- Email: [email protected]
Asymmetrical vertebral collapse from spinal metastasis in lower thoracic and lumbar spine
Journal of Orthopaedic Science xxx (2016) 1e6
Contents lists available at ScienceDirect
Journal of Orthopaedic Science journal homepage: http://www.elsevier.com/locate/jos
Original Article
Asymmetrical vertebral collapse from spinal metastasis in lower thoracic and lumbar spine Takayoshi Suzuki a, *, 1, Hirohisa Katagiri a, 1, Tatsuya Noda b, 2, Shusuke Ota c, 3, Hideki Murata a, 1, Junji Wasa a, 1, Seiichi Hosaka a, 1, Tetsuo Shimoyama a, 1, Mitsuru Takahashi a, 1 a b c
Division of Orthopedic Oncology, Shizuoka Cancer Center Hospital, 1007 Shimonagakubo, Nagaizumi-cho, Shizuoka 411-8777, Japan Department of Public Heath, Health Management and Policy, Nara Medical University, 840 Shijyou-cho, Kashihara City, Nara 634-8521, Japan Division of Orthopedic Surgery, National Hospital Organization Shizuoka Medical Center, 762e1 Nagasawa, Shimizu-cho, Shizuoka 411-8611, Japan
a r t i c l e i n f o
a b s t r a c t
Article history: Received 7 July 2016 Received in revised form 8 November 2016 Accepted 14 December 2016 Available online xxx
Objective: The purpose of this study was to investigate the differences between spinal metastasis and osteoporotic compression fractures on plain X-ray images, focusing on asymmetrical vertebral collapse and fracture level. Materials and methods: This study included 180 patients with pathological collapse from spinal metastasis (188 vertebrae) who were treated at our institution and 70 patients (92 vertebrae) with osteoporotic compression fractures. Anteroposterior X-ray images of the lower thoracic and lumbar spine were evaluated for asymmetrical collapse deformity. Results: Asymmetrical collapse was found in 134 vertebrae (71.3%) with metastasis, and in 20 osteoporotic vertebrae (21.7%); this difference was significant (p < 0.0001). The asymmetrical collapse angle in spinal metastasis patients ranged from 0 to 18 , with a mean of 7.0 and a standard deviation (SD) of 4.5. In contrast, the asymmetrical collapse angle in patients with osteoporotic fractures ranged from 0 to 13 , with a mean of 3.1 and a SD of 2.8. The difference in collapse angle between the two groups was statistically significant (p < 0.001). The cutoff value to suspect spinal metastasis was determined to be 5 or more (sensitivity 0.67, specificity 0.74). Fracture at Th10 or below L3 was found in 20.2% of spinal metastasis patients; only 3% of osteoporotic fractures occurred at these levels. Conclusion: Asymmetrical collapse with an angle of 5 or more and fractures at atypical levels on plain radiographs can be useful clues to spinal metastasis. © 2016 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.
1. Introduction With recent advances in chemotherapy, the survival of patients with advanced cancer has been extended. As a result, the number of patients with skeletal metastasis has increased. It has been
* Corresponding author. Present address: 1632 Higashiyokoti, Kikugawa city, Shizuoka 439-0022, Japan. Fax: þ81 537 35 4484. E-mail addresses: [email protected] (T. Suzuki), h.katagiri@ scchr.jp (H. Katagiri), [email protected] (T. Noda), [email protected] (S. Ota), [email protected] (H. Murata), [email protected] (J. Wasa), s.hosaka@scchr. jp (S. Hosaka), [email protected] (T. Shimoyama), [email protected] (M. Takahashi). 1 Fax: þ81 55 989 5783. 2 Fax: þ81 744 22 0037. 3 Fax: þ81 55 975 2725.
reported that 60e80% of breast and prostate cancer patients, and 30e40% of lung cancer patients develop bone metastases [1e3]. The spine is the most common site for bone metastasis, with spinal metastasis occurring in approximately 60e70% of patients with systemic cancer [4,5]. Spinal metastasis initially causes severe pain; without appropriate treatment, it can eventually cause paraplegia with loss of bladder and bowel control. Paraplegia from spinal metastasis severely deteriorates quality of life. Therefore, it is important to differentiate spinal metastases from benign compression fractures before the development of paraplegia and to perform appropriate treatment to prevent paraplegia. This differentiation is especially important for lesions in the lower thoracic and lumbar spine, where osteoporotic compression fractures frequently occur [6,7]. The vertebral pedicle sign [8] is well known as a specific finding of spinal metastasis on plain X-ray films, but is only seen in
http://dx.doi.org/10.1016/j.jos.2016.12.013 0949-2658/© 2016 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.
Please cite this article in press as: Suzuki T, et al., Asymmetrical vertebral collapse from spinal metastasis in lower thoracic and lumbar spine, Journal of Orthopaedic Science (2016), http://dx.doi.org/10.1016/j.jos.2016.12.013
2
T. Suzuki et al. / Journal of Orthopaedic Science xxx (2016) 1e6
advanced cases [9]. Braunstein and Kuhns reported that only 11 of 33 cases with spinal metastasis showed cancer invasion of the vertebral pedicle [10]. Relying on the pedicle sign to differentiate spinal metastases from osteoporotic compression fractures makes it difficult to diagnose metastasis in its early stages. Magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET) have enabled us to differentiate spinal metastasis from osteoporotic compression fracture more easily and accurately [4,11,12]; however, these imaging studies require time and cost for patients, and plain X-rays remain the initial imaging study at first presentation. At our practice, we have frequently found asymmetrical vertebral collapse in patients with spinal metastasis. The purpose of this study was to clarify the differences on plain X-ray images between spinal metastasis and osteoporotic compression fracture in the lower thoracic and lumbar spine, focusing on asymmetrical collapse and fracture location. 2. Materials and methods Between 2005 and 2007, 481 patients (664 vertebrae) with pathological collapse resulting from spinal metastasis were treated at our institution. Three lesions in the cervical region, where osteoporotic compression fracture is rarely seen, and 311 lesions above the 10th thoracic vertebra (Th10), where plain X-ray images are often difficult to evaluate accurately, were excluded. We also excluded 162 patients with severe deformity caused by multiple spinal metastases or severe degenerative spinal deformity caused by aging. The remaining 180 patients (188 vertebrae) with compression fractures in one or two vertebral bodies from Th10 to the 5th lumbar vertebra (L5) were the subject of this study. The primary site of cancer was lung in 41 patients (23%), breast in 41 (23%), stomach in 18 (10%), colon in 15 (8%), liver in 13 (7%), prostate in 12 (6%), larynx in 6 (3%), pancreas in 6 (3%), unknown in 6 (3%), bone and soft tissue sarcoma in 4 (2%), lymph node in 3 (1.7%), kidney in 3 (1.7%), uterus in 3 (1.7%), thymus in 2 (1%), skin in 2 (1%), ovary in 1 (0.5%), bone marrow in 1 (0.5%), bladder in 1 (0.5%), ureter in 1 (0.5%), esophagus in 1 (0.5%) (Table 1). These patients' records were compared with those of 70 patients (92 vertebrae) with osteoporotic compression fractures between Th10 and L5 treated at a nearby general hospital. The spinal metastasis group
Table 1 Patient characteristics. Characteristic
Spinal metastasis
Osteoporosis
Number of participants (male/female) Age, years [median (range)] Primary cancer site (n) Lung Breast Stomach Colon Liver Prostate Head and neck Pancreas Unknown Sarcoma Lymph node Kidney Uterus Thymus Skin Ovary Bone marrow Bladder Ureter Esophagus
180 (90/90) 61 (31e82)
70 (22/48) 76 (43e94)
41 41 18 15 13 12 6 6 6 4 3 3 3 2 2 1 1 1 1 1
