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Published online before print February 27, 2004, 10.1148/radiol.2311030382
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(Radiology 2004;231:24-30.)
© RSNA, 2004

Musculoskeletal Imaging

Effect of Calcium Channel Blockers on Vertebral Bone Marrow Perfusion of the Lumbar Spine1

Tiffany Ting-Fang Shih, MD, Chee-Jen Chang, PhD, Wen-Yih Isaac Tseng, MD, PhD, Jong-Kai Hsiao, MD, Ling-Chun Shen, BS, Tsang-Wu Liu, MD and Pan-Chyr Yang, MD, PhD

1 From the Departments of Radiology (T.T.F.S., J.K.H., L.C.S.) and Internal Medicine (P.C.Y.), National Taiwan University, Medical College and Hospital, 7 Chung-Shan S Rd, Taipei 100, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei (C.J.C.); Center for Optoelectronic Biomedicine, National Taiwan University, Medical College, Taipei (W.Y.I.T.); and Division of Cancer Research, National Health Research Institutes, Taipei, Taiwan (T.W.L.). Received March 3, 2003; revision requested May 23; final revision received October 6; accepted October 21. Address correspondence to P.C.Y. (e-mail: ttfshih@ha.mc.ntu.edu.tw).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
PURPOSE: To investigate the effect of calcium channel blockers on blood perfusion of vertebral bone marrow in the lumbar spine.

MATERIALS AND METHODS: Sixteen healthy volunteers (eight men and eight women) underwent dynamic contrast material–enhanced magnetic resonance (MR) imaging of the lumbar spine. One hundred twenty minutes after the first MR examination, each subject ingested 10 mg sublingual nifedipine before undergoing a second MR examination 20–25 minutes later. Semiquantitative (peak enhancement ratio and enhancement slope) and quantitative (amplitude and rate constant of the exchange [Kout]) parameters were analyzed with the time-intensity curve. Data obtained before and after administration of nifedipine were compared. The Wilcoxon signed rank test and Spearman rank correlation test were used.

RESULTS: Median peak enhancement ratio of vertebral bodies decreased from 0.60 (mean ± SD, 0.68 ± 0.29) to 0.51 (mean, 0.56 ± 0.24) after administration of nifedipine. Median and mean decreases were 0.11 and 0.12 ± 0.15, respectively, and the percentage difference was 17% (P = .005). A P value of less than .05 was considered to indicate a statistically significant difference. Median enhancement slope changed from 0.45 (mean, 0.45 ± 0.13) to 0.41 (mean, 0.40 ± 0.24). Median and mean changes were 0.05 and 0.04 ± 0.23, respectively, and the percentage difference was 9% (P = .334). Median amplitude changed from 0.059 (mean, 0.059 ± 0.028) to 0.045 (mean, 0.048 ± 0.023). Median and mean changes were 0.008 and 0.011 ± 0.025, respectively, and the percentage difference was 18% (P = .072). Median Kout changed from 0.068 (mean, 0.063 ± 0.018) to 0.067 (mean, 0.066 ± 0.028). Median and mean changes were 0.011 and 0.004 ± 0.028, respectively (P = .404). Nifedipine affected peak enhancement ratio significantly but did not affect enhancement slope, amplitude, or Kout. Data before and after administration of nifedipine showed no differences between men and women. Spearman rank correlation coefficients suggest no significance between the differences in heart rate and blood pressure and the differences in peak enhancement ratio, enhancement slope, amplitude, or Kout.

CONCLUSION: After sublingual administration of nifedipine, the peak enhancement ratio of vertebral bone marrow decreased.

© RSNA, 2004

Index terms: Bone marrow, MR, 331.12143, 331.12144 • Drugs, side effects, 331.12143, 331.12144 • Magnetic resonance (MR), perfusion study, 331.12143, 331.12144 • Spine, MR, 331.1214


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
The link between arteriosclerosis and osteoporosis has been studied, and researchers have noted that bone tissue could be altered by vascular aging and arteriosclerosis (1). In the histomorphometric study conducted by Demmler et al (2), the numbers of arterial capillaries and sinuses per unit area were reduced in osteoporotic bone. Burkhardt et al (3) also showed diminution of bone marrow capillaries in patients with geriatric and primary osteopenia. Bone turnover was studied with nuclear isotopes, and the skeletal blood flow, as measured with flourine 18, correlated with an index of strontium 85 uptake into the exchangeable pools of bone (4,5). That is, the skeletal blood flow correlated with the work rate of osteoblasts in each unit of bone. These results indicated the possible role of a microvascular defect in the pathogenesis of osteoporosis.

