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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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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).”
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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.
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Items 401–500 of 999
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Gavriatopoulou, M., Dimopoulos, M. A., Christoulas, D., Migkou, M., Iakovaki, M., Gkotzamanidou, M. A., & Terpos, E. (2009) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728220903025770 · Cited by 69
“Dexamethasone, an important component of MM therapy, is known to induce osteoporosis by reducing the lifespan of osteoblasts [62].”
BackgroundMoriishi, T., Maruyama, Z., Fukuyama, R., Ito, M., Miyazaki, T., Kitaura, H., Ohnishi, H., Furuichi, T., Kawai, Y., Masuyama, R., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0027487 · Cited by 68
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Luo, P., Gao, F., Han, J., Sun, W. M., & Li, Z. (2018) · International Orthopaedics · doi:10.1007/s00264-018-3994-8 · Cited by 68
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Miner, J. N., Hong, M. H., & Negro-Vilar, A. F. (2005) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.14.12.1527 · Cited by 70
“Several groups have demonstrated that glucocorticoids are capable of inducing apoptosis in both osteoblasts and osteocytes in cell culture and in vivo experiments [61,62].”
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Kulak, C. A. M., Borba, V. Z. C., Júnior, J. K., & Custódio, M. R. (2012) · Current Osteoporosis Reports · doi:10.1007/s11914-011-0083-y · Cited by 67
“Bone formation is inhibited by decreased proliferation, function (by reducing levels of type I collagen, insulin-like growth factor 1, and osteocalcin), and lifespan (by induction of osteoblast apoptosis) [6].”
Sensitivity of bone to glucocorticoids
Cooper, M. S. (2004) · Clinical Science · doi:10.1042/cs20040070 · Cited by 68
High prevalence of vertebral deformity in premenopausal systemic lupus erythematosus patients
Borba, V. C., Matos, P. G., Viana, P. R. D. S., Fernandes, A. D. R. C., Sato, E. I., & Lazaretti‐Castro, M. (2005) · Lupus · doi:10.1191/0961203305lu2154oa · Cited by 66
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Henneicke, H., Herrmann, M., Kalak, R., Brennan‐Speranza, T. C., Heinevetter, U., Bertollo, N., Day, R. E., Huscher, D., Buttgereit, F., Dunstan, C. R., et al. (2011) · Bone · doi:10.1016/j.bone.2011.06.013 · Cited by 67
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Urayama, S., Kawakami, A., Nakashima, T., Tsuboi, M., Yamasaki, S., Hida, A., Ichinose, Y., Nakamura, H., Ejima, E., Aoyagi, T., et al. (2000) · Journal of Laboratory and Clinical Medicine · doi:10.1067/mlc.2000.108754 · Cited by 66
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Uncertainties in the prevention and treatment of glucocorticoid-induced osteoporosis
Hansen, K. E., Wilson, H. A., Zapalowski, C., Fink, H. A., Minisola, S., & Adler, R. A. (2011) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.362 · Cited by 65
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BackgroundGlucocorticoid-induced autophagy and apoptosis in bone
Wang, T., Liu, X., & He, C. (2020) · APOPTOSIS · doi:10.1007/s10495-020-01599-0 · Cited by 67
Psarra, A. G., Solakidi, S., Trougakos, I. P., Margaritis, L. H., Spyrou, G., & Sekeris, C. E. (2005) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2005.06.015 · Cited by 65
Kim, J. H., Lee, H.-J., Kang, K. S., Chun, K., & Hwang, G. S. (2014) · Journal of Ginseng Research · doi:10.1016/j.jgr.2014.06.001 · Cited by 65
“Weinstein et al [4] demonstrated that prednisone increases the rate of apoptosis in both osteoblasts and osteocytes in adult mice.”