included 90 men and 90 women with a mean age of 61 years (31e82 years). The osteoporotic fracture group included 22 men and 48 women with a mean age of 76 years (43e94 years). For each patient, diagnosis of bone metastasis was confirmed at a bone metastasis board meeting at our institute after thorough review of the patient's clinical course and imaging studies. All patients in the metastasis group underwent CT scan to identify lesions and to confirm irregular bone destruction with or without sclerotic change. In addition, MRI was performed in 95 metastasis group patients, bone scan in 19, and FDG-PET in 6 to confirm the diagnosis. For the 5 patients in whom diagnosis of bone metastasis was not certain with the above-mentioned imaging studies, bone biopsy was performed. No previously irradiated lesions were included in this series. The diagnosis of benign osteoporotic compression fracture was verified by the clinical course and MRI findings. We evaluated plain anteroposterior X-ray images of affected vertebrae in both groups, assessing the four points described below. First, we evaluated whether there was a difference in the locations of metastatic versus osteoporotic fractures. Second, we evaluated whether asymmetrical collapse and/or the pedicle sign was visible on the anteroposterior view in each case. Representative asymmetrical and symmetrical collapse images are shown in Fig. 1. The frequency of asymmetrical collapse in each group was compared using the chi-square test. Third, the angle formed by the upper and lower vertebral end plates (asymmetrical collapse angle) was measured in each case. Our measurement method is shown in Fig. 2. To measure the asymmetrical collapse angle, perpendicular lines were drawn to bisect both pedicles. Next, we determined the points where these perpendicular bisectors intersected the upper and lower end plates of the affected vertebral body. Connecting the two upper and the two lower points and extending both lines, we were able to measure the intersection angle (Fig. 2). Vertebrae with the pedicle sign do not have a clear pedicle contour. In these cases, we first measured the distance from the lateral edge of the vertebral body to the center of the pedicle on the unaffected side. We then determined the point that was that distance from the lateral edge of the vertebral body on the affected side as an approximation of the center of the pedicle. Next we drew a perpendicular line at that point and determined the point at which this line intersected the upper or lower end plate (Fig. 3). The mean asymmetrical collapse angles in the spinal metastasis group and in the osteoporotic compression fracture group were compared using an unpooled t test.
Fig. 1. Representative examples of asymmetrical collapse (a) and symmetrical collapse (b) on plain X-ray images.
Please cite this article in press as: Suzuki T, et al., Asymmetrical vertebral collapse from spinal metastasis in lower thoracic and lumbar spine, Journal of Orthopaedic Science (2016), http://dx.doi.org/10.1016/j.jos.2016.12.013
T. Suzuki et al. / Journal of Orthopaedic Science xxx (2016) 1e6
3
Fig. 2. Measurement of vertebral asymmetrical collapse angle. Vertebral collapse angles were measured on anteroposterior X-ray images. A perpendicular bisector was drawn through each pedicle. The points where these perpendicular bisectors intersected the upper and lower end plates of the affected vertebral body were located. The lines connecting these points were extended and their intersection angle was measured as the collapse angle.
3. Results 3.1. Distribution of vertebral fractures The affected vertebra in the metastasis group was Th10 in eight patients, Th11 in 18, Th12 in 43, L1 in 30, L2 in 29, L3 in 30, L4 in 22, and L5 in eight. The fracture site in osteoporotic patients was Th11 in eight patients, Th12 in 19, L1 in 28, L2 in 20, L3 in 14, and L4 in three (Fig. 4). Osteoporotic compression fracture occurred most frequently at L1, and its distribution was limited mostly to vertebrae between Th11 and L3. Only three osteoporotic fractures (3%) were found at Th10, L4, or L5. In contrast, 38 out of 188 (20.2%) metastatic fractures occurred at Th10, L4, or L5. This difference was statistically significant (p < 0.001, Fisher's exact test). 3.2. Frequency of asymmetrical collapse
Fig. 3. Measurement of vertebral asymmetrical collapse angle in patients with the pedicle sign. First, the distance from the lateral edge of the vertebral body to the center of the pedicle on the unaffected side (a) was measured. We then determined the point that was that distance (a0 ) from the lateral edge of the vertebral body on the affected side as an approximation of the center of the pedicle. Next we drew a perpendicular line at that point and determined the point at which this line intersected the upper or lower end plate.
Fourth, the discriminating power of the asymmetrical collapse angle was evaluated using the area under the receiver operating characteristic curve (AUC) and the optimal cutoff point was determined using the Youden index. Analyses were performed with JMP version 9 (SAS Institute Inc., Cary, NC). Two senior orthopedic surgeons separately measured the collapse angle using the SYNAPSE medical imaging system (Fuji Film Company, Japan) on a medical imaging display. The reliability was evaluated by comparing the measurements obtained by the two surgeons. Inter-interpreter reliability was determined with the intraclass correlation coefficient (ICC). Because the two orthopedic surgeons evaluated each X-ray image separately, ICC(2,1) was calculated. In addition, we analyzed the clinical symptoms of patients in the metastasis group, including history of skeletal related events (SREs) and neurological deficits evaluated using the Frankel classification [13]. The study protocol was approved by the ethics committees of both institutions.
We found visible asymmetrical collapse in 134 of 188 vertebrae (71.3%) with spinal metastasis, and in 20 of 92 vertebrae (21.7%) with osteoporotic compression fractures. Asymmetrical collapse was found more frequently among metastasis patients than among osteoporotic fracture patients (p < 0.0001; Table 2). The pedicle sign was found in 42 vertebral bodies (22.4%) with spinal metastasis and in none of the osteoporotic fractures. The relationship between asymmetrical collapse and the pedicle sign in spinal metastasis is shown in Table 3. Asymmetrical collapse without the pedicle sign was found in 102 vertebrae, while the pedicle sign without asymmetrical collapse was found in only 11 vertebrae. 3.3. Asymmetrical collapse angle In spinal metastasis patients, the asymmetrical collapse angle ranged from 0 to 18 , with a mean of 7.0 and a standard deviation (SD) of 4.5. In contrast, patients with osteoporotic fractures had asymmetrical collapse angles ranging from 0 to 13 , with a mean of 3.1 and a SD of 2.8. The asymmetrical collapse angle was larger in the spinal metastasis group compared with the osteoporotic compression fracture group (Fig. 5). The difference between the groups was significant (unpooled t test, p < 0.001). 3.4. Cutoff value for asymmetrical collapse angle The AUC of the asymmetrical collapse angle was 0.75 (95% confidence interval: 0.69e0.81) (Fig. 6). The cutoff value for the
Please cite this article in press as: Suzuki T, et al., Asymmetrical vertebral collapse from spinal metastasis in lower thoracic and lumbar spine, Journal of Orthopaedic Science (2016), http://dx.doi.org/10.1016/j.jos.2016.12.013
4
T. Suzuki et al. / Journal of Orthopaedic Science xxx (2016) 1e6
Fig. 4. Level of vertebral fracture, according to etiology.
Table 2 Asymmetrical collapse by group. Group
Number of affected vertebrae
Asymmetrical collapse Positive
Negative
Metastasis Osteoporosis
188 92
134 (71.3%) 20 (21.7%)
54 (28.7%) 72 (78.3%)
The difference between the two groups was significant (chi-square test, p < 0.0001).
Table 3 Relationship between asymmetrical collapse and pedicle sign among 188 vertebrae with spinal metastasis.