Low bone mineral density has also been associated with vascular diseases or atherosclerosis. In one study (6), mean bone mineral density was much more decreased in a lower extremity severely affected by arterial disease when compared with the lower extremity on the less affected side in male patients. In another study (7), patients with fractures of the femoral neck had substantially fewer arterioles and capillaries. In an epidemiologic study of elderly women with osteoporosis (8,9), diminished bone mineral density was associated with increased risk of death from stroke. Accelerated bone loss characteristically affects women 15–20 years after menopause (10). As osteoporosis progresses in aging women, there is an increased incidence of atherosclerosis (11). Men develop osteoporosis at a later age than women. Thus, both atherosclerosis and osteoporosis are prevalent in old men and old women (10,11). These reports suggest that there is an effect of ischemia on bone metabolism; however, the involvement of a vascular component in the pathogenesis of osteoporosis may be multidimensional and have long-term effects. Furthermore, other factors, such as the effects of antihypertensive drugs—which are often used in patients who have arteriosclerosis or cardiovascular diseases— on bone mineral density or bone blood perfusion have seldom been mentioned.

Calcium channel blockers are an important group of vasodilators in the treatment of hypertension and coronary artery disease. All of the calcium channel blockers relax arterial smooth muscle and decrease peripheral vascular resistance, while exerting little effect on most venous beds (12). They cause a decrease in systolic and diastolic blood pressure that is accompanied by an increase in cardiac output because of the reduction in the afterload and a compensatory increase in heart rate and ejection fraction. The effects of calcium channel blockers on regional blood flow have been discussed in previous reports (13–17). After the administration of nifedipine, liver blood flow increases 15%–22%, as measured with indocyanine green infusion, Doppler ultrasonography, or microsphere measurement (13–15). The renal blood flow or effective renal plasma flow increased after administration of nifedipine, as shown by using different measurement methods (13,16,17), and the skeletal muscle blood flow was maintained or slightly increased (13,14,16). In short, the systemic blood pressure and vascular resistance decreased, while blood flow to the liver, kidney, and skeletal muscle increased after administration of nifedipine. Nevertheless, bone acts as a closed chamber, and cancellous bone may be regarded functionally as a closed compartment, with small collapsible vessels providing blood perfusion within this closed chamber (18,19). Unlike in other organs, in bone there is no known autoregulatory mechanism for a compensatory change to maintain blood flow. When calcium channel blockers decrease the systemic blood pressure, the vasodilatation effects on arterioles within the bone might be limited. The changes of blood flow in bone and the influences of long-term use of calcium channel blockers on bone metabolism remain unknown.

Dynamic magnetic resonance (MR) imaging with contrast material enhancement has proved useful in the evaluation of bone marrow perfusion (20,21). There are strong correlations between dynamic MR images and microsphere blood-flow measurements (20). Dynamic MR imaging is also commonly used in the evaluation of musculoskeletal neoplasms and the monitoring of patient response to chemotherapy (22,23). It is also useful in differential diagnoses of benign and malignant compression fractures in the spine (24). In a previous study, we demonstrated the use of dynamic MR imaging in the evaluation of vertebral bone marrow perfusion and noted significant changes based on age and sex (25). Thus, the purpose of this study was to investigate the influence of calcium channel blockers on blood perfusion of vertebral bone marrow in the lumbar spine.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Subjects
Sixteen healthy volunteers were included in this study. Participants were medical or paramedical personnel and included physicians, nurses, and technologists. Our Institutional Review Board approved this research project, and all subjects gave their signed informed consent before participating. There were eight men (age range, 30–48 years; mean age ± SD, 38.6 years ± 7.3) and eight women (age range, 36–50 years; mean age, 44.9 years ± 5.5). All of the women were premenopausal.

