Modeling the interactions between osteoblast and osteoclast activities in bone remodeling

Lemaire, Vincent; Tobin, Frank L.; Greller, Larry D.; Cho, Carolyn R.; Suva, Larry J.

doi:10.1016/j.jtbi.2004.03.023

Cited by 452Bone Metabolism and DiseasesBone health and osteoporosis researchBone health and treatments

Modeling the interactions between osteoblast and osteoclast activities in bone remodeling

Lemaire, Vincent, Tobin, Frank L., Greller, Larry D., Cho, Carolyn R., Suva, Larry J.·2004·Journal of Theoretical Biology

DOI 10.1016/j.jtbi.2004.03.023

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Abstract

We propose a mathematical model explaining the interactions between osteoblasts and osteoclasts, two cell types specialized in the maintenance of the bone integrity. Bone is a dynamic, living tissue whose structure and shape continuously evolves during life. It has the ability to change architecture by removal of old bone and replacement with newly formed bone in a localized process called remodeling. The model described here is based on the idea that the relative proportions of immature and mature osteoblasts control the degree of osteoclastic activity. In addition, osteoclasts control osteoblasts differentially depending on their stage of differentiation. Despite the tremendous complexity of the bone regulatory system and its fragmentary understanding, we obtain surprisingly good correlations between the model simulations and the experimental observations extracted from the literature. The model results corroborate all behaviors of the bone remodeling system that we have simulated, including the tight coupling between osteoblasts and osteoclasts, the catabolic effect induced by continuous administration of PTH, the catabolic action of RANKL, as well as its reversal by soluble antagonist OPG. The model is also able to simulate metabolic bone diseases such as estrogen deficiency, vitamin D deficiency, senescence and glucocorticoid excess. Conversely, possible routes for therapeutic interventions are tested and evaluated. Our model confirms that anti-resorptive therapies are unable to partially restore bone loss, whereas bone formation therapies yield better results. The model enables us to determine and evaluate potential therapies based on their efficacy. In particular, the model predicts that combinations of anti-resorptive and anabolic therapies provide significant benefits compared with monotherapy, especially for certain type of skeletal disease. Finally, the model clearly indicates that increasing the size of the pool of preosteoblasts is an essential ingredient for the therapeutic manipulation of bone formation. This model was conceived as the first step in a bone turnover modeling platform. These initial modeling results are extremely encouraging and lead us to proceed with additional explorations into bone turnover and skeletal remodeling.

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The QSP model used by FDA was built on two earlier published models: a model of systemic calcium homeostasis and a cellular model of the behavior of bone morphogenic units.
“This QSP model was built on two earlier published models: a model of systemic calcium homeostasis13 and a cellular model of the behavior of bone morphogenic units.14”
From Best Practices to Maximize the Use and Reuse of Quantitative and Systems Pharmacology Models: Recommendations From the United Kingdom Quantitative and Systems Pharmacology Network (2019) · cites this paper as [14]

Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation.
Lacey, D. L., Timms, E., Tan, H.-L., Kelley, M. J., Dunstan, C. R., Burgess, T., Elliott, R., Colombero, A., Elliott, G., Scully, S., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)81569-x · Cited by 5,439 · see citing works
Osteoprotegerin: a novel secreted protein involved in the regulation of bone density.