Asymmetrical collapseþ Asymmetrical collapse
Pedicle signþ
Pedicle sign
31 11
103 43
Asymmetrical collapse was more frequently found than the pedicle sign among vertebrae with spinal metastasis. Fig. 6. The receiver operating characteristic curve to find the maximum Youden value. The cutoff value for collapse angle was determined to be 5 (sensitivity 0.67, specificity 0.74), based on the ROC curve to find the max Youden value (0.43).
asymmetrical collapse angle was determined to be 5 (i.e., an asymmetrical collapse angle of 5 or more was considered spinal metastasis). Using this threshold, the sensitivity of the cutoff value was 0.67 and its specificity was 0.74. In the current series, 107 (57%) of 188 vertebrae with spinal metastasis had an asymmetrical collapse angle of 5 or more, while only 14 (15%) of 92 vertebral bodies with osteoporotic compression fractures had angles of 5 or more. The ICC, which indicates the degree of consistency between two evaluators, was 0.79 (95% CI: 0.72e0.84), indicating substantial consistency between evaluators. 3.5. Asymmetrical collapse and symptoms
Fig. 5. Distribution of asymmetrical collapse angle in the two groups. The angle was significantly larger in the metastasis group (unpooled t test, p < 0.001).
All but one patient in the metastasis group had pain caused by spinal metastasis. In three patients the bone lesions assessed in this study were the first manifestation of malignancy; all three of these patients showed asymmetrical collapse. Of the remaining 177
Please cite this article in press as: Suzuki T, et al., Asymmetrical vertebral collapse from spinal metastasis in lower thoracic and lumbar spine, Journal of Orthopaedic Science (2016), http://dx.doi.org/10.1016/j.jos.2016.12.013
T. Suzuki et al. / Journal of Orthopaedic Science xxx (2016) 1e6
patients, 109 (61%) had no previous SRE, while 68 patients (39%) had already experienced SRE. Among the 109 patients without a previous history of SRE, 84 (77%) showed asymmetrical collapse. Forty-one (60%) of the 68 patients with a previous history of SRE showed asymmetrical collapse. As for neurological deficits, 16 patients had non-ambulatory neurological deficits (Frankel grade AeC), 12 were Frankel D, and 152 were Frankel E. Among non-ambulatory patients, 13 showed asymmetrical collapse; the pedicle sign was observed in only 4 of these patients. Among 164 patients with Frankel D or E status, 115 (70%) had asymmetrical collapse; the pedicle sign was found in 35 (21%) of these patients (Table 4). 4. Discussion Diagnosis of spinal metastasis before the onset of paraplegia, followed by appropriate radiotherapy palliates pain and prevents spinal cord injuries in 90% of cases [14,15]. Diagnosis of spinal metastasis has become easier with the advent of cutting-edge imaging technologies such as MRI and PET scans. On MRI, pathologic compression fractures from spinal metastases often have convex bowing of the ventral and/or dorsal margins, unlike traumatic or osteoporotic compression fractures, which have sharply angulated cortical margins [16,17]. Furthermore, intravenous gadolinium administration improves the visibility of metastatic foci, especially in those with extravertebral extension [4,12,16,17]. Bone scans are useful in the early stage of metastasis before pathological fracture, revealing lesions several months (0e18 months) earlier than radiography [11,18,19], which requires at least 50% bone destruction before a lesion becomes evident [11,20]. Because 18F-fluorodeoxyglucose PET reveals tumor metabolism, it enables the detection of bone metastasis at an even earlier stage than bone scans [11]. However, there is typically a waiting period of several days for MRI or PET scans in many countries. Furthermore, scanning takes at least 20 min and is expensive. For these reasons, plain X-ray remains the initial imaging study at first presentation for compression fractures or back pain. It is sometimes difficult to differentiate spinal metastases from osteoporotic compression fractures with radiographs before paraplegia occurs because both develop in elderly patients and cause intractable pain and vertebral deformity. This is an especially serious dilemma in the lower thoracic and lumbar spine, because the thoracolumbar transition zone is the most frequent site for osteoporotic vertebral fractures. Cooper et al. reported that 32% of osteoporotic vertebral fractures occurred in either Th12 or L1 [6]. Nearly 60% of osteoporotic vertebral fractures are reported to occur between Th10 and L5 [7]. In the present study, metastatic fractures most commonly occurred in Th12, but these fractures had a broad distribution from Th10 to L5. Fracture below L3 or at Th10 accounted for 20.2% of fractures in the metastasis group but only 3% in the osteoporosis group. This difference in fracture distribution can raise suspicion for spinal metastasis. The pedicle sign can be seen in advanced spinal metastasis, after destruction of the affected vertebral pedicle [9,10]. The current study found that the pedicle sign was not present in the
Table 4 Relationships between neurological symptoms and asymmetrical collapse. Frankel classification
No. of patients
Asymmetrical collapseþ (%)
Pedicle signþ (%)
AeC D E Total
16 12 152 180
13 (81%) 10 (83%) 105 (69%) 128 (71%)
4 (25%) 3 (25%) 32 (21%) 39 (22%)
5
osteoporotic fracture group, but its prevalence in the metastasis group was much lower than that of asymmetrical collapse. Only 11 (5.9%) of 188 vertebrae with metastasis showed the pedicle sign before developing asymmetrical collapse, while 103 (54.8%) vertebrae showed asymmetrical collapse without the pedicle sign. Even in patients with non-ambulatory neurological deficits, the pedicle sign was only present 25% of the time. Therefore, although the vertebral pedicle sign has high specificity, its sensitivity is not sufficient to detect spinal metastasis. Based on the analysis of the relationships between clinical symptoms and radiological findings, it cannot be concluded that the asymmetrical collapse sign is useful in patients with no history of cancer who present with skeletal metastasis of unknown origin, because there were only three such patients included in this study. However, the asymmetrical collapse sign can be a useful clue to identify spinal metastasis before paraplegia occurs during the follow-up of patients with a history of cancer. This sign was found in 70% of patients who had painful metastasis but who were still ambulatory (Frankel D or E) and in 77% of patients without previous history of SRE. In this study, we focused on angulated deformity caused by onesided fragility with asymmetrical collapse. Guillevin et al. [12] described this phenomenon briefly in a textbook on bone metastasis, but there have been no detailed studies of asymmetrical collapse. The current study revealed that both the frequency of asymmetrical collapse detected visually on plain X-ray images and the angle of collapse are significantly higher in patients with spinal metastases than in those with osteoporotic fractures. Previous studies have described the relationship between bone destruction and vertebral collapse. Taneichi et al. reported the close correlation between vertebral collapse and bone destruction area, demonstrating that collapse occurs when 50e60% of the vertebral body is affected in the thoracic spine and when 35e40% is affected in the thoracolumbar and lumbar spine [21]. An experimental study by Ebihara et al. showed that as unilateral trabecular bone is