Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin
Open accessAbstract
Glucocorticoid-induced osteoporosis may be due, in part, to increased apoptosis of osteocytes and osteoblasts, and bisphosphonates (BPs) are effective in the management of this condition. We have tested the hypothesis that BPs suppress apoptosis in these cell types. Etidronate, alendronate, pamidronate, olpadronate, or amino-olpadronate (IG9402, a bisphosphonate that lacks antiresorptive activity) at 10(-9) to 10(-6) M prevented apoptosis of murine osteocytic MLO-Y4 cells, whether it was induced by etoposide, TNF-alpha, or the synthetic glucocorticoid dexamethasone. BPs also inhibited apoptosis of primary murine osteoblastic cells isolated from calvaria. Similar antiapoptotic effects on MLO-Y4 and osteoblastic cells were seen with nanomolar concentrations of the peptide hormone calcitonin. The antiapoptotic effect of BPs and calcitonin was associated with a rapid increase in the phosphorylated fraction of extracellular signal regulated kinases (ERKs) and was blocked by specific inhibitors of ERK activation. Consistent with these in vitro results, alendronate abolished the increased prevalence of apoptosis in vertebral cancellous bone osteocytes and osteoblasts that follows prednisolone administration to mice. These results suggest that the therapeutic efficacy of BPs or calcitonin in diseases such as glucocorticoid-induced osteoporosis may be due, in part, to their ability to prevent osteocyte and osteoblast apoptosis.
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In MLO/Y4 cells, apoptosis induced by etoposide, TNF-α, or glucocorticoids was prevented by pretreatment with 5-10 ng/mL sCT.
“Induction of apoptosis in MLO/Y4 cells by etoposide, TNF-␣, or glucocorticoids was prevented by pretreatment of the cells with 5-10 ng/mL sCT.”
From The Activity of Peptides of the Calcitonin Family in Bone (2019) · cites this paper as [167]
The therapeutic effect of calcitonin in diseases such as glucocorticoid-induced osteoporosis may be partly due to inhibition of osteocyte apoptosis.
“The authors suggest that the therapeutic effect of calcitonin in diseases such as glucocorticoid-induced osteoporosis may be partly due to inhibition of osteocyte apoptosis (167).”
From The Activity of Peptides of the Calcitonin Family in Bone (2019) · cites this paper as [167]
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Cites
Thornberry, N. A., & Lazebnik, Y. A. (1998) · Science · doi:10.1126/science.281.5381.1312 · Cited by 6,857 · see citing works
Death Receptors: Signaling and Modulation
Ashkenazi, A., & Dixit, V. M. (1998) · Science · doi:10.1126/science.281.5381.1305 · Cited by 5,866 · see citing works
Opposing Effects of ERK and JNK-p38 MAP Kinases on Apoptosis
Xia, Z., Dickens, M., Raingeaud, J., Davis, R. J., & Greenberg, M. E. (1995) · Science · doi:10.1126/science.270.5240.1326 · Cited by 5,290 · see citing works
Alessi, D. R., Cuenda, A., Cohen, P., Dudley, D. T., & Saltiel, A. R. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.46.27489 · Cited by 3,396 · see citing works
Identification of a Novel Inhibitor of Mitogen-activated Protein Kinase Kinase
Favata, M. F., Horiuchi, K. Y., Manos, E. J., Daulerio, A. J., Stradley, D. A., Feeser, W. S., Dyk, D. E. V., Pitts, W. J., Earl, R. A., Hobbs, F. W., et al. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.29.18623 · Cited by 3,016 · see citing works
The Fire of Life: An Introduction to Animal Energetics
Kleiber, M. (1975) · Medical Entomology and Zoology · Cited by 2,556 · see citing works
A short amino acid sequence able to specify nuclear location
Kalderon, D., Roberts, B., Richardson, W. D., & Smith, A. E. (1984) · Cell · doi:10.1016/0092-8674(84)90457-4 · Cited by 2,511 · see citing works
Weinstein, R. S., Jilka, R. L., Parfitt, A. M., & Manolagas, S. C. (1998) · Journal of Clinical Investigation · doi:10.1172/jci2799 · Cited by 1,753 · cited 12× · see citing works
“The TUNEL reaction was performed according to the manufacturer’s instructions, using 0.15% CuSO4 for color enhancement.”
BackgroundMethodResultInfluentialSelf-citationLuckman, S. P., Hughes, D. E., Coxon, F. P., Russell, R. G. G., & Rogers, M. J. (1998) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1998.13.4.581 · Cited by 1,170 · see citing works
DNA binding of the glucocorticoid receptor is not essential for survival
Reichardt, H. M., Kaestner, K. H., Tuckermann, J., Kretz, O., Wessely, O., Bock, R., Gass, P., Schmid, W., Herrlich, P., Angel, P., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)81183-6 · Cited by 1,068 · 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
Self-citationBisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo
Hughes, D. E., Wright, K. R., Uy, H. L., Sasaki, A., Yoneda, T., Roodman, D., Mundy, G. R., & Boyce, B. F. (1995) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650101008 · Cited by 1,039 · see citing works
Cyclic Administration of Pamidronate in Children with Severe Osteogenesis Imperfecta
Glorieux, F. H., Bishop, N. J., Plotkin, H., Chabot, G., Lanoue, G., & Travers, R. (1998) · New England Journal of Medicine · doi:10.1056/nejm199810013391402 · Cited by 1,011 · see citing works
Bisphosphonates: mechanisms of action.
