BONE DENSITOMETRY

Principles of Bone Densitometry

Bone densitometry^* is a general term encompassing the art and science of measuring the bone mineral content (BMC) and bone mineral density (BMD) of specific skeletal sites or the whole body. The bone measurement values are used to assess bone strength, assist with diagnosis of diseases associated with low bone density (especially osteoporosis), monitor the effects of therapy for such diseases, and predict risk of future fractures.

Several techniques are available to perform bone densitometry using ionizing radiation or ultrasound. The most versatile and widely used is dual energy x-ray absorptiometry (DXA) (Fig. 35-1).¹ This procedure has the advantages of low radiation dose, wide availability, ease of use, short scan time, high-resolution images, good precision, and stable calibration. DXA is the focus of this chapter, but summaries of other procedures are also presented.

Fig. 35-1 A, DXA spine scan being performed on a Hologic model Discovery. B, DXA spine scan being performed on a GE Lunar model Advance. C, DXA whole-body scan being performed on a Norland model XR-46. (A, Courtesy Hologic, Inc, Bedford, MA. B, Courtesy GE Lunar Corp, Madison, WI. C, Courtesy Norland, Inc, Ft. Atkinson, WI.)

DUAL ENERGY X-RAY ABSORPTIOMETRY AND CONVENTIONAL RADIOGRAPHY

The differences between DXA and conventional radiography are as follows:

1. DXA can be conceptualized as a subtraction technique. To quantitate BMD, it is necessary to eliminate the contributions of soft tissue and measure the x-ray attenuation of bone alone. This is accomplished by scanning at two different x-ray photon energies (hence the term dual energy x-ray) and mathematically manipulating the recorded signal to take advantage of the differing attenuation properties of soft tissue and bone at the two energies. The density of the isolated bone is calculated on the basis of the principle that denser, more mineralized bone attenuates (absorbs) more x-ray. Having adequate amounts of artifact-free soft tissue is essential to help ensure the reliability of the bone density results.

2. The bone density results are computed by proprietary software from the x-ray attenuation pattern striking the detector, not from the scan image. Scan images are only for the purpose of confirming correct positioning of the patient and correct placement of the regions of interest (ROI). The images may not be used for diagnosis, and any medical conditions apparent on the image must be followed up by appropriate diagnostic tests. The referring and interpreting physicians must be skilled in interpreting the clinical and statistical aspects of the numeric density results and relating them to the specific patient.

3. In conventional radiography, x-ray machines from different manufacturers are operated in essentially the same manner and produce identical images. This is not the case with DXA. Three major DXA manufacturers are in the United States (see Fig. 39-1), and technologists must be educated about the specific scanner model in their facility. The numeric bone density results cannot be compared between manufacturers without proper standardization. This chapter presents general scan positioning and analysis information, but the manufacturers’ specific procedures must be used when actual scans are performed.

4. The effective radiation dose for DXA is considerably lower than the radiation dose for conventional radiography. The specific personnel requirements vary among states and countries. All bone density technologists should be instructed in core competencies, including radiation protection, patient care, history taking, basic computer operation, knowledge of scanner quality control, patient positioning, scan acquisition and analysis, and proper record keeping and documentation.

History of Bone Densitometry

Osteoporosis was an undetected and overlooked disease until the 1920s, when the advent of x-ray film methods allowed the detection of markedly decreased density in bones. The first publications indicating an interest in bone mass quantification methods appeared in the 1930s, and much of the pioneering work was performed in the field of dentistry. Radiographic absorptiometry involved taking a radiograph of bone with a known standard, placing it in the ROI and optically comparing the densities.

Radiogammetry was introduced in the 1960s, partly in response to the measurements of bone loss performed in astronauts. As bone loss progresses, the thickness of the outer shell of phalanges and metacarpals decreases and the inner cavity enlarges. By measuring and comparing the inner and outer diameter and comparing them, indices of bone loss are established.

In the late 1970s, the emerging technique of computed tomography (CT) (see Chapter 31) was adapted, through the use of specialized software and reference phantoms, enabling quantitative measurement of the central area of the vertebral body, where early bone loss occurs. This technique, called quantitative computed tomography (QCT), is still used.

