Different doses of nitric oxide donor prevent osteoporosis in ovariectomized rats
Abstract
Nitric oxide has important effects on bone cell function. To verify that nitric oxide can protect against bone loss associated with estrogen deficiency, which is dependent on different concentrations of nitric oxide, we applied different doses of nitric oxide to ovariectomized rats. Fifty 12-week-old Sprague-Dawley female rats had ovariectomies, and 10 rats had sham operations. The ovariectomized rats were randomized into five groups: ovariectomized only; 17-beta-estradiol; low-dose nitroglycerin; middle-dose nitroglycerin; and high-dose nitroglycerin. After 12 weeks, the bone mineral density, dry weight, ash weight, calcium content, and nitric oxide concentration were determined. Compared with these same measurements in the sham-operated group, the bone mineral density, dry weight, ash weight, calcium content, and nitric oxide concentration decreased in the control group. Treatment with low-dose nitroglycerin, middle-dose nitroglycerin, and 17-beta-estradiol maintained bone mineral density and reversed the effects of ovariectomy on dry weight, ash weight and calcium content when compared with those in the control group. There were no differences in the bone mineral density, dry weight, ash weight, or calcium concentration between the ovariectomized-only rats and the rats treated with high-dose nitroglycerin. Results of this study suggest that nitric oxide treatment can counteract bone loss in ovariectomized rats. Furthermore, supplementation with a similar or slightly greate…
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Organic nitrate NO donors such as glycerol trinitrate, isosorbide dinitrate, and mononitrate all have beneficial effects on experimental and clinical osteoporosis, and a number of epidemiological studies indicated that high fruit and vegetable intake appears protective against osteoporosis in men and pre- and postmenopausal women.
“In this context, it has been shown that organic nitrate NO donors, such as glycerol trinitrate, isosorbide dinitrate and mononitrate all have beneficial effects on experimental and clinical osteoporosis [161,162,163], and a number of epidemiological studies also indicated that a high fruit and vegetable intake appears to have a protective effect against osteoporosis in men and pre- and post”
From NO-Rich Diet for Lifestyle-Related Diseases (2015) · cites this paper as [162]
Cites
Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor
Palmer, R. M. J., Ferrige, A. G., & Moncada, S. (1987) · Nature · doi:10.1038/327524a0 · Cited by 10,704 · see citing works
The L-Arginine-Nitric Oxide Pathway
Epstein, F. H., Moncada, S., & Higgs, A. (1993) · New England Journal of Medicine · doi:10.1056/nejm199312303292706 · Cited by 6,678 · see citing works
Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis
Garnero, P., Sornay‐Rendu, E., Chapuy, M. C., & Delmas, P. D. (1996) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650110307 · Cited by 1,000 · see citing works
Van'T Hof, R. J., & Ralston, S. H. (2001) · Immunology · doi:10.1046/j.1365-2567.2001.01261.x · Cited by 518 · see citing works
Kitazawa, R., Kimble, R. B., Vannice, J. L., Kung, V. T., & Pacifici, R. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117606 · Cited by 336 · see citing works
Nitric Oxide Synthase Expression in Bone Cells
Fox, S. W., & Chow, J. W. M. (1998) · Bone · doi:10.1016/s8756-3282(98)00070-2 · Cited by 320 · see citing works
Arnal, J., Clamens, S., Pechet, C., Nègre‐Salvayre, A., Allera, C., Girolami, J. P., Salvayre, R., & Bayard, F. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.9.4108 · Cited by 254 · see citing works
Nitric oxide donor alleviates ovariectomy-induced bone loss
Wimalawansa, S. J., De Marco, G., Gangula, P., & Yallampalli, C. (1996) · Bone · doi:10.1016/8756-3282(96)00005-1 · Cited by 189 · see citing works
Evans, D. M., & Ralston, S. H. (1996) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650110303 · Cited by 186 · see citing works
Onyango, E., Hester, P. Y., Stroshine, R. L., et al. (2003) · Poultry Science · doi:10.1093/ps/82.11.1787 · Cited by 180 · see citing works