Rodan, G. A., & Fleisch, H. A. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118722 · Cited by 920 · see citing works
Estrogen promotes apoptosis of murine osteoclasts mediated by TGF–β
Hughes, D. E., Dai, A., Tiffee, J. C., Li, H. H., Mundy, G. R., & Boyce, B. F. (1996) · Nature Medicine · doi:10.1038/nm1096-1132 · Cited by 813 · cited 3× · see citing works
“Opposite effects on osteoclast and osteoblast apoptosis have also been demonstrated for TGF-β (31, 62).”
BackgroundWang, X., Martindale, J. L., Liu, Y., & Holbrook, N. J. (1998) · Biochemical Journal · doi:10.1042/bj3330291 · Cited by 735 · 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
Self-citationEstablishment of an Osteocyte-like Cell Line, MLO-Y4
Kato, Y., Windle, J. J., Koop, B. A., Mundy, G. R., & Bonewald, L. F. (1997) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1997.12.12.2014 · Cited by 549 · see citing works
Chavassieux, P., ARLOT, M. E., Reda, C. V., Wei, L., Yates, A. J. P., & Meunier, P. J. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119668 · Cited by 523 · see citing works
Bisphosphonates in Bone Disease: From the Laboratory to the Patient
Fleisch, H. A. (1995) · LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) · Cited by 472 · see citing works
Schlegel, J., Peters, I., Orrenius, S., Miller, D. K., Thornberry, N. A., Yamin, T.-T., & Nicholson, D. W. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.4.1841 · Cited by 467 · see citing works
Bursch, W., Paffe, S., Putz, B., Barthel, G., & Schulte‐Hermann, R. (1990) · Carcinogenesis · doi:10.1093/carcin/11.5.847 · Cited by 444 · see citing works
Bisphosphonates act on rat bone resorption through the mediation of osteoblasts.
Sahni, M. S., Guenther, H. L., Fleisch, H. A., Collin, P., & Martin, T. J. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116422 · Cited by 411 · see citing works
Function of osteocytes in bone
Aarden, E. M., Nijweide, P. J., & Burger, E. H. (1994) · Journal of Cellular Biochemistry · doi:10.1002/jcb.240550304 · Cited by 410 · see citing works
Balena, R., Toolan, B. C., Shea, M., Markatos, A., Myers, E. R., Lee, S. C., Opas, E. E., Seedor, J. G., Klein, H., & Frankenfield, D. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116872 · Cited by 396 · see citing works
New Developments in the Pathogenesis and Treatment of Steroid-Induced Osteoporosis
Manolagas, S. C., & Weinstein, R. S. (1999) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1999.14.7.1061 · Cited by 385 · see citing works
Self-citationPeel, N. F. A., Moore, D., Barrington, N. A., Bax, D. E., & Eastell, R. (1995) · Annals of the Rheumatic Diseases · doi:10.1136/ard.54.10.801 · Cited by 377 · see citing works
Hughes, D. E., MacDonald, B. R., Russell, R. G. G., & Gowen, M. (1989) · Journal of Clinical Investigation · doi:10.1172/jci114100 · Cited by 357 · see citing works
Grignani, F., Kinsella, T. J., Mencarelli, A., Valtieri, M., Riganelli, D., Grignani, F., Lanfrancone, L., Peschle, C., Nolan, G. P., & Pelicci, P. G. (1998) · PubMed · Cited by 349 · see citing works
Jilka, R. L., Weinstein, R. S., Takahashi, K., PARFITT, A. M., & Manolagas, S. C. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118600 · Cited by 339 · see citing works
Self-citationPARFITT, 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
Self-citationBisphosphonates induce osteoblasts to secrete an inhibitor of osteoclast-mediated resorption.
Vitté, C., Fleisch, H. A., & Guenther, H. L. (1996) · Endocrinology · doi:10.1210/endo.137.6.8641182 · Cited by 281 · see citing works
Giuliani, N., Pedrazzoni, M., Negri, G., Passeri, G., Impicciatore, M., & Girasole, G. (1998) · Bone · doi:10.1016/s8756-3282(98)00033-7 · Cited by 269 · see citing works
Identification of apoptotic changes in osteocytes in normal and pathological human bone
Noble, B. S., Stevens, H., Loveridge, N., & Reeve, J. (1997) · Bone · doi:10.1016/s8756-3282(96)00365-1 · Cited by 230 · see citing works
Gardner, A. M., & Johnson, G. L. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.24.14560 · Cited by 215 · see citing works
Jilka, R. L., Takahashi, K., Munshi, M., Williams, D. C., Roberson, P. K., & Manolagas, S. C. (1998) · Journal of Clinical Investigation · doi:10.1172/jci1039 · Cited by 213 · see citing works
Self-citationBellido, T., Borba, V. Z. C., Roberson, P. K., & Manolagas, S. C. (1997) · Endocrinology · doi:10.1210/endo.138.9.5364 · Cited by 212 · see citing works
Self-citationForrest, S., Ng, K. W., Findlay, D. M., Michelangeli, V. P., Livesey, S. A., Partridge, N. C., Zajac, J. D., & Martin, T. J. (1985) · Calcified Tissue International · doi:10.1007/bf02557679 · Cited by 190 · see citing works
The structure of bone tissues and the cellular control of their deposition.
