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Low back pain

S Kunanayagam^1,*, MRCP, Dip. Med. Elderly, D Harichandra², MD, MMed, S Sargunan¹, MBBS, MMed

¹ Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
² Department of Biomedical Imaging, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia

A 68-year-old woman presented to the orthopaedics clinic with a 3-month history of low back pain. She was unable to recall any falls recently but claimed to have first felt the pain when she tried to look for her cat in the drain after it went missing. She had taken paracetamol regularly for the pain. However, the pain persisted so she decided to see a doctor. There were no other significant medical illnesses such as diabetes, hypertension or renal impairment.

On physical examination, there were no positive findings except for a mild kyphosis and tenderness over the thoraco-lumbar junction. Plain radiographs of her spine and a Dual Energy X-ray Absorptiometry (DEXA) study of her spine and femur were performed (Figures 1 and 2).

Questions:

1.        What is the most likely diagnosis?

2.        What is the differential diagnosis and how are they distinguished using the imaging methods available?

3.        What are the limitations of the imaging method that is used to diagnose this condition?

4.        This condition has obvious serious complications. What are the risk factors and how are they currently managed?

Answers:

1. What is the most likely diagnosis?

On the plain radiographs of the spine, there is generalized osteopenia with loss of the heights of the L1, L2, and L3 vertebral bodies with preservation of the disc spaces (cod fish vertebra) (Figures 1a and 1b in the answer). There are no associated soft tissue masses and the pedicles appear intact. No evidence of any erosion of the ribs or pelvic bones. The loss of heights of the vertebral spaces indicates an obvious compression fracture of the L1, L2 and L3, which is most likely due to osteoporosis.

The DEXA of the spine (Figure 2a) shows the T scores for L1-L5 range from -1.9 to -2.8. The mean T-score of L2-L4 lumbar vertebra was -2.3. The DEXA of the hip (Figure 2b) shows femoral neck T-score of -3.0 and Total T-score of -2.4.

The higher bone mineral density values for L1 and L3 are related to the compression fractures. The L2 vertebra although having a lower bone mineral density appears collapsed in the plain film. Compression fractures give a higher bone mineral density values and consequently may increase the T score value. Thus, they are not reflective of the true density of the vertebra. In this case, the L4 lumbar vertebra with the T-score of -2.8 should be used as the reference vertebra.

These findings then would be consistent with severe (established) osteoporosis.

2. What is the differential diagnosis and how are they distinguished using the imaging methods available?

The important differential diagnosis in this situation would be:

1.        Pathological fractures due to metastatic lesions.

2.        Pathological fractures due to benign lesions.

Since most bony metastases are haematogeneous in origin, the axial skeleton with its abundant vascularisation and red bone marrow, is the most common site of skeletal metastases (39%) [1]. However, osteoporotic compression fractures, which occur commonly, can be confused with metastatic compression fracture in the acute phase. Since the prognosis and management differs in these two entities, accurate diagnosis is important [2]. Although metastases on plain radiographs are classically associated with soft tissue masses and destruction of the pedicles, these findings have low sensitivity.

In today�s clinical environment, the specific discrimination between benign and malignant vertebral compression fractures relies heavily on magnetic resonance (MR) imaging features.

However, a confident diagnosis is not always possible in routine MR sequences because signal changes can be similar [3]. Common morphologic signs for assessing the cause of the fracture include the degree and pattern of bone marrow replacement, multiplicity of lesions, para-vertebral soft tissue masses and infiltration of posterior elements of the vertebra that indicate metastatic lesions [4]. Benign vertebral fractures may have enhancement after intravenous administration of contrast media due to breach in blood tissue barrier [5]. When the findings on routine MR sequences are inconclusive for the diagnosis of acute benign or malignant vertebral body compression fracture, the use of diffusion weighted MR sequence is recommended [6]. Malignant pathological fractures have high signal intensity compared to normal bone marrow (Figure 4), while benign osteoporotic and traumatic fractures are found to be low in signal intensity (Figure 3). Diffusion weighted imaging (DWI) has a higher specificity (92%) in detecting malignant vertebral compression fractures than the contrast enhanced MR images although the usefulness and efficacy is still controversial [7]. However, in another study it was found that absence of contrast enhancement had a high negative predictive value (90%) while steady-state free-precession (SSFP) DWI had both a high positive predictive value (90%) and high negative predictive value (90%) in detecting malignant vertebral compression fractures. This study also found that the ratio of lesion intensity technique offers another excellent criterion to differentiate between benign and malignant lesions [8].

