DMFR
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kozai, Y
Right arrow Articles by Kashima, I
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kozai, Y
Right arrow Articles by Kashima, I
Dentomaxillofacial Radiology (2009) 38, 34-41
© 2009 British Institute of Radiology
doi: 10.1259/dmfr/28859075

RESEARCH

Influence of prednisolone-induced osteoporosis on bone mass and bone quality of the mandible in rats

Y Kozai*, R Kawamata, T Sakurai, M Kanno and I Kashima

Division of Radiology, Department of Maxillofacial Diagnostic Science, Kanagawa Dental College, Yokosuka, Japan

*Correspondence to: Yusuke Kozai, Department of Radiology, Kanagawa Dental College, 82 Inaoka, Yokosuka, Kanagawa, 238-8580, Japan. E-mail: kozai{at}kdcnet.ac.jp

Received 6 December 2007; revised 11 January 2008; accepted 27 January 2008


   Abstract
Top
 Abstract
Introduction
 Materials and methods
 Results
 Discussion
 Conclusions
 References
 
Objectives: The aim of this study was to clarify the effects of steroid treatment on the mandible.

Methods: We divided 24 male Fisher rats, aged 10 weeks, into 2 groups: a control group (n = 11) and a prednisolone (Pred) treatment group (n = 13). The dose for the Pred group was 40 mg kg–1 and was administered orally three times per week for 8 weeks. At the end of the experiment, we measured bone mass, bone strength and trabecular structure of the mandible and femur.

Results: Pred treatment decreased cortical bone mineral content (BMC), cortical thickness, stress/strain index and tissue volume of the mandible. However, there were no marked changes in trabecular structure parameters. A strong correlation was seen between mandibular and femoral cortical BMC (r = 0.71).

Conclusions: These findings suggest that steroid treatment decreases the cortical BMC, bone area and bone strength of the mandible.

Keywords: osteoporosis; mandible; corticosteroids; diagnosis; rats


   Introduction
Top
 Abstract
 Introduction
Materials and methods
 Results
 Discussion
 Conclusions
 References
 
Corticosteroids are used in the treatment of various diseases because they possess potent anti-inflammatory actions and suppress immunocompetent cell activities. However, corticosteroids are known to cause bone loss and this is a major problem in clinical practice.1 According to a study conducted by the American College of Rheumatology in 1996, 20% of osteoporosis patients in the USA (about 2 million) had glucocorticoid-induced osteoporosis and 25% of patients on long-term steroid therapy had bone fractures.2 This report reaffirms the seriousness of steroid-induced osteoporosis. Compared with primary osteoporosis, the risk of fracture for steroid-induced osteoporosis is clearly higher, even at comparable bone mineral density. Recent meta-analyses have shown that the overall risks of femoral neck and spinal fractures from corticosteroid-induced osteoporosis are 1.57, 2.25 and 2.00 times higher, respectively, than those from primary osteoporosis.3, 4 In other words, corticosteroids appear not only to decrease bone mineral density, but also to markedly damage bone quality; this is a serious clinical problem. Osteoporosis was defined in 2001 as follows: "osteoporosis is a skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture. Bone strength primarily reflects the integration of bone density and bone quality."5

In the dental field, investigators have conducted clinical studies to establish the relationship between the mandible and primary osteoporosis. In particular, primary osteoporosis is considered to be a risk factor for periodontal diseases, temporomandibular disorders, failed implant therapy and denture instability due to alveolar ridge absorption.6, 7 In a number of basic studies with rats, investigators have reported a correlation between osteoporosis and reduction of bone mineral density (BMD) in the mandibular body and head.8, 9 Based on previous studies, primary osteoporosis appears to affect long bones the same way it affects the mandible. Recent studies have shown that mandibular cortical erosion detected on panoramic radiographs may be useful for identifying post-menopausal women with low skeletal BMD.10 However, those studies examined primary osteoporosis. Few studies have investigated the relationship between steroid-induced osteoporosis and the mandible. Therefore, in this study, we evaluated the effects of steroid treatment on the mandible and the femur.


