The Role of the Radiologist When Encountering Osteoporosis in Women

Women s Imaging Perspective Bennett and Post Role of Radiologists in Osteoporosis in Women Women s Imaging Perspective FOCUS ON: D. Lee Bennett 1 Robert D. Post Bennett DL, Post RD Keywords: bisphosphonate, medical imaging, osteoporosis, osteoporotic vertebral fracture, women s imaging DOI:10.2214/AJR.10.5606 1 Both authors: Department of Radiology, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, 200 Hawkins Dr., Iowa City, IA 52246. Address correspondence to D. L. Bennett (lee-bennett@uiowa.edu). AJR 2011; 196:331 337 0361 803X/11/1962 331 American Roentgen Ray Society WOMEN S IMAGING Received August 25, 2010; accepted after revision October 17, 2010. The Role of the Radiologist When Encountering Osteoporosis in Women OBJECTIVE. This article describes the extent and potentially devastating consequences of osteoporosis in adult women. There is discussion of the importance of radiologists in the correct diagnosis and reporting of probable osteoporotic vertebral fractures on medical imaging studies. CONCLUSION. The Genant semiquantitative method for diagnosing osteoporotic vertebral fractures is presented. The importance of dual-energy x-ray absorptiometry reproducibility is also briefly discussed. Osteoporosis in Women Definition In women, primary osteoporosis is defined as a bone mineral density (BMD) of 2.5 SD below that of a young healthy adult (i.e., a T- score at or below 2.5). Restrictions of this definition are that it must be based on a BMD measurement optimally obtained with two sites at the spine, hip, or forearm by use of a dual-energy x-ray absorptiometry (DXA) device, with forearm DXA measurements limited to patients without an alternate second site (e.g., spine or either hip); the patient should be postmenopausal; and a cause for secondary osteoporosis should not be present [1 3]. Please note that young healthy refers to the normative data from the most recent National Health and Nutrition Examination survey (currently survey III) for white women aged 20 29 years [4]. Significance and Epidemiology of Osteoporosis Primary osteoporosis affects a large number of people worldwide, involving at least 75 million people in the United States, Europe, and Japan alone. In the United States, 10 million people are estimated to have osteoporosis, of which 8 million are women. To put this in perspective, 8 million is roughly the entire population of New York City. Of these 8 million people, 50% will experience an osteoporosis-related fracture. According to estimated figures, osteoporosis was responsible for more than 2 million fractures in 2005, including approximately 297,000 hip fractures, 547,000 vertebral body fractures, 397,000 wrist fractures, 135,000 pelvic fractures, and 675,000 fractures at other sites. The number of fractures due to osteoporosis is expected to increase to more than 3 million by 2025 [3]. Vertebral fractures are a frequent consequence of osteoporosis. As one of the more common kinds of fractures in the United States, with an occurrence rate of approximately 700,000 cases per year [5], an estimated 547,000 vertebral fractures are secondary to osteoporosis [2]. Vertebral fractures cause back pain and lead to loss of mobility and pulmonary difficulties [6]. With regard to hip fractures, on average, 24% of patients with hip fractures who are 50 years old and older die during the year following their fracture. One (20%) of five patients who were ambulatory before their hip fracture requires long-term care afterward. At 6 months after a hip fracture, only 15% of patients can ambulate across a room without help [2]. Importance of Diagnosis and Treatment Osteoporotic fractures and their concomitant association with mortality and morbidity are potentially preventable. Bisphosphonates are one of the advancements in the treatment of osteoporosis in the past decade, with results of clinical trials showing risk reductions of 40 50% for osteoporosis-associated vertebral fractures and 20 40% for nonvertebral fractures, including hip fractures [7 10]. Because there is increased morbidity and mortality with osteoporosis-associated AJR:196, February 2011 331

Bennett and Post fractures, decreasing their incidence (such as with bisphosphonates) will decrease the ageadjusted morbidity and mortality rates in patients with osteoporosis. Therefore, it is desirable to diagnose osteoporosis as early as reasonably possible so that treatment can be instituted before the first osteoporosis-associated fracture occurs or before additional fractures occur. When Should Screening Occur? Screening for osteoporosis is indicated in women [2] 65 years old and older; who are postmenopausal or perimenopausal and have risk factors for fracture; who have a fragility fracture, regardless of age or menopausal status; or who have a disease or condition or take a medication associated with low bone mass or bone loss. It should be noted