replaced by tumor it no longer supports the vertebral endplate, and vertebral collapse can easily occur [22]. Both studies emphasize the importance of unilateral destruction of the vertebral body and other spinal components. These studies and experience suggest that the reason for asymmetrical collapse is that vertebral metastasis does not always develop centrally, but often begins with destruction of only one side of the vertebral body [12]. In contrast, osteoporosis decreases the strength of the vertebral body evenly along its horizontal axis; therefore, osteoporosis tends to lead to symmetrical collapse. There are some limitations of this study. First, the presence of asymmetric vertebral collapse would be of little diagnostic use in patients with scoliosis, because asymmetric collapse deformity is commonly seen among these patients. Second, we did not evaluate patients with severe deformity or multiple fractures. Therefore, the asymmetrical collapse sign cannot be applied in patients with severe age-related deformity. Multiple fracture lesions can be caused not only by metastasis, but also by hormonal disorders such as severe osteoporosis. These lesions should be evaluated with MRI and/or CT. Third, asymmetrical collapse was seen in 21.7% of patients with osteoporotic fractures, raising concerns about false positives. Fourth, all but three patients in this study had previously diagnosed malignancies. Therefore, it is not certain whether the results of the current study can be applied to patients without previously diagnosed malignancy. Fifth, we did not verify whether the asymmetric collapse sign can be applied to the cervical spine or to the thoracic spine above Th10. However, in clinical practice, osteoporotic compression fractures in the cervical and upper thoracic spine are not common, and non-traumatic fractures in these regions raise suspicion of pathological fracture, regardless of
Please cite this article in press as: Suzuki T, et al., Asymmetrical vertebral collapse from spinal metastasis in lower thoracic and lumbar spine, Journal of Orthopaedic Science (2016), http://dx.doi.org/10.1016/j.jos.2016.12.013
6
T. Suzuki et al. / Journal of Orthopaedic Science xxx (2016) 1e6
collapse symmetry. Sixth, there were differences in gender and age distribution between the osteoporosis and bone metastasis groups. These differences result from the nature of bone metastasis and osteoporosis. Finally, this study was retrospective; a prospective study enrolling more patients is necessary to verify our findings. The thoracolumbar transition zone is a frequent site of osteoporotic compression fracture, which sometimes occurs without a causative event. The current study revealed that asymmetrical collapse raises suspicion of spinal metastasis in this region, and provides a clue to the cause of fracture. If a patient has asymmetrical collapse with an angulation of five degrees or more, or if the fracture occurs at an atypical level such as below L3, it is reasonable to suspect pathological fracture and to perform CT, MRI, or PET scan to differentiate spinal metastasis from osteoporotic fracture. Conflict of interest The authors declare that they have no conflict of interest. References [1] Plunkett TA, Rubens RD. Clinical features and prognosis of bone metastases. In: Jasmin C, Coleman RE, Coia LR, Capanna R, Saillant G, editors. Textbook of bone metastases. 1st ed. West Sussex, England: WILEY; 2005. p. 65e75. [2] Coleman RE. Skeletal complications of malignancy. Cancer 1997 Oct 15;80(8): 1588e94. [3] Berrettoni BA, Carter JR. Mechanisms of cancer metastasis to bone. J Bone Jt Surg Am 1986 Feb;68(2):308e12. [4] Shah LM, Salzman KL. Imaging of spinal metastatic disease. Int J Surg Oncol 2011;2011:769753. http://dx.doi.org/10.1155/2011/769753. Epub 2011 Nov 3. [5] Harrington KD. Chapter 12 metastatic disease of the spine. In: Harrington KD, editor. Orthopaedic management of metastatic bone disease. 2nd ed. St. Louis, Mo: The C.V. Mosby Company; 1988. p. 309e83. [6] Cooper C, Atkinson EJ, O'Fallon WM, Melton 3rd LJ. Incidence of clinically diagnosed vertebral fractures: a population-based study in Rochester, Minnesota, 1985e1989. J Bone Min Res 1992 Feb;7(2):221e7. [7] Kilincer C, Kabayel DD, Cagli B, Unlu E, Wicki B, Ozdemir F. Frequency, distribution and severity of prevalent osteoporotic vertebral fractures in postmenopausal women. Turk Neurosurg 2013;23(4):476e83. http://dx.doi.org/ 10.5137/1019-5149. JTN.7442-12.0.
[8] Jacobson HG, Poppel MH, Shapiro JH, Grossberger S. The vertebral pedicle sign: a roentgen finding to differentiate metastatic carcinoma from multiple myeloma. Am J Roentgenol Radium Ther Nucl Med 1958 Nov;80(5):817e21. [9] Asdourian PL, Weidenbaum M, Dewald RL, Hammerberg KW, Ramsey RG. The pattern of vertebral involvement in metastatic vertebral breast cancer. Clin Orthop Relat Res 1990 Jan;(250):164e70. [10] Braunstein EM, Kuhns LA. Computed tomographic demonstration of spinal metastases. Spine(Phila Pa 1976) 1983 Nov-Dec;8(8):912e5. [11] Cook GJR, Fogelman I. Radioisotope and PET imaging of bone metastases. In: Jasmin C, Coleman RE, Coia LR, Capanna R, Saillant G, editors. Textbook of bone metastases. 1st ed. West Sussex, England: WILEY; 2005. p. 77e90. [12] Guillevin R, Vallee JN, Martin-Duverneuil N, Lo D, Lafitte F, Maillard JC, Chiras J. Imaging of spinal bone metastases. In: Jasmin C, Coleman RE, Coia LR, Capanna R, Saillant G, editors. Textbook of bone metastases. 1st ed. West Sussex, England: WILEY; 2005. p. 91e104. [13] Frankel HL, Hancock DO, Hyslop G, Melzak J, Michaelis LS, Ungar GH, Vernon JD, Walsh JJ. The value of postural reduction in the initial management of closed injuries of the spine with paraplegia and tetraplegia. I. Paraplegia 1969 Nov;7(3):179e92. [14] Loblaw DA, Laperriere NJ. Emergency treatment of malignant extradural spinal cord compression: an evidence-based guideline. J Clin Oncol 1998 Apr;16(4):1613e24. [15] Katagiri H, Takahashi M, Inagaki J, Kobayashi H, Sugiura H, Yamamura S, Iwata H. Clinical results of nonsurgical treatment for spinal metastases. Int J Radiat Oncol Biol Phys 1998 Dec 1;42(5):1127e32. [16] Meyers Steven P. Metastatic lesion. In: MRI of bone and soft tissue tumors and tumor like lesions. 1st ed. New York, NY: Thieme; 2008. p. 601e8. [17] Abdel-Wanis ME, Solyman MT, Hasan NM. Sensitivity, specificity and accuracy of magnetic resonance imaging for differentiating vertebral compression fractures caused by malignancy, osteoporosis, and infections. J Orthop Surg (Hong Kong) 2011 Aug;19(2):145e50. [18] Galasko CSB. The significance of occult skeletal metastases, detected by skeletal scintigraphy, in patients with otherwise apparently ‘early’ mammary carcinoma. Br J Surg 1975 Sep;62(9):694e6. [19] Coleman RE, Foglman I, Habibollahi F, North WRS, Rubens RD. Selection of patients with breast cancer for routine follow-up bone scans. Clin Oncol (R Coll Radiol) 1990 Nov;2(6):328e32. [20] Edelstyn GA, Gillespie PJ, Grebbel FS. The radiological demonstration of osseous metastases. Experimental observations. Clin Radiol 1967 Apr;18(2): 158e62. [21] Taneichi H, Kaneda K, Takeda N, Abumi K, Satoh S. Risk factors and probability of vertebral body collapse in metastases of the thoracic and lumbar spine. Spine (Phila Pa 1976) 1997 Feb 1;22(3):239e45. [22] Ebihara H, Ito M, Abumi K, Taneichi H, Kotani Y, Minami A, Kaneda K. A biomechanical analysis of metastatic vertebral collapse of the thoracic spine, a sheep model study. Spine (Phila Pa 1976) 2004 May 1;29(9):994e9.