BackgroundSowa, H., Kaji, H., Iu, M.-F., Tsukamoto, T., Sugimoto, T., & Chihara, K. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m302566200 · Cited by 65
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Ng, J.-S., & Chin, K.-Y. (2021) · International Journal of Medical Sciences · doi:10.7150/ijms.50680 · Cited by 66
“In murine cell culture studies, cortisol dose-dependently impairs osteoclastogenesis and osteoblastogenesis, and increases osteoblast and osteocyte apoptosis in cortical bone [28].”
Sakaguchi, M., Tanaka, T., Fukushima, W., Kubo, T., & Hirota, Y. (2010) · Journal of Orthopaedic Science · doi:10.1007/s00776-009-1439-3 · Cited by 64
Manolagas, S. C., & PARFITT, A. M. (2012) · Bone · doi:10.1016/j.bone.2012.09.017 · Cited by 65
“In areas of very low turnover, osteocytes may die by apoptosis, leaving lacunae which appear empty in histologic sections [12], but which may contain the remnants of osteocytes which have not undergone phagocytosis [13], but are lost during section preparation.”
BackgroundSelf-citationRole of nutritional vitamin D in osteoporosis treatment
Hou, Y., Wu, C., Liao, M.-T., Shyu, J., Hung, C., Yen, T., Lu, C., & Lu, K. (2018) · Clinica Chimica Acta · doi:10.1016/j.cca.2018.05.035 · Cited by 65
Yang, P., Lv, S., Wang, Y., Peng, Y., Ye, Z.-X., Xia, Z., Ding, G.-X., Cao, X., & Crane, J. L. (2018) · Bone · doi:10.1016/j.bone.2018.05.025 · Cited by 60
“In vitro studies have previously found that murine osteoclast cultures exposed to glucocorticoids led to prolonged baseline survival of osteoclasts [16], while in vivo adult mouse studies have reported a transient increase in osteoclast numbers, followed by a decrease with more prolonged treatment [13, 16].”
BackgroundResultInfluentialYanbeiy, Z. A., & Hansen, K. E. (2019) · Drug Design Development and Therapy · doi:10.2147/dddt.s148654 · Cited by 67
“With long-term use, the main effect of glucocorticoid therapy is reduced bone formation, via increased osteoblast and osteocyte apoptosis.(4) Glucocorticoid therapy can also contribute to osteoporosis pathogenesis by causing hypogonadotropic hypogonadism, reduced intestinal calcium absorption and hypercalciuria.”
BackgroundSasaki, N., Kusano, E., Ando, Y., Nemoto, J., Iimura, O., Ito, C., Takeda, S., Yano, K., Tsuda, E., & Asano, Y. (2002) · Bone · doi:10.1016/s8756-3282(02)00742-1 · Cited by 63
Cavalier, E., Bergmann, P., Bruyère, O., Delanaye, P., Durnez, A., Devogelaer, J.-P., Ferrari, S. L., Gielen, E., Goemaere, S., Kaufman, J.-M., et al. (2016) · Osteoporosis International · doi:10.1007/s00198-016-3561-3 · Cited by 63
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“Several hormonal agents are involved in this regulation, including PTH [10], 1,25 (OH) Vitamin D [4], calcitonin [41], thyroid hormone [42], growth hormone [43], glucocorticoids [44] and sex hormones [45].”
BackgroundKoromila, T., Baniwal, S. K., Song, Y. S., Martin, A., Xiong, J., & Frenkel, B. (2013) · Journal of Cellular Biochemistry · doi:10.1002/jcb.24646 · Cited by 75
“Exposure of osteoblasts to GCs at pharmacological concentrations results in both attenuation of cell cycle progression and acceleration of apoptosis [Canalis, 1984; Weinstein et al., 1998; Smith et al., 2000].”
