DOI: 10.1148/radiol.2302011842
(Radiology 2004;230:499-503.)
© RSNA, 2004
Intervertebral Disk Calcification of the Spine in an Elderly Population: Radiographic Prevalence, Location, and Distribution and Correlation with Spinal Degeneration1
Kullanuch Chanchairujira, MD,
Christine B. Chung, MD,
Jee Young Kim, MD,
Olympia Papakonstantinou, MD,
Min Hee Lee, MD,
Paul Clopton, MS and
Donald Resnick, MD
1 From the Departments of Radiology (K.C., C.B.C., J.Y.K., O.P., M.H.L., D.R.) and Research Service (P.C.), Veterans Administration Medical Center, University of California San Diego, 3350 La Jolla Village Dr, San Diego, CA 92161. From the 2001 RSNA scientific assembly. Received November 16, 2001; revision requested January 30, 2002; final revision received May 9, 2003; accepted June 24. Address correspondence to C.B.C. (e-mail cbchung@ucsd.edu).
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ABSTRACT
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PURPOSE: To determine the prevalence, distribution, and location of intervertebral disk calcification (IDC) in the thoracic and lumbar spine and the association of IDC with radiographically evident spinal degenerative changes in cadavers.
MATERIALS AND METHODS: Anterior vertebral columns comprising T1 through L5 were removed from 223 cadavers (183 men, 40 women; mean age at death, 67 years; range, 37–94 years). Approximately 5-mm-thick parasagittal sections were investigated with high-contrast radiography. The presence of IDC, osteophytes, vertebral endplate abnormalities, and vacuum phenomena was recorded, and the height of disk space was measured at 3,568 intervertebral levels. Logistic regression analysis was performed.
RESULTS: IDC was identified in 178 (80%) of the 223 cadavers. Of 3,568 disks, 459 (13%) had IDC, and 289 cases (63%) were located in the annulus fibrosus. IDC was most common in the lower thoracic spine, occurring in 275 (60%) of 459 disks. IDC occurred in 159 (87%) of 183 men and 19 (48%) of 40 women. Logistic regression analysis was adjusted for age, and results showed that the frequency of IDC was significantly higher in men in upper, middle, and lower segments of the thoracic spine (P < .05) but not in the lumbar spine (P = .09). IDC correlated with increasing age (P < .001) and disk space loss (P < .001) at all spinal levels. There was no association of IDC with vacuum phenomena or vertebral endplate abnormalities at any spinal level.
CONCLUSION: IDC is common in elderly persons, especially in the annulus fibrosus and lower thoracic spine. The prevalence of IDC increases with age and extent of disk space loss.
© RSNA, 2004
Index terms: Spine, abnormalities, 326.821, 336.821 • Spine, intervertebral disks, 326.821, 336.821 • Spine, mineralization, 326.821, 336.821
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INTRODUCTION
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In 1897 Benecke used radiography to depict intervertebral disk calcification (IDC) in a cadaver (1), and in 1922 Calvé and Galland (2) depicted IDC in a patient. IDC has been associated with systemic conditions that result in biochemical alterations (eg, alkaptonuria, hemochromatosis, calcium pyrophosphate dihydrate crystal deposition disease, hyperparathyroidism, acromegaly, and amyloidosis) and conditions that result in immobilization or fusion of the spine (eg, poliomyelitis, ankylosing spondylitis, juvenile chronic arthritis, and vertebral fusion from surgery or local trauma) (3,4). In elderly patients without systemic disease, IDC is frequently detected with radiography. The prevalence of IDC in the general adult population has been reported as 5% with analysis of chest radiographs and as 6% with analysis of abdominal radiographs (4–6). Extensive epidemiologic or pathologic studies are not available to support these data, and the prevalence of IDC may be even higher (4). Indeed, the prevalence of IDC has varied from 35% to 71% in autopsy studies (7–10), but such studies included a limited number of specimens, and only a few spinal levels were analyzed.
