_______________________________________________________ Osteoporosis: Diagnosis and Management
since been applied to radiography [40]. Radiographs are an insensitive measure of bone loss and may only demonstrate abnormalities after 30% of bone loss has occurred [41]. Generally, radiographic absorptiometry is not recommended as a screening or diagnostic test for osteoporosis or osteopenia. It can be used to assess vertebral and overall fracture risk in postmenopausal women; there is lack of sufficient evidence for fracture prediction in men [20]. Magnetic Resonance Imaging Most people today are familiar with MRI and aware that it uses a strong magnetic field, limiting its use in patients with ferromagnetic implants. Essentially, cells in the bony region studied emit a signal as they respond to the radio frequency waves of the device. The detector transmits the skeletal information to the computer, which then produces the familiar detailed images. MRI is valuable in the assessment of vertebral body fractures, nonspinal insufficiency fractures, bone mass and strength, and bone marrow edema. The signal-intensity characteristics of bone marrow may allow the differentiation of neoplastic fractures from accompanying osteoporosis [41]. The use of MRI in diagnosing osteoporosis is still evolving and is unlikely to become widely used due to the expense and time required to obtain a scan [41]. Also, more research must be done to improve the sensitivity and specificity of MRI as well as to calculate appropriate T- and Z-scores. Its use, therefore, is mainly limited to certain centers, which generally use MRI for osteoporosis detection as part of a research study. Selection of Tests Given the multitude of tests, there are some general factors to keep in mind when ordering them. For women 65 years of age and younger, vertebral fractures are more common than hip fractures [42]. Therefore, it is prudent to also consider ordering DXA of the spine. For women older than 65 years of age, hip fractures are more common. At the same time, degenerative spinal changes and aortic calcifications make spine imaging more difficult to assess. Therefore, one should consider DXA of the hip or lateral spine, as well as quantitative CT of the hip. DXA of the hip is the best predictor of future hip fracture risk [20]. DXA is also preferred when patients exhibit multiple risk factors. Measurements at two sites are preferable, as this increases sensitivity and specificity. Again, these are general considerations; individual physician’s preferences may differ.
Serial measurements may be helpful to assess bone loss rates; however, they should not be performed too often. Follow-up measurements, one to two years apart, may be useful in determining whether patients with normal baseline bone mass demonstrate a rapid loss of BMD. They may also be helpful when assessing persons undergoing treatment to discern whether the treatment has been effective [20]. Presently, DXA is the only method that has been validated for use in serial measurements. Keep in mind that a minimum of two years is typically required to measure any changes in BMD [6; 20]. Patient D should undergo DXA of the hip. She has a history of degenerative joint disease, which makes spine-imaging results more difficult to interpret. In addition, she has numerous risk factors, which make DXA a preferred test.
LABORATORY TESTS AND BIOCHEMICAL MARKERS
There are currently no specific laboratory tests of blood or urine that are diagnostic of osteoporosis. Most laboratory tests will be normal. A physician or other clinical provider, however, should still order lab tests that include a complete serum chemistry, including calcium and phosphorus, CBC, thyroid function tests, parathyroid hormone (PTH), 25-hydroxyvitamin D, free testosterone, liver function tests, and urine calcium, in order to diagnose secondary causes, such as hyperthyroidism or hyperparathyroidism [6]. The strength of bone is determined by bone density and bone quality, but the overall rate of remodeling also plays an important role. The remodeling process, including the breakdown of bone and protein matrix, generates breakdown products, many of which may be measured in the blood or urine. Additionally, the formation of bone increases other markers ( Table 3 ). Studies of these biochemical markers have not been encouraging for their use in clinical practice, and their routine use in clinical practice is not generally recommended [35; 44]. The levels of the markers change daily, even hourly, so many measurements would have to be made to determine an accurate level. Although biochemical markers have not yet proven to be predictive of bone mineral density or fracture risk, studies have shown that they may be able to estimate fracture risk and rate of bone loss, particularly when combined with BMD [23; 31]. They have also demonstrated an early estimation of treatment effect [31].
BIOCHEMICAL MARKERS OF BONE FORMATION AND RESORPTION
Formation Markers
Resorption Markers
Bone specific alkaline phosphatase (BSAP) Osteocalcin
Calcium Hydroxyproline Free and total deoxypyridinolines (Dpd) Free and total pyridinolines (Pyd)
C-Amino-terminal propeptide of type I procollagen (PINP) Carboxy-terminal propeptide of type I collagen (PICP)
Type I collagen cross-linked C-telopeptide (CTx) Type I collagen cross-linked N-telopeptide (NTX)
Source: [43; 44]
Table 3
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