Marotti, G. (1997) · PubMed · Cited by 185 · see citing works
Dexamethasone induces apoptosis of multiple myeloma cells in a JNK/SAP kinase independent mechanism
Chauhan, D., Pandey, P., Ogata, A., Teoh, G. K. H., Treon, S. P., Urashima, M., Kharbanda, S. M., & Anderson, K. C. (1997) · Oncogene · doi:10.1038/sj.onc.1201253 · Cited by 170 · see citing works
Bisphosphonates act on osteoblastic cells and inhibit osteoclast formation in mouse marrow cultures
Nishikawa, M., Akatsu, T., Katayama, Y., Yasutomo, Y., Kado, S., Kugai, N., Yamamoto, M., & Nagata, N. (1996) · Bone · doi:10.1016/8756-3282(95)00426-2 · Cited by 161 · see citing works
Storm, T., Steiniche, T., Thamsborg, G., & Melsen, F. (1993) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650080211 · Cited by 160 · see citing works
Drug dosage in laboratory animals: A handbook
(1966) · Food and Cosmetics Toxicology · doi:10.1016/s0015-6264(66)80455-8 · Cited by 148 · see citing works
Weinstein, R. S., Jilka, R. L., Parfitt, A. M., & Manolagas, S. C. (1997) · Endocrinology · doi:10.1210/endo.138.9.5359 · Cited by 126 · see citing works
Self-citationPrevention of Corticosteroid-Induced Osteoporosis with Alendronate in Sarcoid Patients
Gonnelli, S., Rottoli, P., Cepollaro, C., Pondrelli, C. R., Cappiello, V., Vagliasindi, M., & Gennari, C. (1997) · Calcified Tissue International · doi:10.1007/s002239900352 · Cited by 124 · see citing works
Structure-function relationships in the osteocyte.
Marotti, G., Canè, V., Palazzini, S., & Palumbo, C. (1990) · IRIS UNIMORE (University of Modena and Reggio Emilia) · Cited by 108 · see citing works
Hall, B. K. (1990) · Medical Entomology and Zoology · Cited by 104 · see citing works
Boyce, R. W., Paddock, C. L., Gleason, J. R., Sletsema, W. K., & Eriksen, E. F. (1995) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650100207 · Cited by 99 · see citing works
Clevenger, C. V., Thickman, K. R., Ngo, W., Chang, W., Takayama, S.-I. J., & Reed, J. C. (1997) · Molecular Endocrinology · doi:10.1210/mend.11.5.9925 · Cited by 97 · see citing works
van Beek, E. R., Löwik, C. W. G. M., Que, I., & Papapoulos, S. E. (1996) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650111016 · Cited by 94 · see citing works
Verheijen, M. H. G., & Defize, L. H. K. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.6.3423 · Cited by 90 · see citing works
Wu, W. X., Hong, X., Zhang, Q., Buchwalder, L. F., & Nathanielsz, P. W. (1997) · Endocrinology · doi:10.1210/endo.138.9.5394 · Cited by 72 · see citing works
Prevention of glucocorticoid-induced osteoporosis
Reid, I. R., SCHOOLER, B. A., & Stewart, A. W. (1990) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650050611 · Cited by 69 · see citing works
Inhibition of etoposide-induced apoptosis with peptide aldehyde inhibitors of proteasome
Stefanelli, C., Bonavita, F., Stanić, I., Pignatti, C., Farruggia, G., Masotti, L., Guarnieri, C., & Caldarera, C. M. (1998) · Biochemical Journal · doi:10.1042/bj3320661 · Cited by 59 · see citing works
Effects of bisphosphonates and inorganic pyrophosphate on osteogenesis in vitro
Tenenbaum, H. C., Torontali, M., & Sukhu, B. D. (1992) · Bone · doi:10.1016/8756-3282(92)90205-b · Cited by 58 · see citing works
Farley, J. R., Wergedal, J. E., Hall, S. L., Herring, S., & Tarbaux, N. M. (1991) · Calcified Tissue International · doi:10.1007/bf02556147 · Cited by 55 · see citing works
Sphingosine Kinase Mediates Cyclic AMP Suppression of Apoptosis in Rat Periosteal Cells
Machwate, M., Rodan, S. B., Rodan, G. A., & Harada, S.-I. (1998) · Molecular Pharmacology · doi:10.1124/mol.54.1.70 · Cited by 54 · see citing works
Falcini, F., Trapani, S., Ermini, M., & Brandi, M. L. (1996) · Calcified Tissue International · doi:10.1007/bf02526882 · Cited by 48 · see citing works
SAKAGAMI, Y., Girasole, G., Yu, X., Boswell, H. S., & Manolagas, S. C. (1993) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650080706 · Cited by 46 · see citing works
Self-citationExploiting and Bypassing the Bone Remodeling Cycle to Optimize the Treatment of Osteoporosis
Dempster, D. W. (1997) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1997.12.8.1152 · Cited by 40 · see citing works
Iida‐Klein, A., Yee, D. C., Brandli, D. W., Mirikitani, E. J., & Hahn, T. J. (1992) · Endocrinology · doi:10.1210/endo.130.1.1309338 · Cited by 25 · see citing works
Pompeiano, M., Hvala, M., & Chun, J. J. M. (1998) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4400403 · Cited by 21 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- [2]2. Papapoulos, S. 1996. Bisphosphonates. Pharmacology and use in the treatment of osteoporosis. In Osteoporosis. R. Marcus, D. Feldman, and J. Kelsey, editors. Academic Press. San Diego, CA. 1209-1234.
