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Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone.
Open accessAbstract
Glucocorticoid-induced bone disease is characterized by decreased bone formation and in situ death of isolated segments of bone (osteonecrosis) suggesting that glucocorticoid excess, the third most common cause of osteoporosis, may affect the birth or death rate of bone cells, thus reducing their numbers. To test this hypothesis, we administered prednisolone to 7-mo-old mice for 27 d and found decreased bone density, serum osteocalcin, and cancellous bone area along with trabecular narrowing. These changes were accompanied by diminished bone formation and turnover, as determined by histomorphometric analysis of tetracycline-labeled vertebrae, and impaired osteoblastogenesis and osteoclastogenesis, as determined by ex vivo bone marrow cell cultures. In addition, the mice exhibited a threefold increase in osteoblast apoptosis in vertebrae and showed apoptosis in 28% of the osteocytes in metaphyseal cortical bone. As in mice, an increase in osteoblast and osteocyte apoptosis was documented in patients with glucocorticoid-induced osteoporosis. Decreased production of osteoclasts explains the reduction in bone turnover, whereas decreased production and apoptosis of osteoblasts would account for the decline in bone formation and trabecular width. Furthermore, accumulation of apoptotic osteocytes may contribute to osteonecrosis. These findings provide evidence that glucocorticoid-induced bone disease arises from changes in the numbers of bone cells.
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“A high level of glucocorticoid in smokers alters bone metabolism and decreases bone mass either directly by changing the osteoblast and osteoclast activities or indirectly by altering the gastrointestinal absorption and renal reabsorption of calcium [39–42].”
From The Effect of Tobacco Smoking on Bone Mass: An Overview of Pathophysiologic Mechanisms (2018) · cites this paper as [39]
Experimental — accuracy not yet measuredIn the citing paper
“In mice, BMD loss with prednisolone was associated with decreased osteocalcin and decreased bone formation, with no histological or biochemical evidence for increased bone resorption (251).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [251]
In the citing paper
“bone marrow harvested from mice treated with prednisolone showed reduced osteoclastogenic potential (251).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [251]
In the citing paper
“One important component of glucocorticoid biology that is lacking in most cell culture models is the marked depletion of osteoblast numbers in animals treated with glucocorticoids (251).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [251]
In the citing paper
“Bone marrow harvested from mice treated with prednisolone was shown to have markedly reduced osteoblastogenic capacity (251).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [251]
In the citing paper
“Glucocorticoids can also inhibit osteoblast differentiation (249 -251), osteoblast attachment to bone matrix (252), and osteoblast production of IGF-I (253).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [251]
In the citing paper
“The prednisolonerelated increase in bone volume in rats, confirmed in a study described immediately below (262), is not consistent with histological data from patients with glucocorticoid-induced osteoporosis (194) and is a recognized limitation of the model (251).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [251]
In the citing paper
“Glucocorticoids decrease BMD in rats (262, 263), mice (251), and minipigs (264).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [251]
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Cites
PARFITT, A. M., Drezner, M. K., Glorieux, F. H., Kanis, J. А., Malluche, H. H., Meunier, P. J., Ott, S. M., & Recker, R. R. (1987) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650020617 · Cited by 5,344
Self-citationBone Histomorphometry : Standardization of Nomenclature, Symbols, and Units
PARFITT, A. M., Drezner, M. K., Glorieux, F. H., Kanis, J. А., Malluche, H. H., Meunier, P. J., Ott, S. M., & Recker, R. R. (1987) · Journal of Bone and Mineral Research · Cited by 3,258
Self-citationThe Fire of Life: An Introduction to Animal Energetics
Kleiber, M. (1975) · Medical Entomology and Zoology · Cited by 2,529
PARFITT, A. M., Mathews, C. H. E., Villanueva, A. R., Kleerekoper, M., Frame, B., & Rao, D. S. (1983) · Journal of Clinical Investigation · doi:10.1172/jci111096 · Cited by 1,542
Self-citationIncreased Osteoclast Development After Estrogen Loss: Mediation by Interleukin-6
Jilka, R. L., Hangoc, G., Girasole, G., Passeri, G., Williams, D. C., Abrams, J. S., Boyce, B. F., Broxmeyer, H. E., & Manolagas, S. C. (1992) · Science · doi:10.1126/science.1621100 · Cited by 1,440
Self-citationIdiopathic bone necrosis of the femoral head. Early diagnosis and treatment
Ficat, R. P. (1985) · Journal of Bone and Joint Surgery - British Volume · doi:10.1302/0301-620x.67b1.3155745 · Cited by 1,339
Parfitt, A. M. (1994) · Journal of Cellular Biochemistry · doi:10.1002/jcb.240550303 · Cited by 1,001
Self-citationNontraumatic Necrosis of Bone (Osteonecrosis)
Desforges, J. F., & Mankin, H. J. (1992) · New England Journal of Medicine · doi:10.1056/nejm199205283262206 · Cited by 965
Cushing, H. (1964) · Journal of neurosurgery · doi:10.3171/jns.1964.21.4.0318 · Cited by 849
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 · cited 3×
“In addition, TUNEL has been used with DNA fragmentation and immunohistochemical studies to demonstrate apoptosis of osteoblastic cells and osteoblasts both in vitro and in vivo (8, 20).”