This investigation is based on 223 cadavers and 3,568 spinal levels that include 16 intervertebral disk spaces (T1–2 through L4–5). The purpose of this study was to determine the prevalence, distribution, and location of IDC in the thoracic and lumbar spine and its relationship with radiographically evident spinal degenerative changes in cadavers of middle-aged and elderly persons.
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MATERIALS AND METHODS
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Cadavers
Complete spinal radiographs were obtained in 223 cadavers with approval of our institutional review board. Informed consent was not required from relatives of the deceased for this study. Patient histories were reviewed to document the cause of death, and specimens from patients who had a history of malignant tumor with severe vertebral destruction were excluded. Sex and age distribution are shown in Table 1. The mean age of subjects at death was 67 years (range, 37–94 years). The mean age at death was 68 years in men and 60 years in women.
The anterior portion of the vertebral columns comprising T1 through L5 was removed in one piece with a saw. All 223 specimens contained the vertebral bodies and intervertebral disks, resulting in a total of 3,568 intact intervertebral spaces. In the first days after harvest, the anterior portions of the thoracic and lumbar spine were examined with conventional radiography in frontal and lateral projections. The specimens were frozen at -40°C (Bio-Freezer; Forma Scientific, Marietta, Ohio) for 48–72 hours and subsequently cut into approximately 5-mm-thick parasagittal slabs with a band saw. Lateral radiographs of each section were obtained with an x-ray unit (Faxitron; Hewlett-Packard, McMinnville, Ore) with fine-grain film (Kodak, Rochester, NY). X-ray beam factors included 45 kVp and a focus-to-film distance of 20.3 cm. Exposure was adjusted with an automatic exposure control device.
Radiographic Analysis
All radiographs were interpreted with consensus of two musculoskeletal radiologists (K.C. and M.H.L.) who were not blinded to the purpose of the study, the spinal levels imaged, or patient information. The presence of IDC on both frontal and lateral radiographs in whole specimens and on lateral radiographs in each slab was recorded. Only those calcifications that were clearly separate from osteophytes were included in the study. The location of IDC was characterized as peripheral, central, or diffuse corresponding to involvement of the peripheral one-third, central two-thirds, or entire region of the disk, as determined with analyses of sequential lateral slab radiographs. These locations were compared with the expected locations of the annulus fibrosus, nucleus pulposus, or both. The distribution of IDC was recorded at 16 intervertebral levels in regions that were defined arbitrarily as the upper thoracic spine (T1–2 through T4–5), middle thoracic spine (T5–6 through T8–9), lower thoracic spine (T9–10 through T12-L1), and lumbar spine (L1–2 through L4–5). The presence or absence of vertebral endplate abnormality (sclerosis and erosion), vacuum phenomena in the intervertebral disk, and vertebral osteophytes at each intervertebral level was recorded. Diffuse idiopathic skeletal hyperostosis was recorded according to the presence of continuous linear new bone formation along the anterolateral aspect of at least four vertebral bodies with or without associated localized pointed excrescences of the vertebral bodies, relative preservation of intervertebral disk height in the involved vertebral segment, and the absence of extensive radiographic changes of degenerative disk changes, including vacuum phenomena and vertebral body marginal sclerosis (11). The height of each disk space was recorded as the largest distance on the midsagittal section.
Statistical Analysis
The goodness-of-fit test was used to compare the location (eg, peripheral, central, or diffuse) of IDC with the distribution of IDC in the thoracic and lumbar spine. The associations between the frequency of IDC and sex of the person and the presence of degenerative changes (eg, vertebral endplate abnormalities, diffuse idiopathic skeletal hyperostosis, and vacuum phenomena) were compared with the 
2 test. Logistic regression analysis was used to evaluate the effect of sex and age on the prevalence of IDC. Mean age, intervertebral disk height, and presence of vertebral osteophytes were recorded in specimens with and without IDC and compared with the t test. Results were confirmed with the Mann-Whitney U test. Age was reported as mean ± SD. P values less than .05 were significant.
