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Musculoskeletal Imaging |
1 From the Departments of Diagnostic Radiology and Organ Imaging (J.F.G., D.K.W.Y., G.E.A., F.K.H.L.), Community and Family Medicine (A.W.L.H., S.Y.S.W., E.M.C.L.), and Orthopaedics and Traumatology (P.C.L.), Chinese University of Hong Kong, Prince of Wales Hospital, 30-32 Ngan Shing St, Shatin, Hong Kong SAR, China. Received August 16, 2004; revision requested October 27; revision received November 24; accepted December 24. Supported by a Direct Grant for Research, Chinese University of Hong Kong, reference no. 2004.1.066. Address correspondence to J.F.G. (e-mail: griffith{at}ruby.med.cuhk.edu.hk).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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MATERIALS AND METHODS: This study had institutional review board approval, and all participants provided informed consent. DXA, 1H MR spectroscopy, and dynamic contrast-enhanced MR imaging of the lumbar spine were performed in 90 men (mean age, 73 years; range, 67–101 years). Vertebral marrow fat content and perfusion (maximum enhancement and enhancement slope) were compared for subject groups with differing bone densities (normal, osteopenic, and osteoporotic). The t test was used for comparisons between groups, and the Pearson test was used to determine correlation between marrow fat content and perfusion indexes.
RESULTS: Eight subjects were excluded, yielding a final cohort of 82 subjects (mean age, 73 years; range, 67–101 years) that included 42 subjects with normal bone density (mean T score, 0.8 ± 1.1 [standard deviation]), 23 subjects with osteopenia (mean T score, –1.6 ± 0.4), and 17 subjects with osteoporosis (mean T score, –3.2 ± 0.5). Vertebral marrow fat content was significantly increased in subjects with osteoporosis (mean fat content, 58.23% ± 7.8) (P = .002) or osteopenia (mean fat content, 55.68% ± 10.2) (P = .034) compared with that in subjects with normal bone density (50.45% ± 8.7). Vertebral marrow perfusion indexes were significantly decreased in osteoporotic subjects (mean enhancement slope, 0.78%/sec ± 0.3) compared with those in osteopenic subjects (mean enhancement slope, 1.15%/sec ± 0.6) (P = .007) and those in subjects with normal bone density (mean enhancement slope, 1.48%/sec ± 0.7) (P < .001).
CONCLUSION: Subjects with osteoporosis have decreased vertebral marrow perfusion and increased marrow fat compared with these parameters in subjects with osteopenia. Similarly, subjects with osteopenia have decreased vertebral marrow perfusion and increased marrow fat compared with these parameters in subjects with normal bone density.
© RSNA, 2005
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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In the past decade, magnetic resonance (MR) imaging–based studies have documented physiologic differences in aging bone. Dynamic contrast material–enhanced MR imaging studies across different age groups have revealed that vertebral marrow perfusion is reduced in older subjects (3–5). Hydrogen 1 (1H) MR spectroscopy–based studies have revealed an age-dependent linear increase in vertebral marrow fat content (6,7). These investigators examined the relationship between aging, perfusion, and fat content, although they did not specifically examine whether a relationship exists between marrow perfusion, fat content, and bone mineral density (BMD).
Thus, the aim of our study was to prospectively use 1H MR spectroscopy and dynamic contrast-enhanced MR imaging to measure vertebral body marrow fat content and bone marrow perfusion in older men with varying BMDs as documented with dual x-ray absorptiometry (DXA).
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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DXA Examinations
A DXA examination (Hologic QDR-4500W; Hologic, Waltham, Mass) of the lumbar region (L1 through L4) was performed in each subject within 1 month before the MR imaging examination. On the basis of their DXA results, subjects were grouped into three categories according to their T scores and World Health Organization criteria (8). A T score greater than –1.0 indicated normal BMD; a T score between –1.0 and –2.5, osteopenia; and a T score of less than –2.5, osteoporosis.
MR Imaging Examinations
MR imaging examinations were performed with a 1.5-T whole-body MR imaging system (Intera NT; Philips Medical Systems, Best, the Netherlands) that had a 30 mT/m maximum gradient capability. A 20-cm-diameter circular surface coil centered at the third lumbar vertebra (L3) was used to optimize the sensitivity of both the 1H MR spectroscopic and the dynamic contrast-enhanced MR imaging examinations. L3 was chosen because optimal coil positioning was facilitated by surface landmarks (iliac crests). After scout images in the transverse, coronal, and sagittal planes were acquired, T1-weighted (repetition time msec/echo time msec, 450/1; section thickness, 4 mm with 0.4-mm gap; field of view, 325 mm; matrix, 256 x 256; number of signals acquired, two) and T2-weighted (3500/120; section thickness, 4 mm with 0.4-mm gap; field of view, 325 mm; matrix, 256 x 256; number of signals acquired) imaging of the lumbar spine in the sagittal plane was performed.