3. What are the limitations of the imaging method that is used to diagnose this condition?

Osteoporosis is a skeletal disorder characterized by low bone mass, microarchitectural disruption and increased skeletal fragility. The presence of low bone mass is usually determined by radiologic testing. Plain radiographs can demonstrate osteopenia.

Quantitative X-ray densitometry gives an accurate estimate of bone mineral density (BMD) and is the method of choice.

The difference between the patient�s BMD and that of a healthy young adult is referred to as a standard deviation (SD). As outlined in the World Health Organization�s diagnostic categories, individuals whose T-score is within one standard deviation of the �norm� are considered to have normal bone density. Scores below the �norm� are indicated in negative numbers. For example, a score from -1 to -2.5 SD below the norm indicates low bone mass, or osteopenia, and a score of more than -2.5 SD below the norm is considered a diagnosis of osteoporosis. For most BMD tests, -1 SD equals a 10 to 12% decrease in bone density (Table 1). Since there are many more persons with osteopenia than persons with osteoporosis, approximately half of fragility fractures occur in the osteopenic group, although the relative risk of fracture is higher in the osteoporotic population. An additional procedure called Lateral Vertebral Assessment (LVA) (using the DEXA machine to obtain a lateral view of the lumbosacral spine) may be used to screen for vertebral fractures. It may be recommended for older patients, especially if they have lost more than an inch of height, have unexplained back pain, or if the DEXA scan gives borderline readings. The increased risk, if the patient has evidence of fracture, would influence decisions with regards to treatment. The current recommendation is to perform dual-energy X-ray absorptiometry of the lumbar vertebra (L1 to L4), the hip [including the femoral neck, Ward�s triangle, the greater trochanter, and the total hip (which includes all these measures)] or both (Figures 1 and 2). The results are presented visually, including both T scores and Z scores (the bone density in the patient as compared with other people of the same age and size expressed as the number of SDs above or below the mean). The BMD measurements of the hip, femoral neck and total hip, in particular, are the most useful in predicting fracture, whereas measurements of Ward�s triangle show great variation and are of little clinical value. Although it has been suggested that the WHO definition of osteoporosis should be reserved for patients with low T scores for the total hip, low T scores at other sites are also considered diagnostic of osteoporosis. Spinal measurements may be particularly important in younger postmenopausal women, since they may show osteoporotic values earlier than the hip measurements.

Z scores are more informative than T scores in young persons, since the scoring allows comparison of bone density with persons of similar age, height, and weight. Generally, a Z score of -2.0 or lower is considered an indication of the need for more intensive evaluation of possible secondary causes of bone loss, although such causes should be considered in all cases. The decision to test for BMD should be based on an individual�s risk profile, and testing is never indicated unless the results could influence a treatment decision.

However, using DEXA as the gold standard has its limitations especially in older women, where sclerotic changes that occur with age, largely owing to osteoarthritis, may result in an artefactual increase in measured BMD. The presence of vertebral compression fractures or osteoarthritis may interfere with the accuracy of the test. CT scans may be more useful in such instances. A careful examination of the actual DEXA printout may help resolve this issue. However, in such instances, clinical history, a thorough re-assessment of the patient�s risk factors and spinal radiographs will help in establishing a diagnosis of osteoporosis.

The sites at which the DEXA measurements are taken (either centrally or peripherally [pDEXA]) also have an important bearing on the validity of the examination. Central DEXA devices are more sensitive than pDEXA devices but they are also somewhat more expensive. The peripheral devices do not accurately follow changes in bones during therapy. A pDEXA on heel or wrist, may help predict the risk of fracture in the spine or hip but since bone mass tends to vary from one location to the other, measuring the heel is not as accurate as measuring the spine or hip. Small changes may normally be observed between scans due to differences in positioning and may not be significant. BMD measurement in the forearm bone is not used routinely but is recommended for patients with primary hyperparathyroidism, since this site may show the greatest bone loss. Most importantly, the examination must be done with great care to maximise accuracy.