Simonet, W. S., Lacey, D. L., Dunstan, C. R., Kelley, M., Chang, M.-S., Lüthy, R., Nguyen, H. Q., Wooden, S., Bennett, L., Boone, T., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80209-3 · Cited by 5,130 · see citing works
Effect of Parathyroid Hormone (1-34) on Fractures and Bone Mineral Density in Postmenopausal Women with Osteoporosis
Neer, R. M., Arnaud, C. D., Zanchetta, J. R., Prince, R., Gaich, G. A., Reginster, J.-Y., Hodsman, A. B., Eriksen, E. F., Ish-Shalom, S., Genant, H. K., et al. (2001) · New England Journal of Medicine · doi:10.1056/nejm200105103441904 · Cited by 4,602 · see citing works
Targeted Disruption of Results in a Complete Lack of Bone Formation owing to Maturational Arrest of Osteoblasts
Komori, T., Yagi, H., Nomura, S., Yamaguchi, A., Sasaki, K., Deguchi, K., Shimizu, Y., Bronson, R. T., Gao, Y.-H., Inada, M., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80258-5 · Cited by 4,244 · see citing works
Bone Resorption by Osteoclasts
Teitelbaum, S. L. (2000) · Science · doi:10.1126/science.289.5484.1504 · Cited by 3,962 · see citing works
Birth and Death of Bone Cells: Basic Regulatory Mechanisms and Implications for the Pathogenesis and Treatment of Osteoporosis
Manolagas, S. C. (2000) · Endocrine Reviews · doi:10.1210/edrv.21.2.0395 · Cited by 2,575 · see citing works
Sex Steroids and the Construction and Conservation of the Adult Skeleton
Riggs, B. L., Khosla, S., & Melton, L. J. (2002) · Endocrine Reviews · doi:10.1210/edrv.23.3.0465 · Cited by 1,846 · see citing works
Therapeutic Approaches to Bone Diseases
Rodan, G. A., & Martin, T. J. (2000) · Science · doi:10.1126/science.289.5484.1508 · Cited by 1,767 · see citing works
Cytostatic and apoptotic actions of TGF-β in homeostasis and cancer
Siegel, P. M., & Massagué, J. (2003) · Nature reviews. Cancer · doi:10.1038/nrc1208 · Cited by 1,600 · see citing works
Birth and Death of Bone Cells: Basic Regulatory Mechanisms and Implications for the Pathogenesis and Treatment of Osteoporosis
Manolagas, S. C. (2000) · Endocrine Reviews · doi:10.1210/er.21.2.115 · Cited by 1,318 · see citing works
The Roles of Osteoprotegerin and Osteoprotegerin Ligand in the Paracrine Regulation of Bone Resorption
Hofbauer, L. C., Khosla, S., Dunstan, C. R., Lacey, D. L., Boyle, W. J., & Riggs, B. L. (2000) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2000.15.1.2 · Cited by 1,167 · see citing works
The Osteoblast: A Sophisticated Fibroblast under Central Surveillance
Ducy, P. F., Schinke, T., & Karsenty, G. (2000) · Science · doi:10.1126/science.289.5484.1501 · Cited by 1,121 · see citing works
Increased bone formation by prevention of osteoblast apoptosis with parathyroid hormone
Jilka, R. L., Weinstein, R. S., Bellido, T., Roberson, P. K., PARFITT, A. M., & Manolagas, S. C. (1999) · Journal of Clinical Investigation · doi:10.1172/jci6610 · Cited by 1,042 · see citing works
Role of osteoblasts in hormonal control of bone resorption—A hypothesis
Rodan, G. A., & Martin, T. J. (1981) · Calcified Tissue International · doi:10.1007/bf02409454 · Cited by 982 · see citing works
Receptors; models for binding, trafficking and signaling
(1997) · General Pharmacology The Vascular System · doi:10.1016/s0306-3623(97)90087-2 · Cited by 855 · see citing works
Stimulation of Osteoprotegerin Ligand and Inhibition of Osteoprotegerin Production by Glucocorticoids in Human Osteoblastic Lineage Cells: Potential Paracrine Mechanisms of Glucocorticoid-Induced Osteoporosis1
Hofbauer, L. C., Gori, F., Riggs, B. L., Lacey, D. L., Dunstan, C. R., Spelsberg, T. C., & Khosla, S. (1999) · Endocrinology · doi:10.1210/endo.140.10.7034 · Cited by 794 · see citing works
Numerical bifurcation analysis of delay differential equations using DDE-BIFTOOL
Engelborghs, K., Luzyanina, T., & Roose, D. (2002) · ACM Transactions on Mathematical Software · doi:10.1145/513001.513002 · Cited by 757 · see citing works
Anabolic Actions of Parathyroid Hormone on Bone*
Dempster, D. W., Cosman, F., Parisien, M. V., Shen, V., & Lindsay, R. (1993) · Endocrine Reviews · doi:10.1210/edrv-14-6-690 · Cited by 717 · see citing works
Estrogen stimulates gene expression and protein production of osteoprotegerin in human osteoblastic cells.
