Definition Of Osteoporosis

In the most recent National Institutes of Health consensus statement, osteoporosis is defined as ‘a skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture. Bone strength primarily reflects the integration of bone density and bone quality. What is clear is that osteoporosis is an asymptomatic condition until fragility fracture occurs, but, unfortunately, the consequences of fracture have great significance both to the individual and to public health.

Etiology

Osteoporosis is a multi-factorial condition with etiologic contributions from both genetic and environmental factors. The importance of genetic factors is demonstrated by the fact that a family history of fracture is an independent predictor of fracture with a relative risk of 1.5-3.0, with the greatest risk seen with maternal hip fracture. There are several genetic polymorphisms of interest including the vitamin D receptor gene, the estrogen receptor gene, the collagen 1A1 gene and genes for various cytokines including interleukin-6 and tumor growth factor-β. The environmental factors will be discussed in the section on prevention ofosteoporosis.

Outcome

It is estimated that one in three women and one in 12 men over the age of 50 will develop osteoporosis. The financial cost to the UK Exchequer for the acute and social care of males and females following a fracture has been estimated as £1.7 billion per annum. As the prevalence of osteoporosis rises as the population ages it can be anticipated that these cost will continue to rise.

In addition to the financial costs of osteoporotic fracture there are significant personal costs. The 1-year mortality rate following hip fracture is reported as 21% for women and 36% for men. Survivors of hip fracture experience significant morbidity with on-going pain, impairment in mobility and increased dependence. One year post hip-fracture, 40% of survivors are unable to walk unaided while 60% require assistance in at least one essential activity of daily living.

In view of these personal and financial costs there is an imperative to identify those at risk of fragility fracture and initiate measures to reduce their risk.

Diagnosis

Bone mineral density accounts for between 75 and 90% of the variance in bone strength. The association between bone mineral density and fracture is superior to the association between serum lipids and risk of coronary artery disease. It is possible to estimate bone mineral density by a number of techniques and on this basis assess fracture risk.

Dual energy X-ray absorptiometry (DEXA)

Dual energy X-ray absorptiometry involves measuring the attenuation of X-rays of two different energies to estimate bone mineral density. Axial dual energy X-ray absorptiometry scanners allow estimation of bone mineral density at the spine and hip which are important sites of fracture. Measurement of bone mineral density at sites where the risk of morbidity and mortality are greatest allows axial dual energy X-ray absorptiometry to be the most useful tool in the assessment of osteoporosis. Axial dual energy X-ray absorptiometry involves the patient lying on a table whilst a radiation source and detector assembly moves over the area being scanned. Conventional pencil-beam scanners take 10-15 minutes to complete a scan, while more modern scanners using a fan beam take only a few minutes. The scan is painless and the patient is not enclosed.

Peripheral dual energy X-ray absorptiometry scanners have been produced that have the advantage of being less expensive and more portable. They can scan sites such as the distal radius, hand and heel. While these scans give useful information about the site measured, they are slightly less predictive of fracture risk at clinically more significant sites. The rate of bone loss is lower at the os calcis than at the lumbar spine or hip and it may be inappropriate to use the current thresholds for diagnosis of osteoporosis at this site. Furthermore, the effect of therapies on peripheral sites is less predictable and of lesser magnitude, so monitoring response to treatment with peripheral devices is problematic. Thus the ideal role of peripheral dual energy X-ray absorptiometry scans in the diagnosis, assessment, and monitoring of intervention in osteoporosis is yet to be fully elucidated.

Quantitative computed tomography (QCT)

While dual energy X-ray absorptiometry produces an estimate of bone mineral density in g/cm, quantitative computed tomography is able to make a true volumetric estimate of bone mineral density in mg/cm. This has advantages as it allows assessment of both cancellous and cortical bone and can assess the cancellous bone structure. The use of this technique to assess the lumbar spine or hip is limited as the radiation dose is 12-fold greater than a dual energy X-ray absorptiometry scan. quantitative computed tomography can be used to assess peripheral sites such as the distal radius. This involves lower doses of radiation but also gives a less useful prediction of fracture risks at sites other than that directly measured.