Please cite this article in press as: Suzuki T, et al., Asymmetrical vertebral collapse from spinal metastasis in lower thoracic and lumbar spine, Journal of Orthopaedic Science (2016), http://dx.doi.org/10.1016/j.jos.2016.12.013
Contents lists available at ScienceDirect
Journal of Orthopaedic Science journal homepage: http://www.elsevier.com/locate/jos
Original Article
Asymmetrical vertebral collapse from spinal metastasis in lower thoracic and lumbar spine Takayoshi Suzuki a, *, 1, Hirohisa Katagiri a, 1, Tatsuya Noda b, 2, Shusuke Ota c, 3, Hideki Murata a, 1, Junji Wasa a, 1, Seiichi Hosaka a, 1, Tetsuo Shimoyama a, 1, Mitsuru Takahashi a, 1 a b c
Division of Orthopedic Oncology, Shizuoka Cancer Center Hospital, 1007 Shimonagakubo, Nagaizumi-cho, Shizuoka 411-8777, Japan Department of Public Heath, Health Management and Policy, Nara Medical University, 840 Shijyou-cho, Kashihara City, Nara 634-8521, Japan Division of Orthopedic Surgery, National Hospital Organization Shizuoka Medical Center, 762e1 Nagasawa, Shimizu-cho, Shizuoka 411-8611, Japan
a r t i c l e i n f o
a b s t r a c t
Article history: Received 7 July 2016 Received in revised form 8 November 2016 Accepted 14 December 2016 Available online xxx
Objective: The purpose of this study was to investigate the differences between spinal metastasis and osteoporotic compression fractures on plain X-ray images, focusing on asymmetrical vertebral collapse and fracture level. Materials and methods: This study included 180 patients with pathological collapse from spinal metastasis (188 vertebrae) who were treated at our institution and 70 patients (92 vertebrae) with osteoporotic compression fractures. Anteroposterior X-ray images of the lower thoracic and lumbar spine were evaluated for asymmetrical collapse deformity. Results: Asymmetrical collapse was found in 134 vertebrae (71.3%) with metastasis, and in 20 osteoporotic vertebrae (21.7%); this difference was significant (p < 0.0001). The asymmetrical collapse angle in spinal metastasis patients ranged from 0 to 18 , with a mean of 7.0 and a standard deviation (SD) of 4.5. In contrast, the asymmetrical collapse angle in patients with osteoporotic fractures ranged from 0 to 13 , with a mean of 3.1 and a SD of 2.8. The difference in collapse angle between the two groups was statistically significant (p < 0.001). The cutoff value to suspect spinal metastasis was determined to be 5 or more (sensitivity 0.67, specificity 0.74). Fracture at Th10 or below L3 was found in 20.2% of spinal metastasis patients; only 3% of osteoporotic fractures occurred at these levels. Conclusion: Asymmetrical collapse with an angle of 5 or more and fractures at atypical levels on plain radiographs can be useful clues to spinal metastasis. © 2016 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.
1. Introduction With recent advances in chemotherapy, the survival of patients with advanced cancer has been extended. As a result, the number of patients with skeletal metastasis has increased. It has been
* Corresponding author. Present address: 1632 Higashiyokoti, Kikugawa city, Shizuoka 439-0022, Japan. Fax: þ81 537 35 4484. E-mail addresses: [email protected] (T. Suzuki), h.katagiri@ scchr.jp (H. Katagiri), [email protected] (T. Noda), [email protected] (S. Ota), [email protected] (H. Murata), [email protected] (J. Wasa), s.hosaka@scchr. jp (S. Hosaka), [email protected] (T. Shimoyama), [email protected] (M. Takahashi). 1 Fax: þ81 55 989 5783. 2 Fax: þ81 744 22 0037. 3 Fax: þ81 55 975 2725.
reported that 60e80% of breast and prostate cancer patients, and 30e40% of lung cancer patients develop bone metastases [1e3]. The spine is the most common site for bone metastasis, with spinal metastasis occurring in approximately 60e70% of patients with systemic cancer [4,5]. Spinal metastasis initially causes severe pain; without appropriate treatment, it can eventually cause paraplegia with loss of bladder and bowel control. Paraplegia from spinal metastasis severely deteriorates quality of life. Therefore, it is important to differentiate spinal metastases from benign compression fractures before the development of paraplegia and to perform appropriate treatment to prevent paraplegia. This differentiation is especially important for lesions in the lower thoracic and lumbar spine, where osteoporotic compression fractures frequently occur [6,7]. The vertebral pedicle sign [8] is well known as a specific finding of spinal metastasis on plain X-ray films, but is only seen in
http://dx.doi.org/10.1016/j.jos.2016.12.013 0949-2658/© 2016 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.
Please cite this article in press as: Suzuki T, et al., Asymmetrical vertebral collapse from spinal metastasis in lower thoracic and lumbar spine, Journal of Orthopaedic Science (2016), http://dx.doi.org/10.1016/j.jos.2016.12.013
2
T. Suzuki et al. / Journal of Orthopaedic Science xxx (2016) 1e6
advanced cases [9]. Braunstein and Kuhns reported that only 11 of 33 cases with spinal metastasis showed cancer invasion of the vertebral pedicle [10]. Relying on the pedicle sign to differentiate spinal metastases from osteoporotic compression fractures makes it difficult to diagnose metastasis in its early stages. Magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET) have enabled us to differentiate spinal metastasis from osteoporotic compression fracture more easily and accurately [4,11,12]; however, these imaging studies require time and cost for patients, and plain X-rays remain the initial imaging study at first presentation. At our practice, we have frequently found asymmetrical vertebral collapse in patients with spinal metastasis. The purpose of this study was to clarify the differences on plain X-ray images between spinal metastasis and osteoporotic compression fracture in the lower thoracic and lumbar spine, focusing on asymmetrical collapse and fracture location. 2. Materials and methods Between 2005 and 2007, 481 patients (664 vertebrae) with pathological collapse resulting from spinal metastasis were treated at our institution. Three lesions in the cervical region, where osteoporotic compression fracture is rarely seen, and 311 lesions above the 10th thoracic vertebra (Th10), where plain X-ray images are often difficult to evaluate accurately, were excluded. We also excluded 162 patients with severe deformity caused by multiple spinal metastases or severe degenerative spinal deformity caused by aging. The remaining 180 patients (188 vertebrae) with compression fractures in one or two vertebral bodies from Th10 to the 5th lumbar vertebra (L5) were the subject of this study. The primary site of cancer was lung in 41 patients (23%), breast in 41 (23%), stomach in 18 (10%), colon in 15 (8%), liver in 13 (7%), prostate in 12 (6%), larynx in 6 (3%), pancreas in 6 (3%), unknown in 6 (3%), bone and soft tissue sarcoma in 4 (2%), lymph node in 3 (1.7%), kidney in 3 (1.7%), uterus in 3 (1.7%), thymus in 2 (1%), skin in 2 (1%), ovary in 1 (0.5%), bone marrow in 1 (0.5%), bladder in 1 (0.5%), ureter in 1 (0.5%), esophagus in 1 (0.5%) (Table 1). These patients' records were compared with those of 70 patients (92 vertebrae) with osteoporotic compression fractures between Th10 and L5 treated at a nearby general hospital. The spinal metastasis group
Table 1 Patient characteristics. Characteristic
Spinal metastasis
Osteoporosis
Number of participants (male/female) Age, years [median (range)] Primary cancer site (n) Lung Breast Stomach Colon Liver Prostate Head and neck Pancreas Unknown Sarcoma Lymph node Kidney Uterus Thymus Skin Ovary Bone marrow Bladder Ureter Esophagus
180 (90/90) 61 (31e82)
70 (22/48) 76 (43e94)
41 41 18 15 13 12 6 6 6 4 3 3 3 2 2 1 1 1 1 1