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RESULTS
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Prevalence of IDC
The frequency of IDC is shown in Table 2. IDC was identified in 178 (80%) of the 223 specimens, some with multiple level deposits. IDC was present in 459 (13%) of the 3,568 disks and was classified as peripheral in 289 (63%), central in 115 (25%), and diffuse in 55 (12%) (Figs 1, 2). IDC was present in the upper thoracic spine in 37 (8%) of 459 disks, in the middle thoracic spine in 78 (17%), in the lower thoracic spine in 275 (60%), and in the lumbar spine in 69 (15%). IDC was most prevalent in the peripheral location in each of these four spinal segments, followed by central and diffuse locations. All locations of IDC (peripheral, central, and diffuse) within the disk were significantly more prevalent in the lower thoracic spine than in the upper thoracic (P < .01), middle thoracic (P < .05), and lumbar spine (P < .05). Peripheral IDC was also significantly more prevalent in the middle thoracic spine than in the lumbar (P < .05) or upper thoracic (P < .05) spine.
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Figure 1a. (a) Anteroposterior, (b) lateral, and (c) sagittal slab contact radiographs of the spine show vertebral endplate abnormality (black arrows) and IDC (white arrow), which was found in 459 (13%) of 3,568 disks.
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Figure 1b. (a) Anteroposterior, (b) lateral, and (c) sagittal slab contact radiographs of the spine show vertebral endplate abnormality (black arrows) and IDC (white arrow), which was found in 459 (13%) of 3,568 disks.
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Figure 1c. (a) Anteroposterior, (b) lateral, and (c) sagittal slab contact radiographs of the spine show vertebral endplate abnormality (black arrows) and IDC (white arrow), which was found in 459 (13%) of 3,568 disks.
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Relationship of IDC to Age and Sex
Mean age was significantly greater in cadavers with IDC (70 years ± 10) than in cadavers without IDC (53 years ± 10) (P < .001). Furthermore, mean age of subjects with IDC was significantly greater than mean age of subjects without IDC for each spinal level (P < .001) (Table 3). IDC was found in 159 (87%) of 183 men and 19 (48%) of 40 women (P < .001). Logistic regression analysis was performed to adjust for age differences and revealed that the frequency of IDC was significantly higher in men than in women in all three segments of the thoracic spine (P < .05) but not in the lumbar spine (P = .09).
Relationship of IDC to Spinal Degeneration
The association of frequency of IDC with intervertebral disk space height and the number of osteophytes is summarized in Table 4. The decrease of disk space height was significantly greater in subjects with IDC than in subjects without IDC (P < .001) for all spinal levels. The association of IDC with the number of osteophytes was not significant in the thoracic spine; however, this association was significant in the lumbar spine. There was no association of IDC with vacuum phenomena, vertebral endplate abnormalities (erosion and sclerosis), or presence of diffuse idiopathic skeletal hyperostosis at all spinal levels.
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DISCUSSION
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The identification of IDC dates to the 19th century. While IDC is reportedly associated with such systemic entities as metabolic or rheumatologic disorders or previous trauma or infection, the prevalence of IDC in elderly persons without one of these associated processes remains a point of contention (4,7–10). The prevalence of IDC in the general adult population has been previously reported as 5%–6% with conventional radiography (4–6), while radiographic inspection of cadavers has revealed a higher prevalence of 35%–71% (7–9).
Our analysis certainly indicates an increased prevalence of IDC in elderly persons and supports the findings of other authors (4,7–9). Whereas similar cadaveric studies were limited by small specimen populations and few analyzed spinal levels, the number of specimens in this study created few limitations with regard to statistical power. Not only do we report an overall increase in the occurrence of IDC in elderly persons, our data show a significant increase in the prevalence of IDC with increasing age for all spinal levels. These findings suggest that IDC may be a common phenomenon of aging that does not require further investigation for association with a systemic disease.
The divergence of our data from that of previous studies may stem from the technique used to detect IDC and the patient population examined. Clinical studies of IDC have generally been performed with conventional radiography in a population with a lower mean age. Postmortem studies, including our own, have been performed by using specimens from elderly persons and have allowed high-contrast radiography. This technique is clearly more sensitive for detection of IDC when compared with conventional radiography.