that radiologists can play a role in the diagnosis of fragility or insufficiency fractures even if they are not involved in interpreting screening DXA studies. The Valuable Role of the Radiologist in the Diagnosis of Osteoporosis Identifying and Reporting Fragility and Insufficiency Fractures How can the radiologist help patients with undiagnosed osteoporosis? One immediate response would be to say that radiologists can report fragility and insufficiency fractures (even when they are incidental and asymp tomatic) and make recommendations or suggestions for BMD testing if clinically warranted. Radiologists also play a role in notifying the referring physician that the fracture identified is not an osteoporotic fracture but is due to some other cause (e.g., a pathologic fracture due to metastatic disease or an insufficiency fracture due to Paget disease), thereby preventing unnecessary BMD testing in women younger than 65 years. The most common type of insufficiency fracture in a patient with osteoporosis is of the vertebra. Unfortunately, large-scale prospective studies have found that only about one-fourth of incident radiographic vertebral osteoporotic fractures are diagnosed [11]. Retrospective studies of standard upright posteroanterior and lateral chest radiographs obtained in emergency treatment centers revealed a 55 65% diagnosis rate for osteoporotic vertebral fractures [12, 13]. Even more concerning is that one of these studies found that only about one-fourth (25%) of patients with osteoporotic vertebral fractures already had a diagnosis of osteoporosis. Therefore, three-fourths (75%) of the patients in this study with an osteoporotic vertebral fracture needed screening. In a follow-up study of these patients, a chart review showed that, of those patients with an osteoporotic vertebral fracture, osteoporosis was more likely to have been screened for, diagnosed, and treated if the official radiology report just mentioned the presence of a vertebral fracture without necessarily any recommendation for osteoporosis screening (37% of patients were screened for osteoporosis if the fracture was reported and only 7% were screened if the fracture was not reported) [13]. These results would tend to support the importance of radiologists diagnosing and reporting unexpected osteoporotic vertebral fractures. Surprisingly, the trend of underreporting appears to be even worse with MDCT studies of the chest. A recent retrospective chronological study discovered a diagnosis rate for osteoporotic vertebral fractures of only 13% by radiologists (based on their official radiology report) on MDCT in the emergency treatment center setting [14]. Fig. 1 65-year-old woman with facet arthropathy in lumbar spine. Radiograph shows potential pitfall of overdiagnosing osteoporotic fracture that parallax can cause. One might mistakenly measure vertebral body height from closest projecting vertebral body endplates (black line) and overdiagnose vertebral fracture. However, correctly corresponding vertebral endplate lines are shown by white line. The Difficulty in Reporting Osteoporotic Vertebral Fractures: Is It Really an Osteoporotic Vertebral Fracture? The standard imaging approach for assessment of vertebral fracture is radiography of the thoracolumbar spine; however, there is no universal reference standard for the definition of osteoporotic vertebral fracture [15], because the normal radiographic appearance of the vertebrae can vary, parallax effect can cause normal vertebrae to appear compressed (Fig. 1), and strict morphometric measurements on radiographs can overor underestimate osteoporotic fractures [16, 17]. The Genant semiquantitative method is and has been used as a surrogate reference standard in several studies of osteoporosis [16 18]. The reported inter- and intraobserver agreement is substantial [16]. Genant Semiquantitative Method for Diagnosing Osteoporotic Vertebral Fractures and Reporting Osteoporotic Fractures The method for evaluating vertebrae for an osteoporotic fracture is shown in Figure 2. Twenty percent or more loss of height in the anterior aspect (wedge fracture), middle aspect (biconcave fracture), or posterior aspect (crush fracture) is diagnosed as an osteoporotic fracture [19] (Fig. 2). Radiographic examples of wedge, biconcave, and crush fractures are shown in Figures 3, 4, and 5. This method is known as the semiquantitative method because it is essential that changes at the vertebral endplate, changes along the cortical margin, the presence of a normal variant (Fig. 6), and lack of consistency with adjacent vertebrae need to be taken into consideration when diagnosing an osteoporotic vertebral fracture [19]. A strong knowledge of mimickers of osteoporotic vertebral fractures will help the radiologist correctly diagnose osteoporotic vertebral fractures and not overcall them. Some of the more common mimickers are normal variants (e.g., Cupid s bow or limbus vertebra), metastatic disease (including marrow tumors such as multiple myeloma), Scheuermann disease (Fig. 7), and Schmorl nodes. The mechanisms of injury and history need to be considered also when diagnosing 332 AJR:196, February 2011