Hofbauer, L. C., Khosla, S., Dunstan, C. R., Lacey, D. L., Spelsberg, T. C., & Riggs, B. L. (1999) · Endocrinology · doi:10.1210/endo.140.9.7131 · Cited by 692 · see citing works
The ligand for osteoprotegerin (OPGL) directly activates mature osteoclasts.
Burgess, T. L., Qian, Y.-X., Kaufman, S., Ring, B. D., Van, G., Capparelli, C., Kelley, M., Hsu, H., Boyle, W. J., Dunstan, C. R., et al. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.145.3.527 · Cited by 689 · see citing works
Parathyroid Hormone Stimulates the Bone Apposition Rate Independently of Its Resorptive Action: Differential Effects of Intermittent and Continuous Administration*
Tam, C. S., Heersche, J. N. M., Murray, T. M., & PARSONS, J. A. (1982) · Endocrinology · doi:10.1210/endo-110-2-506 · Cited by 611 · see citing works
Osteoblast Programmed Cell Death (Apoptosis): Modulation by Growth Factors and Cytokines
Jilka, R. L., Weinstein, R. S., Bellido, T., Parfitt, A. M., & Manolagas, S. C. (1998) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1998.13.5.793 · Cited by 578 · see citing works
Cell biology of the osteoclast
Roodman, G. D. (1999) · Experimental Hematology · doi:10.1016/s0301-472x(99)00061-2 · Cited by 570 · see citing works
TGF‐β‐induced repression of CBFA1 by Smad3 decreases cbfa1 and osteocalcin expression and inhibits osteoblast differentiation
Alliston, T., Choy, L., Ducy, P., Karsenty, G., & Derynck, R. (2001) · The EMBO Journal · doi:10.1093/emboj/20.9.2254 · Cited by 526 · see citing works
Advances in the osteoblast lineage
Aubin, J. E. (1998) · Biochemistry and Cell Biology · doi:10.1139/bcb-76-6-899 · Cited by 444 · see citing works
Sex Steroids and the Construction and Conservation of the Adult Skeleton
Riggs, B. L. (2002) · Endocrine Reviews · doi:10.1210/er.23.3.279 · Cited by 434 · see citing works
Catabolic effects of continuous human PTH (1-38) in vivo is associated with sustained stimulation of RANKL and inhibition of osteoprotegerin and gene-associated bone formation.
Ma, Y. L., Cain, R. L., Halladay, D. L., Yang, X., Zeng, Q., Miles, R. R., Chandrasekhar, S., Martin, T. J., & Onyia, J. E. (2001) · Endocrinology · doi:10.1210/endo.142.9.8356 · Cited by 428 · see citing works
Receptor Activator of NF-κB and Osteoprotegerin Expression by Human Microvascular Endothelial Cells, Regulation by Inflammatory Cytokines, and Role in Human Osteoclastogenesis
Collin-Osdoby, P., Rothe, L., Anderson, F., Nelson, M., Maloney, W., & Osdoby, P. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m010153200 · Cited by 398 · see citing works
Advances in the osteoblast lineage
Aubin, J. E. (1998) · Biochemistry and Cell Biology · doi:10.1139/o99-005 · Cited by 346 · see citing works
Theoretical perspective: A new model for the regulation of bone resorption, with particular reference to the effects of bisphosphonates
PARFITT, A. M., Mundy, G. R., Roodman, G. D., Hughes, D. E., & Boyce, B. F. (1996) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650110203 · Cited by 334 · see citing works
Osteoprotegerin and its Ligand: A New Paradigm for Regulation of Osteoclastogenesis and Bone Resorption
Aubin, J. E., & Bonnelye, E. (2000) · Osteoporosis International · doi:10.1007/s001980070028 · Cited by 325 · see citing works
Mathematical model predicts a critical role for osteoclast autocrine regulation in the control of bone remodeling
Komarova, S. V., Smith, R. J., Dixon, S. J., et al. (2003) · Bone · doi:10.1016/s8756-3282(03)00157-1 · Cited by 319 · see citing works