In addition, DEXA cannot predict who will experience fractures but will indicate relative risk. BMD can also be measured by quantitative computed tomography (QCT). This technique can analyze trabecular and cortical bone separately and is a sensitive measure of early bone loss in the vertebra. However, the application of T scores to predict the risk of fracture with the use of quantitative CT has not been validated, and this technique is usually more costly and results in greater exposure to radiation than does DEXA.

4. This condition has obvious serious complications. What are the risk factors and how are they currently managed?

The National Osteoporosis Foundation (NOF) Physicians� Guide to Prevention and Treatment of Osteoporosis [9] suggests BMD testing should be performed on:

●         All women aged 65 and older regardless of risk factors.

●         Younger postmenopausal women with one or more risk factors (other than being Caucasian, postmenopausal and female).

●         Postmenopausal women who present with fractures (to confirm the diagnosis and determine disease severity).

The risk factors for this condition are listed in Table 2. The most important risk factor for fracture, independent of BMD, is a previous fragility fracture. Falls are another important predictor, particularly for hip fractures in the elderly. Hence, factors that increase the risk of falling - such as impaired vision, neuromuscular deficits, or medications that affect balance - should also be assessed. Screening for osteoporosis should ideally provide an estimate of the absolute risk of any fragility fracture during the subsequent 5 or 10 years. Estimates of relative risk associated with various factors differ among studies, but there is general consensus regarding the importance of several key factors in risk assessment.

For example, the absolute 10-year risk of a fragility fracture in a postmenopausal woman with a T score of -2.5 or less and no other risk factors is less than 5 percent at the age of 50 but more than 20 percent at the age of 65. Absolute risk increases further with additional risk factors, particularly with a previous fragility fracture. In postmenopausal Caucasian women, the relative risk of fracture is increased by a factor of 1.5 to 3 for each decrease of 1.0 in the T score, depending on the site measured. The relative risk increases by a factor of 2 to 3 per decade after the age of 50. The risk increases by a factor of 1.2 to 2 for patients who have a family history of fracture in a first-degree relative, who weigh less than 126 lb (57 kg), who have recently lost 10 lb or more of weight, who had a delayed menarche (e.g., at an age of more than 15 years), or who currently smoke. These factors are also associated with a greater likelihood of low BMD [10]. Osteoporosis has no clinical manifestations until there is a fracture. One in two women and one in four men over age 50 will have an osteoporosis-related fracture in her/his remaining lifetime. Osteoporosis is responsible for more than 1.5 million fractures annually. Vertebral fractures are the most important clinical manifestation of osteoporosis. Successive crush fractures can lead to an increased thoracic (dorsal) kyphosis with height loss and the development of �dowager�s hump� [11].

Other fractures include hip fractures that are relatively common affecting 15% of women and 5% of men by the age of 80. The rate of hip fractures is two to three times higher in women than men; however, the one-year mortality following a hip fracture is nearly twice as high for men as for women. A woman�s risk of hip fracture is equal to her combined risk of breast, uterine and ovarian cancer. An average of 24% of hip fracture patients aged 50 and over dies in the year following their fracture. One in five of those who were ambulatory before their hip fracture required long-term care afterward. At 6 months after a hip fracture, only 15% of patients could walk across a room unaided. Vertebral fractures are also linked with an increased risk of death. In addition, distal radial fractures (Colles� fractures) may occur.

Prevention and treatment of osteoporosis consists of non-pharmacological, pharmacological or hormonal therapy.

Pharmacologic therapy

Among the antiresorptive therapies, bisphosphonates such as alendronate and risedronate have demonstrated consistent efficacy in reducing vertebral and non-vertebral fracture risk. Once-weekly alendronate and risedronate produced similar improvements in BMD compared with their once-daily counterparts with similar tolerability. Daily injections of teriparatide resulted in statistically significant reductions in the risk of vertebral and non-vertebral fractures. Trials of ibandronate, raloxifene and calcitonin nasal spray showed reductions in vertebral fracture risk. Hormone therapy has demonstrated clinical fracture risk reduction; however, safety outcomes from the Women�s Health Initiative study have raised concerns regarding long-term use of these preparations [12].