   Materials and methods
Top
 Abstract
 Introduction
 Materials and methods
Results
 Discussion
 Conclusions
 References
 
Experimental animals
We obtained 24 male Fischer rats, aged 9 weeks, from Clea Japan Inc. (Tokyo) and acclimated them for 1 week prior to experiments with a standard synthesized diet containing 0.5% calcium per 100 g of food (CE-2; Clea Japan Inc,. Tokyo, Japan). Animals had access to distilled water ad libitum. The rats were 10 weeks of age at the start of the experiments. We kept the rats in a room maintained at 23±3°C and 55±15% humidity with a 12 h light–dark cycle. The ethics committee at our institution approved all animal procedures, which comply with institutional guidelines for the care and handling of experimental animals.

Experimental design
We divided 24 male Fischer rats, 10 weeks of age, into a control group (n = 11) and a prednisolone (Pred) treatment group (n = 13). The dose of Pred (prednisolone sodium succinate; Shionogi & Co., Ltd., Osaka, Japan) was 40 mg kg–1 body weight, administered orally to the rats three times per week for 8 weeks. At the end of the experiment, we euthanized the animals using pentobarbital anaesthesia (Nembutal; Dainippon Pharmaceutical Co., Ltd, Osaka, Japan) and took blood samples from the abdominal aorta with heparinization. After blood sampling, we harvested the right femur and the mandible. We measured the bone mass of the right femur and the mandible using peripheral quantitative CT (pQCT), and measured bone strength with the three-point bending strength test. We measured the three-dimensional (3D) trabecular structure of the mandible using micro-CT (µCT). Figure 1Go shows the experimental protocol of this study.


Figure 1
View larger version (23K):
[in this window]
[in a new window]

  		Figure 1 Experimental protocol. pQCT, peripheral quantitative CT

 
Plasma components
To separate plasma, we centrifuged blood samples with heparin sodium at 3000 rpm for 10 min at 4°C. We measured osteocalcin (OC) in plasma with a rat ELISA system (Amersham Pharmacia Bioteck KK, Uppsala, Sweden).

Urinary components
7 weeks after beginning the experiment, we forced each animal to consume 3 ml of distilled water, placed the animal in an individual metabolic cage without food and recorded total urine output after 17 h fasting. We measured urinary deoxypyridinoline by EIA (Osteolinks DPd; Sumitomo Pharmaceutical, Tokyo, Japan) and creatinine levels with a creatinine test (Wako Pure Chemical Industries Ltd, Osaka, Japan). We used the creatinine level to correct the deoxypyridinoline level.

Bone mass parameters
We measured bone-mass parameters using pQCT (XCT-µScope; Stratec, Birkenfeld, Germany), taking femur measurements in the diaphysial region (at the mid-point of the bone) and in the metaphysical region (3.0 mm mesial from the growth plate). The diameter, voxel size, CT speed and block number of our tomographic imaging were 15 mm, 0.1 mm, 10 mm s–1 and 1, respectively. We extracted the cortical region from the total region covered by tomographic images using an algorithm (separation mode three) and we calculated bone mineral content (BMC), BMD and bone area. We measured the bone mass of the mandible at the medial root apex region of the first molar using the same tomographic imaging settings as for the femur except voxel size was 0.08 mm and CT speed was 8 mm s–1. We manually extracted the cortical and trabecular regions from the total region, and we calculated BMC, BMD, bone area and cortical thickness. We calculated the stress/strain index (SSI),11 a non-invasive bone-strength index, from the cortical BMC and the polar second moment of inertia of the cross-sectional bone area. We verified that all system components were performing properly by running a hydroxyapatite standard embedded in acrylic plastic each day before scanning samples.

Mechanical properties
We established the mechanical properties of each femur with the three-point bending strength test using a tester (AG500E; Shimadzu, Kyoto, Japan). With the femur placed on a sample holder with the two fulcrums fixed at a separation of 13 mm, the compression arm of the tester applied increasing force perpendicularly to the centre by advancing at a crosshead speed of 1 mm min–1 until the femur fractured. Software for measuring bone strength automatically calculated the maximum load and stiffness (Shikibu; Shimadzu Co., Ltd, Kyoto, Japan).