included 90 men and 90 women with a mean age of 61 years (31e82 years). The osteoporotic fracture group included 22 men and 48 women with a mean age of 76 years (43e94 years). For each patient, diagnosis of bone metastasis was confirmed at a bone metastasis board meeting at our institute after thorough review of the patient's clinical course and imaging studies. All patients in the metastasis group underwent CT scan to identify lesions and to confirm irregular bone destruction with or without sclerotic change. In addition, MRI was performed in 95 metastasis group patients, bone scan in 19, and FDG-PET in 6 to confirm the diagnosis. For the 5 patients in whom diagnosis of bone metastasis was not certain with the above-mentioned imaging studies, bone biopsy was performed. No previously irradiated lesions were included in this series. The diagnosis of benign osteoporotic compression fracture was verified by the clinical course and MRI findings. We evaluated plain anteroposterior X-ray images of affected vertebrae in both groups, assessing the four points described below. First, we evaluated whether there was a difference in the locations of metastatic versus osteoporotic fractures. Second, we evaluated whether asymmetrical collapse and/or the pedicle sign was visible on the anteroposterior view in each case. Representative asymmetrical and symmetrical collapse images are shown in Fig. 1. The frequency of asymmetrical collapse in each group was compared using the chi-square test. Third, the angle formed by the upper and lower vertebral end plates (asymmetrical collapse angle) was measured in each case. Our measurement method is shown in Fig. 2. To measure the asymmetrical collapse angle, perpendicular lines were drawn to bisect both pedicles. Next, we determined the points where these perpendicular bisectors intersected the upper and lower end plates of the affected vertebral body. Connecting the two upper and the two lower points and extending both lines, we were able to measure the intersection angle (Fig. 2). Vertebrae with the pedicle sign do not have a clear pedicle contour. In these cases, we first measured the distance from the lateral edge of the vertebral body to the center of the pedicle on the unaffected side. We then determined the point that was that distance from the lateral edge of the vertebral body on the affected side as an approximation of the center of the pedicle. Next we drew a perpendicular line at that point and determined the point at which this line intersected the upper or lower end plate (Fig. 3). The mean asymmetrical collapse angles in the spinal metastasis group and in the osteoporotic compression fracture group were compared using an unpooled t test.
Fig. 1. Representative examples of asymmetrical collapse (a) and symmetrical collapse (b) on plain X-ray images.
Please cite this article in press as: Suzuki T, et al., Asymmetrical vertebral collapse from spinal metastasis in lower thoracic and lumbar spine, Journal of Orthopaedic Science (2016), http://dx.doi.org/10.1016/j.jos.2016.12.013
T. Suzuki et al. / Journal of Orthopaedic Science xxx (2016) 1e6
3
Fig. 2. Measurement of vertebral asymmetrical collapse angle. Vertebral collapse angles were measured on anteroposterior X-ray images. A perpendicular bisector was drawn through each pedicle. The points where these perpendicular bisectors intersected the upper and lower end plates of the affected vertebral body were located. The lines connecting these points were extended and their intersection angle was measured as the collapse angle.
3. Results 3.1. Distribution of vertebral fractures The affected vertebra in the metastasis group was Th10 in eight patients, Th11 in 18, Th12 in 43, L1 in 30, L2 in 29, L3 in 30, L4 in 22, and L5 in eight. The fracture site in osteoporotic patients was Th11 in eight patients, Th12 in 19, L1 in 28, L2 in 20, L3 in 14, and L4 in three (Fig. 4). Osteoporotic compression fracture occurred most frequently at L1, and its distribution was limited mostly to vertebrae between Th11 and L3. Only three osteoporotic fractures (3%) were found at Th10, L4, or L5. In contrast, 38 out of 188 (20.2%) metastatic fractures occurred at Th10, L4, or L5. This difference was statistically significant (p < 0.001, Fisher's exact test). 3.2. Frequency of asymmetrical collapse
Fig. 3. Measurement of vertebral asymmetrical collapse angle in patients with the pedicle sign. First, the distance from the lateral edge of the vertebral body to the center of the pedicle on the unaffected side (a) was measured. We then determined the point that was that distance (a0 ) from the lateral edge of the vertebral body on the affected side as an approximation of the center of the pedicle. Next we drew a perpendicular line at that point and determined the point at which this line intersected the upper or lower end plate.
Fourth, the discriminating power of the asymmetrical collapse angle was evaluated using the area under the receiver operating characteristic curve (AUC) and the optimal cutoff point was determined using the Youden index. Analyses were performed with JMP version 9 (SAS Institute Inc., Cary, NC). Two senior orthopedic surgeons separately measured the collapse angle using the SYNAPSE medical imaging system (Fuji Film Company, Japan) on a medical imaging display. The reliability was evaluated by comparing the measurements obtained by the two surgeons. Inter-interpreter reliability was determined with the intraclass correlation coefficient (ICC). Because the two orthopedic surgeons evaluated each X-ray image separately, ICC(2,1) was calculated. In addition, we analyzed the clinical symptoms of patients in the metastasis group, including history of skeletal related events (SREs) and neurological deficits evaluated using the Frankel classification [13]. The study protocol was approved by the ethics committees of both institutions.
We found visible asymmetrical collapse in 134 of 188 vertebrae (71.3%) with spinal metastasis, and in 20 of 92 vertebrae (21.7%) with osteoporotic compression fractures. Asymmetrical collapse was found more frequently among metastasis patients than among osteoporotic fracture patients (p < 0.0001; Table 2). The pedicle sign was found in 42 vertebral bodies (22.4%) with spinal metastasis and in none of the osteoporotic fractures. The relationship between asymmetrical collapse and the pedicle sign in spinal metastasis is shown in Table 3. Asymmetrical collapse without the pedicle sign was found in 102 vertebrae, while the pedicle sign without asymmetrical collapse was found in only 11 vertebrae. 3.3. Asymmetrical collapse angle In spinal metastasis patients, the asymmetrical collapse angle ranged from 0 to 18 , with a mean of 7.0 and a standard deviation (SD) of 4.5. In contrast, patients with osteoporotic fractures had asymmetrical collapse angles ranging from 0 to 13 , with a mean of 3.1 and a SD of 2.8. The asymmetrical collapse angle was larger in the spinal metastasis group compared with the osteoporotic compression fracture group (Fig. 5). The difference between the groups was significant (unpooled t test, p < 0.001). 3.4. Cutoff value for asymmetrical collapse angle The AUC of the asymmetrical collapse angle was 0.75 (95% confidence interval: 0.69e0.81) (Fig. 6). The cutoff value for the
Please cite this article in press as: Suzuki T, et al., Asymmetrical vertebral collapse from spinal metastasis in lower thoracic and lumbar spine, Journal of Orthopaedic Science (2016), http://dx.doi.org/10.1016/j.jos.2016.12.013
4
T. Suzuki et al. / Journal of Orthopaedic Science xxx (2016) 1e6
Fig. 4. Level of vertebral fracture, according to etiology.
Table 2 Asymmetrical collapse by group. Group
Number of affected vertebrae
Asymmetrical collapse Positive
Negative
Metastasis Osteoporosis
188 92
134 (71.3%) 20 (21.7%)
54 (28.7%) 72 (78.3%)
The difference between the two groups was significant (chi-square test, p < 0.0001).
Table 3 Relationship between asymmetrical collapse and pedicle sign among 188 vertebrae with spinal metastasis.