- [4]4. Azria, M., and Avioli, L.V. 1996. Calcitonin. In Principles of bone biology. J.P. Bilezikian, L.G. Raisz, and G.A. Rodan, editors. Academic Press. San Diego, CA. 1083-1097.
- [18]18. Nijweide, P.J., Burger, E.H., Klein-Nulend, J., and Van Der Plas, A. 1996. The osteocyte. In Principles of bone biology. J.P. Bilezikian, L.G. Raisz, and G.A. Rodan, editors. Academic Press. San Diego, CA. 115-126.
Cited by
Sorted by citations
Manolagas, S. C. (2000) · Endocrine Reviews · doi:10.1210/edrv.21.2.0395 · Cited by 2,575 · see citing works
Self-citationBisphosphonates: Mechanism of action and role in clinical practice
Drake, M. T., Clarke, B. L., & Khosla, S. (2008) · Mayo Clinic Proceedings · doi:10.4065/83.9.1032 · Cited by 1,644 · see citing works
Russell, R. G. G., Watts, N. B., Ebetino, F. H., & Rogers, M. J. (2008) · Osteoporosis International · doi:10.1007/s00198-007-0540-8 · Cited by 1,407 · see citing works
Nongenotropic, Sex-Nonspecific Signaling through the Estrogen or Androgen Receptors
Kousteni, S., Bellido, T., Plotkin, L. I., O’Brien, C. A., Bodenner, D., Li, H., Han, K., Gregorio, G. B. D., Katzenellenbogen, J. A., Katzenellenbogen, B. S., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00268-9 · Cited by 1,163 · see citing works
Self-citationBisphosphonates: The first 40years
Russell, R. G. G. (2011) · Bone · doi:10.1016/j.bone.2011.04.022 · Cited by 1,134 · see citing works
The Osteocyte: An Endocrine Cell … and More
Dallas, S. L., Prideaux, M., & Bonewald, L. F. (2013) · Endocrine Reviews · doi:10.1210/er.2012-1026 · Cited by 1,042 · see citing works
Cyclic Administration of Pamidronate in Children with Severe Osteogenesis Imperfecta
Glorieux, F. H., Bishop, N. J., Plotkin, H., Chabot, G., Lanoue, G., & Travers, R. (1998) · New England Journal of Medicine · doi:10.1056/nejm199810013391402 · Cited by 1,011 · see citing works
The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis
Staa, T. P. V., Staa, T. P. V., Staa, T. P. V., Leufkens, H. G. M., & Cooper, C. (2002) · Osteoporosis International · doi:10.1007/s001980200108 · Cited by 1,294 · see citing works
The Epidemiology of Distal Radius Fractures
Nellans, K. W., Kowalski, E., & Chung, K. C. (2012) · Hand Clinics · doi:10.1016/j.hcl.2012.02.001 · Cited by 902 · see citing works
Intravenous Zoledronic Acid in Postmenopausal Women with Low Bone Mineral Density
Reid, I. R., Brown, J. P., Burckhardt, P., Horowitz, Z. D., Richardson, P. A., Trechsel, U., Widmer, A., Devogelaer, J.-P., Kaufman, J., Jaeger, P., et al. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa011807 · Cited by 875 · see citing works
Kearns, A. E., Khosla, S., & Kostenuik, P. J. (2008) · Endocrine Reviews · doi:10.1210/er.2007-0014 · Cited by 824 · see citing works
O’Brien, C. A., Jia, D., Plotkin, L. I., Bellido, T., Powers, C. C., Stewart, S. A., Manolagas, S. C., & Weinstein, R. S. (2003) · Endocrinology · doi:10.1210/en.2003-0990 · Cited by 771 · see citing works
Self-citationBeyond the gap: functions of unpaired connexon channels
Goodenough, D. A., & Paul, D. L. (2003) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1072 · Cited by 729 · see citing works
Denosumab and bisphosphonates: Different mechanisms of action and effects
Baron, R., Ferrari, S., & Russell, R. G. G. (2010) · Bone · doi:10.1016/j.bone.2010.11.020 · Cited by 716 · see citing works
Glucocorticoid-Induced Bone Disease
Weinstein, R. S. (2011) · New England Journal of Medicine · doi:10.1056/nejmcp1012926 · Cited by 698 · see citing works
Self-citationSignaling and transcriptional regulation in osteoblast commitment and differentiation
Huang, W. (2007) · Frontiers in bioscience · doi:10.2741/2296 · Cited by 649 · see citing works
Physiological Bone Remodeling: Systemic Regulation and Growth Factor Involvement
Siddiqui, J. A., & Partridge, N. C. (2016) · Physiology · doi:10.1152/physiol.00061.2014 · Cited by 546 · see citing works
Manolagas, S. C. (2002) · Recent Progress in Hormone Research · doi:10.1210/rp.57.1.385 · Cited by 523 · see citing works
Self-citationBisphosphonates: Mode of Action and Pharmacology
Russell, R. G. G. (2007) · PEDIATRICS · doi:10.1542/peds.2006-2023h · Cited by 504 · see citing works
Aguirre, J. I., Plotkin, L. I., Stewart, S. A., Weinstein, R. S., Parfitt, A. M., Manolagas, S. C., & Bellido, T. (2006) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.060107 · Cited by 494 · see citing works
Self-citationThe Pathogenesis of Bisphosphonate-Related Osteonecrosis of the Jaw: So Many Hypotheses, So Few Data