3D trabecular structure analysis
A microCT equipped with a microfocus X-ray tube (focus size 8x8 µm, MCT-100MF; Hitachi Medical Corporation, Tokyo, Japan) produced a 3D image of each mandible from 201 image slices. The tube voltage, tube current, magnification and voxel size were 70 kV, 100 µA, x4, and 32.0x32.0x32.0 µm, respectively. Trabecular structure analysis software (TRI/3D BON; Ratoc System Engineering Co. Ltd, Tokyo, Japan) calculated the 3D trabecular structure parameters from the image information of 100 slices at the medial root apex region of the first molar. As for the procedure, we separated cortical bone and trabecular bone regions by 3D space filtration of the bone marrow cavity and we converted data from the trabecular bone region of each slice to binary using a threshold obtained by discriminant analysis. In other words, we assumed the pixel-value histograms of background and bone to be normally distributed. We chose the threshold to be an intermediate pixel value lying on the tails of the two normal distributions.

From binary images, we measured the trabecular structure parameters, including tissue volume (TV), bone volume (BV), bone surface per bone volume (BS/BV), and trabecular thickness (Tb-Th). Tb-Th was measured according to the parallel plate model.12 We measured the fractal dimension (FD) of the trabecular bone as a representative of complexity using the box-counting method.13 The trabecular continuity was star volume analysis, described by Gundersen et al.14 The star volume is defined as the mean volume of all parts of an object that can be seen unobscured in all directions from a particular point with the mean value taken over all points inside the object. It is defined for any type of object and includes cavities such as marrow space and networks such as the trabecular system. A frame and grid with points and lines guided measurements. We calculated the star volume of marrow space (V*m.space) and the star volume of trabeculae (V*tr) by star volume analysis. The trabecular connectivity was measured using node-strut analysis described by Garrahan et al.15 We identified nodes (Nd; connective point of three or more trabeculae), termini (Tm; terminal of trabeculae) and cortex (Ct; connective point of trabeculae and cortical bone) by node-strut analysis, and we obtained the parameter of the number (n) of Nd per tissue volume (nNd/TV), the number of Tm per tissue volume (nTm/TV), the number of Ct per tissue volume (nCt/TV), and the total strut length per tissue volume (TSL/TV) by node-strut analysis.

Statistics
Values in the tables are shown as the mean ± standard deviation (SD). We used the Student's t-test to determine if differences between the two groups were significant.

We used linear regression analyses to assess relations between cortical BMC of the mandible or mandibular cortical thickness and cortical BMC of the femoral diaphysis.


   Results
Top
 Abstract
 Introduction
 Materials and methods
 Results
Discussion
 Conclusions
 References
 
Parameters in plasma and urinary components
The concentration of OC, a bone formation marker, in the control group was 39.16 ng ml–1, while that in the Pred group was lower at 37.16 ng ml–1 (–5%). In the control group, urinary deoxypyridinoline excretion (a bone resorption marker) was 125.8 nM mM–1, while that in the Pred group was lower at 119.0 nM mM–1 (–5%). There was no significant difference in OC or deoxypyridinoline/creatinine between the control and the Pred group.

Parameters in femur
Bone mass parameters   Table 1Go shows bone mass parameters in the femur. Pred treatment significantly decreased the total BMC and BMD in the femoral metaphysis (–16% and –13%, respectively; P < 0.01). The cortical BMC and bone area in the femoral diaphysis were also decreased significantly by Pred treatment (–9% and –8%, respectively; P < 0.01). BMD in the femoral diaphysis was decreased by Pred treatment (–1%), but there was no significant difference.


View this table:
[in this window]
[in a new window]

  		Table 1 Effects of prednisolone on bone parameters in the femur after 8 weeks of treatment

 
Mechanical properties   The results of the three-point bending strength test show that the maximum load in the control group was 108.31 N, while that in the Pred group was significantly lower at 98.18 N (–9%; P < 0.01), confirming that steroid treatment reduces the bone strength of the femur. Stiffness in the control group was 291.98 N mm–1 and that in the Pred group was lower at 261.14 N mm–1 (–11%), but there was no significant difference.

Parameters in mandible
Bone mass parameters   Table 2Go shows bone mass parameters in the mandible. Pred treatment significantly decreased the trabecular BMC and bone area (–22% and –25%, respectively; P < 0.01). The trabecular BMD in the Pred group was 3.5% higher than the control group, but there was no significant difference. The cortical BMC and bone area in the Pred group were significantly decreased (–6% and –7%, respectively; P < 0.01). The cortical BMD of the control group was nearly the same as that of the Pred group; there was no significant intergroup difference. These bone mass parameters in the mandible were comparable with those for the femur.