The first scanners dedicated to bone densitometry appeared in the 1970s and early 1980s. Single photon absorptiometry (SPA) (Fig. 35-2) and dual photon absorptiometry (DPA) are based on physical principles similar to those for DXA. The SPA approach was not a subtraction technique but relied on a water bath or other medium to eliminate the effects of soft tissue. SPA found application only in the peripheral skeleton. DPA used photons of two energies and was used to assess sites in the central skeleton (lumbar spine and proximal femur). The radiation source was a highly collimated beam from a radioisotope (¹²⁵I [iodine-125] for SPA and ¹⁵³Gd [gadolinium-153] for DPA). The intensity of the attenuated beam was measured by a collimated scintillation counter, and the bone mineral was quantified.

Fig. 35-2 SPA wrist scan being performed on a Lunar model SP2. This form of bone densitometry is obsolete. (Courtesy GE Lunar Corp, Madison, WI.)

The first commercial DXA scanner was introduced in 1987. In this scanner, the expensive, rare, and short-lived radioisotope source was replaced with an x-ray tube. Improvements over time have included the choice of pencil-beam or array-beam collimation; a rotating C-arm to allow supine lateral spine imaging; shorter scan time; improved detection of low bone density; improved image quality; and enhanced computer power, multimedia, and networking capabilities.

Since the late 1990s, renewed attention has been given to smaller, more portable, less complex techniques for measuring the peripheral skeleton. This trend has been driven by the introduction of new therapies for osteoporosis and the resultant need for simple, inexpensive screening tests to identify persons with osteoporosis who are at increased risk for fracture. DXA of the hip and spine is still the most widely accepted method for measuring bone density, however, and it remains a superior procedure for monitoring the effects of therapy.

Bone Biology and Remodeling

The skeleton serves the following purposes:

• Supports the body and protects vital organs so that movement, communication, and life processes can be carried on

• Manufactures red blood cells

• Stores the minerals that are necessary for life, including calcium and phosphate

The two basic types of bone are cortical (or compact) and trabecular (or cancellous). Cortical bone forms the dense, compact outer shell of all bones and the shafts of the long bones. It supports weight, resists bending and twisting, and accounts for about 80% of the skeletal mass. Trabecular bone is the delicate, latticework structure within bones that adds strength without excessive weight. It supports compressive loading in the spine, hip, and calcaneus, and it is also found at the ends of long bones, such as the distal radius. The relative amounts of trabecular and cortical bone differ by bone densitometry technique used and anatomic site measured (Table 35-1).

TABLE 35-1

Bone densitometry regions of interest: estimated percentage of trabecular and cortical bone and preferred measurement sites

Data from Bonnick SL: Bone densitometry in clinical practice: application and interpretation, Totowa, NJ, 1998, Humana Press. Humana Press

Bone is constantly going through a remodeling process in which old bone is replaced with new bone. With this bone remodeling process (Fig. 35-3), the equivalent of a new skeleton is formed about every 7 years. Bone-destroying cells called osteoclasts break down and remove old bone, leaving pits. This part of the process is called resorption. Bone-building cells called osteoblasts fill the pits with new bone. This process is called formation. The comparative rates of resorption and formation determine whether bone mass increases (more formation than resorption), remains stable (equal resorption and formation), or decreases (more resorption than formation).

Fig. 35-3 Bone remodeling process. A, Osteoclasts break down bone in the process of resorption. B, Pits in the bone. C, Osteoblasts form new bone. D, With equal amounts of resorption and formation, the bone mass is stable. (From National Osteoporosis Foundation: Boning up on osteoporosis, Washington, DC, 1997, National Osteoporosis Foundation.) National Osteoporosis Foundation

Osteoclasts and osteoblasts operate as a bone-remodeling unit. A properly functioning bone remodeling cycle is a tightly coupled physiologic process in which resorption equals formation, and the net bone mass is maintained. The length of the resorption process is about 1 week compared with a longer formation process of about 3 months. At any point in time, millions of remodeling sites within the body are in different phases of the remodeling cycle or at rest.