Allen, M. R., & Burr, D. B. (2009) · Journal of Oral and Maxillofacial Surgery · doi:10.1016/j.joms.2009.01.007 · Cited by 449 · see citing works
Periosteum: biology, regulation, and response to osteoporosis therapies
Allen, M. R., Hock, J. M., & Burr, D. B. (2004) · Bone · doi:10.1016/j.bone.2004.07.014 · Cited by 433 · see citing works
Blood flow controls bone vascular function and osteogenesis
Ramasamy, S. K., Kusumbe, A. P., Schiller, M., Zeuschner, D., Bixel, M. G., Milia, C., Gamrekelashvili, J., Limbourg, A., Medvinsky, A., Santoro, M. M., et al. (2016) · Nature Communications · doi:10.1038/ncomms13601 · Cited by 433 · see citing works
Glucocorticoid-induced osteonecrosis
Weinstein, R. S. (2011) · Endocrine · doi:10.1007/s12020-011-9580-0 · Cited by 430 · see citing works
Self-citationRussell, R. G. G. (2006) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1346.041 · Cited by 409 · see citing works
Almeida, M., Li, H., Bellido, T., Manolagas, S. C., & Kousteni, S. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m502168200 · Cited by 394 · see citing works
Self-citationOsteoblast proliferation and maturation by bisphosphonates
Im, G., Qureshi, S. A., Kenney, J., Rubash, H. E., & Shanbhag, A. S. (2004) · Biomaterials · doi:10.1016/j.biomaterials.2003.11.024 · Cited by 393 · see citing works
Russell, R. G. G., Xia, Z., Dunford, J. E., Oppermann, U. C. T., Kwaasi, A. A. A., Hulley, P. A., Kavanagh, K. L., Triffitt, J. T., Lundy, M. W., Phipps, R. J., et al. (2007) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1402.089 · Cited by 399 · see citing works
Association of low-energy femoral fractures with prolonged bisphosphonate use: a case control study
Lenart, B. A., Neviaser, A. S., Lyman, S. L., Chang, C. C., Edobor‐Osula, F., Steele, B., van der Meulen, M. C. H., Lorich, D. G., & Lane, J. M. (2008) · Osteoporosis International · doi:10.1007/s00198-008-0805-x · Cited by 383 · see citing works
Osteocyte-Driven Bone Remodeling
Bellido, T. (2014) · Calcified Tissue International · doi:10.1007/s00223-013-9774-y · Cited by 384 · see citing works
Self-citationRiggs, B. L., & PARFITT, A. M. (2005) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.041114 · Cited by 379 · see citing works
Self-citationBellido, T., Ali, A., Plotkin, L. I., Fu, Q., Gubrij, I. B., Roberson, P. K., Weinstein, R. S., O’Brien, C. A., Manolagas, S. C., & Jilka, R. L. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m307444200 · Cited by 377 · see citing works
Self-citationThe role of the wnt/β-catenin signaling pathway in formation and maintenance of bone and teeth
Duan, P., & Bonewald, L. F. (2016) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2016.05.015 · Cited by 374 · see citing works
Reinholz, G. G., Getz, B., Pederson, L. G., Sanders, E. S., Subramaniam, M., Ingle, J. N., & Spelsberg, T. C. (2000) · PubMed · Cited by 367 · see citing works
Glucocorticoid-Induced Osteoporosis and Osteonecrosis
Weinstein, R. S. (2012) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2012.04.004 · Cited by 367 · see citing works
Self-citationTao, S., Yuan, T., Rui, B., Zhu, Z., Guo, S., & Zhang, C. (2017) · Theranostics · doi:10.7150/thno.17450 · Cited by 345 · see citing works
Transduction of Cell Survival Signals by Connexin-43 Hemichannels
Plotkin, L. I., Manolagas, S. C., & Bellido, T. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m108625200 · Cited by 334 · see citing works
Self-citationWeinstein, R. S., Chen, J., Powers, C. C., Stewart, S. A., Landes, R. D., Bellido, T., Jilka, R. L., PARFITT, A. M., & Manolagas, S. C. (2002) · Journal of Clinical Investigation · doi:10.1172/jci14538 · Cited by 396 · see citing works
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Zhao, S., Kato, Y., Zhang, Y., Harris, S., Ahuja, S. S., & Bonewald, L. F. (2002) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2002.17.11.2068 · Cited by 322 · see citing works
Ambrogini, E., Almeida, M., Martín-Millán, M., Paik, J.-H., DePinho, R. A., Li, H., Goellner, J. J., Weinstein, R. S., Jilka, R. L., O’Brien, C. A., et al. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2009.12.009 · Cited by 312 · see citing works
Self-citationViereck, 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
von Knoch, F., Jaquiéry, C., Kowalsky, M. S., Schaeren, S., Alabre, C. I., Martín, I., Rubash, H. E., & Shanbhag, A. S. (2005) · Biomaterials · doi:10.1016/j.biomaterials.2005.04.059 · Cited by 287 · see citing works
Martin-Millan, M., Almeida, M., Ambrogini, E., Han, L., Zhao, H., Weinstein, R. S., Jilka, R. L., O'Brien, C. A., & Manolagas, S. C. (2010) · Molecular Endocrinology · doi:10.1210/me.2009-0354 · Cited by 282 · see citing works