Non-pharmacological therapy

Non-pharmacologic therapy consists of three components:

1.        Diet: an optimal intake of calories is needed to prevent malnutrition. Post menopausal women and older men (above 65 years old) should take an adequate amount of elemental calcium i.e. 500-1000 mg/day [13] and vitamin D. Women should ingest approximately 800 IU vitamin D per day with higher doses required for those with malabsorption and patients on concomitant anticonvulsant therapy.

2.        Exercise: women with osteoporosis or those aiming to prevent it should exercise for at least 30 minutes three times per week. Exercise has been associated with an improvement in BMD and decreased risk of hip fractures in women [14].

3.        Cessation of smoking: Smoking one pack per day throughout adult life is associated with a 5 to 10% reduction in bone density [15].

Discussion

The case discussed illustrates the importance of considering the diagnosis of osteoporosis in a patient with low back pain. As shown in the answer to question 1, plain radiographs of the spine are often sufficient to make a diagnosis of osteoporosis, hence treatment can be initiated. This is a readily available imaging method.

Question 2 addresses the importance of the differential diagnosis, in this case a metastatic compression fracture. Treatment and approach will be different; hence an MRI will be important when the clinical suspicion is high. DWI MRI can give a clearer picture to the clinical scenario when the physician needs to differentiate between an osteoporotic and a malignant fracture.

BMD is a popular method used to diagnose osteoporosis. It is a screening test, which is not without its limitations. The decision to subject a patient to a DEXA scan is based upon a set of criteria while the decision to treat osteoporosis is based on a careful study of the patient�s BMD.

The risk factor for a new osteoporotic fracture is a previous fragility fracture. It is important to note that falls need to be prevented in the first place. Untreated fractures can lead to significant immobility in the elderly which predispose them to the need for long-term care. Bisphosphonates such as alendronate and risedronate have shown good efficacy in reducing vertebral and non-vertebral fracture risk. Other drugs such as teriparatide (daily injections of synthetic parathyroid hormone) have also been similarly effective.

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Figure 1 X-ray of the lumbosacral spine (AP and Lateral views).

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Figure 1a There is generalised osteopenia with collapsed L1, L2 and L3 vertebral bodies (arrows) with normal disc spaces. The pedicles appear intact and no soft tissue masses are seen.

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Figure 2 DEXA of the a) spine, and b) hip. The DEXA of the spine shows the T-scores for L1-L5 range from -1.9 to -2.8, Mean T-score of L2-L4 is -2.3. The DEXA of the hip shows femoral neck Tscore of -3.0 and Total score of -2.4. The higher values for L1 and L3 are related to the compression fractures. L4 should be the reference vertebra in this case. These findings would be consistent with that of severe (established) osteoporosis.

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Figure 3 Mid sagittal MR images of the spine with an osteoporotic fracture of L1 vertebral body. Mid sagittal SSFP DWI MRI at a TE of 5 ms (A) and 3 ms (B) show low signal intensity (arrow) in the collapsed L1 vertebral body compared to the normal bone marrow in adjacent vertebral bodies. There is no contrast enhancement of the L1 vertebra (C) after gadolinium administration (in homogeneous fat suppression).T1 W MR image (D) shows low signal in the L1 vertebra.

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Figure 4 MR images of a patient who presented with compression fracture of L2 vertebral body. There are low signals on both T1 (A) and T2 (B) � weighted images, with marked contrast enhancement (D) of L2 and S1 vertebral bodies. SSFP DWI MRI image shows high signal in the compressed L2 (arrow) as well as in S1 vertebral bodies (C) suggestive of malignancy. Further investigation revealed a bronchogenic carcinoma.

[View this Table]

Table 1 WHO definition of osteopenia/ osteoporosis based on bone mass measurements

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Table 2 Risk factors for osteoporosis [16]

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