When the cycle becomes uncoupled, the result is a net loss of bone mass. Some reasons for uncoupling are enhanced osteoclastic recruitment; impaired osteoblastic activity; and increased number of cycles, which results in shorter time for each cycle. The increased number of cycles favors the shorter resorption phase over the longer formation phase.

Bone mass increases in youth until peak bone mass is reached at approximately 20 to 30 years of age. This is followed by a stable period in middle age. A period of decreasing bone mass starts at approximately age 50 in women and approximately age 65 in men. The decrease in bone mass becomes pronounced in women at menopause because of the loss of bone-preserving estrogen. If the peak bone mass is low or the resorption rate is excessive, or both, at menopause, osteoporosis may result (Fig. 35-4).

Fig. 35-4 Trabecular bone obtained from vertebrae. A, Normal bone. B, Osteoporotic bone. C, Severely osteoporotic bone. Note progressive loss of trabecular continuity resulting from resorptive perforations in the severely osteoporotic subject. (From Eriksen E: Bone histomorphometry, Philadelphia, 1994, Lippincott-Raven.) Lippincott-Raven

Osteoporosis ^*

Osteoporosis is a disease characterized by low bone mass and structural deterioration of bone tissue. This decrease in bone mass and degradation of bone architecture may not support the mechanical stress and loading of normal activity. As a result, the bones are at increased risk for fragility fractures. An estimated 10 million Americans have osteoporosis; 80% (8 million) are women. Another 34 million Americans have low bone mass, putting them at risk of developing osteoporosis and related fractures. Persons with osteoporosis may experience decreased quality of life from the pain, deformity, and disability of fragility fractures. An increased risk of morbidity and mortality exists, especially from hip fractures. In the United States, annual medical costs for osteoporosis, including hospitalization for osteoporotic hip fractures, were $19 billion in 2005, and the cost is increasing. By 2025, it is expected to be $25.3 billion.

Many risk factors for osteoporosis have been identified and studied. The following are considered primary risk factors:

• Female gender

• Increased age

• Estrogen deficiency

• Caucasian race

• Low body weight (<127 lb [>58 kg]) or low body mass index (BMI) (weight in kg divided by height in meters squared), or both

• Family history of osteoporosis or fracture

• History of prior fracture as an adult

• Smoking tobacco

Osteoporosis is often overlooked in older men because it is considered a woman’s disease; however, 2 million American men have osteoporosis, and another 12 million are at risk. Of Americans diagnosed with osteoporosis, 20% are men. In contrast, men sustain 33% of all hip fractures, and one third of these men do not survive 1 year. Men are at risk for the devastating effects of fragility fracture and would benefit from increased prevention, diagnosis, and treatment of osteoporosis.

The exact cause of osteoporosis is unknown, but it is clearly a multifactorial disorder. Major contributors are genetics, metabolic factors regulating internal calcium equilibrium, lifestyle, aging, and menopause. Peak bone mass attained in young adulthood, coupled with the rate of bone loss in older age, determines whether an individual’s bone mass becomes low enough to be diagnosed as osteoporosis. Genetic factors are estimated to account for 70% of the peak bone mass attained. This is why family history is an important risk factor for osteoporosis and fracture. Calcium equilibrium is maintained by a complex mechanism involving hormones (parathyroid, calcitonin, and vitamin D) controlling key ions (calcium, magnesium, and phosphate) within target tissues (blood, intestine, and bone). Calcium and phosphate enter the blood from the intestine and are stored in bone. The process also occurs in reverse, moving calcium out of the bones for other uses within the body. Nutritional and lifestyle factors can upset the balance and cause too much calcium to move out of bone. In the course of normal aging, the loss of estrogen at menopause tends to increase the rate of bone turnover, which increases the number of remodeling cycles and shortens the length of each cycle. Enough time is allowed for the shorter resorption process, but the longer formation process is cut short. Various combinations of these factors can result in a net loss of bone mass and increase the risk of osteoporosis and fracture.