Self-citationWeinstein, R. S., Wan, C., Liu, Q., Wang, Y., Almeida, M., O’Brien, C. A., Thostenson, J., Roberson, P. K., Boskey, A. L., Clemens, T. L., et al. (2009) · Aging Cell · doi:10.1111/j.1474-9726.2009.00545.x · Cited by 276 · see citing works
Self-citationBivi, N., Condon, K. W., Allen, M. R., Farlow, N., Passeri, G., Brun, L. R., Rhee, Y., Bellido, T., & Plotkin, L. I. (2012) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.548 · Cited by 261 · see citing works
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Rochefort, G. Y., Pallu, S., & Benhamou, C. L. (2010) · Osteoporosis International · doi:10.1007/s00198-010-1194-5 · Cited by 268 · see citing works
Peter, B., Pioletti, D. P., Laı̈b, S., Bujoli, B., Pilet, P., Janvier, P., Guicheux, J., Zambelli, P., Bouler, J., & Gauthier, O. (2004) · Bone · doi:10.1016/j.bone.2004.10.004 · Cited by 269 · see citing works
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Delgado‐Calle, J., & Bellido, T. (2021) · Physiological Reviews · doi:10.1152/physrev.00043.2020 · Cited by 269 · see citing works
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Miura, M., Chen, X., Allen, M. R., Bi, Y., Gronthos, S., Seo, B., Lakhani, S. A., Flavell, R. A., Feng, X., Robey, P. G., et al. (2004) · Journal of Clinical Investigation · doi:10.1172/jci20427 · Cited by 262 · see citing works
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van Staa, T. P. (2006) · Calcified Tissue International · doi:10.1007/s00223-006-0019-1 · Cited by 257 · see citing works
Age-Related Bone Loss: Old Bone, New Facts
Chan, G. K., & Duque, G. (2002) · Gerontology · doi:10.1159/000048929 · Cited by 259 · see citing works
Glucocorticoids and bone: consequences of endogenous and exogenous excess and replacement therapy
Hardy, R. S., Zhou, H., Seibel, M. J., & Cooper, M. S. (2018) · Endocrine Reviews · doi:10.1210/er.2018-00097 · Cited by 258 · see citing works
Estrogen receptor-α signaling in osteoblast progenitors stimulates cortical bone accrual
Almeida, M., Iyer, S. V., Martín-Millán, M., Bartell, S. M., Han, L., Ambrogini, E., Onal, M., Xiong, J., Weinstein, R. S., Jilka, R. L., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci65910 · Cited by 253 · see citing works
Self-citationKimmel, D. B. (2007) · Journal of Dental Research · doi:10.1177/154405910708601102 · Cited by 250 · see citing works
Clines, G. A., & Guise, T. A. (2005) · Endocrine Related Cancer · doi:10.1677/erc.1.00543 · Cited by 249 · see citing works
Karsdal, M. A., Larsen, L., Engsig, M. T., Lou, H., Ferreras, M., Lochter, A., Delaissé, J., & Foged, N. T. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m207205200 · Cited by 249 · see citing works
Weinstein, R. S., & Manolagas, S. C. (2000) · The American Journal of Medicine · doi:10.1016/s0002-9343(99)00420-9 · Cited by 250 · see citing works
Self-citationHartmann, K., Koenen, M., Schauer, S., Wittig-Blaich, S., Ahmad, M., Baschant, U., & Tuckermann, J. P. (2016) · Physiological Reviews · doi:10.1152/physrev.00011.2015 · Cited by 249 · see citing works
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Coxon, F. P., Thompson, K., Roelofs, A. J., Ebetino, F. H., & Rogers, M. J. (2008) · Bone · doi:10.1016/j.bone.2007.12.225 · Cited by 241 · see citing works
Plotkin, L. I., Aguirre, J. I., Kousteni, S., Manolagas, S. C., & Bellido, T. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m412817200 · Cited by 239 · see citing works
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Rogers, M. J., Frith, J. C., Luckman, S. P., Coxon, F. P., Benford, H. L., Mönkkönen, J., Auriola, S. O. K., Chilton, K., & Russell, R. G. G. (1999) · Bone · doi:10.1016/s8756-3282(99)00070-8 · Cited by 236 · see citing works
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Paiva, K. B. S., & Granjeiro, J. M. (2017) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2017.05.001 · Cited by 237 · see citing works
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Iyer, S. V., Ambrogini, E., Bartell, S. M., Li, H., Roberson, P. K., de Cabo, R., Jilka, R. L., Weinstein, R. S., O’Brien, C. A., Manolagas, S. C., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci68049 · Cited by 232 · see citing works
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Allen, M. R., & Burr, D. B. (2008) · Journal of Oral and Maxillofacial Surgery · doi:10.1016/j.joms.2008.01.038 · Cited by 228 · see citing works
Glucocorticoid-induced osteoporosis: mechanisms, management, and future perspectives