Role of Radiologists in Osteoporosis in Women Fig. 2 Diagram of Genant semiquantitative method for diagnosing osteoporotic vertebral fractures. Vertebra that is suspicious for being fractured should be carefully compared with adjacent vertebrae to rule out normal variants or Scheuermann disease. Fractured vertebra also needs to be carefully inspected for any evidence of nonosteoporotic vertebral fracture (e.g., metastasis or multiple myeloma). Osteoporotic vertebral fracture is diagnosed if there is more than 20% loss of height at site of maximum compression and there are no nonosteoporotic causes of fracture. Type of fracture should also be described in report as wedge, biconcave, or crush (predominantly anterior, midportion, or posterior compression, respectively). Reprinted from [32]. Fig. 3 70-yearold woman with osteoporotic fracture. L1 vertebra (asterisk) shows severe (grade 3, > 40% loss of height) wedge osteoporotic fracture. a probable osteoporotic vertebral fracture. The history is relevant in that vertebral fractures associated with significant trauma may not be osteoporotic in nature. The radiologist should not be dissuaded from diagnosing an acute or subacute osteoporotic vertebral fracture in the absence of back pain. In addition, the presence or absence of a paraspinal mass or hematoma can aid in determining whether a vertebral fracture is acute or nonacute. Clinically silent radiographically confirmed osteoporotic vertebral fractures do occur [20]. In one study that followed patients after treatment of osteoporotic vertebral fractures, 50% of new osteoporotic vertebral fractures were asymptomatic [21]. Therefore, one should be careful in assuming that a painless vertebral fracture seen incidentally on a chest radiograph is an old injury. Please note that the 50% statistic quoted above may not be correct for patients without known osteoporosis because that study focused on patients who already had a diagnosis of osteoporosis. The radiologist can increase the likelihood that a referring physician will make a new clinical diagnosis of osteoporosis in a patient by reporting vertebral fractures as probable osteoporotic vertebral fractures (when appropriate), thus increasing the likelihood of treatment and, therefore, the prevention of future osteoporotic fractures in the spine, hip, wrist, and elsewhere [13]. This will most likely help decrease the elevated mortality and morbidity rates in women diagnosed with osteoporosis. Depending on the rapport the radiologist has with the referring physician, one can possibly recommend BMD testing with DXA in the radiology report when probable osteoporotic fractures are detected. This, of course, is subject to the discretion of the referring provider. The correct diagnosis and reporting of probable osteoporotic vertebral fractures by the radiologist affects patient treatment by enabling the diagnosis of osteoporosis, helps select patients for effective pharmacologic therapy, improves the physician s ability to correctly assess the risk of future fracture, and provides a documented rationale for BMD testing. Radiologist s Role in Complications Resulting From Therapy: Bisphosphonates and Fractures of the Subtrochanteric Femur An association between long-term bisphosphonate therapy and low-energy insufficiency subtrochanteric femoral fractures has been recently reported [22 24]. Data from three large placebo-controlled randomized trials indicate that the risk of fracture of the subtrochanteric or diaphyseal femur associated with the use of bisphosphonates was low. There were 12 subtrochanteric femoral insufficiency fractures during 51,287 patient-years in the three studies; the combined rate was 2.3 fractures per 10,000 patient-years [25]. Even among women with up to 10 years of bisphosphonate treatment, the risk of fracture of the subtrochanteric or diaphyseal femur ranged from one to six cases per 10,000 patient-years. However, the radiologist should be aware that results from case series suggest that, in patients taking bisphosphonates who have persistent thigh pain, evidence of an incomplete insufficiency fracture or a contralateral femur fracture should prompt consideration of further testing and AJR:196, February 2011 333