Osteoprotegerin Production by Human Osteoblast Lineage Cells Is Stimulated by Vitamin D, Bone Morphogenetic Protein-2, and Cytokines
Hofbauer, L. C., Dunstan, C. R., Spelsberg, T. C., Riggs, B. L., & Khosla, S. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.9394 · Cited by 311 · see citing works
Bisphosphonates Pamidronate and Zoledronic Acid Stimulate Osteoprotegerin Production by Primary Human Osteoblasts
Viereck, V., Emons, G., Lauck, V., Frosch, K., Blaschke, S., Gründker, C., & Hofbauer, L. C. (2002) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2002.6510 · Cited by 310 · see citing works
Role of active and latent transforming growth factor β in bone formation
Bonewald, L. F., & Dallas, S. L. (1994) · Journal of Cellular Biochemistry · doi:10.1002/jcb.240550312 · Cited by 297 · see citing works
Effects of spaceflight on trabecular bone in rats
Jee, W. S. S., Wronski, T. J., Morey, E. R., & Kimmel, D. B. (1983) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1983.244.3.r310 · Cited by 225 · see citing works
Effects of Immunosuppressants on Receptor Activator of NF-κB Ligand and Osteoprotegerin Production by Human Osteoblastic and Coronary Artery Smooth Muscle Cells
Hofbauer, L. C., Shui, C., Riggs, B. L., Dunstan, C. R., Spelsberg, T. C., O’Brien, T., & Khosla, S. (2001) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.4130 · Cited by 211 · see citing works
Age-related decreases in insulin-like growth factor-I and transforming growth factor-beta in femoral cortical bone from both men and women: implications for bone loss with aging
Nicolas, V., Prewett, A., Bettica, P. U., Mohan, S., Finkelman, R. D., Baylink, D. J., & Farley, J. R. (1994) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.78.5.8175953 · Cited by 209 · see citing works
Vitamin D Control of Osteoblast Function and Bone Extracellular Matrix Mineralization
van Leeuwen, J. P. T. M., van Driel, M., van den Bemd, G. J. C. M., & Pols, H. A. P. (2001) · Critical Reviews in Eukaryotic Gene Expression · doi:10.1615/critreveukargeneexpr.v11.i1-3.100 · Cited by 199 · see citing works
The Role of Parathyroid Hormone in the Pathogenesis of Glucocorticoid-Induced Osteoporosis: A Re-Examination of the Evidence
Rubin, M. R., & Bilezikian, J. P. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-012101 · Cited by 191 · see citing works
Glucocorticoid-Induced Osteoporosis
Weinstein, R. S. (2001) · Reviews in Endocrine and Metabolic Disorders · doi:10.1023/a:1010007108155 · Cited by 189 · see citing works
Stimulation of Osteoprotegerin Ligand and Inhibition of Osteoprotegerin Production by Glucocorticoids in Human Osteoblastic Lineage Cells: Potential Paracrine Mechanisms of Glucocorticoid-Induced Osteoporosis
Hofbauer, L. C. (1999) · Endocrinology · doi:10.1210/en.140.10.4382 · Cited by 187 · see citing works
Changing RANKL/OPG mRNA expression in differentiating murine primary osteoblasts
Thomas, G. P., Baker, S., Eisman, J. A., & Gardiner, E. M. (2001) · Journal of Endocrinology · doi:10.1677/joe.0.1700451 · Cited by 184 · see citing works
A two-receptor model for the action of parathyroid hormone on osteoblasts: A role for intracellular free calcium and cAMP
Löwik, C. W. G. M., van Leeuwen, J. P. T. M., van der Meer, J. M., van Zeeland, J. K., Scheven, B. A. A., & Herrmann-Erlee, M. P. M. (1985) · Cell Calcium · doi:10.1016/0143-4160(85)90002-8 · Cited by 177 · see citing works
Mechanisms by which cells of the osteoblast lineage control osteoclast formation and activity
Martin, T. J., & Ng, K. W. (1994) · Journal of Cellular Biochemistry · doi:10.1002/jcb.240560312 · Cited by 173 · see citing works
