Osteoporosis and Bone Mineral Density
What is osteoporosis?
Osteoporosis is the end result of bone loss. When enough bone mineral density is lost so that the remaining bone will not support normal loads, the bone collapses. Simple measurement of bone mineral density using SXA, DXA, QCT, or ultrasound does not predict which patient will develop osteoporosis. However, low bone density as measured by any of these techniques is a strong risk factor for the occurrence of the non-traumatic bone fractures which are characteristic of osteoporosis.
Who develops osteoporosis?
Postmenopausal women over 60 who have had limited or no estrogen replacement therapy at menopause are the major high-risk group. Asthmatics or other lung patients, or rheumatoid arthritis patients, treated with high-dose corticosteroids, lose trabecular bone and experience fractures, as do patients with Cushing's Syndrome. Other disorders including renal failure and certain types of cancer cause bone loss, along with chronic use of drugs such as anticonvulsants, anticoagulants, excess alcohol, and too much thyroid medication. Young women who experience amenorrhea due to athletic activity, weight loss, stress, or the nutritional deficiency of bulemia or anorexia nervosa lose bone; so do young women who have an early natural or surgical menopause and are not given estrogen replacement therapy. Not all of the patients in all of these groups will develop osteoporosis. However, most of them will lose some bone and thus increase their long-term risk for fractures.
Why do we measure bone density?
Slightly more than half of the overall risk for development of osteoporosis is associated with low bone density as measured quantitatively using SXA, DXA, QCT, or ultrasound. The other factors contributing to fractures are varied, including the internal structure of bone, level of physical activity, neuromuscular coordination, and lifestyle factors that are difficult to quantify. Because of this, bone density is the single most useful measurement in estimating an individual patient's relative risk for osteoporosis.
How do we measure bone density?
All commercially-available methods for bone density measurement pass a low-intensity beam of x-rays or gamma-rays through a patient, and a radiation detector on the other side measures how much of the beam is absorbed. Part of the beam is absorbed by the bone and part by the surrounding soft tissue, and each technique measures these differently. Quantitative Computed Tomography (QCT) provides a cross-sectional or 3-dimensional image from which the bone is measured directly, independent of the surrounding soft tissue. Dual energy x-ray absorptiometry (DXA) measures the bone by computing the difference in absorption of low-energy photons and high energy photons by the mixture of soft tissue and bone in the path of the beam, and can generate a 2-dimensional image for localization of the bone. Single energy x-ray absorptiometry (SXA) computes bone mineral from the increased absorption of the beam as it passes from a constant thickness of soft tissue or water bag into the bone. Localization for SXA is normally done using external landmarks without an image. Radiographic absorptiometry (RA) measures bone density in the fingers relative to an aluminum calibration wedge on the film. Non absorptiometric methods such as ultrasound of bone do not measure bone density directly, but give alternative information about properties of bone such as the speed of sound that are related to bone density and structure.
What is quantitative computed tomography?
QCT refers to a class of techniques in which the CT numbers, or x-ray attenuation, of a tissue is properly referenced to a calibration standard and then used to quantify some property of the tissue. Techniques were developed and published from 1978 to 1982 for bone mineral density, lung nodule calcification, liver and brain tumor volumes, body fat measurement, muscle mass, liver iron measurement, kidney stone composition, and tissue blood flow. Of these, bone mineral density, lung nodule calcification, and tissue blood flow have been commercialized.
How does QCT compare to DXA or SXA?
QCT is the only commercially-available technique which is 3-dimensional, meaning it can be used to measure 100% isolated trabecular bone. All other techniques measure the mixture of trabecular bone and the overlying compact bone. In the spine, trabecular bone is 30-35% of the total, in the ultradistal radius it is 35-50% and in the calcaneus it is 60-75%. Trabecular bone is important to measure because it is more metabolically active than compact bone and it is the first to change in response to a stimulus such as estrogen deficiency. Trabecular bone in the spine is a more reliable indicator of overall skeletal response than the heavily weight-bearing bone in the calcaneus. However, it is also important to consider that any measurement must be done precisely, otherwise the measurement will be insensitive. For the same precision, QCT is 2-3 times more sensitive than DXA and 5 times more than SXA for detecting a change in bone mineral density in early postmenopausal women.
How is bone density measured by QCT?
Two conceptually different methods are used. Simultaneous calibration, where a patient lies on a calibration standard, is specific for each image and was developed at UCSF in 1978. The original standard contained K2HPO4 and over 850 copies of this design have been placed in research and clinical centers, with several hundred publications and worldwide normative data resulting from their use. Recent commercial modifications of this design, including both liquid and solid bone-equivalent materials, provide slightly different scanning geometries and require scanner-specific cross-calibration to this standard reference using patient data, or development of their own normative databases.
Sequential calibration, abandoned in 1978 because of scanner instabilities, has been resurrected recently by some manufacturers. This method requires duplication of all patient scanning parameters, including size and gantry angulation, but cannot correct for CT number variation due to bowel gas or patient body composition. This technique also requires its own normative data base. Several investigators have published preliminary comparisons of these various techniques in limited patient studies. All the techniques provide a result for trabecular bone mineral density in terms of mg/cm3 relative to the K2HPO4 or calcium hydroxyapatite mineral equivalent standard.
A third technique for measurement of bone by QCT, but without an external reference standard of known composition, has been developed using a patient's own soft tissue for the calibration data. This method relies on major assumptions about the constancy of soft tissue and bone density across a normal population, and therefore results must be interpreted carefully.
How do we interpret QCT results?
QCT, like any bone density measurement, is used to compare a patient to normal control data or to an absolute reference value, and to measure the change in bone density with time in a given patient. Researchers have established a "fracture threshold" level for all bone density methods; patients with bone density above this level are rarely seen with osteoporotic fractures, while below it the prevalence of patients with fractures rises. This level is about 100-110 mg/cm3 for QCT. As the value decreases below this the fracture prevalence increases, so that below 50 mg/cm3 most patients seen already have spinal fractures. The QCT value for a patient, when added to other diagnostic information, can be helpful in deciding an approach to treatment. Serial QCT measurements can establish the rate of change of bone mineral density in both treated and untreated patients, but the sensitivity of the method depends on how well the technique is done at a given hospital. In most cases, a change of 8-10 mg/cm3 can be significant or at least indicate a trend, and several serial measurements all changing the same way improve confidence in the result. Women within 1-3 years after menopause average 7 mg/cm3/yr loss, so yearly measurements can be helpful. Bone loss may be slower in older individuals. The frequency for each patient will depend on other diagnostic and treatment factors, and it is important to interpret the bone density results within the context of each individual's clinical status.
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