Bennett and Post possible interventions [22 25]. From case studies, factors for increased likelihood of having a subtrochanteric insufficiency fracture of the femur in patients receiving bisphosphonates are corticosteroid use, proton-pump inhibitor use, and markedly suppressed bone turnover (perhaps owing to the use of multiple antiresorptive medications). This fracture tends to be transverse in orientation and located in the subtrochanteric region of the femur (Fig. 8). This fracture can be preceded by signs of uninterrupted periostitis (Fig. 8A). Fig. 4 90-year-old woman with multiple osteoporotic fractures. Diffuse demineralization of bones is present. There is moderate (grade 2, 26 40% loss of height) biconcave fracture (black asterisk) of T5 vertebra. T6 vertebra (white asterisk) does not have probable osteoporotic fracture because any height loss is less than 20%. Diagnosing Osteoporosis in Women Women Older Than 50 Years In women older than 50 years, primary osteoporosis is defined as a BMD of 2.5 SD below that of a young healthy adult (T-score at or below 2.5). Restrictions of this definition are that it should be based on a BMD measurement optimally obtained with two sites at the spine, hip, or forearm by use of a DXA device, with forearm DXA measurements limited to patients without an alternative second site (e.g. spine or either hip); the patient should be postmenopausal; and a cause for secondary osteoporosis should not be present [1 3]. Please note that young healthy refers to the normative data from the most recent National Health and Nutrition Examination survey (currently survey III) for white women aged 20 29 years [4]. In premenopausal women younger than 50 years, the Z score (which is age and population matched, unlike the T-score which is age matched to 20 29-year-old white women) is used for determining whether the patient has low BMD. The use of peripheral measurements, including quantitative ultrasound, can suggest low BMD; however, such measurements are not thought to be diagnostic of low BMD or osteoporosis. They are not currently recommended for diagnostic purposes by published guidelines [2, 26, 27]. Important Considerations for Radiologists Performing DXA Scans Lack of reproducibility of BMD measurements using DXA can be a problem. This lack of reproducibility can be due to variation in patient positioning, lack of consistency in data analysis, and the inherent precision error of the technique. Some common operator errors include poor patient positioning, inconsistent selection of vertebral levels, poor placement of disk markers for the lumbar spine, improper hip rotation, and the inconsistent determination of regions of interest for the hip [26]. A For a facility to have the best reproducibility, calibration and precision assessment should be done. Each DXA facility should determine its precision error and calculate its own least significant change; the precision error supplied by the manufacturer should not be used. An average precision error and least significant change should be calculated by combining the data of all technologists if each of the technologist s performance is within the preestablished acceptable range. More detailed information on how to calculate this precision assessment can be found in the medical literature [2]. Each technologist must perform an in vivo precision assessment when starting at your clinic using representative patients from your patient population. Precision assessment of technologists should occur after initial training, after the first 100 scans, when new DXA equipment is installed, and if the technologist s skill level has changed [2]. Maximizing precision in follow-up studies is also essential for determining the success of treatment or the progression of disease. To maximize follow-up precision, it is essential (if at all possible) to perform the followup study on the same machine as the prior studies. At the very least, the follow-up study should be done on the same type of machine or on a machine by the same manufacturer. If this is impossible, then one should use the standardized BMD that has been developed in an attempt to address this unfortunate scenario [28]. Fig. 5 95-year-old woman with multiple osteoporotic fractures. A, Radiograph shows mild (grade 1, 20 25% loss of height posteriorly) crush fracture (black asterisk) of L5 vertebra. L4 vertebral body moderate biconcave fracture (white asterisk) (26 40% loss of height centrally) is also seen. B, T1-weighted MRI scan shows fractures to better advantage. Biconcave fracture (white asterisk) is more acute as evidenced by horizontally oriented bandlike edema at superior endplate (low signal). L5 crush fracture (black asterisk) is old because vertebra contains all fatlike signal. B 334 AJR:196, February 2011

