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Division of Endocrinology & Metabolism, Center for Osteoporosis & Metabolic Bone Diseases, University of Arkansas for Medical Sciences, and the Central Arkansas Veterans Healthcare System, Little Rock, Arkansas 72205, USA
The adult skeleton regenerates by temporary cellular structures that comprise teams of juxtaposed osteoclasts and osteoblasts and replace periodically old bone with new. A considerable body of evidence accumulated during the last decade has shown that the rate of genesis of these two highly specialized cell types, as well as the prevalence of their apoptosis, is essential for the maintenance of bone homeostasis; and that common metabolic bone disorders such as osteoporosis result largely from a derangement in the birth or death of these cells. The purpose of this article is 3-fold: 1) to review the role and the molecular mechanism of action of regulatory molecules, such as cytokines and hormones, in osteoclast and osteoblast birth and apoptosis; 2) to review the evidence for the contribution of changes in bone cell birth or death to the pathogenesis of the most common forms of osteoporosis; and 3) to highlight the implications of bone cell birth and death for a better understanding of the mechanism of action and efficacy of present and future pharmacotherapeutic agents for osteoporosis.
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S. Evio, A. Tiitinen, K. Laitinen, O. Ylikorkala, and M. J. Valimaki Effects of Alendronate and Hormone Replacement Therapy, Alone and in Combination, on Bone Mass and Markers of Bone Turnover in Elderly Women with Osteoporosis J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 626 - 631. [Abstract] [Full Text] [PDF]
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E. Hay, J. Lemonnier, O. Fromigue, H. Guenou, and P. J. Marie Bone Morphogenetic Protein Receptor IB Signaling Mediates Apoptosis Independently of Differentiation in Osteoblastic Cells J. Biol. Chem., January 16, 2004; 279(3): 1650 - 1658. [Abstract] [Full Text] [PDF]
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F. E. Vegni, C. Corradini, G. Privitera, T. Sugiyama, H. Tanaka, S. Kawai, P. D. Miller, K. E. Fuller, D. M. Black, J. Bilezikian, et al. Effects of Parathyroid Hormone and Alendronate Alone or in Combination in Osteoporosis N. Engl. J. Med., January 8, 2004; 350(2): 189 - 192. [Full Text] [PDF]
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 G. Barera, S. Beccio, M. C. Proverbio, and S. Mora Longitudinal changes in bone metabolism and bone mineral content in children with celiac disease during consumption of a gluten-free diet Am. J. Clinical Nutrition, January 1, 2004; 79(1): 148 - 154. [Abstract] [Full Text] [PDF]
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X. Wu, M. A. McKenna, X. Feng, T. R. Nagy, and J. M. McDonald Osteoclast Apoptosis: The Role of Fas in Vivo and in Vitro Endocrinology, December 1, 2003; 144(12): 5545 - 5555. [Abstract] [Full Text] [PDF]
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J. N. VanHouten and J. J. Wysolmerski Low Estrogen and High Parathyroid Hormone-Related Peptide Levels Contribute to Accelerated Bone Resorption and Bone Loss in Lactating Mice Endocrinology, December 1, 2003; 144(12): 5521 - 5529. [Abstract] [Full Text] [PDF]
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S. Nakayamada, Y. Okada, K. Saito, M. Tamura, and Y. Tanaka {beta}1 Integrin/Focal Adhesion Kinase-mediated Signaling Induces Intercellular Adhesion Molecule 1 and Receptor Activator of Nuclear Factor {kappa}B Ligand on Osteoblasts and Osteoclast Maturation J. Biol. Chem., November 14, 2003; 278(46): 45368 - 45374. [Abstract] [Full Text] [PDF]
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 E. Seeman Invited Review: Pathogenesis of osteoporosis J Appl Physiol, November 1, 2003; 95(5): 2142 - 2151. [Abstract] [Full Text] [PDF]