Two points are important to note about osteoporosis. First, an older person with a normal rate of bone loss may still develop osteoporosis if his or her peak bone mass was low. Second, it is a common misconception that proper exercise and diet at menopause prevent bone loss associated with the decrease in estrogen. This is not true. Persons concerned about their risk of osteoporosis should consult their physician.

Osteoporosis can be classified as primary or secondary. A DXA scan result should not automatically lead to a diagnosis of primary osteoporosis. Secondary causes of systemic or localized disturbances in bone mass must be ruled out before a final diagnosis can be made. Proper choice of treatment should be based on the type of osteoporosis and the underlying cause, if secondary osteoporosis is present. The choice of skeletal site to measure depends on the disease process, whether it has a predilection for certain types of bone, and the composition of various skeletal sites (see Table 35-1).

Primary osteoporosis can be type I (postmenopausal) or type II (senile or age-related), or both. Type I osteoporosis is caused by bone resorption exceeding bone formation owing to estrogen deprivation in women. Type II osteoporosis occurs in aging men and women from a decreased ability to build bone.

Secondary osteoporosis is osteoporosis caused by a heterogeneous group of skeletal disorders resulting in imbalance of bone turnover. Disorder categories include genetic, endocrine and metabolic, hypogonadal, connective tissue, nutritional and gastrointestinal, hematologic, malignancy, and use of certain prescription drugs. Common causes of secondary osteoporosis include hyperparathyroidism; gonadal insufficiency (including estrogen deficiency in women and hypogonadism in men); osteomalacia (rickets in children); rheumatoid arthritis; anorexia nervosa; gastrectomy; adult sprue (hypersensitivity to gluten [wheat protein]); multiple myeloma; and use of corticosteroids, heparin, anticonvulsants, or excessive thyroid hormone treatment.

Several prescription medications arrest bone loss and may increase bone mass, including traditional estrogen or hormone replacement therapies, bisphosphonates, selective estrogen receptor modulators, parathyroid hormone, and calcitonin. Other therapies are in clinical trials and may be available in the future (Table 35-2). The availability of therapies beyond the traditional estrogens has led to the widespread use of DXA to diagnose osteoporosis.

TABLE 35-2

Therapies for osteoporosis: some FDA-approved formulations as of 2002

A, antiresorptive; F, formation.

Laboratory tests for biochemical markers of bone turnover may be used in conjunction with DXA to determine the need for or the effectiveness of therapy. Problems of poor precision and individual variability have limited their use. Some markers of bone formation found in blood are alkaline phosphatase, osteocalcin, and C- and N-propeptides of type I collagen. Some markers of bone resorption excreted in urine are pyridinium cross-links of collagen, C- and N-telopeptides of collagen, galactosyl hydroxylysine, and hydroxyproline.

TABLE 35-3

^*A cup of milk or fortified orange juice has about 300 mg of calcium.

From the Office of the Surgeon General’s Report, 2004.

Adequate intake of vitamin D (National Osteoporosis Foundation recommends at least 1000 IU/day for adults >50 years old) is essential for calcium absorption and bone health. Some calcium supplements and most multivitamins contain vitamin D. Dietary sources are vitamin D–fortified milk and cereals, egg yolks, saltwater fish, and liver. The National Osteoporosis Foundation is working on updating its daily minimum requirements.

Weight-bearing exercise occurs when bones and muscles work against gravity as the feet and legs bear the body’s weight. Some examples are weight lifting to improve muscle mass and bone strength, low-impact aerobics, walking or jogging, tennis, dancing, stair climbing, gardening, and household chores.

Physical and Mathematic Principles of Dual Energy X-Ray Absorptiometry

The measurement of bone density requires separation of the x-ray attenuating effects of soft tissue and bone. The mass attenuation coefficients of soft tissue and bone differ and depend on the energy of the x-ray photons. The use of two different photon energies (dual energy x-ray) optimizes the differentiation of soft tissue and bone. GE Lunar model Advance (GE Lunar Corp, Madison, WI) and Norland model XR-46 (Norland, Inc, Ft. Atkinson, WI) use a different method of producing the two energies than Hologic model Discovery (Hologic, Inc, Bedford, MA).