Quantitative ultrasound (QUS)

It is possible to measure several peripheral sites by QUS. At present it is not entirely clear what parameters of the bone are being assessed. How the changes detected by ultrasound are influenced by therapy is also unclear. It is possible to measure the speed of travel of ultrasound through the tissue or the speed of a reflected wave (speed of sound) and the degree of attenuation (broadband ultrasound attenuation), or a combination of these values, to estimate bone mineral density and fracture risk. The technique is portable and free from radiation and may have some role to play in population screening, although there remain some technical issues to resolve. However, not all QUS scanners have the same precision or modus operandi.

Interpretation of results

The World Health Organization (WHO) has defined categories for the diagnosis of osteoporosis in women based on the young adult mean bone mineral density as follows:

Normal: within 1 standard deviation (SD) of the young adult mean;

Osteopenia: >1 SD below the young adult mean but <2.5 SD below this value;

Osteoporosis: >2.5 SD below the young adult mean; and

Severe osteoporosis: >2.5 SD below the young adult mean in the presence of one or more fragility fractures.

This allows fracture risk to be estimated and has come to provide a threshold for initiation of therapy although the latter was not the initial aim. UK guidelines have recommended that individuals with a T-score <-2.5, that is, more than 2.5 SD below the young adult mean, should be considered for therapeutic intervention to reduce their risk of fracture. The proposed threshold for initiation of therapy is lower for patients on glucocorticoid therapy, where a T-score <-1.5 has recently been proposed for subjects less than 65 years of age.

Prevention

As reduction in bone mass is an inevitable consequence of aging, achieving peak bone mass in the young adult years is important in delaying the development of bone density that would fall within the osteoporotic range. Strategies to ensure the achievement of peak bone mass begin in utero; evidence suggests the skeletal growth trajectory is established during intrauterine development or early (first 2 years) postnatally. Maternal nutrition and lifestyle factors thus appear to influence skeletal development of the child with consequences that may manifest several decades later.

Nutrition

Sustained optimal intakes of calcium and vitamin D are important to allow an individual to attain their peak bone mineral density during their young adult years. Several studies have demonstrated increases in bone mineral density in children given calcium supplementation. The benefit of supplementation began to fade once the supplements were discontinued, demonstrating the importance of sustained intake. However, calcium and vitamin D are not the only nutritional factors important in bone development, with other trace elements such as potassium and magnesium, and food groups such as fruit and vegetables, having a potential role.

Exercise

Exercise during the growth years of childhood has been shown to increase the accumulation of bone in the young skeleton. Similar positive effects have been demonstrated in young adults. In older individuals there is some evidence to suggest exercise may constrain the rate of bone loss. The beneficial effect of exercise on falls-prevention in older people has a greater benefit in reducing their fracture risks than the change in bone mineral density.

Lifestyle

Cigarette smoking lowers bone mineral density with current smokers having a lower bone mineral density than former smokers, who have a lower bone mineral density than individuals who have never smoked.

Excessive alcohol consumption may induce osteopenia and increase fracture risk; it also predisposes to falls resulting in a further increase in fracture risk. However, moderate doses of alcohol may have a beneficial effect on bone health.

Treating Osteoporosis

Conclusions

Osteoporosis is a major public health issue for the twenty-first century. It has the potential to cause significant morbidity and mortality and result in huge financial cost. Osteoporosis is a treatable condition with increasingly effective and well-tolerated therapies emerging. These therapies also come at considerable expense. Population strategies to ensure that every individual maximizes their peak bone density, combined with appropriate investigation and management of those at risk of osteoporosis and thus fragility fracture, should enable us to reduce the burden of this disease.

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