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Science 3 December 1999:
Vol. 286. no. 5446, pp. 1946 - 1949
DOI: 10.1126/science.286.5446.1946
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Reports

Stimulation of Bone Formation in Vitro and in Rodents by Statins

G. Mundy, 1* R. Garrett, 1 S. Harris, 2 J. Chan, 1 D. Chen, 1 G. Rossini, 1 B. Boyce, 3 M. Zhao, 1 G. Gutierrez 1

Osteoporosis and other diseases of bone loss are a major public health problem. Here it is shown that the statins, drugs widely used for lowering serum cholesterol, also enhance new bone formation in vitro and in rodents. This effect was associated with increased expression of the bone morphogenetic protein-2 (BMP-2) gene in bone cells. Lovastatin and simvastatin increased bone formation when injected subcutaneously over the calvaria of mice and increased cancellous bone volume when orally administered to rats. Thus, in appropriate doses, statins may have therapeutic applications for the treatment of osteoporosis.

1 OsteoScreen, 2040 Babcock Road, San Antonio, TX 78229, USA.
2 Department of Medicine,
3 Department of Pathology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78284-7877, USA.
*   To whom correspondence should be addressed. E-mail: mundy{at}uthscsa.edu

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H. Kawaguchi, K. Nakamura, Y. Tabata, Y. Ikada, I. Aoyama, J. Anzai, T. Nakamura, Y. Hiyama, and M. Tamura (2001)
J. Clin. Endocrinol. Metab. 86, 875-880
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Risk of Breast Cancer with Progestins in Combination with Estrogen as Hormone Replacement Therapy.
R. J. Santen, J. Pinkerton, C. McCartney, and G. R. Petroni (2001)
J. Clin. Endocrinol. Metab. 86, 16-23
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Suppression of Endothelial Nitric Oxide Production After Withdrawal of Statin Treatment Is Mediated by Negative Feedback Regulation of Rho GTPase Gene Transcription.
U. Laufs, M. Endres, F. Custodis, K. Gertz, G. Nickenig, J. K. Liao, and M. Bohm (2000)
Circulation 102, 3104-3110
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Role of Lipids in Osteoporosis.
F. Parhami, A. Garfinkel, and L. L. Demer (2000)
Arterioscler. Thromb. Vasc. Biol. 20, 2346-2348
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Statin Drugs and the Risk of Fracture.
A. El-Sohemy, T. R. Pedersen, J. Kjekshus, C. R. Meier, R. G. Schlienger, M. E. Kraenzlin, B. Schlegel, and H. Jick (2000)
JAMA 284, 1921-1922
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Lack of Positive Correlation Between Statin Use and Bone Mineral Density in Japanese Subjects With Type 2 Diabetes.
Y. Wada, Y. Nakamura, and H. Koshiyama (2000)
Arch Intern Med 160, 2865
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Targeting Rho in Cardiovascular Disease.
U. Laufs and J. K. Liao (2000)
Circ. Res. 87, 526-528
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Therapeutic Approaches to Bone Diseases.
G. A. Rodan and T. J. Martin (2000)
Science 289, 1508-1514
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Regulation of Osteoblast Differentiation Mediated by Bone Morphogenetic Proteins, Hedgehogs, and Cbfa1.
A. Yamaguchi, T. Komori, and T. Suda (2000)
Endocr. Rev. 21, 393-411
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Introduction: the evolving role of bisphosphonate therapy in multiple myeloma.
N. Raje and K. C. Anderson (2000)
Blood 96, 381-383
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HMG-CoA Reductase Inhibitors and the Risk of Fractures.
C. R. Meier, R. G. Schlienger, M. E. Kraenzlin, B. Schlegel, and H. Jick (2000)
JAMA 283, 3205-3210
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HMG-CoA Reductase Inhibitors and the Risk of Hip Fractures in Elderly Patients.
P. S. Wang, D. H. Solomon, H. Mogun, and J. Avorn (2000)
JAMA 283, 3211-3216
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Do Statins Prevent Both Cardiovascular Disease and Fracture?.
S. R. Cummings and D. C. Bauer (2000)
JAMA 283, 3255-3257
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Signaling by Fibroblast Growth Factors (FGF) and Fibroblast Growth Factor Receptor 2 (FGFR2)-activating Mutations Blocks Mineralization and Induces Apoptosis in Osteoblasts.
A. Mansukhani, P. Bellosta, M. Sahni, and C. Basilico (2000)
J. Cell Biol. 149, 1297-1308
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The Role of Bisphosphonates in Multiple Myeloma.
R. A. Kyle (2000)
Ann Intern Med 132, 734-736
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Multiple Myeloma: New Insights and Therapeutic Approaches.
K. C. Anderson, R. A. Kyle, W. S. Dalton, T. Landowski, K. Shain, R. Jove, L. Hazlehurst, and J. Berenson (2000)
Hematology 2000, 147-165
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