Comparison of the effects of intermittent and continuous administration of human parathyroid hormone(1?34) on rat bone
Uzawa, T. (1995) · EMC - Cardiologie-Angéiologie · doi:10.1016/8756-3282(95)90194-9 · Cited by 163 · see citing works
Treatment with human parathyroid hormone (1-34) for 18 months increases cancellous bone volume and improves trabecular architecture in ovariectomized cynomolgus monkeys (Macaca fascicularis)
Jerome, C. P., Burr, D. B., Bibber, T. V., et al. (2001) · Bone · doi:10.1016/s8756-3282(00)00430-0 · Cited by 162 · see citing works
The actions of parathyroid hormone on bone: Relation to bone remodeling and turnover, calcium homeostasis, and metabolic bone diseases
PARFITT, A. M. (1976) · Metabolism · doi:10.1016/0026-0495(76)90124-4 · Cited by 160 · see citing works
Reduction in Transforming Growth Factor β Receptor I Expression and Transcription Factor CBFa1 on Bone Cells by Glucocorticoid
Chang, D. J., Ji, C., Kim, K. K., Casinghino, S. R., & McCarthy, T. L. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.9.4892 · Cited by 157 · see citing works
Steroid hormone receptor expression and action in bone
Bland, R. (2000) · Clinical Science · doi:10.1042/cs0980217 · Cited by 149 · see citing works
Parathyroid Hormone Temporal Effects on Bone Formation and Resorption
Kroll, M. H. (2000) · Bulletin of Mathematical Biology · doi:10.1006/bulm.1999.0146 · Cited by 146 · see citing works
Recent advances in bone biology provide insight into the pathogenesis of bone diseases.
Boyce, B. F., Hughes, D. E., Wright, K. R., Xing, L., & Dai, A. (1999) · PubMed · Cited by 145 · see citing works
Relationship between epidermal growth factor receptor occupancy and mitogenic response. Quantitative analysis using a steady state model system.
Knauer, D. J., Wiley, H. S., & Cunningham, D. D. (1984) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)91060-4 · Cited by 145 · see citing works
Parathyroid hormone regulates osteoblast differentiation positively or negatively depending on the differentiation stages
Isogai, Y., Akatsu, T., Ishizuya, T., et al. (1996) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650111003 · Cited by 139 · see citing works
Glucocorticoid-Induced Osteoporosis: Summary of a Workshop
CANALIS, E. M., & Giustina, A. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.12.8066 · Cited by 132 · see citing works
Glucocorticoid decreases circulating osteoprotegerin (OPG): possible mechanism for glucocorticoid induced osteoporosis
Sasaki, N., Kusano, E., Ando, Y., Yano, K., Tsuda, E., & Asano, Y. (2001) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/16.3.479 · Cited by 123 · see citing works
Space Flight: A Challenge for Normal Bone Homeostasis
Carmeliet, G., & Bouillon, R. (2001) · Critical Reviews in Eukaryotic Gene Expression · doi:10.1615/critreveukargeneexpr.v11.i1-3.70 · Cited by 123 · see citing works
Regulation of Osteoprotegerin Secretion from Primary Cultures of Human Bone Marrow Stromal Cells
Brändström, H., Björkman, T., & Ljunggren, Ö. (2001) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.4223 · Cited by 113 · see citing works
Increased frequency ofATM mutations in breast carcinoma patients with early onset disease and positive family history
Teraoka, S. N., Malone, K. E., Doody, D. R., Suter, N. M., Ostrander, E. A., Daling, J. R., & CONCANNON, P. J. (2001) · Cancer · doi:10.1002/1097-0142(20010801)92:3 · Cited by 111 · see citing works
Age-related bone loss. A hypothesis and initial assessment in mice.