View this table:
[in this window]
[in a new window]

  		Table 2 Effects of prednisolone on bone parameters in the mandible after 8 weeks of treatment

 
The mandibular cortical bone thickness in the control group was 0.715 mm and Pred treatment decreased that significantly to 0.701 mm (P < 0.05). The SSI value (a non-invasive bone strength index) in the control group was 5.16 mm3, while that in the Pred group was significantly lower at 4.87 mm3 (P < 0.01).

3D trabecular structure parameters   Table 3Go shows the results of 3D trabecular structure analysis of the mandible. TV in the Pred group was 7.1% lower than in the control group, and there was a significant difference (P < 0.01). The values of BV, BS/BV, and Tb-Th of the control group were nearly the same as those of the Pred group, and there were no significant differences. The FD values in the control and Pred group were exactly the same, and there was no significant difference. These findings show that steroid treatment decreases the volume of the entire mandible but does not cause marked changes in internal structures. Star volume analysis showed that the V*m.space in the Pred group was 15% lower than that for the control group, and there was a significant difference (P < 0.01). The V*tr in the Pred group was 12% higher than in the control group, but there was no significant difference. These findings suggest that steroid treatment decreases marrow space but does not markedly change trabecular continuity. Node-strut analysis showed that when compared with the control group, the nNd/TV, nTm/TV, nCt/TV, and TSL/TV for the Pred group were –6.5, –26.2, 0.0 and –1.0%, respectively, but there were no significant differences. These findings suggest that steroid treatment does not markedly affect the connectivity of internal structures. Figure 2Go shows a typical reconstructed 3D image using one mandible from each group. While the volume for the Pred group was lower, there were no marked changes in internal structure. The mandibular cortical thickness of the Pred group showed thinness as compared with the control group.


View this table:
[in this window]
[in a new window]

  		Table 3 Effects of prednisolone on three-dimensional trabecular structure parameters in the mandible after 8 weeks of treatment

 

Figure 2
View larger version (48K):
[in this window]
[in a new window]

  		Figure 2 Reconstructed three-dimensional images of the mandible in (a) the control and (b) the prednisolone treatment groups. There were no marked changes in internal structure. The mandibular cortical thickness of the prednisolone group showed thinness compared with control group (arrows)

 
Relationship between the femur and mandible
There was a strong correlation between the mandibular cortical BMC and femur cortical BMC (r = 0.7138) (Figure 3aGo). There was a correlation between mandibular cortical thickness and femoral cortical BMC (r = 0.5231) (Figure 3bGo). This suggests a correlation between femoral and mandibular bone mass parameters.


Figure 3
View larger version (10K):
[in this window]
[in a new window]

  		Figure 3 Relationship between (a) femoral cortical bone mineral content (BMC) and mandibular cortical BMC, and (b) between femoral cortical BMC and mandibular cortical thickness

 

   Discussion
Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
Conclusions
 References
 
Steroids have been used clinically for about 50 years to treat Cushing's syndrome, bronchial asthma, chronic rheumatoid arthritis, collagen disease and other diseases. Studies have shown, however, that steroid treatment induces bone loss as a side effect.16 In recent years, the seriousness of this adverse effect has been recognized internationally and different countries have prepared guidelines for the prevention and treatment of steroid-induced osteoporosis.17–19 This side effect is believed to be due in part to the direct inhibition of osteoblasts,20 a decrease in the amount of calcium absorbed by the intestine,21 enhanced secretion of parathyroid hormone (PTH)22 and a decrease in renal tubular calcium reabsorption.23 Although workers in various medical fields have documented the seriousness of steroid-induced osteoporosis, these results are not fully disseminated among dental professionals. To help close this gap, we have therefore investigated the effects of Pred treatment on the rat mandible.