BackgroundSafety of inhaled corticosteroids: Room for improvement
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Wang, B.-L., Sun, W., Shi, Z.-C., Lou, J.-N., Zhang, N.-F., Shi, S.-H., Guo, W. S., Cheng, L.-M., Ye, L.-Y., Zhang, W.-J., et al. (2008) · Orthopedics · doi:10.3928/01477447-20080501-33 · Cited by 63
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Clowes, J. A., Peel, N. F. A., & Eastell, R. (2001) · Current Opinion in Rheumatology · doi:10.1097/00002281-200107000-00015 · Cited by 62
Bone metabolism in renal transplant patients treated with cyclosporine or sirolimus
Campistol, J. M., Holt, D. W., Epstein, S., Gioud-Paquet, M., Rutault, K., Burke, J. T., & the Sirolimus European Renal Transplant Study Group* (2005) · Transplant International · doi:10.1111/j.1432-2277.2005.00163.x · Cited by 63
Sasaki, N., Kusano, E., Takahashi, H., Ando, Y., Yano, K., Tsuda, E., & Asano, Y. (2004) · Journal of Bone and Mineral Metabolism · doi:10.1007/s00774-004-0539-6 · Cited by 63
“Possible mechanisms by which GC reduces bone density are: (1) GC-induced direct impairment of osteoblast [6] or osteoclast function and (2) secondary hyperparathyroidism, due to the increased renal excretion and decreased intestinal absorption of calcium [18].”
BackgroundWoltman, A. M., Massacrier, C., de Fijter, J. W., Caux, C., & van Kooten, C. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.12.6181 · Cited by 63
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BackgroundGrowth and Puberty in Children with Inflammatory Bowel Diseases
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“In agreement with previous reports, 18,28 osteoblast apoptosis was obviously induced by Dex exposure in vivo and in vitro in the present study.”
Nicolaije, C., Koedam, M., & van Leeuwen, J. P. T. M. (2011) · Journal of Cellular Physiology · doi:10.1002/jcp.22841 · Cited by 60
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BackgroundTakano, Y., Yamauchi, K., Hiramatsu, N., Kasai, A., Hayakawa, K., Yokouchi, M., Yao, J. Q., & Kitamura, M. (2007) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00423.2006 · Cited by 62
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BackgroundAdipocytes and the Regulation of Bone Remodeling: A Balancing Act
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Cartilage restoration of the hip using fresh osteochondral allograft
Khanna, V., Tushinski, D. M., Drexler, M., Backstein, D. B., Gross, A. E., Safir, O. A., & Kuzyk, P. R. T. (2014) · The Bone & Joint Journal · doi:10.1302/0301-620x.96b11.34734 · Cited by 61
Bone Health in Disorders of Sex Differentiation
Bertelloni, S., Baroncelli, G., & Mora, S. (2010) · Sexual Development · doi:10.1159/000315961 · Cited by 62
“…effects of glucocorticoids on the skeleton are directed to all bone cells, decreasing the activity of both osteoblasts and osteoclasts, increasing apoptosis of osteoblasts and osteocytes, and extending the lifespan of osteoclasts [Weinstein et al., 1998; O’Brien et al., 2004; Jia et al., 2006].”
BackgroundEndogenous Glucocorticoids and Bone
Zhou, H., Cooper, M. S., & Seibel, M. J. (2013) · Bone Research · doi:10.4248/br201302001 · Cited by 63
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Battaglia, S. L., Cardillo, I., Lavorini, F., Spatafora, M., & Scichilone, N. (2014) · Drugs & Aging · doi:10.1007/s40266-014-0213-1 · Cited by 61
“A meta-analysis [51] on risk of pneumonia associated with long-term use of ICS in COPD showed a significantly increased risk of pneumonia (risk ratio of 1.”