BackgroundMethodSelf-citation
Flagged first, then by citations
4 of the 56 references couldn’t be matched to a known paper.
Research works printed but not linked: 3
- [11]11. Cope, C.L. 1972. The synthetic analogues. In Adrenal Steroids and Dis- ease. Lippincott, Philadelphia, PA. 488-491.
- [17]17. Owen, M. 1985. Lineage of osteogenic cells and their relationship to the stromal system. In Bone and Mineral Research. Volume 3. W.A. Peck, editor. Elsevier, Amsterdam. 1-25.
- [42]42. Manolagas, S.C., R.L. Jilka, T. Bellido, C.A. O'Brien, and A.M. Parfitt. 1996. Interleukin-6-type cytokines and their receptors. In Principles of Bone Bi- ology. J.P. Bilezikian, L.G. Raisz, and G.A. Rodan, editors. Academic Press, San Diego, CA. 701-713.
Cited by
Sorted by citations
Manolagas, S. C. (2000) · Endocrine Reviews · doi:10.1210/edrv.21.2.0395 · Cited by 2,639
“loss of estrogen, or glucocorticoid excess (130), could increase”
BackgroundSelf-citationMechanisms involved in the side effects of glucocorticoids
SCHACKE, H. (2002) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(02)00297-8 · Cited by 1,847
Immune regulation by glucocorticoids
Cain, D. W., & Cidlowski, J. A. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2017.1 · Cited by 1,846
Therapeutic Approaches to Bone Diseases
Rodan, G. A., & Martin, T. J. (2000) · Science · doi:10.1126/science.289.5484.1508 · Cited by 1,767
Hadjidakis, D., & Androulakis, I. I. (2006) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1365.035 · Cited by 1,531
Matrix-embedded cells control osteoclast formation
Xiong, J., Onal, M., Jilka, R. L., Weinstein, R. S., Manolagas, S. C., & O'Brien, C. A. (2011) · Nature Medicine · doi:10.1038/nm.2448 · Cited by 1,304
“And third, administration of glucocorticoids potently reduces the number of osteoblasts on bone, as well as the abundance of their precursors in the bone marrow, but not the number of osteoclast”
BackgroundSelf-citationUse of Inhaled Corticosteroids and Risk of Fractures
van Staa, T. P., Leufkens, H. G. M., & Cooper, C. C. (2001) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2001.16.3.581 · Cited by 1,297
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
“oid excess has been found to promote the apoptosis of osteoblasts [124].”
Feng, X., & McDonald, J. M. (2011) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-011110-130203 · Cited by 1,272
“GC levels promote apoptosis of osteocytes (Figure 4c) (118); GC-induced apoptosis of osteocytes is unlikely to significantly affect the ongoing bone-remodeling process (active BMUs).”
BackgroundUse of oral corticosteroids and risk of fractures
Van Staa, T. P., Leufkens, H. G. M., Abenhaim, L., Zhang, B., & Cooper, C. (2000) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2000.15.6.993 · Cited by 1,263
“(30) An alternative interpretation would be that a marked alteration in bone turnover, through induction of microarchitectural changes in bone quality, was responsible for the rapid change in fracture risk.”
BackgroundManolagas, S. C. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0024 · Cited by 1,234
Self-citationNongenotropic, 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
Self-citationOsteocytes, mechanosensing and Wnt signaling
Bonewald, L. F., & Johnson, M. L. (2008) · Bone · doi:10.1016/j.bone.2007.12.224 · Cited by 1,076
“We have further examined the role of theWnt/β-catenin signaling pathway in bone with regard to dexamethasone induced apoptosis of osteocytes, which has been postulated to be the major mechanism underlying glucocorticoid mediated osteoporosis [125,77].”