These images were acquired so that we could exclude the presence of lumbar vertebral fractures or other abnormalities and define a region of interest (ROI) for evaluation of dynamic contrast-enhanced MR images, as well as to guide positioning of a volume of interest within the boundaries of the L3 vertebral body for 1H MR spectroscopy (Fig 1). A vertebral fracture was diagnosed if vertebral height was decreased by 20% or greater (9). Volume of interest size ranged from 8 to 17 cm3, depending on vertebral body size. After local shimming and gradient adjustments were performed, data were acquired at a spectral bandwidth of 1000 Hz, and 64 non–water suppressed signals were obtained by using a point-resolved spectroscopic sequence (3000/25).
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Data Analysis
Spectroscopic data.—Spectra acquired from the L3 vertebral body of each subject were exported and analyzed at an off-line computer (Precision 650 Workstation; Dell, Austin, Tex) by using a time-domain fitting routine known as the variable projection, or VARPRO, method in the MRUI software (available at www.mrui.uab.es/mrui/mruiHomePage.html) (10). Manually selected resonance frequency and line width of water (4.65 ppm) and fat (1.3 ppm) peaks were used as starting values in the nonlinear least squares fitting algorithm. The rules applied to the fitting procedure were as follows: Line widths of water and fat were unconstrained, zero- and first-order phase corrections were estimated with VARPRO, and a Lorentzian model function was assumed for both water and fat peaks. Line widths of unsuppressed water and lipid peaks, as determined with MRUI, were measured as an indicator of overall spectral quality.
Vertebral body fat content, or FC, defined as the relative fat signal intensity amplitude in terms of a percentage of total signal intensity amplitude (water and fat), was calculated according to the following equation (6): FC = [Ifat/(Ifat + Iwat)] · 100, where Ifat and Iwat are the peak amplitudes of fat and water, respectively (Fig 1). Fat and water signal intensity amplitudes, which were determined with spectral fitting, were not corrected for T2 decay because a relatively short echo time was used in data acquisition and no T1-dependent saturation correction was performed.
Perfusion data.—Dynamic contrast-enhanced MR images acquired during the first-pass phase of enhancement were analyzed semiquantitatively. On a midsagittal T1-weighted image, an ROI (Fig 2) encompassing the L3 vertebral body was drawn manually by a single observer (D.K.W.Y., with 9 years of working experience with musculoskeletal MR imaging) at a radiology workstation (Viewforum; Philips Medical Systems). Average signal intensity changes caused by the arrival of contrast material within the ROI at each time point were recorded and further processed at the off-line computer.
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On the basis of the Imax and Ibase values obtained from the fitted time–signal intensity curve, two perfusion parameters were calculated—namely, maximum enhancement and enhancement slope. Maximum enhancement, or ME, was defined as the maximum percentage increase (Imax – Ibase) in signal intensity from baseline (Ibase). Enhancement slope, or ES, was defined as the rate of enhancement between 10% and 90% of the maximum signal intensity difference between Imax and Ibase. These perfusion parameters were calculated according to the following equations:
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Statistical Analysis
Overall mean values for vertebral marrow fat content, maximum enhancement, and enhancement slope were obtained in addition to the mean values for each of the three bone density groups (the group with normal bone density, the group with osteopenia, and the group with osteoporosis). Student t testing was performed for comparing the mean ages of the subject groups. Pearson correlation testing was used to assess correlations between marrow fat content, maximum enhancement, and enhancement slope and bone density (T score) for the three bone density groups. Analyses were performed by using SPSS for Windows, release 11.0 (SPSS, Chicago, Ill). P < .05 was considered to indicate a statistically significant difference.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Vertebral Marrow Fat Content
The mean line widths of the unsuppressed water and lipid peaks for all 82 subjects were 34.4 Hz ± 3.6 and 32.5 Hz ± 5.4, respectively. Average vertebral marrow fat content for all 82 subjects was 54.8% ± 8.9. When vertebral marrow fat content was analyzed according to bone density, subjects with osteoporosis had the highest mean value (58.23% ± 7.8), followed by subjects with osteopenia (55.68% ± 10.2) and subjects with normal bone density (50.45% ± 8.7) (Fig 1). The observed difference between subjects with osteoporosis and those with normal bone density was significant (P = .002), as was the observed difference between subjects with osteopenia and those with normal bone density (P = .034) (Fig 1). The observed increase in marrow fat content in subjects with osteoporosis compared with the fat content in subjects with osteopenia was not significant (P = .394) (Fig 1).
