Diagnosis and Follow-Up

Diagnosis of osteoporosis

Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture (1). Osteoporosis is related to decreased bone strength, which encompasses both bone quantity and quality.

Bone mineral density (BMD), assessed by dual-energy X-ray absortiometry (DXA) remains the gold standard for the diagnosis of osteoporosis.

BMD can be expressed as:

• T-score (the number of standard deviations (SD) above or below the mean BMD values for a young healthy adult)
• Z-score (the number deviations above or below the mean BMD values for a population of the same age and gender)

Based on the 1994 WHO report (1), osteoporosis in women is defined as a BMD value at least -2.5 SD below the mean value of a young healthy population (T-score≤-2.5).

	Status		Hip BMD
	Normal		T-score of -1or above
	Osteopenia		T-score lower than -1 and greater than -2.5
	Osteoporosis		T-score of -2.5 or lower
	Severe osteoporosis		T-score of -2.5 or lower, and presence of at least one fragility fracture

Bone density and fracture risk

 

Clinical risk factors can provide information on the risk of fractures in individual patients. However the indices which have been developed, based on the use of clinical risk factors, can only be used as screening tools. BMD assessment is required to confirm the diagnosis since fractures only occur at advanced stages of the disease.

 

BMD measurement

Dual-energy X-ray Absorptiometry (DXA)

Diagnosis of osteoporosis is generally based on assessment of BMD at the spine and proximal femur by DXA. There is currently some debate about the use of DXA in a mass screening scenario or in more focused case-finding strategies. The decision will be mainly based on economical grounds.
DXA has demonstrated good performance characteristics for diagnosis, assessment of prognosis, monitoring of natural history of the disorder, and assessment of response to some pharmacological treatments.

Quantitative Ultrasound (QUS)

This technique provides some information on the structural organisation of bone in addition to bone mass, with no exposure to ionising radiation. Some studies have suggested a similar ability like DXA to discriminate between osteoporotic and non-osteoporotic patients. However, QUS has not been extensively validated for monitoring the effect of treatment. It can be used to predict fracture risk, but it cannot be used for the diagnosis of osteoporosis or for monitoring the effects of treatment (3).

Quantitative Computer Tomography (QCT)

This technique measures true volumetric bone mineral content by separately measuring trabecular and cortical bone three-dimensionally. QCT is extensively used in clinical research. However, it remains much more expensive, less accessible and uses higher radiation exposure than DXA.

Radiological assessment of vertebral fracture

Back pain and loss of height can be the first symptoms of vertebral fractures induced by osteoporosis. In order to assess the severity of vertebral fractures, a semiquantitative method based on visual inspection has been developed. It has been extensively used in clinical trials and epidemiological studies. The severity of the fracture is assessed by measuring the extent of vertebral height reduction, by its morphological changes, and by differentiating the fracture from nonfracture deformities (4). Grades are assigned to each vertebra based on the degree of height reduction.
This method does not link the type of deformity with the grading of the fracture. One advantage of this method is that by assessing the severity of the deformation, new deformities occurring on a prevalent vertebral fracture can be assessed within the range of grading.

Vertebral Fractures Semi-Quantitative Grading Genant H. et al J Bone Miner Res. 1993; 8:1137-42

Quantitative methods such as morphometry or magnetic resonance imaging (MRI) have been developed over the past years and can be used to assess more precisely the features of vertebral fractures.

 

Bone turnover markers (BTM)

BTM have been extensively used in clinical research to monitor the efficacy and mechanisms of action of new drugs. There are three categories of BTM depending on their origination from the bone mineral unit (BMU): bone resorption markers, bone formation markers and markers of osteoclast regulatory proteins (5).

These markers, measured in serum or urine, are not disease-specific. They assess alterations in skeletal metabolism, regardless of the underlying cause.

Combining BMD with BTM could improve fracture prediction in postmenopausal women (6,7,8).
One advantage of biochemical markers compared to BMD is early estimation of treatment effect. Significant changes in BTM can be seen during antiresorptive therapy after a few weeks of treatment; whereas individual monitoring with DXA usually requires 1-2 years to identify significant changes.
As adherence is an important issue of long-term therapy in chronic disease, it has been suggested that BTM could be used in clinical practice to assess the patient's adherence to treatment and also provide feedback on the effectiveness of the medication (9).

Assessment of fracture risk

The aim of assessment of fracture risk is to detect individuals at high risk, who deserve the initiation of antiosteoporotic treatment, and conversely to avoid unnecessary treatments in people at low risk (2).

Clinical risk factors that contribute to fracture risk independently of BMD include:

• Age
• BMI
• Previous fragility fracture
• Premature menopause
• A family history of hip fracture
• The use of corticosteroids

In countries with limited or no access to densitometry, it has been suggested that clinical risk factors should be used for individual assessment of fracture risk.

Intervention thresholds

WHO and IOF recommend that risk of fracture should be expressed as an absolute risk, i.e., a 10-year probability (10). Absolute risk depends on age, life-expectancy and present relative risk (11).
The cutoff value that provides an intervention threshold has to be determined on several criteria, such as (12):

• clinical practice and the priority which osteoporosis has in a country
• willingness to pay
• ability to pay
• absolute risk of fracture

Several models have been developed in Sweden and in the United Kingdom (13,14). 

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