BackgroundLiu, D., Ahmet, A., Ward, L., Krishnamoorthy, P., Mandelcorn, E. D., Leigh, R., Brown, J. P., Cohen, A., & Kim, H. (2013) · Allergy, Asthma & Clinical Immunology · doi:10.1186/1710-1492-9-30 · Cited by 1,268
“GCs have been shown to stimulate osteoclastic activity initially (first 6–12 months of therapy), followed by a decrease in bone formation by suppressing osteoblastic activity in the bone marrow, decreasing osteoblast function and life span, and promoting the apoptosis of osteoblasts and osteocytes [11-13].”
BackgroundThe 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
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
“Although this dose is relatively high, our findings are consistent with previous evidence that the anabolic effect of 400 ng/g/d hPTH(1-34) in rats occurred without an increase in bone resorption (9).”
BackgroundMethodResultInfluentialSelf-citationTeriparatide or Alendronate in Glucocorticoid-Induced Osteoporosis
Saag, K. G., Shane, E., Boonen, S., Marín, F., Donley, D. W., Taylor, K. A., Dalsky, G. P., & Marcus, R. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa071408 · Cited by 914
Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin
Plotkin, L. I., Weinstein, R. S., Parfitt, A. M., Roberson, P. K., Manolagas, S. C., & Bellido, T. (1999) · Journal of Clinical Investigation · doi:10.1172/jci6800 · Cited by 890
“The TUNEL reaction was performed according to the manufacturer’s instructions, using 0.15% CuSO4 for color enhancement.”
BackgroundMethodResultInfluentialSelf-citationKearns, A. E., Khosla, S., & Kostenuik, P. J. (2008) · Endocrine Reviews · doi:10.1210/er.2007-0014 · Cited by 824
Pathogenesis and natural history of osteonecrosis
Assouline-Dayan, Y., Chang, C. C.-C., Greenspan, A., Shoenfeld, Y., & Gershwin, M. E. (2002) · Seminars in Arthritis and Rheumatism · doi:10.1053/sarh.2002.33724b · Cited by 818
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
“uted to glucocorticoid effects on osteoblastogenesis (10), osteo-”
BackgroundGlucocorticoids in T Cell Development and Function
Ashwell, J. D., Lu, F. W. M., & Vacchio, M. S. (2000) · Annual Review of Immunology · doi:10.1146/annurev.immunol.18.1.309 · Cited by 777
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
“, Decatur, GA) as previously described (3, 4, 15).”
BackgroundMethodResultInfluentialSelf-citationOsteoclasts: What Do They Do and How Do They Do It?
Teitelbaum, S. L. (2007) · The American Journal of Pathology · doi:10.2353/ajpath.2007.060834 · Cited by 730
Molecular and cellular mechanisms of the anabolic effect of intermittent PTH
Jilka, R. L. (2007) · Bone · doi:10.1016/j.bone.2007.03.017 · Cited by 736
“Consistent with this notion, the reduced osteoblast number and bone formation rate observed in mice and humans receiving glucocorticoids [31], as well as in aging mice [32], is associated with increased osteoblast apoptosis.”
BackgroundResultInfluentialSelf-citationSkeletal Involution by Age-associated Oxidative Stress and Its Acceleration by Loss of Sex Steroids
Almeida, M., Li, H., Martín-Millán, M., Plotkin, L. I., Stewart, S. A., Roberson, P. K., Kousteni, S., O’Brien, C. A., Bellido, T., PARFITT, A. M., et al. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m702810200 · Cited by 719
Self-citationKenkre, J. E., & Bassett, J. H. D. (2018) · Annals of Clinical Biochemistry International Journal of Laboratory Medicine · doi:10.1177/0004563218759371 · Cited by 775
“Increase in osteoblast and osteocyte apoptosis.(121) While glucocorticoids lead to reduced numbers of osteoclast progenitors, in the initial phase of glucocorticoidinduced bone loss, the lifespan of osteoclasts is prolonged.”