BackgroundPsychological stress and aging: role of glucocorticoids (GCs)
Hasan, K., Rahman, M. S., Arif, K. M. T., & Sobhani, M. E. (2011) · AGE · doi:10.1007/s11357-011-9319-0 · Cited by 62
Osteoporosis due to Glucocorticoid Use in Children with Chronic Illness
Ward, L. M. (2005) · Hormone Research in Paediatrics · doi:10.1159/000088976 · Cited by 60
“at high doses GCs diminish the number of osteoblasts by promoting apoptosis [”
BackgroundOptimized Bioactive Glass: the Quest for the Bony Graft
Granel, H., Bossard, C., Nucke, L., Wauquier, F., Rochefort, G. Y., Guicheux, J., Jallot, É., Lao, J., & Wittrant, Y. (2019) · Advanced Healthcare Materials · doi:10.1002/adhm.201801542 · Cited by 60
Type I Collagen Structure, Synthesis, and Regulation
Bou–Gharios, G., & Crombrugghe, B. D. (2008) · Elsevier eBooks · doi:10.1016/b978-0-12-373884-4.00034-3 · Cited by 61
Rangaswamaiah, S., Gangathimmaiah, V., Nordenstrom, A., & Falhammar, H. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00493 · Cited by 59
Regulation of bim in glucocorticoid‐mediated osteoblast apoptosis
Espiña, B., Liang, M., Russell, R. G. G., & Hulley, P. A. (2007) · Journal of Cellular Physiology · doi:10.1002/jcp.21335 · Cited by 59
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BackgroundAlonso, V., Gortázar, A. R., Ardura, J. A., Andrade‐Zapata, I., Alvarez-Arroyo, M. V., & Esbrit, P. (2008) · Journal of Cellular Physiology · doi:10.1002/jcp.21547 · Cited by 59
“…promotes human osteoblastic cell survival To assess the pro-survival effect of PTHrP (107–139) in human osteoblastic cells, we used two well known pro-apoptotic agents, dexamethasone and the chemotherapeutic drug etoposide (Weinstein et al., 1998; Jilka et al., 1999; Bellido et al., 2003).”
BackgroundMethodKerachian, M. A., Cournoyer, D., Harvey, E. J., Chow, T. Y.-K., Bégin, L. R., Nahal, A., & Séguin, C. (2010) · Arthritis Research & Therapy · doi:10.1186/ar3062 · Cited by 59
“reported that the number of apoptotic bone cells increased significantly in mice after steroid administration [28].”
Dexamethasone induces caspase activation in murine osteoblastic MC3T3-E1 cells
Chua, C. C., Chua, B. H. L., Chen, Z., Landy, C., & Hamdy, R. C. (2003) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/s0167-4889(03)00100-9 · Cited by 59
The Emerging Role of Osteocytes in Cancer in Bone
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Cerri, P. S., Boabaid, F., & Katchburian, E. (2003) · Journal of Periodontal Research · doi:10.1034/j.1600-0765.2003.02006.x · Cited by 57
Secondary osteoporosis in patients with an osteoporotic fracture
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“The predominant effect of glucocorticoids is the inhibition of osteoblasts and osteoblast precursors, but increased osteoctye apoptosis has also been implicated as an important mechanism [4].”
Dominici, M., Marino, R., Rasini, V., Spano, C., Paolucci, P., Conte, P., Hofmann, T. J., & Horwitz, E. M. (2008) · Blood · doi:10.1182/blood-2007-10-115725 · Cited by 59
The Intravertebral Cleft in Acute Osteoporotic Fractures
Linn, J., Birkenmaier, C., Hoffmann, R., Reiser, M. F., & Baur‐Melnyk, A. (2009) · Spine · doi:10.1097/brs.0b013e318193ca06 · Cited by 58
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BackgroundRole for β1 integrins in cortical osteocytes during acute musculoskeletal disuse
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Mechanisms of palmitate-induced lipotoxicity in osteocytes
Saedi, A. A., Bermeo, S., Plotkin, L. I., Myers, D. E., & Duque, G. (2019) · Bone · doi:10.1016/j.bone.2019.06.016 · Cited by 54
Luppen, C. A., Leclerc, N., Noh, T., Barski, A., Khokhar, A., Boskey, A. L., Smith, E., & Frenkel, B. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306730200 · Cited by 58
CircRNA–miRNA networks in regulating bone disease
Huang, W., Wu, Y., Qiao, M., Xie, Z., Cen, X. B., Huang, X., & Zhao, Z. (2021) · Journal of Cellular Physiology · doi:10.1002/jcp.30625 · Cited by 56
“On the other hand, it is noticed that sclerostin secreted by osteocytes has a negative effect on bone formation playing an inhibitory role in Wnt/β‐catenin signaling pathway (Ohnaka et al., 2005; Weinstein et al., 1998).”