Asymmetrical collapseþ Asymmetrical collapse
Pedicle signþ
Pedicle sign
31 11
103 43
Asymmetrical collapse was more frequently found than the pedicle sign among vertebrae with spinal metastasis. Fig. 6. The receiver operating characteristic curve to find the maximum Youden value. The cutoff value for collapse angle was determined to be 5 (sensitivity 0.67, specificity 0.74), based on the ROC curve to find the max Youden value (0.43).
asymmetrical collapse angle was determined to be 5 (i.e., an asymmetrical collapse angle of 5 or more was considered spinal metastasis). Using this threshold, the sensitivity of the cutoff value was 0.67 and its specificity was 0.74. In the current series, 107 (57%) of 188 vertebrae with spinal metastasis had an asymmetrical collapse angle of 5 or more, while only 14 (15%) of 92 vertebral bodies with osteoporotic compression fractures had angles of 5 or more. The ICC, which indicates the degree of consistency between two evaluators, was 0.79 (95% CI: 0.72e0.84), indicating substantial consistency between evaluators. 3.5. Asymmetrical collapse and symptoms
Fig. 5. Distribution of asymmetrical collapse angle in the two groups. The angle was significantly larger in the metastasis group (unpooled t test, p < 0.001).
All but one patient in the metastasis group had pain caused by spinal metastasis. In three patients the bone lesions assessed in this study were the first manifestation of malignancy; all three of these patients showed asymmetrical collapse. Of the remaining 177
Please cite this article in press as: Suzuki T, et al., Asymmetrical vertebral collapse from spinal metastasis in lower thoracic and lumbar spine, Journal of Orthopaedic Science (2016), http://dx.doi.org/10.1016/j.jos.2016.12.013
T. Suzuki et al. / Journal of Orthopaedic Science xxx (2016) 1e6
patients, 109 (61%) had no previous SRE, while 68 patients (39%) had already experienced SRE. Among the 109 patients without a previous history of SRE, 84 (77%) showed asymmetrical collapse. Forty-one (60%) of the 68 patients with a previous history of SRE showed asymmetrical collapse. As for neurological deficits, 16 patients had non-ambulatory neurological deficits (Frankel grade AeC), 12 were Frankel D, and 152 were Frankel E. Among non-ambulatory patients, 13 showed asymmetrical collapse; the pedicle sign was observed in only 4 of these patients. Among 164 patients with Frankel D or E status, 115 (70%) had asymmetrical collapse; the pedicle sign was found in 35 (21%) of these patients (Table 4). 4. Discussion Diagnosis of spinal metastasis before the onset of paraplegia, followed by appropriate radiotherapy palliates pain and prevents spinal cord injuries in 90% of cases [14,15]. Diagnosis of spinal metastasis has become easier with the advent of cutting-edge imaging technologies such as MRI and PET scans. On MRI, pathologic compression fractures from spinal metastases often have convex bowing of the ventral and/or dorsal margins, unlike traumatic or osteoporotic compression fractures, which have sharply angulated cortical margins [16,17]. Furthermore, intravenous gadolinium administration improves the visibility of metastatic foci, especially in those with extravertebral extension [4,12,16,17]. Bone scans are useful in the early stage of metastasis before pathological fracture, revealing lesions several months (0e18 months) earlier than radiography [11,18,19], which requires at least 50% bone destruction before a lesion becomes evident [11,20]. Because 18F-fluorodeoxyglucose PET reveals tumor metabolism, it enables the detection of bone metastasis at an even earlier stage than bone scans [11]. However, there is typically a waiting period of several days for MRI or PET scans in many countries. Furthermore, scanning takes at least 20 min and is expensive. For these reasons, plain X-ray remains the initial imaging study at first presentation for compression fractures or back pain. It is sometimes difficult to differentiate spinal metastases from osteoporotic compression fractures with radiographs before paraplegia occurs because both develop in elderly patients and cause intractable pain and vertebral deformity. This is an especially serious dilemma in the lower thoracic and lumbar spine, because the thoracolumbar transition zone is the most frequent site for osteoporotic vertebral fractures. Cooper et al. reported that 32% of osteoporotic vertebral fractures occurred in either Th12 or L1 [6]. Nearly 60% of osteoporotic vertebral fractures are reported to occur between Th10 and L5 [7]. In the present study, metastatic fractures most commonly occurred in Th12, but these fractures had a broad distribution from Th10 to L5. Fracture below L3 or at Th10 accounted for 20.2% of fractures in the metastasis group but only 3% in the osteoporosis group. This difference in fracture distribution can raise suspicion for spinal metastasis. The pedicle sign can be seen in advanced spinal metastasis, after destruction of the affected vertebral pedicle [9,10]. The current study found that the pedicle sign was not present in the
Table 4 Relationships between neurological symptoms and asymmetrical collapse. Frankel classification
No. of patients
Asymmetrical collapseþ (%)
Pedicle signþ (%)
AeC D E Total
16 12 152 180
13 (81%) 10 (83%) 105 (69%) 128 (71%)
4 (25%) 3 (25%) 32 (21%) 39 (22%)
5
osteoporotic fracture group, but its prevalence in the metastasis group was much lower than that of asymmetrical collapse. Only 11 (5.9%) of 188 vertebrae with metastasis showed the pedicle sign before developing asymmetrical collapse, while 103 (54.8%) vertebrae showed asymmetrical collapse without the pedicle sign. Even in patients with non-ambulatory neurological deficits, the pedicle sign was only present 25% of the time. Therefore, although the vertebral pedicle sign has high specificity, its sensitivity is not sufficient to detect spinal metastasis. Based on the analysis of the relationships between clinical symptoms and radiological findings, it cannot be concluded that the asymmetrical collapse sign is useful in patients with no history of cancer who present with skeletal metastasis of unknown origin, because there were only three such patients included in this study. However, the asymmetrical collapse sign can be a useful clue to identify spinal metastasis before paraplegia occurs during the follow-up of patients with a history of cancer. This sign was found in 70% of patients who had painful metastasis but who were still ambulatory (Frankel D or E) and in 77% of patients without previous history of SRE. In this study, we focused on angulated deformity caused by onesided fragility with asymmetrical collapse. Guillevin et al. [12] described this phenomenon briefly in a textbook on bone metastasis, but there have been no detailed studies of asymmetrical collapse. The current study revealed that both the frequency of asymmetrical collapse detected visually on plain X-ray images and the angle of collapse are significantly higher in patients with spinal metastases than in those with osteoporotic fractures. Previous studies have described the relationship between bone destruction and vertebral collapse. Taneichi et al. reported the close correlation between vertebral collapse and bone destruction area, demonstrating that collapse occurs when 50e60% of the vertebral body is affected in the thoracic spine and when 35e40% is affected in the thoracolumbar and lumbar spine [21]. An experimental study by Ebihara et al. showed that as unilateral trabecular bone is replaced by tumor it no longer supports the vertebral endplate, and vertebral collapse can easily occur [22]. Both