BackgroundGlucocorticoid-Induced Bone Disease
Weinstein, R. S. (2011) · New England Journal of Medicine · doi:10.1056/nejmcp1012926 · Cited by 711
Self-citationVan Staa, T. P., Laan, R. F., Barton, I. P., Cohen, S., Reid, D. M., & Cooper, C. (2003) · Arthritis & Rheumatism · doi:10.1002/art.11283 · Cited by 559
“Osteocyte apoptosis is prevalent in GC-induced osteoporosis (24), and preliminary results of an animal study demonstrated that osteocyte viability was an important determinant of bone strength independent of BMD (25).”
BackgroundResultInhibition of Osteoblast Differentiation by Tumor Necrosis Factor-α*
Gilbert, L., He, X., Farmer, P., Boden, S., Kozlowski, M., Rubin, J., & Nanes, M. S. (2000) · Endocrinology · doi:10.1210/endo.141.11.7739 · Cited by 555
Combs, T. P., Berg, A. H., Rajala, M. W., Klebanov, S., Iyengar, P., Jimenez-Chillaron, J. C., Patti, M. E., Klein, S. L., Weinstein, R. S., & Scherer, P. E. (2003) · Diabetes · doi:10.2337/diabetes.52.2.268 · Cited by 544
“prednisolone were implanted, as previously described (13).”
BackgroundSelf-citationManolagas, S. C. (2002) · Recent Progress in Hormone Research · doi:10.1210/rp.57.1.385 · Cited by 532
“Specifically, we have found that in rodents as well as in humans increased apoptosis of osteoblast and osteocytes is a key pathogenetic mechanism of the adverse effects of glucocorticoid excess on bone (Weinstein et al., 1998; Manolagas and Weinstein, 1999).”
BackgroundSelf-citationSclerostin Stimulates Osteocyte Support of Osteoclast Activity by a RANKL-Dependent Pathway
Wijenayaka, A. R., Kogawa, M., Lim, H. P., Bonewald, L. F., Findlay, D. M., & Atkins, G. J. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025900 · Cited by 503
“However, glucocorticoid-induced osteocyte apoptosis is associated with reduced osteoclastogenesis [63].”
BackgroundAguirre, 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
“BMD determinations by DXA (Hologic) were performed at 2-wk intervals.((7,9)) Groups of 8–12 mice that have reached adult peak bone mass (4–5 months old) were used for the experiments.”
BackgroundMethodSelf-citationPathogenesis of glucocorticoid-induced osteoporosis and options for treatment
Chotiyarnwong, P., & McCloskey, E. V. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-0341-0 · Cited by 489
Bone remodeling: an operational process ensuring survival and bone mechanical competence
Bolamperti, S., Villa, I., & Rubinacci, A. (2022) · Bone Research · doi:10.1038/s41413-022-00219-8 · Cited by 482
“Apoptosis exerts a significant effect on the number of osteoblasts producing bone matrix at a bone formation site.(283) The balance between the expression of proapoptotic factors Bim and Bak and the prosurvival factor Bcl determines the osteoblast life span and, therefore, bone volume and strength.”
BackgroundSikavitsas, V. I., Bancroft, G. N., Holtorf, H. L., Jansen, J. A., & Mikos, A. G. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2434367100 · Cited by 472
Glucocorticoid-induced osteoporosis: an update
Compston, J. E. (2018) · Endocrine · doi:10.1007/s12020-018-1588-2 · Cited by 494
“Direct effects of glucocorticoids on bone formation are mediated largely through upregulation of peroxisome proliferator-activated receptor gamma receptor 2 (PPARγ2) [24] and effects on the Wnt/βcatenin signaling pathway [25, 26].”
BackgroundRegulation of Osteoblast Formation and Function
Aubin, J. E. (2001) · Reviews in Endocrine and Metabolic Disorders · doi:10.1023/a:1010011209064 · Cited by 468
The 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
Rosiglitazone Causes Bone Loss in Mice by Suppressing Osteoblast Differentiation and Bone Formation
Ali, A., Weinstein, R. S., Stewart, S. A., PARFITT, A. M., Manolagas, S. C., & Jilka, R. L. (2005) · Endocrinology · doi:10.1210/en.2004-0735 · Cited by 444
“Variables were measured and reported as previously described (23, 25, 26) using the terminology recommended by the Histomorphometry Nomenclature Committee of American Society for Bone and Mineral Research (27).”