GE Lunar and Norland use a rare-earth, filtered x-ray source. The primary x-ray beam is passed through selected rare-earth filters to produce a spectrum with peaks near 40 kiloelectron volts (keV) and 70 keV compared with the usual continuous spectrum with one peak near 50 keV (Fig. 35-6, A and B). Sophisticated pulse-counting detectors are used to separate and measure the low-energy and high-energy photons (Fig. 35-7). Calibration must be performed externally by scanning a calibration phantom on a regular basis.

Fig. 35-6 Energy spectra (keV) for x-ray sources used in bone densitometry instruments. A, Continuous spectrum from x-ray tube. B, Continuous x-ray spectrum modified by K-edge filter. C, High-energy and low-energy spectra from kV-switching system. (From Blake G et al: The evaluation of osteoporosis: dual energy x-ray absorptiometry and ultrasound in clinical practice, London, 1998, Martin Dunitz.) Martin Dunitz

Fig. 35-7 Schematic drawing of a Norland model XR-35 illustrating the principle of operation of a rare-earth filtered system. A, High-energy detector. B, Low-energy detector. C, Laser indicator. D, Samarium filter module (one fixed, three selectable). E, Ultrastable 100 kV x-ray source.

Hologic scanners use an energy-switching system that synchronously switches the x-ray potential between 100 kVp and 140 kVp. This system produces a primary beam with two photon energies with peaks near 40 keV and 80 keV (see Fig. 35-6, C). The energy-switching system continuously calibrates the beam by passing it through a calibration wheel or drum (Fig. 35-8) containing three sectors for an open-air gap, a soft tissue equivalent, and a bone equivalent. Each sector is divided so that it can differentiate and measure the low-energy and high-energy photons. This permits the use of a relatively simple current-integrating detector that does not have to separate the photons.

Fig. 35-8 Calibration drum used as internal reference standard in Hologic energyswitching instruments. Different segments represent bone standard, soft tissue standard, and empty segment for air value.

Common physics problems of DXA are as follows:

• Beam hardening in energy-switching systems. With increasing body thickness, a higher proportion of low-energy photons are absorbed within the body, shifting the spectral distribution toward high-energy photons.

• Scintillating detector pileup in K-edge filtration systems. A detector can process only one photon at a time and assign it to the high-energy or low-energy channel. An incoming photon may be missed if the preceding photon has not yet been processed. Digital detectors do not have this problem.

• Crossover in K-edge filtration systems. Some high-energy photons lose energy passing through the body and are counted as low-energy photons by the detector. This problem is solved by subtracting a fraction of the highenergy counts from the low-energy channel, depending on body thickness.

The low-energy and high-energy x-rays are attenuated differently within each patient; this produces a unique attenuation pattern at the detector, which is transmitted electronically to the scanner software. Mathematic computations that subtract the soft tissue signals, producing a profile of the bone, are then performed (Fig. 35-9). Proprietary bone edge detection algorithms are next applied, and a two-dimensional area is calculated. The average BMD is calculated for all areas, and finally the BMD is calculated as BMD = BMC II area. The three bone densitometry parameters reported on the DXA printouts are area in centimeters squared (cm²), BMC in grams (g), and BMD in g/cm². BMD is the most widely used parameter because it reduces the effect of body size.

Fig. 35-9 Soft tissue compensation using DXA. By obtaining data at two energies, the soft tissue attenuation can be mathematically eliminated. The remaining attenuation is due to the amount of bone present. (From Faulkner KG: DXA basic science, radiation use and safety, quality assurance, unpublished certification report, personal communication, 1996, Madison, WI.) Madison

BMD can be calculated if BMC and area are known by the equation BMD × BMC II area. This equation can be used to determine if a change in BMD is due to a change in BMC, area, or both. A decrease in BMC results in a decrease in BMD; conversely, a decrease in area results in an increase in BMD. If BMC and area move proportionally in the same direction, BMD remains unchanged. Generally, a change in a patient’s BMD over time should be from a change in BMC, not area. A change in area could be from the technologist not reproducing the baseline positioning or from a change in the software’s bone edge detection. Changes in area over time should be investigated and corrected, if possible.