To our knowledge, only four previously reported postmortem studies relate to the prevalence of IDC (7–9), and none has investigated the prevalence of IDC at different disk locations and spinal levels in the thoracic and lumbar spine. Our results show that IDC is most prevalent in the annulus fibrosus (63%) for all spinal levels and that the most common level of IDC was the lower thoracic spine (60%). Moreover, the prevalence of IDC at all specific locations (eg, annulus fibrosus, nucleus pulposus, or entire disk) in the lower thoracic spine was significantly higher than that in the upper or middle thoracic or lumbar spine. IDC involving the annulus fibrosus was also more prevalent in the middle thoracic spine than in the lumbar or upper thoracic spine.
Our results also showed that the prevalence of IDC increased with advanced age in both sexes. In our cadaveric population, men had a higher prevalence of IDC than women; however, the mean age of men was 8 years greater than that of women. When adjusted for the influence of age, the frequency of IDC in men was significantly higher than in women in the thoracic spine but not in the lumbar spine. The reported sex differences in the prevalence of IDC identified with radiography have also been widely divergent. In one cadaveric study, the frequency of IDC was higher in women than in men; however, on average, women were about 9 years older than men (8).
We are aware of only one study that has examined the relationship between IDC and global spinal degenerative change of the lumbar spine in cadavers. Cheng et al (8) did not investigate the association of the frequency of IDC with degenerative changes of the spine, including intervertebral disk space loss, osteophytes, vacuum phenomena, and vertebral endplate abnormalities. Furthermore, their study was limited by the small sample population and number of spinal levels. In our study, the prevalence of IDC was associated with a decrease in disk space height at all spinal levels. This suggests that the development of IDC may be somehow related to intervertebral disk space collapse. The relationship of IDC with the number of osteophytes was not significant in the thoracic spine, but the relationship was significant in the lumbar spine. Nevertheless, the association is a modest one, because both the frequency of IDC and the prevalence of osteophytes in the lumbar spine increase independently with age (6–9,11–15). Our data show that the association of IDC with other degenerative changes of the spine, including the presence of vacuum phenomena, vertebral endplate abnormalities, and diffuse idiopathic skeletal hyperostosis was not significant.
Our study is unique not only in the large number of cadavers and disk levels analyzed but also in the utilization of radiography of sections of the specimen rather than of the whole specimen, a technique that would be expected to increase sensitivity for detection of IDC. Our study does, however, have limitations. Direct inspection of the gross specimens and histologic characterization of IDC were not accomplished; therefore, the nature of the deposited crystal was not determined. Another limitation of our study relates to its cross-sectional design. Spinal degeneration and IDC were assessed at the same time; therefore, whether spinal degeneration preceded the development of IDC cannot be evaluated. Furthermore, our study was performed with many tests, so significant results could have happened by chance; however, because the pattern of statistical results shown in Tables 3 and 4 are so consistent, we feel confident in our findings. Other limitations relate to the fact that the two observers did not independently analyze the radiographs and were not blinded to the purpose of the study, the spinal level, or the age and sex of the patient. Consequently, some bias may have been introduced.
In conclusion, IDC is common in cadavers of elderly persons. The most common site and distribution of IDC are the annulus fibrosus and lower thoracic spine, respectively. Although IDC may accompany some systemic diseases, it is probable that the main common factor in patients with IDC is aging rather than biochemical alterations or immobilization of the spine. Results of this study show that the prevalence of IDC increases significantly with advancing age and extent of disk space loss and indicate that the reported prevalence of IDC in patients assessed with conventional radiography has been underestimated.
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FOOTNOTES
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Abbreviation: IDC = intervertebral disk calcification
Author contributions: Guarantors of integrity of entire study, all authors; study concepts and design, K.C., C.B.C., D.R.; literature research, K.C., J.Y.K., O.P., M.H.L.; experimental studies, K.C., J.Y.K., O.P., M.H.L.; data acquisition, K.C., P.C.; data analysis/interpretation, K.C., J.Y.K.; statistical analysis, P.C.; manuscript preparation, definition of intellectual content, editing, and revision/review, K.C., C.B.C., D.R.; manuscript final version approval, K.C., D.R.
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ABSTRACT
INTRODUCTION