Backgroundvon Scheven, E., Corbin, K. J., Stagi, S., & Cimaz, R. (2014) · Current Osteoporosis Reports · doi:10.1007/s11914-014-0228-x · Cited by 58
Sutter, S. A., Nishiyama, K. K., Kepley, A. L., Zhou, B., Wang, J., McMahon, D. J., Guo, X., & Stein, E. M. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-2177 · Cited by 57
Jensen, P. R., Andersen, T. L., Hauge, E., Bollerslev, J., & Delaissé, J. (2014) · Bone · doi:10.1016/j.bone.2014.12.004 · Cited by 57
“If one considers the present study in the general context of themode of action of GCs, it should be mentioned that pharmacological levels of GCs have adverse effects on all osteoblast-lineage cells, including bone forming osteoblasts, osteocytes, and bone lining cells [15].”
BackgroundResultInfluentialGeurtzen, K., Vernet, A., Freidin, A. J., Rauner, M., Hofbauer, L. C., Schneider, J. E., Brand, M., & Knopf, F. (2017) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3231 · Cited by 60
“In the initial phase of GIO, glucocorticoid treatment increases genesis, lifespan, and activity of mammalian osteoclasts, leading to increased bone resorption.((4,57)) Longer treatments, however, rather impair osteoclast function in mammalian bone tissue by decreasing osteoclastogenesis.”
BackgroundMethodResultOsteonecrosis in stroke-prone spontaneously hypertensive rats: effect of glucocorticoid
Murata, M., Kumagai, K., Miyata, N., Osaki, M., & Shindo, H. (2007) · Journal of Orthopaedic Science · doi:10.1007/s00776-007-1129-y · Cited by 57
Editorial: Cell Number Versus Cell Vigor--What Really Matters to a Regenerating Skeleton?
Manolagas, S. C. (1999) · Endocrinology · doi:10.1210/endo.140.10.7129 · Cited by 59
Self-citationvan der Burgh, A. C., de Keyser, C. E., Zillikens, M. C., & Stricker, B. H. C. (2021) · Drugs · doi:10.1007/s40265-021-01625-8 · Cited by 60
Conaway, H. H., Henning, P., Lie, A., Tuckermann, J. P., & Lerner, U. H. (2016) · Bone · doi:10.1016/j.bone.2016.08.024 · Cited by 57
Novel insights into the complex architecture of osteoporosis molecular genetics
Saad, F. A. (2019) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.14231 · Cited by 55
Should bisphosphonates be used for long‐term treatment of glucocorticoid‐induced osteoporosis?
Teitelbaum, S. L., Seton, M., & Saag, K. G. (2010) · Arthritis & Rheumatism · doi:10.1002/art.30135 · Cited by 54
“Glucocorticoids suppress osteoblasts directly (6) and probably by inhibiting remodeling (17).”
Zarrinkalam, M. R., Mulaibrahimovic, A., Atkins, G. J., & Moore, R. J. (2011) · Osteoporosis International · doi:10.1007/s00198-011-1672-4 · Cited by 56
Glucocorticoid-Induced Osteoporosis in Growing Rats
Lin, S., Huang, J., Liang, Z., Liu, Y., Liu, G., Li, N., Wang, K., Zou, L., Wu, T., Qin, L., et al. (2014) · Calcified Tissue International · doi:10.1007/s00223-014-9899-7 · Cited by 56
“It was believed that increased apoptosis of osteoblasts in trabecular bone and apoptosis of osteocytes in the metaphyseal cortical bone in the mice treated with GC [17].”