MR Imaging
Before the start of each MR examination, we measured each subject’s heart rate and blood pressure twice, with a 10-minute interval between measurements. Average heart rate and blood pressure were calculated for each subject. A routine MR study of the spine was performed with a 1.5-T superconducting system (Magnetom Vision Plus; Siemens, Erlangen, Germany). A phased-array spine coil was used, and a routine fast spin-echo T1-weighted sequence (repetition time msec/echo time msec, 600/12; turbo factor of three; section thickness, 4 mm; field of view, 28 cm) was performed in the midsagittal plane and covered the area from T11 through the sacrum. A dynamic contrast-enhanced MR study was then performed (section thickness, 10 mm; field of view, 28 cm) at the midsection of the vertebral body and covered the same area. A small degree of the oblique sagittal plane was chosen to avoid flow artifact from the abdominal aorta. The pulse sequence used was a turbo fast low-angle shot gradient-echo sequence (8.5/4.0; prepulse inversion time, 160 msec; flip angle, 10o; acquisition matrix, 72 x 128). Acquisition time was 0.89 second with 0.11-second delay. In total, 100 dynamic images were obtained within 100 seconds (one frame per second) in each subject.

An injection of 0.1 mmol per kilogram of body weight gadopentetate dimeglumine (Magnevist; Schering, Berlin, Germany) was administered manually through a 21-gauge intravenous catheter that was inserted in the right antecubital vein previously. A brief constant injection rate of approximately 2.0 mL/sec and a total injection time of 5–8 seconds were used. This injection was immediately followed with a 20-mL saline flush at the same injection rate. Dynamic imaging started when the injection of the contrast material commenced.

Each subject received 10 mg of sublingual nifedipine 120 minutes after the initial MR examination. Heart rate and blood pressure were measured a second time 20 minutes after sublingual administration of nifedipine. A second MR examination was performed in each subject immediately after the hemodynamic measurement with the same parameters that were described previously. The time between administration of nifedipine and the second MR examination was 20–25 minutes.

Data Analysis
Signal intensity values were measured in an operator-defined region of interest (ROI). One investigator (W.Y.I.T.) placed the ROI with the aid of a cursor and graphic display device, and the ROI was drawn along the border of the bone marrow of each vertebra (Fig 1a). One vertebral body was covered by one ROI measurement. ROI size was 2.1–3.4 cm2 (mean, 2.79 cm2 ± 0.52). Signal intensity of each ROI was measured at each vertebral body on 100 MR images, and the signal intensity values were then plotted against time as a time-intensity curve. Each vertebral body had one time-intensity curve. The same procedures were performed at all lumbar vertebrae (from L1 through L5) separately. The ROI measurements for each vertebra before and after administration of nifedipine were adjusted approximately identically, with the same location determined with visual inspection and the same area size (measured in square centimeters).



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  		Figure 1a. A 30-year-old healthy subject underwent two dynamic MR studies of the lumbar spine before and after administration of nifedipine. (a) Turbo fast low-angle shot gradient-echo MR image of the lumbar spine (8.5/4.0; prepulse inversion time, 160 msec; flip angle, 10°; acquisition matrix, 72 x 128). The ROIs were placed at vertebral bodies from L1 through L5. Signal intensity was measured at each vertebra and plotted against time as a time-intensity curve. Each vertebra had one ROI measurement and one time-intensity curve. (b) Time-intensity curve for vertebral body before (solid line) and after (dashed line) administration of nifedipine. The baseline signal intensity was subtracted in the y axis. The peak enhancement decreased after administration of nifedipine.

 


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  		Figure 1b. A 30-year-old healthy subject underwent two dynamic MR studies of the lumbar spine before and after administration of nifedipine. (a) Turbo fast low-angle shot gradient-echo MR image of the lumbar spine (8.5/4.0; prepulse inversion time, 160 msec; flip angle, 10°; acquisition matrix, 72 x 128). The ROIs were placed at vertebral bodies from L1 through L5. Signal intensity was measured at each vertebra and plotted against time as a time-intensity curve. Each vertebra had one ROI measurement and one time-intensity curve. (b) Time-intensity curve for vertebral body before (solid line) and after (dashed line) administration of nifedipine. The baseline signal intensity was subtracted in the y axis. The peak enhancement decreased after administration of nifedipine.