Many studies have been conducted regarding steroid-induced osteoporosis in rats, with varying dose rates of Pred; for instance, with intramuscular injection of 10 mg kg–1 three times per week for 4–10 weeks; 80 mg kg–1 twice per week for 12 weeks; subcutaneous injection 0.01–1.0 mg kg–1 three times per week for 8 weeks; 2.5 mg kg–1 six times per week for 4 weeks or 8 weeks, etc.24–27 However, no general consensus has been reached on a useful rat model for steroid-induced osteoporosis. In this study, 40 mg kg–1 of Pred sodium succinate was given orally to the rat three times per week; this dose was based on the research of Jowell et al,28 where histomorphometry showed that a high dose of Pred (33 mg kg–1 and 50 mg kg–1) increased the number of osteoclasts, but a low dose (2 mg kg–1) did not. In the present model, biochemical tests showed that the OC concentration (bone formation marker) and deoxypyridinoline/creatinine (bone resorption maker) were both low. This suggests that steroid treatment causes a low turnover of bone in the present model. Furthermore, steroid treatment significantly decreased the BMC and BMD in the femoral metaphysis (P < 0.01); the cortical BMC and bone area in the femoral diaphysis were also decreased significantly (P < 0.01). Regarding mechanical properties as ascertained by three-point bending strength tests, steroid treatment significantly lowered the maximum load of the femur (P < 0.01). These results suggest the usefulness of the present model as an animal model for steroid-induced osteoporosis.

We used the present model to investigate the effects of steroid treatment on the mandible. Steroid treatment decreased significantly the cortical BMC and bone area of the mandible (P < 0.01). These results were similar to those in the femoral diaphysis. Steroid treatment significantly lowered the cortical thickness and the SSI value of the mandible (P < 0.05 and P < 0.01, respectively). Weinstein et al29 reported that steroids suppress bone formation and resorption and act to lower the entire bone metabolism. In other words, these findings suggest that steroid treatment caused the mandible to be a low turnover bone, suppressing the growth of cortical bone and thus lowering the BMC and bone strength. Furthermore, in the trabecular bone of the mandible, the changes that appeared were comparable with those observed in the cortical bone: steroid treatment lowered trabecular BMC and bone area to suppress growth (Table 2Go).

Regarding the 3D trabecular structure of the mandible, steroid treatment significantly lowered the TV (P < 0.05) and V*m.space (P < 0.05). These results also supported the findings of growth suppression of the mandible. For the other trabecular structure parameters, steroid treatment did not cause marked changes in trabecular thickness, complexity, continuity or connectivity (Table 3Go). This was different from the study of Hara et al,30 where the 3D trabecular structure analysis of rat tibias confirmed that steroid treatment caused a greater decrease of trabecular structures. In other words, the above results suggest that the effects of steroid treatment on cortical bone of the mandible are similar to the effects on cortical bone of long bone diaphysis; however, the effects of steroid treatment on the trabecular bone of the mandible were different from those on the trabecular bone of long bone metaphysis. Asai et al31 investigated the effects of primary osteoporosis on the mandible of mature cynomolgus monkeys and reported that osteoporosis decreased the bone density and cortical thickness of the mandible, but did not bring about marked changes to trabecular structure. This is in agreement with the results of the present rat model for steroid-induced osteoporosis. In their study, Asai et al reported that this was caused by differences in the development of the mandible (intramembranous bone formation) and long bones metaphysis and vertebra (endochondral bone formation), or the effects of occlusal pressure.

There were differences between the results of mandibular trabecular BMC and 3D trabecular structure. The mandibular trabecular BMC of the Pred group is significantly lower than the control group; however, there were no marked changes in 3D trabecular structures. This is due to the growth suppression of the mandible. The results of mandibular trabecular BMD support this hypothesis. In the results of mandibular trabecular BMD, there was no significant difference between the control group and the Pred group. This result shows that there were no marked changes apart from the whole volume in the mandibular trabecular region.

Based on the results of past studies on the effects of steroids, we suspect that steroid treatment has similar effects on cortical bone of the mandible and long bones. Clinical studies of primary osteoporosis using panoramic radiographs show that mandibular cortical width and erosion are effective diagnostic indicators for osteoporosis;10 hence in this study we have also investigated the relationship between mandibular and femoral cortical bone parameters. Our results confirmed a very strong correlation in cortical BMC between the mandible and femur (r = 0.7138) (Figure 3aGo); furthermore, a correlation was seen between the mandibular cortical bone thickness and the femoral cortical BMC (r = 0.5231) (Figure 3bGo). These results suggest that the effects of steroid treatment on the cortical bone parameters of the mandible are related to the low bone mass of other long bones. Therefore, as well as for primary osteoporosis, mandibular cortical morphology detected by dental diagnostic imaging (e.g. panoramic radiograph) may be useful for identifying steroid-induced osteoporosis with bone loss.