Kahn, A., Gibbons, R., Perkins, S., & Gazit, D. (1995) · PubMed · Cited by 104 · see citing works
The skeletal intermediary organization
Frost, H. M. (1983) · Metabolic Bone Disease and Related Research · doi:10.1016/s0221-8747(83)80001-0 · Cited by 104 · see citing works
Prostaglandin E2 prevents bone loss and adds extra bone to immobilized distal femoral metaphysis in female rats
Akamine, T., Jee, W. S. S., Ke, H. Z., Li, X. J., & Lin, B. Y. (1992) · Bone · doi:10.1016/8756-3282(92)90356-2 · Cited by 100 · see citing works
Temporal expression of the anabolic action of PTH in cancellous bone of ovariectomized rats
Meng, X., Liang, X. G., Birchman, R., et al. (1996) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650110402 · Cited by 99 · see citing works
Regulation of osteoclast activity
Greenfield, E. M., Bi, Y., & Miyauchi, A. (1999) · Life Sciences · doi:10.1016/s0024-3205(99)00156-3 · Cited by 97 · see citing works
Dissociation of Second Messenger Activation by Parathyroid Hormone Fragments in Osteosarcoma Cells*
Fujimori, A., Cheng, S., Avioli, L. V., et al. (1991) · Endocrinology · doi:10.1210/endo-128-6-3032 · Cited by 96 · see citing works
Anabolic actions of parathyroid hormone on bone [published erratum appears in Endocr Rev 1994 Apr;15(2):261]
Dempster, D. W. (1993) · Endocrine Reviews · doi:10.1210/er.14.6.690 · Cited by 90 · see citing works
Modeling of bone formation and resorption mediated by parathyroid hormone: response to estrogen/PTH therapy
Rattanakul, C., Lenbury, Y., Krishnamara, N., & Wollkind, D. J. (2003) · Biosystems · doi:10.1016/s0303-2647(03)00040-6 · Cited by 79 · see citing works
Reconstructing the skeleton with intermittent parathyroid hormone
Seeman, E., & Delmas, P. D. (2001) · Trends in Endocrinology and Metabolism · doi:10.1016/s1043-2760(01)00460-x · Cited by 78 · see citing works
Spaceflight results in depressed cancellous bone formation in rat humeri.
Turner, R. T., Evans, G. L., & Wakley, G. K. (1995) · PubMed · Cited by 67 · see citing works
Bone remodelling: A signalling system for osteoclast regulation
Filvaroff, E. H., & Derynck, R. (1998) · Current Biology · doi:10.1016/s0960-9822(98)70434-8 · Cited by 66 · see citing works
Steroid hormone receptor expression and action in bone
Bland, R. (2000) · Clinical Science · doi:10.1042/cs19990252 · Cited by 63 · see citing works
Cytokines and Bone Remodeling
Mundy, G. R., Oyajobi, B. O., Gutierrez, G. E., Sterling, J. A. R., Padalecki, S. S., Elefteriou, F., & Zhao, M. (2008) · Elsevier eBooks · doi:10.1016/b978-012370544-0.50020-3 · Cited by 59 · see citing works
Interactions of PTH and PTHrP with the PTH/PTHrP Receptor and with Downstream Signaling Pathways: Exceptions That Provide the Rules
Goltzman, D. (1999) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1999.14.2.173 · Cited by 59 · see citing works
Coupling of Bone Resorption and Formation during Bone Remodeling
Martin, T. J., & Rodan, G. A. (2001) · Elsevier eBooks · doi:10.1016/b978-012470862-4/50013-1 · Cited by 58 · see citing works
Effects of continuous infusion of parathyroid hormone and parathyroid hormone-related peptide on rat bone in vivo: comparative study by histomorphometry
Kitazawa, R., Imai, Y., Fukase, M., et al. (1991) · Bone and Mineral · doi:10.1016/0169-6009(91)90029-y · Cited by 48 · see citing works
Cellular and molecular regulation of bone turnover
Mundy, G. R. (1999) · Bone · doi:10.1016/s8756-3282(99)00044-7 · Cited by 48 · see citing works
New analogs of vitamin D3
Slatopolsky, E., Dusso, A., & Brown, A. (1999) · Kidney International · doi:10.1046/j.1523-1755.1999.07305.x · Cited by 46 · see citing works
Hindlimb unloading in rat decreases preosteoblast proliferation assessed in vivo with BrdU incorporation
Barou, O., Palle, S., Vico, L., Alexandre, C., & Lafage‐Proust, M. (1998) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1998.274.1.e108 · Cited by 42 · see citing works
Enhanced osteoblast development after continuous infusion of hPTH(1-84) in the rat
Watson, P. H., Fraher, L. J., Kisiel, M., DeSousa, D., Hendy, G. N., & Hodsman, A. B. (1999) · Bone · doi:10.1016/s8756-3282(98)00170-7 · Cited by 41 · see citing works
Vitamin D, parathyroid hormone, and calcium: a complex regulatory network
Feldman, D. N. (1999) · The American Journal of Medicine · doi:10.1016/s0002-9343(99)00283-1 · Cited by 36 · see citing works
Growth factors and bone formation in osteoporosis: roles for IGF-I and TGF-beta.