 
Semiquantitative and quantitative analyses were achieved with the time-intensity curve of each vertebra. The baseline value for signal intensity (SIbase) on a time-intensity curve was defined as the mean signal intensity of the first three images. The maximum signal intensity (SImax) was defined as the maximum value of the first rapidly rising part of the time-intensity curve. Although the time-intensity curve may have had either an equilibrium phase or a slowly rising second curve, the second rising part was not included in SImax measurement. The contrast enhancement rise time (Trise) was defined as the time between SIbase and SImax. The semiquantitative analysis, peak enhancement ratio (SImax - SIbase/SIbase), and enhancement slope (SImax - SIbase/Trise) were calculated for each ROI. Quantitative analysis was performed with a bicompartmental model proposed by Brix et al (26) and Buckley et al (27). The tissue-specific information contained in a time-intensity curve can be condensed to two parameters: (a) the amplitude, as the initial rising slope of the time-intensity curve, and (b) Kout, as the rate constant of the exchange of tracers between extravascular extracellular space and intravascular plasma. From nonlinear fitting of the individual time-intensity curve, values for amplitude and Kout were obtained. Amplitude is reflective of the permeability and extravascular extracellular space volume, and Kout is related to the permeability surface product per unit volume of extravascular extracellular space (28,29). We measured four MR parameters—two were semiquantitative data (ie, peak enhancement ratio and enhancement slope) and two were quantitative data (ie, amplitude and Kout)—at each level of the lumbar vertebrae from L1 through L5. We then obtained the mean value from five vertebrae to represent the data for each subject; for example, in patient 1 the peak enhancement ratio is the sum of data obtained at L1 through L5 divided by five.

Statistical Analysis
Raw data, including age, sex, heart rate, and systolic and diastolic blood pressure of each subject before and after administration of nifedipine, were summarized. The four MR parameters calculated and analyzed were peak enhancement ratio, enhancement slope, amplitude, and Kout. Descriptive statistics such as mean, median, and SD of the continuous variables were calculated. Comparisons before and after administration of nifedipine were analyzed with the Wilcoxon rank sum test and two-sample student t test. Both tests showed the same results. Because of the small sample size (n = 16), we used the Wilcoxon signed rank test for intraindividual comparison. The different values obtained for men and women were also analyzed with the Wilcoxon rank sum test. We further analyzed the differences between the association of heart rate and systolic and diastolic blood pressure versus the four differences of MR parameters by using Spearman rank correlation coefficients. A P value of less than .05 was considered to indicate a statistically significant difference. SAS version 8.1 software (SAS Institute, Cary, NC) was used in the analysis of data.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Table 1 shows demographic and hemodynamic data for the 16 healthy subjects before and after administration of nifedipine. The signal intensity of the ROI was measured at each vertebral body from L1 through L5 (Fig 1a) and was plotted against time as the time-intensity curve (Fig 1b). Each vertebral body has one time-intensity curve. The MR parameters derived from the time-intensity curve (peak enhancement ratio, enhancement slope, amplitde, and Kout) are shown in Table 2. The descriptive statistics of the previously mentioned parameters, including data obtained before and after administration of nifedipine and the differences between these values, are listed in Table 3. The scattergram and box plot of the four MR parameters included in Tables 2 and 3 are illustrated in Figure 2.


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  		TABLE 1. Heart Rate and Systolic and Diastolic Blood Pressure before and after Nifedipine Administration

 

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  		TABLE 2. Peak Enhancement Ratio, Enhancement Slope, Amplitude, and Kout before and after Nifedipine Administration

 

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  		TABLE 3. Characteristics before and after Nifedipine Administration and Difference in Values

 


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  		Figure 2a. Scattergram and box plot of four MR parameters (peak enhancement ratio, enhancement slope, amplitude [A], and Kout) in 16 healthy subjects show (a) data before nifedipine administration, (b) data after nifedipine administration, and (c) the difference between data obtained before and after nifedipine administration.

 


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  		Figure 2b. Scattergram and box plot of four MR parameters (peak enhancement ratio, enhancement slope, amplitude [A], and Kout) in 16 healthy subjects show (a) data before nifedipine administration, (b) data after nifedipine administration, and (c) the difference between data obtained before and after nifedipine administration.

 


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  		Figure 2c. Scattergram and box plot of four MR parameters (peak enhancement ratio, enhancement slope, amplitude [A], and Kout) in 16 healthy subjects show (a) data before nifedipine administration, (b) data after nifedipine administration, and (c) the difference between data obtained before and after nifedipine administration.