   Conclusions
Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Conclusions
References
 
We experimentally induced osteoporosis in rats by orally administering 40 mg kg–1 of prednisolone three times per week. Using this model, we investigated the effects of steroid treatment on the bone mass and quality of the mandible. The results show that while steroid treatment has no marked changes on trabecular structure, it significantly decreases cortical BMC, cortical thickness and SSI. Also, mandibular cortical BMC and thickness exhibit a strong correlation to femoral cortical BMC. These findings suggest that the changes in mandibular cortical bone could be of use in diagnosing steroid-induced osteoporosis with bone loss.


   Acknowledgments
 
The authors express their sincere thanks to Masatoshi Kobayashi, Kuniko Hara and Yasuhiro Akiyama, Department of Applied Drug Research, Eisai Co. Ltd, for their significant advice and support regarding this work.


   References
Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Conclusions
 References
 

  1. Lukert BP, Raisz LG. Glucocorticoid-induced osteoporosis: Pathogenesis and management. Ann Intern Med 1990;112:352–364.[Abstract/Free Full Text]
  2. American College of Rheumatology Task Force on Osteoporosis Guidelines. Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Rheum 1996;39:1791–1801.[Medline]
  3. Kanis JA, Johansson H, Oden A, Johnell O, de Laet C, Melton III LJ, et al. A meta-analysis of prior corticosteroid use and fracture risk. J Bone Miner Res 2004;19:893–899.[CrossRef][Medline]
  4. van Staa TP, Leufkens HG, Cooper C. The epidemiology of corticosteroid induced osteoporosis: a meta-analysis. Osteoporos Int 2002;13:777–787.[CrossRef][Medline]
  5. NIH Consensus Development Panel. Osteoporosis prevention, diagnosis, and therapy. JAMA 2001;285:785–795.[Abstract/Free Full Text]
  6. Wactawski-Wende J. Periodontal diseases and osteoporosis: association and mechanisms. Ann Periodontal 2001;6:197–208.
  7. Tezal M, Wactawski-Wende J, Grossi SG, Ho AW, Dunford R, Genco RJ. The relationship between bone mineral density and periodontitis in postmenopausal women. J Periodontal 2000;71:1492–1498.
  8. Hunziker J, Wronski TJ, Miller SC. Mandibular bone formation rates in aged ovariectomized rats treated with anti-resorptive agent alone and in combination with intermittent parathyroid hormone. J Dent Res 2000;79:1461–1468.
  9. Tanaka M, Ejiri S, Toyooka E, Kohno S, Ozawa H. Effects of ovariectomy on trabecular structures of rat alveolar bone. J Periodont Res 2002;37:161–165.[CrossRef][Medline]
  10. Sutthiprapaporn P, Taguchi A, Nakamoto T, Ohtsuka M, Mallick PC, Tsuda M, et al. Diagnostic performance of general dental practitioners after lecture in identifying post-menopausal woman with low bone mineral density by panoramic radiographs. Dentomaxillofac Radiol 2006;35:249–252.[Abstract/Free Full Text]
  11. Schiessl H, Ferretti JL, Tysarczyk-Niemeyer G, Willnecker J. Noninvasive bone strength index as analyzed by peripheral quantitative computed tomography (pQCT). In: Schonau E (ed). Paediatric oteology. New developments in diagnostic and therapy. Amsterdam, PA: Elsevier, 1996, pp 141–146.
  12. Parfitt AM. Bone histomorphometry: standardization of nomenclature, symbols, and units (summary of proposed system). Bone 1988;9:67–69.[CrossRef][Medline]
  13. Fazzalari NL, Parkinson IH. Fractal dimension and architecture of trabecular bone. J Pathol 1996;178:100–105.[CrossRef][Medline]
  14. Vesterby A, Gundersen HJG, Melsen F. Star volume of marrow space and trabeculae of the first lumber vertebra: Sampling efficiency and biological variation. Bone 1989;10:7–13.