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G. Passeri, G. Pini, L. Troiano, R. Vescovini, P. Sansoni, M. Passeri, P. Gueresi, R. Delsignore, M. Pedrazzoni, and C. Franceschi Low Vitamin D Status, High Bone Turnover, and Bone Fractures in Centenarians J. Clin. Endocrinol. Metab., November 1, 2003; 88(11): 5109 - 5115. [Abstract] [Full Text] [PDF]
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G. Van den Berghe, D. Van Roosbroeck, P. Vanhove, P. J. Wouters, L. De Pourcq, and R. Bouillon Bone Turnover in Prolonged Critical Illness: Effect of Vitamin D J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 4623 - 4632. [Abstract] [Full Text] [PDF]
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 S. S. Budden and M. E. Gunness Possible Mechanisms of Osteopenia in Rett Syndrome: Bone Histomorphometric Studies J Child Neurol, October 1, 2003; 18(10): 698 - 702. [Abstract] [PDF]
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F. Elefteriou, S. Takeda, X. Liu, D. Armstrong, and G. Karsenty Monosodium Glutamate-Sensitive Hypothalamic Neurons Contribute to the Control of Bone Mass Endocrinology, September 1, 2003; 144(9): 3842 - 3847. [Abstract] [Full Text] [PDF]
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 S. Kim, T. Koga, M. Isobe, B. E. Kern, T. Yokochi, Y. E. Chin, G. Karsenty, T. Taniguchi, and H. Takayanagi Stat1 functions as a cytoplasmic attenuator of Runx2 in the transcriptional program of osteoblast differentiation Genes & Dev., August 15, 2003; 17(16): 1979 - 1991. [Abstract] [Full Text] [PDF]
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N. A. McHugh, H. M. Vercesi, R. W. Egan, and J. A. Hey Receptor activator of NF-{kappa}B ligand arrests bone growth and promotes cortical bone resorption in growing rats J Appl Physiol, August 1, 2003; 95(2): 672 - 676. [Abstract] [Full Text] [PDF]
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H. Enomoto, S. Shiojiri, K. Hoshi, T. Furuichi, R. Fukuyama, C. A. Yoshida, N. Kanatani, R. Nakamura, A. Mizuno, A. Zanma, et al. Induction of Osteoclast Differentiation by Runx2 through Receptor Activator of Nuclear Factor-{kappa}B Ligand (RANKL) and Osteoprotegerin Regulation and Partial Rescue of Osteoclastogenesis in Runx2-/- Mice by RANKL Transgene J. Biol. Chem., June 20, 2003; 278(26): 23971 - 23977. [Abstract] [Full Text] [PDF]
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A. M. Delany, I. Kalajzic, A. D. Bradshaw, E. H. Sage, and E. Canalis Osteonectin-Null Mutation Compromises Osteoblast Formation, Maturation, and Survival Endocrinology, June 1, 2003; 144(6): 2588 - 2596. [Abstract] [Full Text] [PDF]
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S. S. Ahuja, S. Zhao, T. Bellido, L. I. Plotkin, F. Jimenez, and L. F. Bonewald CD40 Ligand Blocks Apoptosis Induced by Tumor Necrosis Factor {alpha}, Glucocorticoids, and Etoposide in Osteoblasts and the Osteocyte-Like Cell Line Murine Long Bone Osteocyte-Y4 Endocrinology, May 1, 2003; 144(5): 1761 - 1769. [Abstract] [Full Text] [PDF]
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Y. Hu, E. Chan, S. X. Wang, and B. Li Activation of p38 Mitogen-Activated Protein Kinase Is Required for Osteoblast Differentiation Endocrinology, May 1, 2003; 144(5): 2068 - 2074. [Abstract] [Full Text] [PDF]
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B. H. Ascott-Evans, N. Guanabens, S. Kivinen, B. G. A. Stuckey, C. H. Magaril, K. Vandormael, B. Stych, and M. E. Melton Alendronate Prevents Loss of Bone Density Associated With Discontinuation of Hormone Replacement Therapy: A Randomized Controlled Trial Arch Intern Med, April 14, 2003; 163(7): 789 - 794. [Abstract] [Full Text] [PDF]