 
The differences in previously mentioned parameters were analyzed by using the Wilcoxon signed rank test. The differences in heart rate and systolic blood pressure before compared with after administration of nifedipine were significant. Heart rate increased significantly (P < .001) (median increase, 11.0 beats per minute; mean increase, 11.3 beats per minute ± 8.1; percentage increase, 15.7%). Systolic blood pressure decreased significantly (P = .016) (median decrease, 5.0 mm Hg; mean decrease, 6.0 mm Hg ± 8.3; percentage decrease, 5.1%). Hemodynamic data already showed the changes 20–25 minutes after sublingual administration of nifedipine. Diastolic blood pressure decreased; however, this decrease was not significant (P = .093) (median decrease, 8.0 mm Hg; mean decrease, 4.5 mm Hg ± 9.7; percentage decrease, 5.6%).

The median peak enhancement ratio of vertebral bodies decreased from 0.60 (mean, 0.68 ± 0.29) before administration of nifedipine to 0.51 (mean, 0.56 ± 0.24) after administration of nifedipine. This difference (median decrease, 0.11; mean decrease, 0.12 ± 0.15; percentage decrease, 17%) was statistically significant (P = .005). The median enhancement slope changed from 0.45 (mean, 0.45 ± 0.13) before administration of nifedipine to 0.41 (mean, 0.40 ± 0.24) after administration of nifedipine. This difference (median decrease, 0.05; mean decrease, 0.04 ± 0.23; percentage decrease, 9.4%) was not statistically significant (P = 0.334). The median amplitude changed from 0.059 (mean, 0.059 ± 0.028) before administration of nifedipine to 0.045 (mean, 0.048 ± 0.023) after administration of nifedipine. This difference (median decrease, 0.008; mean decrease, 0.011 ± 0.025; percentage decrease, 18%) was not statistically significant (P = .072). The median Kout changed from 0.068 (mean, 0.063 ± 0.018) before administration of nifedipine to 0.067 (mean, 0.066 ± 0.028) after administration of nifedipine. This difference (median decrease, 0.011; mean decrease, 0.004 ± 0.028; percentage decrease, 6.3%) was not statistically significant (P = .404). In summation, nifedipine affected the peak enhancement ratio but did not affect the enhancement slope, amplitude, or Kout.

We further stratified the subjects into groups of men (n = 8) and women (n = 8) and compared the differences with the Wilcoxon rank sums test. None of the differences between men and women were significant (P > .05) for all four MR parameters. Nifedipine affected the hemodynamic and MR data, but the effect was not influenced by the difference in sex.

The correlation coefficients of those differences were further analyzed for heart rate and systolic and diastolic blood pressure versus peak enhancement ratio, enhancement slope, amplitude, and Kout. The Spearman rank correlation coefficients suggest no statistical significance between any differences of those parameters (Table 4); however, borderline significance (P = .1068) was found between the differences of systolic blood pressure and enhancement slope.


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  		TABLE 4. Spearman Rank Correlation Coefficients

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
REFERENCES
 
In this study, we used dynamic MR imaging to measure vertebral bone marrow blood perfusion in healthy subjects and demonstrated that blood perfusion decreased after administration of nifedipine. The peak enhancement ratio decreased with statistical significance, while the enhancement slope, amplitude, and Kout changed without statistical significance.

Both semiquantitative and quantitative dynamic MR images were used to evaluate the angiogenesis and perfusion of the bone marrow lesions (30). The semiquantitative assessment of time-intensity curves can be evaluated with parameters such as slope value or maximum enhancement. Mainly, tissue microvascularization and perfusion determine the first pass or rapidly rising part (wash-in phase). After the first pass, capillary permeability and interstitial space components contribute to the characteristics of the curve and yield either a further increase, a plateau, or an early washout phase. The rapidly rising part of the time-intensity curve (from the point at SIbase to SImax during the rise period) was considered to be the flushing in of the contrast material from the arterial capillaries into the extracellular space of the vertebral body.

We calculated the peak enhancement ratio and enhancement slope from the first part of the time-intensity curve. We found a decrease in the peak enhancement ratio of the spine that was attributed to the effects of nifedipine. The peak enhancement ratio has to be regarded as a complex process, including blood inflow, outflow, transit, and permeability factors that affect extracellular compartment gadolinium concentration. This indicates that the concentration of contrast material in the extracellular space of the vertebral bone marrow is decreased. Furthermore, we found that a decrease in the peak enhancement ratio did not correlate with hemodynamic factors such as systolic or diastolic blood pressure. It is reasonable to deduce that the decrease in contrast material concentration in the extracellular space might be caused by the relative redistribution of the circulating blood volume by the vasodilative effects of nifedipine. These vasodilative effects on the liver, kidney, or skeletal muscle caused the redistribution of circulating blood volume, and the blood flow or volume to visceral organs such as the liver or kidney was known to increase after administration of nifedipine (13–17). While the bone marrow arteriole failed to respond and its caliber failed to dilate due to the limitation of the closed chamber effect (18,19), the effective blood volume going into the bone and bone marrow thereafter relatively decreased. Thus, the flushing in of contrast material by the inflow blood decreased, and peak concentration of contrast material in the bone marrow also decreased. We observed no differences in this decrease between men and women.