Vertebral Marrow Perfusion
Average maximum enhancement for all 82 subjects was 28.8% ± 11.2. When maximum enhancement was analyzed according to bone density, subjects with osteoporosis had the lowest mean maximum enhancement (23.52% ± 9.9) compared with subjects with osteopenia (28.36% ± 10.8) and subjects with normal bone density (34.49% ± 13) (Fig 2). The observed difference in maximum enhancement between subjects with osteoporosis and those with normal bone density was significant (P < .001), as was the observed difference between subjects with osteopenia and those with normal bone density (P = .023) (Fig 2). However, the reduction in mean maximum enhancement observed between subjects with osteoporosis and subjects with osteopenia was not significant (P = .075) (Fig 2).
Average enhancement slope for all 82 subjects was 1.14%/sec ± 0.5. When average enhancement slope was analyzed according to bone density, subjects with osteoporosis had the least steep average enhancement slope (0.78%/sec ± 0.3) compared with subjects with osteopenia (1.15%/sec ± 0.6) and those with normal bone density (1.48%/sec ± 0.7) (Fig 2). The observed difference in enhancement slope was significant between subjects with osteoporosis and those with either osteopenia (P = .007) or normal bone density (P < .001) (Fig 2). Subjects with osteopenia also had a significantly reduced mean enhancement slope compared with subjects with normal bone density (P < .028) (Fig 2).
Correlation between Bone Density, Vertebral Marrow Perfusion, and Fat Content
Significant correlation was observed between T score and maximum enhancement (r = 0.263, P < .017), between T score and enhancement slope (r = 0.419, P < .001), and between T score and marrow fat content (r = –0.320, P = .003). Across all three groups (the group with normal bone density, the group with osteopenia, and the group with osteoporosis), the increase in marrow fat content correlated strongly with a decrease in both maximum enhancement (r = –0.727, P < .001) (Fig 3) and enhancement slope (r = –0.545, P < .001) (Fig 3). There was also strong correlation between maximum enhancement and enhancement slope (r = 0.706, P < .001) (Fig 3).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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The results of this study show that the observed reduction in vertebral marrow perfusion in older male subjects is related to bone density. Subjects with osteoporosis had significantly reduced vertebral marrow perfusion compared with perfusion in subjects with osteopenia, and subjects with osteopenia had significantly reduced vertebral marrow perfusion compared with that in subjects with normal bone density. Perfusion within the rigid confines of the vertebral body is potentially dependent on a combination of systemic and local factors (cardiac output, arterial sufficiency, vascular tone, vascular density, and intraosseous venous distensibility). Results of histologic and laboratory studies have suggested that there is an association between reduced bone marrow perfusion and reduced bone density.
Burkhardt et al (13) observed, in bone biopsy specimens, an increase in marrow fat and a reduction in the number of marrow arteries and capillary sinusoids in osteoporosis. By using radiolabeled microspheres to assess blood flow, Bloomfield et al (14) observed an age-related reduction in blood flow and bone density in the rat scapula, forelimb, and femur. Reduced perfusion results in a decrease in the local production of nitric oxide and prostaglandin E2 (which stimulate osteoblastic activity and inhibit osteoclastic activity), a decrease in the production of prostaglandin I2 (which inhibits osteoclastic activity), and a decrease in the production of the bone matrix protein osteopontin (14). In other words, reduced perfusion may, through local mediators, alter the balance between osteoblastic and osteoclastic activity (14). Osteoprotegerin, a recently discovered glycoprotein that inhibits osteoclast formation, may also play a role; mice that lack this glycoprotein develop arterial calcification and early onset osteoporosis (15).
Results of epidemiologic studies have also revealed an association between reduced perfusion and bone density. Patients with unilateral peripheral vascular disease have reduced BMD in the affected limb (16). Osteoporosis in the elderly is associated with an increased mortality rate, even when deaths after osteoporotic fractures are not considered (17). Women with osteoporosis soon after menopause have an almost two-fold increase in the risk of cardiovascular mortality, an association that persists after other cardiovascular risk factors are adjusted for (18).