BMD is based on a two-dimensional area, not a three-dimensional volume, making DXA a projectional, or areal, technique. Techniques to estimate volumetric density from DXA scans have been developed but have not been shown to have any improved diagnostic sensitivity over traditional areal density. Fig. 35-10 shows the lateral spine areal and estimated volumetric BMDs.

Fig. 35-10 Lateral spine BMD scan.

BMD values from scanners made by different manufacturers cannot be directly compared. Mathematic formulas have been developed, however, for converting BMD from any manufacturer to standardized BMD (sBMD) values that can be compared.¹,¹ sBMD values are best used for large populations, such as standardizing a reference population database. They must be used with caution for individuals because the sBMD from one manufacturer can vary by 3% to 6% from the sBMD of either of the other manufacturers. For this reason, it is not widely recommended to use sBMD to compare an individual’s scans done on scanners from different manufacturers.

Pencil-Beam and Array-Beam Techniques

The original DXA scanners employed a pencil-beam system. With this system, a circular pinhole x-ray collimator produces a narrow (or pencil-beam) stream of x-ray photons that is received by a single detector. The pencil-beam of x-ray moves in a serpentine (also called rectilinear or raster) fashion across or along the length of the body (Fig. 35-11). This system has good resolution and reproducibility, but the early scanners had relatively long scan times of 5 to 7 minutes. The pencil-beam system may still be in use but is no longer manufactured (N. Fagan, personal communication, August 2009).

Fig. 35-11 DXA system using pencil-beam single detector.

The array-beam (also called fan-beam) system has a wide “slit” x-ray collimator and a multielement detector (Fig. 35-12). The scanning motion is reduced to only one direction, which greatly reduces scan time and permits supine lateral lumbar spine scans to be performed (Fig. 35-13). The array-beam system introduces geometric magnification and a slight geometric distortion at the outer edges. Consequently, careful centering of the object of interest is necessary to avoid parallax (Fig. 35-14). The software takes into account the known degree of magnification and produces an estimated BMC and estimated area.

Fig. 35-13 DXA system using movable C-arm and array-beam multiple detector to perform lateral supine lumbar spine scan.

Fig. 35-12 DXA system using an array-beam multiple detector.

Fig. 35-14 Potential array-beam errors including magnification (top) and parallax (bottom). Area and BMC are influenced by magnification to the same degree, such that BMD is not significantly affected. Parallax errors can cause changes in BMD by altering the beam path through the object being measured. (From Faulkner KG: DXA basic science, radiation use and safety, quality assurance, unpublished certification report, personal communication, 1996, Madison, WI.) Madison

ACCURACY AND PRECISION

Three statistics are particularly important in bone densitometry: mean, standard deviation (SD), and percent coefficient of variation (%CV).

1. The mean is commonly called the average. It is the sum of the data values divided by the number of values.

2. The SD is a measure of variability that measures the spread of the data values around their mean. It takes into account the average distance of the data values from the mean. The smaller the average distance or the spread, the smaller the SD. This is the goal in bone densitometry—a smaller SD is better. Fig. 35-15 plots two sets of phantom BMD data measured over 6 months. The means are the same (1.005 g/cm²), but the red data set has an SD that is twice as large as that of the green data set (0.008 g/cm² vs. 0.004 g/cm²). It is better to have phantom BMD data that look like the green data set.

Fig. 35-15 Two datasets of longitudinal phantom BMD (blue line is mean). Green data set has mean = 1.005 g/cm², SD = 0.004 g/cm², and %CV = 0.35. Red data set has mean = 1.005 g/cm², SD = 0.008 g/cm², and %CV = 0.81.

3. The %CV is a statistic that allows the comparison of variability between different data sets, whether or not they have the same mean. A smaller %CV means less variability and is preferred in bone densitometry. The %CV is calculated using the following equation:

%CV =(SD/Mean) × 100

In Fig. 35-14, the green data set has a %CV of 0.35, and the red data set has a %CV of 0.81. This is the %CV that must be checked on a Hologic spine phantom plot (Fig. 35-16). The red data set would not pass the criteria that the %CV should be less than or equal to 0.6. The %CV is also used to express precision.