MethodSelf-citationYaccoby, S., Ling, W., Zhan, F., Walker, R. C., Barlogie, B., & Shaughnessy, J. D. (2006) · Blood · doi:10.1182/blood-2006-09-047712 · Cited by 429
Glucocorticoid-induced osteonecrosis
Weinstein, R. S. (2011) · Endocrine · doi:10.1007/s12020-011-9580-0 · Cited by 430
Self-citationRauch, A., Seitz, S., Baschant, U., Schilling, A., Illing, A., Stride, B. D., Kirilov, M., Mandic, V., Takacz, A., Schmidt-Ullrich, R., et al. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.05.005 · Cited by 423
Osteocytes as Dynamic Multifunctional Cells
Bonewald, L. F. (2007) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1402.018 · Cited by 457
Manolagas, S. C., & Parfitt, A. M. (2010) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2010.01.010 · Cited by 404
Self-citationGlucocorticoids Act Directly on Osteoclasts to Increase Their Life Span and Reduce Bone Density
Jia, D., O’Brien, C. A., Stewart, S. A., Manolagas, S. C., & Weinstein, R. S. (2006) · Endocrinology · doi:10.1210/en.2006-0459 · Cited by 394
“L1-L4 from wild-type and transgenic mice were fixed and embedded undecalcified in methyl methacrylate and stained for quantitative histological analysis as previously described (4, 5, 9).”
BackgroundMethodResultInfluentialSelf-citationApoptosis of Osteocytes in Glucocorticoid-Induced Osteonecrosis of the Hip
Weinstein, R. S., Nicholas, R. W., & Manolagas, S. C. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.8.6714 · Cited by 446
“In addition, TUNEL has been used with DNA fragmentation and immunohistochemical studies to demonstrate apoptosis of osteoblastic cells and osteoblasts both in vitro and in vivo ( 7 , 12, 13).”
BackgroundMethodInfluentialSelf-citationControl of Bone Mass and Remodeling by PTH Receptor Signaling in Osteocytes
O’Brien, C. A., Plotkin, L. I., Galli, C., Goellner, J. J., Gortázar, A. R., Allen, M. R., Robling, A. G., Bouxsein, M., Schipani, E., Turner, C. H., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002942 · Cited by 396
“Detection of apoptotic osteoblasts and osteocytes by in situ nickend labeling was performed as previously described [6,78].”
MethodSelf-citationGlucocorticoids suppress bone formation via the osteoclast.
Kim, H.-J. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28084 · Cited by 384
“Net bone mass represents the relative activities of osteoblasts and osteoclasts, and there is little question that GCs suppress bone-forming cells, in vivo, via a process involving accelerated apoptosis (1, 2).”
BackgroundNew 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 382
“sion on osteoclastogenesis); as well as by promotion of apoptosis of osteoblasts and osteocytes.((20)) Moreover, our work has demonstrated that the mouse, unlike the rat and other previously examined laboratory animals, is a faithful animal model of the glucocorticoid-induced bone loss in humans.”
BackgroundSelf-citationOsteocyte-Driven Bone Remodeling
Bellido, T. (2014) · Calcified Tissue International · doi:10.1007/s00223-013-9774-y · Cited by 384
“It is now recognized that decreased osteocyte viability accompanies not only the bone fragility syndrome that characterizes estrogen withdrawal but also glucocorticoid excess, mechanical disuse, and aging [34, 50, 51].”
Bellido, 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
Self-citationOverview: animal models of osteopenia and osteoporosis.
Jee, W. S. S., & Yao, W. (2001) · PubMed · Cited by 377
Alikhani, M., Alikhani, Z., Boyd, C. M., MacLellan, C. M., Raptis, M., Liu, R., Pischon, N., Trackman, P. C., Gerstenfeld, L. C., & Graves, D. T. (2006) · Bone · doi:10.1016/j.bone.2006.09.011 · Cited by 376
Transcriptional Regulatory Cascades in Runx2-Dependent Bone Development
Liu, T. M., & Lee, E. H. (2012) · Tissue Engineering Part B Reviews · doi:10.1089/ten.teb.2012.0527 · Cited by 377
Bone loss in inflammatory disorders
Hardy, R., & Cooper, M. S. (2009) · Journal of Endocrinology · doi:10.1677/joe-08-0568 · Cited by 373
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 372
“Inadequate numbers of osteoblasts and incomplete erosion cavity repair during bone remodeling are the main cause of the reduction in cancellous bone area, wall width, trabecular width and bone formation rate typically found in GIO (22).”
