Chapter 2 Literature review
2.10 Measurement of bone mineral density
The gold standard for the measurement of BMD is with DXA. The older method such as single photon absorptiometry (SPA), used to measure changes in the rates of bone loss in the 1980’s, is seldom used today as it does not measure appendicular skeleton bone mass [62]. Conventional radiography [172], quantitative computed tomography (QCT) [173, 174] and quantitative ultrasound (QUS) [2] have specific advantages, but are not recommended for the diagnosis of osteoporosis.
Biochemical markers of bone turnover have several limitations [175], and have no value in the diagnosis of osteoporosis, and bone biopsy has very limited indications [176].
2.10.1 Dual energy x-ray absorptiometry (DXA)
This technique measures the attenuation of transmission of x-rays of two different energy levels through the body, one of which measures soft tissue density and the other both soft tissue and bone. This allows for bone mineral (hydroxyapatite) to be compared to soft tissue and a two dimensional view is obtained. The BMC of area is
measured and expressed as BMD in grams of mineral per unit projected area of bone (areal bone density) [177]. Dual energy x-ray absorptiometry can be performed for the entire skeleton or at specific sites which have been identified as high risk for fracture e.g. hip and wrist.
Dual energy x-ray absorptiometry is the most widely validated instrument in measuring bone mass and interpretation has been standardized with development of a standard international reference range. It is one of the least invasive and most accurate devices available presently. The radiation dose is less than one tenth compared to a standard radiograph, and the procedure fairly short. Dual energy x- ray absorptiometry is fairly accurate and has greater than 90% accuracy at measuring bone mass at the hip. The precision error with DXA for spine, proximal femur and forearm is about 1 - 2% [178].
Potential error sources include osteoarthritis, soft tissue calcification, osteomalacia, previous fracture, scoliosis, extreme obesity, contrast use, overlying metal objects and untrained operators. Dual energy x-ray absorptiometry is the gold standard for BMD for the diagnosis of osteoporosis, monitoring the natural history of the disease and treatment response and predicting fracture risk [174, 179].
The main disadvantage of DXA is that as the relationship between volume and area is non-linear, the BMD calculated by DXA only provides a two dimensional areal measurement. The normal distribution of BMD, allows for it to be expressed in relation to a reference population in SD units. The T - score is areal BMD expressed in grams per centimetre (g/cm2), compared to a young normal adult of same sex
while the Z - score compares BMD of the individual to that of age and gender matched adults [174]. The reference range recommended by the IOF is the NHANES III database III [80].
Lateral vertebral assessment (LVA) from DXA scans also provide detailed analysis from T 7 – L4 [180]. It has significant advantages over lateral thoracic and lumbar radiographs, as it uses both digital x-rays and parallel beam geometry, and is therefore able to measure vertebral height and detect VFs [181]. The dose of radiation is lower and the procedure can be combined with conventional DXA scan avoiding the need for two imaging procedures. The main limitations are that a narrower view is obtained than radiographs, other potential pathologies may be missed, upper thoracic vertebrae are excluded and the spatial resolution is inferior to plain radiographs [182].
2.10.2 Conventional radiology
Although inexpensive and simple to perform, plain radiographs are an insensitive method for detecting osteoporosis [172]. Approximately 30 - 40% bone needs to be lost before it can be detected on plain radiographs. Furthermore up to 25% of individuals diagnosed with osteopenia on radiographs will have a normal BMD on further testing.
Lateral radiographs of the spine however, are of value in the older individual, particularly in the presence of loss of height, to detect clinically silent VF and deformities [183]. Compression fractures by definition require 20% height loss and
can be classified as wedge, biconcave or crush [184]. A number of methods have been used to classify VFs [185]. These include quantitative measures [186, 187], semi-quantitative [188], or an algorithm based qualitative method [154, 189]. The Genant’s semi-quantitative method of staging is most widely used and has been validated and has good intra-and inter-rater reliability and predictability [185].
2.10.3 Quantitative ultrasound (QUS)
Ultrasound variables, broadband ultrasound attenuation (BUA), speed of sound (SOS) and ultrasound critical angle reflectometry have also been used to measure skeletal status [95]. The SOS measures the time taken for a sound wave to travel through bone and is proportionate to bone mass. The BUA determines the amount of sound absorbed in bone and increases with solidity of bone. While QUS is a relatively inexpensive method, free from radiation, can be used at various sites and may provide information on bone quality, there are limitations to its use. The main disadvantage is that the correlation between fracture risk and QUS values are not well established and clinical studies have shown a poor relationship between therapy and QUS response [2].
2.10.4 Quantitative computed tomography (QCT)
Quantitative computed tomography measures BMD at the appendicular skeleton and the spine. Its greatest value is the ability to measure true volumetric density.
Results are also unaffected by degenerative disease. However, there is limited data
on the ability of QCT to predict fracture risk. Additional disadvantages include the high dose of radiation, higher costs and a higher precision error (2 - 5%) due to marrow fat [174, 177].
2.10.5 Bone markers
During the remodelling process, osteoblasts synthetize and release bone specific alkaline phosphatase, procollagen 1 carboxyterminal propeptide, and osteocalcin.
Osteoclasts release degradation products including collagen type 1 cross linked N- telopeptide, C-telopeptide, pyridinoline and hydroxyproline. These bone markers are not useful in the diagnosis of osteoporosis but may assist in identifying subjects with accelerated bone loss [190]. Although resorptive markers help predict fracture risk, there is limited data [191]. The use of bone markers is further limited by inter-assay differences and lack of reproducibility. The IOF recommends that the use of bone markers should be limited to subjects in whom clinical or BMD data is insufficient to make a diagnosis or to monitor treatment responses after short periods in selected individuals [175].
2.10.6 Bone biopsy
Biopsy of the iliac bone crest allows for the examination of trabecular bone including cells, rate of bone resorption and formation. The use of bone biopsy is limited to an individual case basis and for research purposes [176]