Role of Radiologists in Osteoporosis in Women Fig. 6 55-year-old woman with Cupid s bow normal variant. Lumbar spine radiographs show Cupid s bow normal variant in lower lumbar spine. A, On lateral view, inferior endplates at L4 and L5 show unusual indentation of posterior aspect of inferior endplates (arrows). B, Anteroposterior view shows classic biconcave Cupid s bow facing cephalad at L4 (superimposed black outline) and L5 (arrows). This is normal variant and should not be confused with osteoporotic compression fracture or other abnormality [33]. Fig. 7 50-year-old woman with Scheuermann disease. Lateral radiograph of spine shows anterior wedging of multiple vertebrae with accompanying endplate irregularities (arrows) and kyphosis. These are imaging hallmarks of Scheuermann disease [34] and should not be confused with osteoporotic vertebral fractures. A If you have access to a DXA machine with vertebral fracture assessment that provides lateral views and semiautomated software for evaluating vertebral body morphometry [19], then the vertebral fracture assessment should be reported from T4 to L4 inclusively, along with the BMD results [28]. The Genant semiquantitative method is the current technique of choice in identifying osteoporotic vertebral fractures with DXA (as well as radiographs). Vertebral fracture assessment reports should comment on unevaluable vertebrae, deformed vertebrae not consistent with a fracture, and any unexplained vertebral or extravertebral pathologic abnormality. Some indications for follow-up diagnostic imaging B A studies (typically CT or MRI) include two or more grade 1 deformities (with no grade 2 or 3), vertebral lesions that are not benign, and vertebral deformities in a patient with known malignancy [2]. Finally, the World Health Organization s Fracture Risk Assessment Tool can be used to calculate the patient s risk of a future osteoporotic fracture, which can then be reported. The calculator can be found at www.sheffield.ac.uk/frax/. Finally, a succinct but thorough DXA report is essential in maximizing communication between the referring physician and the radiologist [28]. Quantitative CT for Measuring BMD Quantitative CT (QCT) of the spine is another accepted test for determining whether an elderly postmenopausal woman has low BMD. The precision of 3D volumetric QCT is comparable to that of DXA [27, 29]. Like DXA, QCT requires highly trained, motivated, and meticulous technologists in order Fig. 8 89-year-old woman with osteoporosis and long-term treatment with bisphosphonate. A, First anteroposterior radiograph of left hip shows lateral cortical thickening and uninterrupted periostitis (arrow) in left femur (also described as cortical beaking). This represents incomplete insufficiency fracture secondary to long-term bisphosphonate treatment. B, Patient later went on to complete fracture at this level. B AJR:196, February 2011 335

Bennett and Post for the precision to be comparable to that of DXA. QCT cannot diagnose osteoporosis according to current guidelines [1, 2], per se, but it can determine whether a patient has low BMD. QCT is a 3D volumetric measurement of BMD (using helical CT) that provides spatial separation of trabecular from cortical bone; therefore, it is useful in identifying low BMD in patients with extensive degenerative changes of the spine. Degenerative changes of the spine can cause a false-negative DXA result. QCT is also used to follow up patients previously diagnosed with osteoporosis or low BMD to determine whether their current treatment is effective in preventing continued BMD decrease. QCT is usually not recommended in premenopausal women because of the higher radiation exposure relative to DXA [27]. However, in state-of-the-art spiral MDCT scanners, automodulation software is available to significantly reduce radiation exposure to the patient. In addition, a lower CT dosage can be used in QCT because the same image quality as used for diagnostic CT is not necessary with QCT [29]. MRI in Osteoporosis MRI is currently used in researching osteoporosis to further improve our understanding of this disease. MRI studies have primarily focused on evaluating trabecular bone structure in the calcaneus, distal tibia, and distal radius, where trabecular bone is normally quite prominent. Using high-resolution MRI, researchers have found differences in trabecular bone structure of the calcaneus that can differentiate between postmenopausal women with and without osteoporotic hip fractures [30]. Another study showed that high-resolution MRI of the distal radial trabecular bone correlated with patients spinal deformity index (a quantitative measure of the number and severity of osteoporotic vertebral fractures) independently of the BMD [31]. At present, MRI is not used in the routine clinical evaluation of osteoporosis; however, it could become a useful clinical tool in the future. Summary The correct diagnosis and reporting of a probable osteoporotic vertebral fracture by radiologists affects patient treatment by enabling the diagnosis of osteoporosis, helping select patients for effective pharmacologic therapy, improving the physician s ability to correctly assess the risk of future fracture, and providing a documented rationale for BMD testing. Given improved treatments and better diagnostic tests for low BMD, now is the time for some of us to renew our efforts in reporting these fractures [19, 32]. The Genant semiquantitative method is the current technique of choice in identifying osteoporotic vertebral fractures with DXA and radiographs. 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