Osteoporosis

Contributed by Professor Ignac Fogelman, professor of nuclear medicine, Guy's, King's and St Thomas' School of Medicine, Guy's Hospital, London

1. Epidemiology and aetiology

Osteoporosis is the most common metabolic bone disorder, and affects mainly post-menopausal women, although it can occur in younger women, and in men. It is a progressive loss of bone mass and deterioration of bone structure that leads to bone fragility and fracture.

Epidemiology

Estimates for the number of people in the UK with osteoporosis range widely, between one and three million, with the prevalence rising from about 2 per cent in women aged 50 to 25 per cent by age 80.

One woman over 50 in three is likely to have a vertebral fracture, and one in six a hip fracture, and those who have fractures are at increased risk of further fractures. After a vertebral fracture, a woman is over four times more likely to have a further vertebral fracture than one who has not previously fractured, and at least twice as likely to have a hip fracture.

Vertebral fractures can lead to a loss of height, curvature of the spine, pain, breathing and digestive problems, with accompanying adverse effects on quality of life. In addition to their effects on mobility, hip fractures are associated with an estimated two to 10 fold (varying depending on age) increase in mortality risk in the 12 months after the fracture.

Co-morbidities

Recent research showed that middle-aged patients with diabetes have a more than two-fold increased risk of fracture. Other risk factors include  mental illness and excessive alcohol consumption.

Given the ageing population, cost of treatment in England and Wales alone is predicted to rise from between £1.5-£1.8 billion in 2000, to £2.1 billion by 2010.

Risk factors

Risk of developing osteoporosis in women increases with:

Early menopause or hysterectomy (before the age of 45).

Family history.

Smoking.

Low BMI (<19kg/m2).

Long-term use of high-dose corticosteroids.

Co-morbidities, such as thyrotoxicosis and hyperparathyroidism.

2. Making a diagnosis

Clinical features

All too often, the first clinical feature of osteoporosis is a vertebral or other fracture. Evidence to support widespread screening for osteoporosis is lacking, and concerns about the safety of HRT for the prevention of osteoporosis have meant that fewer women with risk factors are being investigated when they reach the menopause. 

Instead, the focus has switched to prompt diagnosis of osteoporosis after a first fracture, with an increasing number of hospitals using fast-track protocols to ensure early referral from fracture clinic to osteoporosis clinic.

Investigations

GPs have an important role to play, not only in checking that women are appropriately assessed after a fracture, but also in ensuring that younger women who reach the menopause and have genuine concerns about osteoporosis (owing to maternal history or other risk factors) can have their bone mineral density (BMD) measured. 

Ease of access to dual energy X-ray absorptiometry (DEXA) scans is still variable across the UK.

BMD is expressed as T-score, which is the number of standard deviations (SDs) from the BMD in an average 25-year-old woman.

WHO criteria

Normal: T-score > -1 SD

Osteopenia : T-score < -1 to > -2.5

Osteoporosis: T-score < -2.5 SD

Established osteoporosis : T-score < -2.5 SD + one or more osteoporotic fractures

3. Treatment and guidelines

Current NICE guidance for secondary prevention of osteoporosis recommends that, unless clinicians are confident that patients receiving osteoporosis treatment have an adequate calcium intake and are vitamin D replete, calcium and/or vitamin D should be provided. 

Bisphosphonates

Bisphosphonates are the most widely used agents for the management of osteoporosis and, once the diagnosis is confirmed, treatment can be initiated in primary or secondary care.

Bisphosphonates inhibit bone resorption, and may cause a modest increase in BMD by inhibiting osteoclast activity or by secondary mineralization. They may be expected to reduce the risk of vertebral fractures by 39–60 per cent, and hip fractures by 26–50 per cent .

Most patients tolerate bisphosphonates well, but the main drawback is their upper GI side effects of nausea, dyspepsia, mild oesophagitis and/or gastritis and abdominal pain. These can be prevented in many patients by following their administration guidance. Bisphosphonates should be used with caution in patients with active GI problems.

Treatment options

Other options include strontium ranelate, raloxifene and teriparatide.

Strontium ranelate reduces the risk of vertebral and hip fractures by a mechanism which (although is not fully understood) appears to lead to a mild increase in bone formation, while simultaneously decreasing bone resorption slightly.

Raloxifene is a selective oestrogen receptor modifier (SERM) which, like bisphosphonates, reduces the risk of fractures by inhibiting bone resorption. While it reduces vertebral fractures by 30 per cent, there appears to be little effect on non-vertebral fractures, though raloxifene has the advantage of a possible protective effect against breast cancer.

Raloxifene is associated with a small increase in risk of venous thromboembolism, and some women experience hot flushes, arthralgia, dizziness and leg cramps .

Teriparatide is a recombinant form of human parathyroid hormone (PTH) which has a potent anabolic effect on bone by stimulating new bone formation and it also improves bone structure. While highly effective it is restricted to the severest cases of osteoporosis due to its high cost.

Guidance in osteoporosis

In January 2005, NICE published guidance on the prevention of fractures in women who have already had a vertebral or other osteoporotic fracture (secondary prevention).

NICE is currently updating its guidance on the secondary prevention of fragility fractures in women with osteoporosis, to include the use of strontium ranelate, which became available after the scope of the original guidance was agreed.

It is also proposed that raloxifene be considered for women who are unable to take bisphosphonates or strontium ranelate, for the reasons above. The proposed recommendations for use of teriparatide have  changed to make the drug available to those over 55. NICE is currently consulting on a new technology assessment of the primary prevention of osteoporotic fragility fractures in postmenopausal women.

The proposed guidance on primary prevention in particular is highly restrictive on the use of drugs in women under the age of 75.

Resources

NICE guidance: alendronate, etidronate, risedronate, raloxifene, strontium ranelate and teriparatide for the secondary prevention of osteoporotic fragility fractures in osteoporosis, NICE, January 2005

NICE Appraisal consultation document: alendronate, etidronate, risedronate, raloxifene, and strontium ranelate for the primary prevention of osteoporotic fragility fractures in osteoporosis, NICE, September 2006

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