Quantitative analysis was also performed with a bicompartment model (26,27), and two parameters—amplitude and Kout—were obtained. Amplitude is related to the microvascular density and leakage space. It incorporates the relative volumes of the intravascular plasma and extravascular interstitial compartments (31,32). In our research, the amplitude of the vertebral bone marrow decreased 18.6% after administration of nifedipine; however, this decrease was only borderline significant (P = .072). Amplitude can be confounded by the size, tissue composition, and inherent imaging characteristics such as T1 that can be variable among both hematopoietic or fatty bone marrow. On the other hand, our sample size is rather small (n = 16), and this may limit the effect of statistical analysis. Thus, the nonsignificant difference in amplitude was considered to be a lack of influence of nifedipine on the microvascular density or relative volume of two compartments of the vertebral bone marrow. This finding is comparable to the hypothesis that the bone marrow arteriole failed to respond and its caliber failed to dilate due to the limitation of the closed chamber effect (18,19).

The exchange parameter, Kout, reflects the rate of the contrast material transfer between intravascular and extravascular interstitial compartments and is related to the vascular permeability (29). The Kout had no significant difference (P = .404) before or after the administration of nifedipine. That is, nifedipine does not influence the vascular permeability of gadopentetate dimeglumine in the vertebral bone marrow.

There are several limitations in this study. The sample size is small (n = 16), and further analysis according to sex may be difficult. Manual injection of contrast material is subject to variation in timing and rate of injection. Though the timing of the injection does not affect our results, variations in the rate of injection lead to increased variability in the slope of enhancement. More accurate injection procedures might resolve differences in this parameter with nifedipine administration. On the other hand, the diurnal fluctuation of blood pressure might confound the correlation of differences between hemodynamic data and bone marrow perfusion data. Although we measured blood pressure twice, had averages for calculation, and the dynamic MR examinations were performed in the afternoon, the utility of a single blood pressure time point might limit the significance of this study. Moreover, all the subjects were younger than 50 years and were considered to be healthy. The effect of antihypertensive drugs on vertebral bone marrow perfusion might be different among subjects older than 50 years with or without cardiovascular disease. The influence of menopause was not examined, since all women in this study were premenopausal. In addition, this study evaluated the acute effect of a single dose of nifedipine and cannot reflect the effects of long-term use of antihypertensive drugs; however, we proposed the possibility of the influence of osseous circulation by the antihypertensive drug and this may provide new research territory.

In conclusion, our results showed that the peak enhancement ratio of vertebral bone marrow decreased after a single dose of sublingual nifedipine. Thus, we raise the question of whether long-term use of calcium channel blockers may decrease bone marrow perfusion and whether this may relate to osteoporosis.


   ACKNOWLEDGMENTS
 
The authors thank the Department of Radiology, National Taiwan University Hospital, Taipei, Taiwan, for support and assistance in the research work of this study.

The authors also thank the volunteers, who are medical or paramedical staff members at National Taiwan University Hospital.


   FOOTNOTES
 
Abbreviation: ROI = region of interest

Author contributions: Guarantors of integrity of entire study, T.T.F.S., P.C.Y., T.W.L.; study concepts, T.T.F.S., P.C.Y., T.W.L.; study design, T.T.F.S., P.C.Y.; literature research, T.T.F.S., T.W.L., J.K.H.; clinical studies, T.T.F.S., T.W.L., J.K.H.; data acquisition, T.T.F.S., L.C.S., W.Y.T.; data analysis/interpretation, T.T.F.S., P.C.Y., C.J.C., W.Y.T.; statistical analysis, C.J.C.; manuscript preparation, L.C.S.; manuscript definition of intellectual content, P.C.Y.; manuscript editing, T.T.F.S., L.C.S.; manuscript revision/review, T.T.F.S., T.W.L.; manuscript final version approval, T.T.F.S., P.C.Y.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 

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