studies emphasize the importance of unilateral destruction of the vertebral body and other spinal components. These studies and experience suggest that the reason for asymmetrical collapse is that vertebral metastasis does not always develop centrally, but often begins with destruction of only one side of the vertebral body [12]. In contrast, osteoporosis decreases the strength of the vertebral body evenly along its horizontal axis; therefore, osteoporosis tends to lead to symmetrical collapse. There are some limitations of this study. First, the presence of asymmetric vertebral collapse would be of little diagnostic use in patients with scoliosis, because asymmetric collapse deformity is commonly seen among these patients. Second, we did not evaluate patients with severe deformity or multiple fractures. Therefore, the asymmetrical collapse sign cannot be applied in patients with severe age-related deformity. Multiple fracture lesions can be caused not only by metastasis, but also by hormonal disorders such as severe osteoporosis. These lesions should be evaluated with MRI and/or CT. Third, asymmetrical collapse was seen in 21.7% of patients with osteoporotic fractures, raising concerns about false positives. Fourth, all but three patients in this study had previously diagnosed malignancies. Therefore, it is not certain whether the results of the current study can be applied to patients without previously diagnosed malignancy. Fifth, we did not verify whether the asymmetric collapse sign can be applied to the cervical spine or to the thoracic spine above Th10. However, in clinical practice, osteoporotic compression fractures in the cervical and upper thoracic spine are not common, and non-traumatic fractures in these regions raise suspicion of pathological fracture, regardless of
Please cite this article in press as: Suzuki T, et al., Asymmetrical vertebral collapse from spinal metastasis in lower thoracic and lumbar spine, Journal of Orthopaedic Science (2016), http://dx.doi.org/10.1016/j.jos.2016.12.013
6
T. Suzuki et al. / Journal of Orthopaedic Science xxx (2016) 1e6
collapse symmetry. Sixth, there were differences in gender and age distribution between the osteoporosis and bone metastasis groups. These differences result from the nature of bone metastasis and osteoporosis. Finally, this study was retrospective; a prospective study enrolling more patients is necessary to verify our findings. The thoracolumbar transition zone is a frequent site of osteoporotic compression fracture, which sometimes occurs without a causative event. The current study revealed that asymmetrical collapse raises suspicion of spinal metastasis in this region, and provides a clue to the cause of fracture. If a patient has asymmetrical collapse with an angulation of five degrees or more, or if the fracture occurs at an atypical level such as below L3, it is reasonable to suspect pathological fracture and to perform CT, MRI, or PET scan to differentiate spinal metastasis from osteoporotic fracture. Conflict of interest The authors declare that they have no conflict of interest. References [1] Plunkett TA, Rubens RD. Clinical features and prognosis of bone metastases. In: Jasmin C, Coleman RE, Coia LR, Capanna R, Saillant G, editors. Textbook of bone metastases. 1st ed. West Sussex, England: WILEY; 2005. p. 65e75. [2] Coleman RE. Skeletal complications of malignancy. Cancer 1997 Oct 15;80(8): 1588e94. [3] Berrettoni BA, Carter JR. Mechanisms of cancer metastasis to bone. J Bone Jt Surg Am 1986 Feb;68(2):308e12. [4] Shah LM, Salzman KL. Imaging of spinal metastatic disease. Int J Surg Oncol 2011;2011:769753. http://dx.doi.org/10.1155/2011/769753. Epub 2011 Nov 3. [5] Harrington KD. Chapter 12 metastatic disease of the spine. In: Harrington KD, editor. Orthopaedic management of metastatic bone disease. 2nd ed. St. Louis, Mo: The C.V. Mosby Company; 1988. p. 309e83. [6] Cooper C, Atkinson EJ, O'Fallon WM, Melton 3rd LJ. Incidence of clinically diagnosed vertebral fractures: a population-based study in Rochester, Minnesota, 1985e1989. J Bone Min Res 1992 Feb;7(2):221e7. [7] Kilincer C, Kabayel DD, Cagli B, Unlu E, Wicki B, Ozdemir F. Frequency, distribution and severity of prevalent osteoporotic vertebral fractures in postmenopausal women. Turk Neurosurg 2013;23(4):476e83. http://dx.doi.org/ 10.5137/1019-5149. JTN.7442-12.0.
[8] Jacobson HG, Poppel MH, Shapiro JH, Grossberger S. The vertebral pedicle sign: a roentgen finding to differentiate metastatic carcinoma from multiple myeloma. Am J Roentgenol Radium Ther Nucl Med 1958 Nov;80(5):817e21. [9] Asdourian PL, Weidenbaum M, Dewald RL, Hammerberg KW, Ramsey RG. The pattern of vertebral involvement in metastatic vertebral breast cancer. Clin Orthop Relat Res 1990 Jan;(250):164e70. [10] Braunstein EM, Kuhns LA. Computed tomographic demonstration of spinal metastases. Spine(Phila Pa 1976) 1983 Nov-Dec;8(8):912e5. [11] Cook GJR, Fogelman I. Radioisotope and PET imaging of bone metastases. In: Jasmin C, Coleman RE, Coia LR, Capanna R, Saillant G, editors. Textbook of bone metastases. 1st ed. West Sussex, England: WILEY; 2005. p. 77e90. [12] Guillevin R, Vallee JN, Martin-Duverneuil N, Lo D, Lafitte F, Maillard JC, Chiras J. Imaging of spinal bone metastases. In: Jasmin C, Coleman RE, Coia LR, Capanna R, Saillant G, editors. Textbook of bone metastases. 1st ed. West Sussex, England: WILEY; 2005. p. 91e104. [13] Frankel HL, Hancock DO, Hyslop G, Melzak J, Michaelis LS, Ungar GH, Vernon JD, Walsh JJ. The value of postural reduction in the initial management of closed injuries of the spine with paraplegia and tetraplegia. I. Paraplegia 1969 Nov;7(3):179e92. [14] Loblaw DA, Laperriere NJ. Emergency treatment of malignant extradural spinal cord compression: an evidence-based guideline. J Clin Oncol 1998 Apr;16(4):1613e24. [15] Katagiri H, Takahashi M, Inagaki J, Kobayashi H, Sugiura H, Yamamura S, Iwata H. Clinical results of nonsurgical treatment for spinal metastases. Int J Radiat Oncol Biol Phys 1998 Dec 1;42(5):1127e32. [16] Meyers Steven P. Metastatic lesion. In: MRI of bone and soft tissue tumors and tumor like lesions. 1st ed. New York, NY: Thieme; 2008. p. 601e8. [17] Abdel-Wanis ME, Solyman MT, Hasan NM. Sensitivity, specificity and accuracy of magnetic resonance imaging for differentiating vertebral compression fractures caused by malignancy, osteoporosis, and infections. J Orthop Surg (Hong Kong) 2011 Aug;19(2):145e50. [18] Galasko CSB. The significance of occult skeletal metastases, detected by skeletal scintigraphy, in patients with otherwise apparently ‘early’ mammary carcinoma. Br J Surg 1975 Sep;62(9):694e6. [19] Coleman RE, Foglman I, Habibollahi F, North WRS, Rubens RD. Selection of patients with breast cancer for routine follow-up bone scans. Clin Oncol (R Coll Radiol) 1990 Nov;2(6):328e32. [20] Edelstyn GA, Gillespie PJ, Grebbel FS. The radiological demonstration of osseous metastases. Experimental observations. Clin Radiol 1967 Apr;18(2): 158e62. [21] Taneichi H, Kaneda K, Takeda N, Abumi K, Satoh S. Risk factors and probability of vertebral body collapse in metastases of the thoracic and lumbar spine. Spine (Phila Pa 1976) 1997 Feb 1;22(3):239e45. [22] Ebihara H, Ito M, Abumi K, Taneichi H, Kotani Y, Minami A, Kaneda K. A biomechanical analysis of metastatic vertebral collapse of the thoracic spine, a sheep model study. Spine (Phila Pa 1976) 2004 May 1;29(9):994e9.
Please cite this article in press as: Suzuki T, et al., Asymmetrical vertebral collapse from spinal metastasis in lower thoracic and lumbar spine, Journal of Orthopaedic Science (2016), http://dx.doi.org/10.1016/j.jos.2016.12.013