor activator of NFkB ligand), administered at 6-monthly intervals, new selective SERMs and oral formulations of parathyroid hormone. Finally, new approaches to the assessment of fracture risk are also being developed, encompassing both bone mineral density measurements and risk factors that are independent of bone mineral density, for example prior fracture, continuing glucocorticoid therapy and family history of hip fracture.
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This Editorial has been written by the specialist opinion leader Professor Juliet Compston
Professor of Bone Medicine, University of Cambridge, School of Clinical Medicine, and published in the latest issue of the serial publication, Drugs in Context.
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