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S. Cuzzocrea, E. Mazzon, L. Dugo, T. Genovese, R. Di Paola, Z. Ruggeri, E. Vegeto, A. P. Caputi, F. A. J. Van de Loo, D. Puzzolo, et al. Inducible Nitric Oxide Synthase Mediates Bone Loss in Ovariectomized Mice Endocrinology, March 1, 2003; 144(3): 1098 - 1107. [Abstract] [Full Text] [PDF]
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 S. Yakar and C. J. Rosen From Mouse to Man: Redefining the Role of Insulin-Like Growth Factor-I in the Acquisition of Bone Mass Experimental Biology and Medicine, March 1, 2003; 228(3): 245 - 252. [Abstract] [Full Text] [PDF]
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Y. Engelbrecht, H. de Wet, K. Horsch, C. R. Langeveldt, F. S. Hough, and P. A. Hulley Glucocorticoids Induce Rapid Up-Regulation of Mitogen-Activated Protein Kinase Phosphatase-1 and Dephosphorylation of Extracellular Signal-Regulated Kinase and Impair Proliferation in Human and Mouse Osteoblast Cell Lines Endocrinology, February 1, 2003; 144(2): 412 - 422. [Abstract] [Full Text] [PDF]
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S. L. Ferrari, L. Ahn-Luong, P. Garnero, S. E. Humphries, and S. L. Greenspan Two Promoter Polymorphisms Regulating Interleukin-6 Gene Expression Are Associated with Circulating Levels of C-Reactive Protein and Markers of Bone Resorption in Postmenopausal Women J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 255 - 259. [Abstract] [Full Text] [PDF]
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Y. Takeuchi, S. Watanabe, G. Ishii, S. Takeda, K. Nakayama, S. Fukumoto, Y. Kaneta, D. Inoue, T. Matsumoto, K. Harigaya, et al. Interleukin-11 as a Stimulatory Factor for Bone Formation Prevents Bone Loss with Advancing Age in Mice J. Biol. Chem., December 6, 2002; 277(50): 49011 - 49018. [Abstract] [Full Text] [PDF]
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A. Grey, Q. Chen, K. Callon, X. Xu, I. R. Reid, and J. Cornish The Phospholipids Sphingosine-1-Phosphate and Lysophosphatidic Acid Prevent Apoptosis in Osteoblastic Cells via a Signaling Pathway Involving Gi Proteins and Phosphatidylinositol-3 Kinase Endocrinology, December 1, 2002; 143(12): 4755 - 4763. [Abstract] [Full Text] [PDF]
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J.-P. David, K. Sabapathy, O. Hoffmann, M. H. Idarraga, and E. F. Wagner JNK1 modulates osteoclastogenesis through both c-Jun phosphorylation-dependent and -independent mechanisms J. Cell Sci., November 15, 2002; 115(22): 4317 - 4325. [Abstract] [Full Text] [PDF]
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M. A. Karsdal, L. Larsen, M. T. Engsig, H. Lou, M. Ferreras, A. Lochter, J.-M. Delaisse, and N. T. Foged Matrix Metalloproteinase-dependent Activation of Latent Transforming Growth Factor-beta Controls the Conversion of Osteoblasts into Osteocytes by Blocking Osteoblast Apoptosis J. Biol. Chem., November 8, 2002; 277(46): 44061 - 44067. [Abstract] [Full Text] [PDF]
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 S. Kousteni, J.-R. Chen, T. Bellido, L. Han, A. A. Ali, C. A. O'Brien, L. Plotkin, Q. Fu, A. T. Mancino, Y. Wen, et al. Reversal of Bone Loss in Mice by Nongenotropic Signaling of Sex Steroids Science, October 25, 2002; 298(5594): 843 - 846. [Abstract] [Full Text] [PDF]
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B. Demiralp, H.-L. Chen, A. J. Koh, E. T. Keller, and L. K. McCauley Anabolic Actions of Parathyroid Hormone during Bone Growth Are Dependent on c-fos Endocrinology, October 1, 2002; 143(10): 4038 - 4047. [Abstract] [Full Text] [PDF]
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B. Arko, J. Prezelj, R. Komel, A. Kocijancic, P. Hudler, and J. Marc Sequence Variations in the Osteoprotegerin Gene Promoter in Patients with Postmenopausal Osteoporosis J. Clin. Endocrinol. Metab., September 1, 2002; 87(9): 4080 - 4084. [Abstract] [Full Text] [PDF]
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