BackgroundSelf-citationLane, N. E., Yao, W., Balooch, M., Nalla, R. K., Balooch, G., Habelitz, S., Kinney, J. H., & Bonewald, L. F. (2006) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.051103 · Cited by 355
“We found greater numbers of apoptotic osteocytes in prednisolone-treated mice compared with the controls, but substantially less than reported by Weinstein et al.(14,25) Bellido et al.(36) reported in an in vitro study that GCs induced apoptosis of osteocytes.”
BackgroundMethodInfluentialKerachian, M. A., Séguin, C., & Harvey, E. J. (2009) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2009.02.007 · Cited by 350
“These changes were accompanied by diminished bone formation and turnover and impaired osteoblastogenesis and osteoclastogenesis [32] .”
BackgroundJoint IOF-ECTS GIO Guidelines Working Group, Lekamwasam, S., Adachi, J. D., Agnusdei, D., Bilezikian, J. P., Boonen, S., Borgström, F., Cooper, C. C., Díez‐Pérez, A., Eastell, R., et al. (2012) · Osteoporosis International · doi:10.1007/s00198-012-1958-1 · Cited by 341
“In addition, apoptosis of osteoblasts and osteocytes is enhanced by glucocorticoids leading to a shorter life span of bone-forming and mechanosensing cells [26].”
BackgroundTransduction 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 338
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 397
“We have reported previously that glucocorticoid administration to mice for 27 days (a period representing chronic rather than short-term drug exposure) decreases the number of osteoblast and osteoclast progenitors, decreases the cancellous osteoblast and osteoclast perimeters, and increases osteoblast apoptosis (20).”
InfluentialSelf-citationThe Relevance of Mouse Models for Investigating Age-Related Bone Loss in Humans
Jilka, R. L. (2013) · The Journals of Gerontology Series A · doi:10.1093/gerona/glt046 · Cited by 342
“7% per day as measured in the distal femur; each episode of remodeling takes about 2 weeks to complete (44).”
BackgroundSelf-citationAbe, E., Yamamoto, M., Taguchi, Y., Lecka‐Czernik, B., O’Brien, C. A., Economides, A. N., Stahl, N., Jilka, R. L., & Manolagas, S. C. (2000) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2000.15.4.663 · Cited by 319
Self-citationAnimal models for osteoporosis
Komori, T. (2015) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2015.03.028 · Cited by 317
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 313
“Detection of apoptotic osteoblasts or osteocytes was performed by in-situ nick-end labeling (ISEL) using the Klenow enzyme (Oncogene Research Products) in sections counterstained with 2% methyl green as previously described (Weinstein et al., 1998).”
Self-citationShear Stress Induces Osteogenic Differentiation of Human Mesenchymal Stem Cells
Yourek, G., McCormick, S. M., Mao, J. J., & Reilly, G. C. (2010) · Regenerative Medicine · doi:10.2217/rme.10.60 · Cited by 304
“Systematic administration of glucocorticoids in human patients has deleterious effects such as bone loss [17] and can induce cell apoptosis [18].”
Glucocorticoid-induced osteoporosis
Briot, K., & Roux, C. (2015) · RMD Open · doi:10.1136/rmdopen-2014-000014 · Cited by 300
Fracture risk with intermittent high‐dose oral glucocorticoid therapy
de Vries, F., Bracke, M., Leufkens, H. G. M., Lammers, J. J., Cooper, C. C., & van Staa, T. P. (2006) · Arthritis & Rheumatism · doi:10.1002/art.22294 · Cited by 297
Molecular Mechanisms and Emerging Therapeutics for Osteoporosis
Noh, J., Yang, Y. D., & Jung, H. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21207623 · Cited by 299
“Glucocorticoids enhance the differentiation and maturation of osteoclasts [23], while inhibiting osteoblastogenesis by promoting osteoblast and osteocyte apoptosis [24], resulting in increased bone resorption and decreased bone formation [25,26].”
BackgroundMartin-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
Self-citationThe pharmacology of bisphosphonates and new insights into their mechanisms of action
Russell, R. G. G., Rogers, M. J., Frith, J. C., Luckman, S. P., Coxon, F. P., Benford, H. L., Croucher, P. I., Shipman, C. M., & Fleisch, H. A. (1999) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650140212 · Cited by 277
Weinstein, 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
“pyknotic nuclei lining the cancellous bone perimeter and apoptotic osteocytes as brown, pyknotic cells buried in lacunae within mineralized bone (Weinstein et al., 1998; Kousteni et al., 2002).”