BackgroundResultInfluentialEffect of kidney transplantation on bone
Kodras, K., & Haas, M. (2006) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.2006.01662.x · Cited by 55
Inhaled Corticosteroids and Bone Health
Chee, C., Sellahewa, L., & Pappachan, J. M. (2015) · The Open Respiratory Medicine Journal · doi:10.2174/1874306401408010085 · Cited by 54
Glucocorticoid-induced osteoporosis
Tamura, Y., Okinaga, H., & Takami, H. E. (2004) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2004.08.018 · Cited by 56
Yamamoto, M., Yamaguchi, T., Yamauchi, M., Kaji, H., & Sugimoto, T. (2007) · Calcified Tissue International · doi:10.1007/s00223-007-9003-7 · Cited by 54
“These studies suggest that diabetic patients may have low bone turnover similar to glucocorticoid users [25, 26].”
BackgroundMutijima, E. N., Maertelaer, V. D., Deprez, M., Malaise, M., & Hauzeur, J. (2014) · Clinical Rheumatology · doi:10.1007/s10067-014-2607-1 · Cited by 54
“Osteocytic apoptosis is increased in mice after corticotherapy and in transiliac bone biopsies from patients treated with corticoids [3].”
BackgroundNew understanding of glucocorticoid action in bone cells
Kim, H. J. (2010) · BMB Reports · doi:10.5483/bmbrep.2010.43.8.524 · Cited by 55
“GCs inhibit osteoblasts, bone-forming cells, in vivo through the induction of apoptosis, which leads to the suppression of bone formation (2, 19).”
Regulation of osteoblast differentiation by interleukin-11 via AP-1 and Smad signaling [Review]
Matsumoto, T., Kuriwaka-Kido, R., Kondo, T., Endo, I., & Kido, S. (2011) · Endocrine Journal · doi:10.1507/endocrj.ej11-0219 · Cited by 55
“While the enhancement of bone resorption is more pronounced during the early phase, the inhibition of osteoblast differentiation along with enhancement of osteoblast apoptosis becomes more pronounced in the later phase of glucocorticoids excess [9].”
BackgroundSpinal Neuroarthropathy: Pathophysiology, Clinical and Imaging Features, and Differential Diagnosis
Ledbetter, L. N., Salzman, K. L., Sanders, R. K., & Shah, L. M. (2016) · Radiographics · doi:10.1148/rg.2016150121 · Cited by 54
Kuroshima, S., Sasaki, M., Nakajima, K., Tamaki, S., Hayano, H., & Sawase, T. (2017) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3292 · Cited by 57
“Remodeling in human trabecular bone takes about 6 to 9 months to complete,((28)) whereas remodeling in mouse trabecular bone takes approximately 2 weeks to complete.((29)) Socket wounds heals within 3 weeks in mice, but require 6 weeks in humans.”
BackgroundAnimal models to explore the effects of glucocorticoids on skeletal growth and structure
Wood, C. L., Souček, O., Wong, S. C., Zaman, F., Farquharson, C., Savendahl, L. S., & Ahmed, S. F. (2017) · Journal of Endocrinology · doi:10.1530/joe-17-0361 · Cited by 56
Cellular and molecular mechanisms of osteoporosis
Manolagas, S. C. (1998) · Aging Clinical and Experimental Research · doi:10.1007/bf03339652 · Cited by 55
Self-citationLeclerc, N., Noh, T., Khokhar, A., Smith, E., & Frenkel, B. (2005) · Arthritis & Rheumatism · doi:10.1002/art.20872 · Cited by 54
Parathyroid hormone (PTH), PTH-derived peptides, and new PTH assays in renal osteodystrophy
Goodman, W. G., Jüppner, H., Salusky, I. B., & Sherrard, D. J. (2003) · Kidney International · doi:10.1046/j.1523-1755.2003.00700.x · Cited by 54
Ikeda, S., Morishita, Y., Tsutsumi, H., Ito, M., Shiraishi, A., Arita, S., Akahoshi, S., Narusawa, K., & Nakamura, T. (2003) · Bone · doi:10.1016/s8756-3282(03)00263-1 · Cited by 53
Glucocorticoid-induced osteoporosis: an update on current pharmacotherapy and future directions
Bultink, I. E. M., Baden, M., & Lems, W. F. (2013) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2013.761975 · Cited by 53
“These histomorphometric studies revealed reduced bone formation, characterized by a low mineral apposition rate (which is related to a reduction in the number of osteoblasts), while bone resorption was unchanged or even elevated [29].”
