The World Health Organisation has defined osteoporosis as a ‘systemic skeletal disease characterised by low bone mass and microar-chitectural deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fracture’. Bone mass or mineral density relies on a balance between osteoblastic and osteoclastic activity. Overall bone mass increases until adulthood, plateaus and then declines from 35 years of age onwards, accelerating in women following the menopause.

By 60–70 years of age, 30% of women have osteoporosis, rising to 70% in those over 80 years. Although the entire skeleton is affected, the commonest sites for osteoporotic fracture are the neck of the femur, the vertebrae and the distal radius. The morbidity associated with neck of femur fractures is particularly significant, and generates an increasing economic burden.

The most important risk factors for osteoporosis are:

• Maternal family history of hip fracture.
  
• Oestrogen deficiency, e.g. due to premature menopause, prolonged secondary amenorrhoea or primary hypogonadism.
  
• Corticosteroid therapy e.g. prednisolone dose >7.5 mg/day for >6 months.
  
• Low body mass index (BMI) of <19 kg/m² due to a combination of reduced oestrogen levels and reduction in impact loading.

• Smoking.
  
• Excess alcohol.
  
• Anorexia nervosa (low weight, menstrual irregularity, low calcium intake).
  
• Endocrine syndromes (hyperparathyroidism, hyperthyroidism, Cushing’s syndrome).
  
• Multiple myeloma.
  
• Inflammatory arthropathy (probably due to increased IL-1 and TNFα levels).
  
• Prolonged immobilisation.

Osteoporosis is diagnosed using a dual energy X-ray absorptiometry or DEXA scan. This allows a measurement of the bone mineral density (BMD) at the lumbar spine and proximal femur for comparison against someone of the same age and gender (Z score) or of the young normal mean – the T score.

• Normal: BMD T score >1 standard deviation (SD) below the young normal mean (more than –1).
  
• Osteopaenia:BMD T score 1–2.5 SD below the young normal mean (between –1 and –2.5).
  
• Osteoporosis: BMD T score >2.5 SD below the young normal mean

(more than –2.5).

• Severe osteoporosis: as above plus previous fragility fracture.

General measures

All patients with osteoporosis must maintain good nutrition with high levels of calcium and vitamin D, by dietary supplementation if necessary. Increased physical activity improves BMD via impact loading and also reduces the overall risk of falls. Patients should also be advised to stop smoking and to avoid alcohol excess, and steroid doses must be reduced or withdrawn wherever possible.

Pharmacological measures

Bisphosphonates: risedronate, alendronate, etidronate and zoledronate

As a group, the bisphosphonates inhibit the action and function of osteoclasts, thereby reducing skeletal resorption and the subsequent risk of fracture at both vertebral and non-vertebral sites. They are available as daily or weekly preparations, but have variable acceptability and compliance due to gastrointestinal side effects. In order to reduce side effects and to maximise otherwise relatively poor absorption, patients must take their bisphosphonate on an empty stomach, with plenty of water, remain upright for 30 minutes after ingestion and have nothing to eat or drink for a further 30 minutes. Zoledronate is given as an annual intravenous infusion for those for whom oral administration is intolerable or contraindicated (severe oesophagitis, structurally or functionally abnormal oesophagus e.g. achalasia).

Selective oestrogen receptor modulators (SERMs): raloxifene

SERMs such as raloxifene have oestrogenic effects on bone, but not breast or endometrium. They have been shown to decrease bone turnover in post-menopausal women with a subsequent increase in BMD and a reduction in vertebral (but not hip) fracture rate. In general they are well-tolerated, but confer an increased risk of deep venous thrombosis.

Strontium

Although its precise mechanism of action is unclear, strontium appears to uncouple bone remodelling, thereby stimulating bone formation and increasing BMD at the lumbar spine and femoral neck. It has a proven role in reducing vertebral fracture rate and preliminary data from a large clinical trial also suggest a reduction in hip fracture risk.

Teriparatide (synthetic parathyroid hormone)

Exogenous parathyroid hormone, given intermittently, has been shown to have anabolic effects on bone, increasing BMD and reducing the osteoporotic fracture rate. Currently licensed for the treatment of severe osteoporosis, it is administered as a once-daily subcutaneous injection. However, treatment is limited to 18 months as toxicology studies have suggested an increased risk of osteosarcoma with prolonged use.

Hormone replacement therapy (HRT)

Although it has been shown to increase BMD and reduce fracture rate, HRT should no longer be prescribed for primary prevention of osteoporosis as the associated risks of venous thromboembolism and breast carcinoma are deemed unacceptably high. The only current indication for HRT is the management of menopausal symptoms; bone protection is simply an additional benefit. Testosterone is used in men when hypogonadism is the underlying aetiology of their osteoporosis.

Vertebroplasty

Percutaneous vertebroplasty is used in patients with vertebral compression fractures and persistent pain. A needle is introduced into the bone and cement injected, filling the spaces and forming an internal cast. It is generally well-tolerated and reasonably effective.

Steroid therapy suppresses bone formation, increases osteoblast apoptosis and disrupts calcium homeostasis. For a given BMD, osteoporosis caused by steroids has the highest rate of fracture. There is a strong correlation between the daily dose and the fracture risk, and the risk both increases and declines rapidly on and off treatment. All physicians must be alert to the profound risk of long-term steroid therapy – particularly in the elderly population. The diagnosis and treatment for corticosteroid-induced osteoporosis is identical to that for idiopathic disease.