Marie, P. (1997) · PubMed · Cited by 34 · see citing works
Identification of signal transduction pathways and promoter sequences that mediate parathyroid hormone 1–38 inhibition of osteoprotegerin gene expression
Halladay, D., Miles, R. R., Thirunavukkarasu, K., Chandrasekhar, S., Martin, T. J., & Onyia, J. E. (2001) · Journal of Cellular Biochemistry · doi:10.1002/jcb.1273 · Cited by 32 · see citing works
Partial maintenance of extra cancellous bone mass by antiresorptive agents after discontinuation of human parathyroid hormone (1–38) in right hindlimb immobilized rats
Ma, Y., Jee, W. S. S., Chen, Y., et al. (1995) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650101116 · Cited by 31 · see citing works
Combination therapy for postmenopausal osteoporosis
Compston, J. E., & Watts, N. B. (2002) · Clinical Endocrinology · doi:10.1046/j.1365-2265.2002.01536.x · Cited by 30 · see citing works
Mouse Genetics Have Uncovered New Paradigms in Bone Biology
Günther, T., & Schinke, T. (2000) · Trends in Endocrinology and Metabolism · doi:10.1016/s1043-2760(00)00256-3 · Cited by 29 · see citing works
1,25-Dihydroxyvitamin D reduces parathyroid hormone receptor number in ROS 17/2.8 cells and prevents the glucocorticoid-induced increase in these receptors: Relationship to adenylate cyclase activation
Titus, L., Jackson, E., Nanes, M. S., et al. (1991) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650060614 · Cited by 29 · see citing works
Endogenous parathyroid hormone-related peptide enhances proliferation and inhibits differentiation in the osteoblast-like cell line ROS 17/2.8
Du, P., Ye, Y., Seitz, P. K., et al. (2000) · Bone · doi:10.1016/s8756-3282(00)00264-7 · Cited by 27 · see citing works
Downregulation of the PTH/PTHrP receptor by vitamin D3 in the osteoblast-like ROS 17/2.8 cells
Xie, L. Y., LEUNG, A. T., Segre, G. V., et al. (1996) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1996.270.4.e654 · Cited by 24 · see citing works
Treatment with PTH Peptides
Mosekilde, L., & REEVE, J. (2001) · Elsevier eBooks · doi:10.1016/b978-012470862-4/50078-7 · Cited by 24 · see citing works
Long-term effects of parathyroid hormone, 1,25-dihydroxyvitamin d3, and dexamethasone on the cell growth and functional activity of human osteogenic alveolar bone cell cultures
Costa, M. A., & Fernandes, M. H. (2000) · Pharmacological Research · doi:10.1006/phrs.2000.0697 · Cited by 23 · see citing works
Bone growth stimulators New tools for treating bone loss and mending fractures
Whitfield, J. F., Morley, P., & Willick, G. E. (2002) · Vitamins and hormones · doi:10.1016/s0083-6729(02)65059-9 · Cited by 20 · see citing works
Deflazacort Increases Osteoclast Formation in Mouse Bone Marrow Culture and the Ratio ofRANKL/OPGmRNA Expression in Marrow Stromal Cells
Chung, H.-Y., Kang, Y. S., Hwang, C. S., Moon, I. K., Yim, C. H., Choi, K. H., Han, K. O., Jang, H. C., Yoon, H. K., & Han, I. K. (2001) · Journal of Korean Medical Science · doi:10.3346/jkms.2001.16.6.769 · Cited by 10 · see citing works
Steroid hormones and bone.