BackgroundPiemontese, M., Onal, M., Xiong, J., Wang, Y., Almeida, M., Thostenson, J. D., Weinstein, R. S., Manolagas, S. C., & O’Brien, C. A. (2015) · Bone · doi:10.1016/j.bone.2015.02.005 · Cited by 54
“Glucocorticoids cause a profound reduction in osteoblast number and bone formation rate [2].”
BackgroundSelf-citationGlucocorticoid-induced delayed fracture healing and impaired bone biomechanical properties in mice
Liu, Y., Akhter, M. P., Gao, X., Wang, X.-Y., Wang, X.-B., Zhao, G., Wei, X., Wu, H.-J., Chen, H., Wang, D., et al. (2018) · Clinical Interventions in Aging · doi:10.2147/cia.s167431 · Cited by 53
“Some studies revealed that a 27-day prednisolone treatment in mice result in decreased bone resorption below normal level.(30) GCs were found to directly block the induction of cytoskeletal changes in osteoclasts, which are required for the resorptive capabilities of the cells.”
Bucaro, M. A., Fertala, J., Adams, C. S., Steinbeck, M. J., AYYASWAMY, P. S., Mukundakrishnan, K., Shapiro, I. M., & Risbud, M. V. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1324.007 · Cited by 53
Chae, H., Chae, S., Kang, J. S., Bang, B.-G., Cho, S. B., Park, R., So, H. S., Kim, Y. K., Kim, H. M., & Kim, H. (2000) · Endocrinology · doi:10.1210/endo.141.8.7604 · Cited by 53
Yang, S., Sun, Y., Капилевич, Л. В., Zhang, X., & Huang, Y. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1249418 · Cited by 52
Osteoblastogenesis and tumor growth in myeloma
Yaccoby, S. (2009) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.3109/10428190903503438 · Cited by 52
“These patients are often treated with the glucocorticoid dexamethasone, a clinical frontline drug known to reduce the life span of osteoblasts and osteocytes and to enhance survival of osteoclasts [84,85].”
The Effects of Medications on Bone
Goodman, S. B., Jiranek, W. A., Petrow, E., & Yasko, A. W. (2007) · Journal of the American Academy of Orthopaedic Surgeons · doi:10.5435/00124635-200708000-00002 · Cited by 51
Shen, G., Ren, H. J., Shang, Q., Zhao, W., Zhang, Z., Yu, X., Huang, J., Tang, J., Yang, Z., Liang, D., et al. (2019) · International Journal of Biological Sciences · doi:10.7150/ijbs.33490 · Cited by 52
“Mechanistically, reduced bone formation is regarded as a crucial process of GIOP and many studies have determined that the glucocorticoid receptor (GR), DKK1, sclerostin, AP‐1, PPARγ2, Runx2, and other critical molecules play key roles in this process [2-5].”
BackgroundSwarbrick, M. M., Zhou, H., & Seibel, M. J. (2021) · European Journal of Endocrinology · doi:10.1530/eje-21-0553 · Cited by 54
Luppen, C. A., Blake, C. A., Ammirati, K. M., Stevens, M. L., Seeherman, H. J., Wozney, J. M., & Bouxsein, M. (2002) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2002.17.2.301 · Cited by 52
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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