Seibel, M. J., Cooper, M. S., & Zhou, H. (2013) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(13)70045-7 · Cited by 230 · see citing works
Osteocyte apoptosis and control of bone resorption following ovariectomy in mice
Emerton, K. B., Hu, B., Woo, A. A., Sinofsky, A., Hernandez, C., Majeska, R. J., Jepsen, K. J., & Schaffler, M. B. (2010) · Bone · doi:10.1016/j.bone.2009.11.006 · Cited by 220 · see citing works
Salmon calcitonin: a review of current and future therapeutic indications
Chesnut, C. H., Azria, M., Silverman, S., Engelhardt, M., Olson, M., & Mindeholm, L. (2008) · Osteoporosis International · doi:10.1007/s00198-007-0490-1 · Cited by 216 · see citing works
Allen, M. R., & Burr, D. B. (2011) · Bone · doi:10.1016/j.bone.2010.10.159 · Cited by 219 · see citing works
Plotkin, L. I., Lezcano, V., Thostenson, J., Weinstein, R. S., Manolagas, S. C., & Bellido, T. (2008) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.080617 · Cited by 214 · see citing works
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Pofi, R., Caratti, G., Ray, D. W., & Tomlinson, J. (2023) · Endocrine Reviews · doi:10.1210/endrev/bnad016 · Cited by 225 · see citing works
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Jilka, R. L., Weinstein, R. S., PARFITT, A. M., & Manolagas, S. C. (2007) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.070518 · Cited by 211 · see citing works
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de Nijs, R. N. J., Jacobs, J. W. G., Lems, W. F., Laan, R., Algra, A., Huisman, A.-M., Buskens, E., Laet, C. E. D. H. D., Oostveen, A. C. M., Geusens, P., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa053569 · Cited by 207 · see citing works
Kitase, Y., Barragan, L., Qing, H., Kondoh, S., Jiang, J. X., Johnson, M. L., & Bonewald, L. F. (2010) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.168 · Cited by 199 · see citing works
Aminobisphosphonates Cause Osteoblast Apoptosis and Inhibit Bone Nodule Formation In Vitro
Idris, A. I., Rojas, J., Greig, I. R., Hof, R. V., & Ralston, S. H. (2008) · Calcified Tissue International · doi:10.1007/s00223-008-9104-y · Cited by 203 · see citing works
Biology of the basic multicellular unit and the pathophysiology of osteoporosis
Jilka, R. L. (2003) · Medical and Pediatric Oncology · doi:10.1002/mpo.10334 · Cited by 203 · see citing works
Involvement of the gut microbiota and barrier function in glucocorticoid-induced osteoporosis
Schepper, J. D., Collins, F., Rios-Arce, N. D., Kang, H. J., Schaefer, L., Gardinier, J. D., Raghuvanshi, R., Quinn, R. A., Britton, R., Parameswaran, N., et al. (2020) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3947 · Cited by 199 · see citing works
Verborgt, O., Tatton, N. A., Majeska, R. J., & Schaffler, M. B. (2002) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2002.17.5.907 · Cited by 192 · see citing works
Noninvasive Loading of the Murine Tibia: An In Vivo Model for the Study of Mechanotransduction
Gross, T. S., Srinivasan, S., Liu, C. C., Clemens, T. L., & Bain, S. D. (2002) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2002.17.3.493 · Cited by 193 · see citing works
Cell Death in Chondrocytes, Osteoblasts, and Osteocytes
Komori, T. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17122045 · Cited by 176 · see citing works
Heino, T. J., Hentunen, T. A., & Väänänen, H. K. (2002) · Journal of Cellular Biochemistry · doi:10.1002/jcb.10109 · Cited by 191 · see citing works
Glucocorticoid induced autophagy in osteocytes
Xia, X., Kar, R., Gluhak-Heinrich, J., Yao, W., Lane, N. E., Bonewald, L. F., Biswas, S. K., Lo, W.-K., & Jiang, J. X. (2010) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.160 · Cited by 193 · 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
Self-citationFracture Healing in the Setting of Endocrine Diseases, Aging, and Cellular Senescence
Saul, D., & Khosla, S. (2022) · Endocrine Reviews · doi:10.1210/endrev/bnac008 · Cited by 185 · see citing works
Osteoclastogenesis, Bone Resorption, and Osteoclast‐Based Therapeutics
Zaidi, M., Blair, H. C., Moonga, B., Abe, E., & Huang, C. L. (2003) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2003.18.4.599 · Cited by 193 · see citing works
Pharmacologic Stem Cell Based Intervention as a New Approach to Osteoporosis Treatment in Rodents
Yamaza, T., Miura, Y., Bi, Y., Liu, Y., Akiyama, K., Sonoyama, W., Patel, V., Gutkind, J. S., Young, M. F., Gronthos, S., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002615 · Cited by 176 · see citing works
Apoptosis in Autoimmune Diseases.
