Raloxifene for the primary prevention of osteoporotic fragility fractures in postmenopausal women

Osteoporosis is a progressive, systemic skeletal disorder characterised by low bone mass and micro-architectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture.

Bone formation exceeds bone resorption in youth, but by the third decade of life there is a gradual loss of bone mass. Osteoporosis is therefore usually an age-related disease. It can affect both sexes, but women are at greater risk because the decrease in oestrogen production after the menopause accelerates bone loss to a variable degree.

The World Health Organization (WHO) has established diagnostic criteria for osteoporosis based on the measurement of BMD, expressed as the T-score, which is the number of SD below the mean BMD of young adults at their peak bone mass:

• normal BMD: T-score of -1 SD or above

• osteopenia: T-score of between -1 and -2.5 SD

• osteoporosis: T-score of -2.5 SD or below

• established (severe) osteoporosis: T-score of -2.5 SD or below with 1 or more associated fractures.

T-score measurements vary depending on the site and method of investigation. Measurement of BMD using central (hip and/or spine) DXA scanning can estimate fracture risk.

It is estimated that more than 2 million women have osteoporosis (that is, have a T-score of -2.5 SD or below) in England and Wales. Osteoporosis is most common in older white women. After the menopause, the prevalence of osteoporosis increases markedly with age, from approximately 2% at 50 years rising to more than 25% at 80 years.

Fragility fracture is the clinically apparent and relevant outcome in osteoporosis (referred to as 'osteoporotic fragility fracture' in the following text). It is often referred to as a low-trauma fracture; that is, a fracture sustained as the result of a force equivalent to the force of a fall from a height equal to, or less than, that of an ordinary chair. In the absence of fracture, osteoporosis is asymptomatic and often remains undiagnosed. Osteoporotic fragility fractures occur most commonly in the vertebrae, hip and wrist, and are associated with substantial disability, pain and reduced quality of life.

In women aged over 50 years, the lifetime risk of a vertebral fracture is estimated to be 1 in 3, and that of hip fracture 1 in 5. Postmenopausal women with an initial fracture are at substantially greater risk of subsequent fractures. For instance, a woman with a vertebral fracture has an increased relative risk (RR) of 4.4 for a further vertebral fracture, 2.3 for a hip fracture, and 1.4 for a wrist fracture.

It is estimated that annually there are 180,000 osteoporosis-related symptomatic fractures in England and Wales. Of these, 70,000 are hip fractures, 25,000 are clinical vertebral fractures, and 41,000 are wrist fractures.

After a hip fracture, a high proportion of women are permanently unable to walk independently or to perform other activities of daily living and, consequently, many are unable to live independently. Hip fractures are also associated with increased mortality; estimates of the relative mortality risk vary from 2 to greater than 10 in the 12 months following hip fracture. However, it is unclear to what extent this can be attributed to fracture alone as opposed to pre-existing comorbidity.

Vertebral fractures can be associated with curvature of the spine and loss of height and can result in pain, breathing difficulties, gastrointestinal problems and difficulties in performing activities of daily living. It is thought that the majority of vertebral fractures (50% to 70%) do not come to clinical attention. Vertebral fractures are also associated with increased mortality; UK-specific data indicate a 4.4-fold increase in mortality related to vertebral fracture. However, as with hip fractures, it is unclear to what extent this may be due to comorbidities.

In addition to increasing age and low BMD, other clinical factors have been associated with increased fracture risk. Some of these clinical risk factors are at least partly independent of BMD, and include parental history of hip fracture, alcohol intake of 4 or more units per day, prior fracture, long-term systemic use of corticosteroids (the latter 2 of which are not covered in this guidance), and rheumatoid arthritis.

Factors that are known to be indicators of low BMD include low body mass index (BMI; defined as less than 22 kg/m²), and medical conditions such as ankylosing spondylitis, Crohn's disease, conditions that result in prolonged immobility, and untreated premature menopause.