BackgroundSelf-citationMechanical stimulation prevents osteocyte apoptosis: requirement of integrins, Src kinases, and ERKs
Plotkin, L. I., Mathov, I., Aguirre, J. I., PARFITT, A. M., Manolagas, S. C., & Bellido, T. (2005) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00278.2004 · Cited by 273
“In support of this notion, the increased bone fragility that results from glucocorticoid excess or sex steroid deficiency in animals and humans is associated with increased prevalence of osteocyte apoptosis (36, 61, 66).”
BackgroundSelf-citationThe effects of smoking on bone metabolism
Yoon, V., Maalouf, N. M., & Sakhaee, K. (2012) · Osteoporosis International · doi:10.1007/s00198-012-1940-y · Cited by 268
Therapeutic glucocorticoids: mechanisms of actions in rheumatic diseases
Hardy, R., Raza, K., & Cooper, M. S. (2020) · Nature Reviews Rheumatology · doi:10.1038/s41584-020-0371-y · Cited by 273
Novel actions of bisphosphonates in bone: Preservation of osteoblast and osteocyte viability
Bellido, T., & Plotkin, L. I. (2010) · Bone · doi:10.1016/j.bone.2010.08.008 · Cited by 265
“Moreover, osteocyte apoptosis is increased inconditionsof increasedbone fragility, such as osteoporosis due to excess of glucocorticoids [44] and sex steroid deficiency [52,53].”
BackgroundThe osteocyte as a signaling cell
Delgado‐Calle, J., & Bellido, T. (2021) · Physiological Reviews · doi:10.1152/physrev.00043.2020 · Cited by 280
The Pathogenesis, Epidemiology and Management of Glucocorticoid-Induced Osteoporosis
van Staa, T. P. (2006) · Calcified Tissue International · doi:10.1007/s00223-006-0019-1 · Cited by 257
“The prolongation of the lifespan of osteoblasts and osteocytes may contribute more than the antiresorptive properties to bone effects of bisphosphonates [14].”
BackgroundGlucocorticoids 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
The OPG/RANKL/RANK system in metabolic bone diseases.
Hofbauer, L. C., Kühne, C. A., & Viereck, V. (2004) · PubMed · Cited by 254
Weinstein, R. S., & Manolagas, S. C. (2000) · The American Journal of Medicine · doi:10.1016/s0002-9343(99)00420-9 · Cited by 250
Self-citationPerspectives on glucocorticoid-induced osteoporosis
CANALIS, E. M., Bilezikian, J. P., Angeli, A., & Giustina, A. (2003) · Bone · doi:10.1016/j.bone.2003.11.026 · Cited by 244
Hartmann, 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 251
Osteoblasts play key roles in the mechanisms of action of strontium ranelate
Brennan‐Speranza, T. C., Rybchyn, M. S., Green, W. L., Atwa, S. M., Conigrave, A. D., & Mason, R. S. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00305.x · Cited by 248
“…fracture risk (Bonewald, 2004; Almeida et al., 2007), and it is well established that the protective mechanism of oestrogen to reduce fracture risk in patients with glucocorticoid-induced osteoporosis includes an increased osteoblast and osteocyte lifespan (Weinstein et al., 1998; Dennison, 1999).”
BackgroundEstrogen Prevents Glucocorticoid-Induced Apoptosis in Osteoblasts in Vivo and in Vitro1
Gohel, A., McCarthy, M.-B., & Gronowicz, G. (1999) · Endocrinology · doi:10.1210/endo.140.11.7135 · Cited by 244
Janssens, K., Vanhoenacker, F. M. H. M., Bonduelle, M., Verbruggen, L., Maldergem, L. V., Ralston, S. H., Guañabens, N., Migone, N., Wientroub, S., Divizia, M. T., et al. (2005) · Journal of Medical Genetics · doi:10.1136/jmg.2005.033522 · Cited by 244
Yao, W., Cheng, Z., Busse, C., Pham, A., Nakamura, M. C., & Lane, N. E. (2008) · Arthritis & Rheumatism · doi:10.1002/art.23454 · Cited by 241
Sclerostin promotes the apoptosis of human osteoblastic cells: a novel regulation of bone formation
Sutherland, M. K., Geoghegan, J. C., Yu, C., Turcott, E., Skonier, J. E., Winkler, D. G., & Latham, J. A. (2004) · Bone · doi:10.1016/j.bone.2004.05.023 · Cited by 238
FOXOs attenuate bone formation by suppressing Wnt signaling
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 233
“Introduction Osteoblasts, the cells responsible for the synthesis of bone matrix, are terminally differentiated postmitotic cells with a short life span (1, 2).”