While vertebral marrow perfusion decreases with age, the reverse is true for marrow fat (3). Vertebral marrow fat content increases with age, although it is unclear whether this increase is due to an increase in adipocyte size or adipocyte number (19,20). Schellinger et al (6) reported an average vertebral marrow fat content of 20.5% in all subjects aged 15–29 years that increased to 49.4% for all subjects aged 70–89 years. Across age groups, men tend to have more vertebral marrow fat than women (6). For the current study group, overall values obtained for vertebral marrow fat content (mean, 54.8%) were comparable to those previously reported. Kugel et al (7) observed a mean vertebral fat content of 55.3% in men older than 61 years, and Schellinger et al (6) observed a mean fat content of 63% in men older than 70 years. Although bone density was not specifically measured in those studies, Schellinger et al observed that vertebral marrow fat content was 45% higher overall in subjects with morphologic evidence of bone weakness (Schmorl nodes, endplate depression, or compression fractures) than in subjects with normal vertebral morphologic features.
Our results show that vertebral marrow fat content is related to bone density. Subjects with osteoporosis or osteopenia had a significantly increased marrow fat content compared with the fat content in subjects with normal bone density. Several potential mechanisms whereby increasing marrow fat interacts with bone strength and density have been proposed. First, an increase in marrow fat may simply represent a compensation for trabecular thinning (6,20). Second, replacement of the more hydrostatic (and less compressible) hemopoietic marrow with the more compressible fatty marrow may potentiate vertebral weakening (6). Third, because osteoblasts and adipocytes share a common precursor in the bone marrow, increased adipogenesis may be associated with decreased osteoblastogenesis (6,20).
Our study results show that decreasing marrow perfusion and increasing marrow fat content accompany a reduction in bone density. It has not been determined whether these represent independent or related variables and whether a temporal relationship exists—that is, whether an increase in vertebral marrow fat precedes a reduction in perfusion or vice versa and whether these changes predate or postdate changes in bone density. Longitudinal studies will help answer these questions. It is conceivable that within the confines of the vertebral body, an increasing amount of fat could simply compress the intraosseous veins, diminishing blood flow. Also, a clear interplay between lipids, arteriosclerosis, and bone density has lately been increasingly recognized. Accumulation of oxidized lipids in the arterial wall induces arterial wall calcification (as a feature of atherosclerosis), while accumulation of the same oxidized lipids within bone can inhibit osteoblastic and promote osteoclastic differentiation (21,22).
Current techniques used to evaluate osteoporosis, such as bone densitometry and quantitative computed tomography, can help assess the end result of osteoporosis (ie, reduced bone density) but provide little information regarding the underlying pathophysiology of the disease. The observed overlap in marrow perfusion indexes and fat content between subjects with normal bone density, subjects with osteopenia, and subjects with osteoporosis in the present study indicates that, although MR perfusion and spectroscopic techniques enable a broad estimation of bone density, marrow perfusion indexes and fat content alone are not specific enough to allow one to accurately determine bone density.
This study had several limitations. First, owing to their simultaneous participation in another osteoporosis-related study, only men were included, although osteoporosis is more common in women. Age-related differences in vertebral marrow perfusion and fat deposition do exist between men and women (3). On average, women younger than 50 years of age have increased marrow perfusion compared with perfusion in men of similar ages, while women older than 50 years of age have a more marked decrease in marrow perfusion compared with that in men of similar ages (3). Conversely, across age groups, men tend to have more vertebral marrow fat than women (6). Therefore, the results of this study cannot necessarily be applied to women (3,6).
Second, contrast material was injected manually rather than with a power injector. Variations in injection rate may have affected the enhancement slope—although we believe this effect to be minimal—and the same potential error was incurred with all participants. Third, the sample size was small, particularly in the osteopenic and osteoporotic groups, because osteoporosis is less common in men. This small sample size may have resulted in some trends observed between groups being within the limits of statistical error. Finally, only one vertebral body, L3, was examined so that we could correlate perfusion and fat content data. Although perfusion data can be simultaneously acquired from all vertebrae within the imaging plane, meaningful single-voxel spectroscopic data can only be obtained from only one vertebra at any one time.
In conclusion, compared with bone perfusion in men with normal bone density, bone perfusion is reduced in men with osteopenia and further reduced in men with osteoporosis. In contrast, vertebral marrow fat content is increased in men with osteopenia or osteoporosis.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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Abbreviations: BMD = bone mineral density • DXA = dual x-ray absorptiometry • ROI = region of interest
Authors stated no financial relationship to disclose.
Author contributions: Guarantor of integrity of entire study, J.F.G.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; approval of final version of submitted manuscript, all authors; literature research, J.F.G., D.K.W.Y.; clinical studies, J.F.G., G.E.A., A.W.L.H., S.Y.S.W., E.M.C.L., P.C.L.; statistical analysis, J.F.G., D.K.W.Y., G.E.A., F.K.H.L.; and manuscript editing, J.F.G., D.K.W.Y., G.E.A.
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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