Eguchi, K. (2001) · Internal Medicine · doi:10.2169/internalmedicine.40.275 · Cited by 168 · see citing works
Glucocorticoids and bone: Local effects and systemic implications
Henneicke, H., Gasparini, S. J., Brennan-Speranza, T. C., Zhou, H., & Seibel, M. J. (2014) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2013.12.006 · Cited by 168 · see citing works
Roelofs, A. J., Coxon, F. P., Ebetino, F. H., Lundy, M. W., Henneman, Z. J., Nancollas, G. H., Sun, S., Błażewska, K. M., Bala, J. L. F., Kashemirov, B. A., et al. (2009) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.091009 · Cited by 163 · see citing works
Regulation of apoptosis in osteoclasts and osteoblastic cells
Xing, L., & Boyce, B. F. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.11.072 · Cited by 163 · see citing works
Plotkin, L. I., Manolagas, S. C., & Bellido, T. (2006) · Bone · doi:10.1016/j.bone.2006.02.060 · Cited by 163 · see citing works
Self-citationIn vitro and in vivo approaches to study osteocyte biology
Kalajzić, I., Matthews, B. G., Torreggiani, E., Harris, M. A., Pajevic, P. D., & Harris, S. E. (2012) · Bone · doi:10.1016/j.bone.2012.09.040 · Cited by 161 · see citing works
Beyond gap junctions: Connexin43 and bone cell signaling
Plotkin, L. I., & Bellido, T. (2012) · Bone · doi:10.1016/j.bone.2012.09.030 · Cited by 153 · see citing works
Self-citationGlucocorticoid dose determines osteocyte cell fate
Jia, J., Yao, W., Guan, M., Dai, W., Shahnazari, M., Kar, R., Bonewald, L., Jiang, J. X., & Lane, N. E. (2011) · The FASEB Journal · doi:10.1096/fj.11-182519 · Cited by 157 · see citing works
Alendronate Has an Anabolic Effect on Bone Through the Differentiation of Mesenchymal Stem Cells
Duque, G., & Rivas, D. (2007) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.070701 · Cited by 156 · see citing works
Forty years of calcitonin—where are we now? A tribute to the work of Iain Macintyre, FRS
Zaidi, M., Inzerillo, A. M., Moonga, B. S., Bevis, P. J. R., & Huang, C. L.-H. (2002) · Bone · doi:10.1016/s8756-3282(02)00688-9 · Cited by 151 · see citing works
Chen, X., Shi, S., Xu, T., Robey, P. G., & Young, M. F. (2002) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2002.17.2.331 · Cited by 150 · see citing works
Mackie, P. S., Fisher, J. L., Zhou, H., & Choong, P. (2001) · British Journal of Cancer · doi:10.1054/bjoc.2000.1679 · Cited by 149 · see citing works
- Authors
- Plotkin, L. I., Weinstein, R. S., Parfitt, A. M., Roberson, P. K., Manolagas, S. C., & Bellido, T.
- Affiliations
- University of Arkansas for Medical Sciences (US)
- Central Arkansas Veterans Healthcare System (US)
- Corresponding author
- Bellido, Teresita
- Venue
- Journal of Clinical Investigation
- Published
- 1999-11-15
- Volume
- 104
- Issue
- 10
- Pages
- 1363-1374
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC409837
- OpenAlex
- W2170680219
- Cited by
- 890
- References
- 62
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 11 · 2023: 13 · 2022: 19 · 2021: 15 · 2020: 21 · 2019: 24 · 2018: 24 · 2017: 29 · 2016: 41 · 2015: 26 · 2014: 54 · 2013: 44 · 2012: 40
- FWCI
- 11.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ar043003-05)
- National Institute on Aging (P01AG/AMS13918, P01AG013918)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01 AR43003, R01AR046191)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Oncology › Bone health and treatments
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Keywords
- bisphosphonates, calcitonin, osteocyte apoptosis, osteoblast apoptosis, glucocorticoid-induced osteoporosis, alendronate, etidronate, pamidronate, extracellular signal-regulated kinase, ERK1/2 phosphorylation, dexamethasone, TNF-α, etoposide, prednisolone, MLO-Y4 cells, trabecular bone
- MeSH terms
- Pamidronate, Animals, Calcitonin, Cell Line, Cells, Cultured, Dexamethasone, Diphosphonates, Etoposide, Osteoblasts, Osteocytes, Prednisolone, Skull, Etidronic Acid, Tumor Necrosis Factor-alpha, Apoptosis, Alendronate, In Situ Nick-End Labeling, Mice
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