Self-citationHenriksen, K., Bollerslev, J., Everts, V. E., & Karsdal, M. A. (2011) · Endocrine Reviews · doi:10.1210/er.2010-0006 · Cited by 236
Lane, N. E., Sanchez, S., Modin, G. W., Genant, H. K., Pierini, E., & Arnaud, C. D. (2000) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2000.15.5.944 · Cited by 228
“(19,20) Although supplementation with calcium and vitamin D and treatment with antiresorptive agents can prevent bone loss and modestly increase bone mass in patients on chronic glucocorticoid therapy, they do not stimulate bone formation.”
BackgroundOsteoblast Apoptosis and Bone Turnover
Hock, J. M., Krishnan, V., Onyia, J. E., Bidwell, J. P., Milas, J., & Stanislaus, D. (2001) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2001.16.6.975 · Cited by 230
“(25) Whether these putative mechanisms are restricted”
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 235
The Determinants of Peak Bone Mass
Gordon, C. M., Zemel, B. S., Wren, T. A. L., Leonard, M. B., Bachrach, L. K., Rauch, F., Gilsanz, V., Rosen, C. J., & Winer, K. K. (2016) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2016.09.056 · Cited by 238
Kim, S., Yamazaki, M., Zella, L. A., Shevde, N. K., & Pike, J. W. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00353-06 · Cited by 227
“At the level of the osteoblast, GCs reduce both the functional capacity of these cells to form bone and the period of time during which this functionality occurs (43, 67).”
BackgroundChavassieux, P., Seeman, E., & Delmas, P. D. (2006) · Endocrine Reviews · doi:10.1210/er.2006-0029 · Cited by 224
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 220
“To determine whether deletion of Cx43 from osteocytes and osteoblasts affects bone accrual, BMD was determined by DXA (Hologic) every 2 wk, starting at 2 mo of age, until the animals reached the adult peak bone mass.((11,28))”
BackgroundMethodSelf-citationTreating the Side Effects of Exogenous Glucocorticoids; Can We Separate the Good From the Bad ?
Pofi, R., Caratti, G., Ray, D. W., & Tomlinson, J. (2023) · Endocrine Reviews · doi:10.1210/endrev/bnad016 · Cited by 237
“Briefly, GCs increase osteocyte apoptosis and suppress osteoblasts activity and therefore limit bone formation (249) while increasing osteoclast-mediated bone resorption (250, 251).”
Background
Metadata
- Authors
- Weinstein, R. S., Jilka, R. L., Parfitt, A. M., & Manolagas, S. C.
- Affiliations
- University of Arkansas for Medical Sciences (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1998-07-15
- Volume
- 102
- Issue
- 2
- Pages
- 274-282
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC508885
- OpenAlex
- W2002315967
- Cited by
- 1,753
- References
- 56
- Citations by year
- 2026: 25 · 2025: 35 · 2024: 44 · 2023: 63 · 2022: 55 · 2021: 69 · 2020: 65 · 2019: 60 · 2018: 59 · 2017: 63 · 2016: 72 · 2015: 59 · 2014: 77 · 2013: 70 · 2012: 74
- FWCI
- 15.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs
- National Institutes of Health (5r01ar043003-05)
- National Institute on Aging (P01 AG-13918, P01AG013918)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01 AR43003)
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Keywords
- glucocorticoid-induced osteoporosis, osteoblastogenesis, osteoblast apoptosis, osteocyte apoptosis, prednisolone, avascular necrosis, bone formation, bone turnover, osteoclastogenesis, trabecular bone, bone mineral density, osteocalcin
- MeSH terms
- Adult, Animals, Bone and Bones, Bone Marrow Cells, Bone Resorption, Cells, Cultured, Female, Glucocorticoids, Humans, Male, Osteoblasts, Osteocytes, Osteoporosis, Prednisolone, Spine, Bone Density, Apoptosis, Mice
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