  15. Garrahan NJ, Mellish RW, Compston JE. A new method for the two-dimensional analysis of bone structure in human iliac crest biopsies. J Microsc 1986;142:341–349.[Medline]
  16. Fujii Y. Quantitative computed tomography of lumbar vertebrae in Japanese patients with steroid induced osteopenia. In: Christiansen C, Johansen JS, Riis BJ (eds). Osteoporosis 1987. Viborg, PA: Norhaven A/S, 1988, pp 1065–1067.
  17. American College of Rheumatology Ad Hoc Committee on Glucocorticoid-induced Osteoporosis. Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Rheum 2001;44:1496–1503.[CrossRef][Medline]
  18. Eastel R, Reid DM, Compston J, Cooper C, Fogelman I, Francis RM, et al. A UK Consensus Group on management of glucocorticoid-induced osteoporosis: an update. J Intern Med 1998;244:271–292.[CrossRef][Medline]
  19. Adachi JD, Olszynski WP, Hanley DA, Hodsman AB, Kendler DL, Siminoski KG, et al. Management of corticosteroid-induced osteoporosis. Semin Arthritis Rheum 2000;129:228–251.
  20. Delmas PD, Malavel L, Arlot ME, Meunier PJ. Serum bone Gla-protein compared to bone histomorphometry in endocrine diseases. Bone 1985;6:339–341.[CrossRef][Medline]
  21. Hahn TJ, Halstead LR, Baran DT. Effects of short term flucocorticoid administration on intestinal calcium absorption and circulating vitamin D metabolite concentrations in man. J Clin Endocrinol Metab 1981;52:111–115.[Abstract/Free Full Text]
  22. Lukert BP, Adams JS. Calcium and phosphorus homeostasis in men. Effect of corticosteroids. Arch Intern Med 1976;139:1249–1253.
  23. Suzuki Y, Ichikawa Y, Saito E, Homma M. Importance of increased urinary calcium excretion in the development of secondary hyperparathyroidism of patients under glucocorticoid therapy. Metabolism 1983;32:151–156.[CrossRef][Medline]
  24. Hara K, Akiyama Y, Ohkawa I, Tajima T. Effects of menatetrenone on prednisolone-induced bone loss in rats. Bone 1993;14:813–818.
  25. Yamazaki I, Shino A, Shimuzu Y, Tsukada R, Shirakawa Y, Kinoshita M, et al. Effect of ipriflavone on glucocorticoid-induced osteoporosis in rats. Life Sci 1986;38:951–958.[CrossRef][Medline]
  26. Nakamura H, Nitta T, Hoshino T, Koida M. Glucocorticoid-induced osteopenia in rats: histomorphometrical and microarchitectural characterization and calcitonin effect. Biol Pharm Bull 1996;19:217–219.[Medline]
  27. Miyakoshi N. Preventive effects of intermittent administration of human parathyroid hormone on steroid-induced osteopenia in rats. J Orthop Sci 1996;1:318–328.
  28. Jowell PS, Epstein S, Fallon MD, Reinharbt TA, Ismail F. 1,25-Dihydroxyvitamin D3 modulates glucocorticoid-induced alteration in serum bone Gla protein and bone histomorphometry. Endocrinology 1987;120:531–536.[Abstract/Free Full Text]
  29. Weinstein RS, Jilka RL, Parfitt AM, Manolagas SC. Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone. J Clin Invest 1998;102:274–282.[Medline]
  30. Hara K, Kobayashi M, Akiyama Y. Vitamin K2 (menatetrenone) inhibits bone loss induced by prednisolone partly through enhancement of bone formation in rats. Bone 2002;31:575–581.
  31. Asai H, Kozai Y, Matsumoto Y, Kawamata R, Kumasaka S, Sakurai T, et al. Radiological morphometric analysis of the mandibular bone structure after ovariectomy in mature cynomolgus monkeys. Oral Sci Int 2005;2:54–63.




This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kozai, Y
Right arrow Articles by Kashima, I
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kozai, Y
Right arrow Articles by Kashima, I

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
BJR DMFR IMAGING ALL BIR JOURNALS