Huang, W. H., & Zheng, M. H. (1999) · PubMed · doi:10.14670/hh-14.1257 · Cited by 8 · see citing works
Linkages of nuclear architecture to biological and pathological control of gene expression
Stein, G. S., van Wijnen, A. J., Stein, J. L., Lian, J. B., Pockwinse, S. M., & McNeil, S. M. (1998) · Journal of Cellular Biochemistry · doi:10.1002/(sici)1097-4644(1998)72:30/31+ · Cited by 6 · see citing works

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A physiologically based mathematical model of integrated calcium homeostasis and bone remodeling
Peterson, M. C., & Riggs, M. M. (2010) · Bone · doi:10.1016/j.bone.2009.08.053 · Cited by 198 · see citing works
Best Practices to Maximize the Use and Reuse of Quantitative and Systems Pharmacology Models: Recommendations From the United Kingdom Quantitative and Systems Pharmacology Network
Cucurull‐Sanchez, L., Chappell, M. J., Chelliah, V., Amy Cheung, S. Y., Derks, G., Penney, M., Phipps, A., Malik‐Sheriff, R. S., Timmis, J., Tindall, M. J., et al. (2019) · CPT: Pharmacometrics & Systems Pharmacology · doi:10.1002/psp4.12381 · Cited by 61 · see citing works
“This QSP model was built on two earlier published models: a model of systemic calcium homeostasis(13) and a cellular model of the behavior of bone morphogenic units.(14) The QSP simulations supported the hypothesis that increased dosing frequency or slow infusion could reduce hypercalciuria.”
Method
A review of mathematical modeling of bone remodeling from a systems biology perspective
Cook, C. V., Lighty, A. M., Smith, B. J., & Ford Versypt, A. N. (2024) · Frontiers in Systems Biology · doi:10.3389/fsysb.2024.1368555 · Cited by 25 · see citing works
Automated Scale Reduction of Nonlinear <scp>QSP</scp> Models With an Illustrative Application to a Bone Biology System
Hasegawa, C., & Duffull, S. B. (2018) · CPT: Pharmacometrics & Systems Pharmacology · doi:10.1002/psp4.12324 · Cited by 18 · see citing works
The bone ecosystem facilitates multiple myeloma relapse and the evolution of heterogeneous drug resistant disease
Bishop, R. T., Miller, A. K., Froid, M., Nerlakanti, N., Li, T., Frieling, J. S., Nasr, M. M., Nyman, K. J., Sudalagunta, P. R., Canevarolo, R. R., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-46594-0 · Cited by 16 · see citing works

Authors: Lemaire, V., Tobin, F. L., Greller, L. D., Cho, C. R., & Suva, L. J.
Affiliations: GlaxoSmithKline (United States) (US)
Corresponding author: Lemaire, Vincent
Tobin, Frank L.
ORCID: Lemaire, Vincent
Cho, Carolyn R.
Suva, Larry J.
Venue: Journal of Theoretical Biology
Publisher: Elsevier BV
Published: 2004-08
Volume: 229
Issue: 3
Pages: 293-309
ISSN: 0022-5193 (ISSN-L)
DOI: 10.1016/j.jtbi.2004.03.023
OpenAlex: W2168376037
Cited by: 452
References: 94
Citations by year: 2026: 13 · 2025: 18 · 2024: 21 · 2023: 18 · 2022: 17 · 2021: 32 · 2020: 26 · 2019: 34 · 2018: 17 · 2017: 16 · 2016: 28 · 2015: 21 · 2014: 30 · 2013: 32 · 2012: 37
FWCI: 2.01
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Journal of Theoretical Biology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
Health Sciences › Medicine › Oncology › Bone health and treatments
Keywords: bone remodeling, osteoblasts, osteoclasts, bone turnover, mathematical model, osteoclastogenesis, parathyroid hormone, RANKL, osteoprotegerin, estrogen deficiency, vitamin D deficiency, glucocorticoid excess, bone loss, antiresorptive therapy, anabolic therapy, combination therapy
MeSH terms: Bone Diseases, Metabolic, Cell Communication, Humans, Models, Biological, Osteoblasts, Osteoclasts, Parathyroid Hormone, Bone Remodeling

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Modeling the interactions between osteoblast and osteoclast activities in bone remodeling

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