Expression and functional role of nitric oxide synthase in osteoblast-like cells
Riancho, J. A., Salas, E., Zarrabeitia, M. T., et al. (1995) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650100315 · Cited by 177 · see citing works
Hof, R. V., Armour, K. J., Smith, L. M., Armour, K. E., Wei, X., Liew, F. Y., & Ralston, S. H. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.130511497 · Cited by 158 · see citing works
Expression of Nitric Oxide Synthase Isoforms in Bone and Bone Cell Cultures
Helfrich, M., Evans, D. M., Grabowski, P., Pollock, J. S., Ohshima, H., & Ralston, S. H. (1997) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1997.12.7.1108 · Cited by 155 · see citing works
Intermittent Use of Nitrates Increases Bone Mineral Density: The Study of Osteoporotic Fractures
Jamal, S. A., Browner, W. S., Bauer, D. C., & Cummings, S. R. (1998) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1998.13.11.1755 · Cited by 131 · see citing works
Wimalawansa, S. J. (2000) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2000.15.11.2240 · Cited by 109 · see citing works
Inducible Nitric Oxide Synthase Mediates Bone Loss in Ovariectomized Mice
Cuzzocrea, S., Mazzon, E., Dugo, L., Genovese, T., Paola, R. D., Ruggeri, Z., Vegeto, E., Caputi, A. P., van de Loo, F. A. J., Puzzolo, D., et al. (2003) · Endocrinology · doi:10.1210/en.2002-220597 · Cited by 83 · see citing works
Prevention of corticosteroid-induced bone loss with nitric oxide donor nitroglycerin in male rats
Wimalawansa, S. J., Chapa, M. T., Yallampalli, C., Zhang, R., & Simmons, D. J. (1997) · Bone · doi:10.1016/s8756-3282(97)00125-7 · Cited by 83 · see citing works
Nitric-Oxide Releasing Molecules : A New Class of Drugs with Several Major Indications
Burgaud, J., Riffaud, J. P., & Soldato, P. D. (2002) · Current Pharmaceutical Design · doi:10.2174/1381612023396357 · Cited by 72 · see citing works
Afzal, F., Polak, J. M., & Buttery, L. D. K. (2004) · The Journal of Pathology · doi:10.1002/path.1536 · Cited by 69 · see citing works
Das, U. N. (2002) · Experimental Biology and Medicine · doi:10.1177/153537020222700202 · Cited by 65 · see citing works
Nitric Oxide Synthase Isoforms During Fracture Healing
Zhu, W. P., Diwan, A. D., Lin, J., & Murrell, G. A. C. (2001) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2001.16.3.535 · Cited by 58 · see citing works
Role of endothelial nitric oxide synthase in estrogen-induced osteogenesis
Samuels, A., Perry, M. J., Gibson, R., Colley, S. M., & Tobias, J. H. (2001) · Bone · doi:10.1016/s8756-3282(01)00471-9 · Cited by 57 · see citing works
Nitric Oxide: Biphasic Dose Responses
Calabrese, E. J. (2001) · Critical Reviews in Toxicology · doi:10.1080/20014091111776 · Cited by 55 · see citing works
Restoration of Ovariectomy-Induced Osteopenia by Nitroglycerin
Wimalawansa, S. J. (2000) · Calcified Tissue International · doi:10.1007/s002230050011 · Cited by 53 · see citing works
Mentaverri, R., Kamel, S., Wattel, A., Prouillet, C., Sévenet, N., Petit, J. P., Tordjmann, T., & Brazier, M. (2003) · Journal of Cellular Biochemistry · doi:10.1002/jcb.10463 · Cited by 43 · see citing works
Kanaoka, K., Kobayashi, Y., Hashimoto, F., Nakashima, T., Shibata, M., Kobayashi, K., Kato, Y., & Sakai, H. (2000) · Endocrinology · doi:10.1210/endo.141.8.7603 · Cited by 37 · see citing works
Changing Views about 'Osteoporoses' (a 1998 Overview)
Frost, H. M. (1999) · Osteoporosis International · doi:10.1007/s001980050239 · Cited by 30 · see citing works
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Weitzmann, M. N. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28550 · Cited by 990 · see citing works
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Kobayashi, J., Ohtake, K., & Uchida, H. (2015) · Nutrients · doi:10.3390/nu7064911 · Cited by 94 · see citing works
- Authors
- Hao, Y.-J., Tang, Y., Chen, F.-B., & Pei, F.-X.
- Affiliations
- Sichuan University (CN)
- Zhengzhou University (CN)
- Corresponding author
- Hao, Ying-Jie
- Pei, Fu-Xing
- ORCID
- Venue
- Clinical Orthopaedics and Related Research
- Published
- 2005-06
- Volume
- &NA;
- Issue
- 435
- Pages
- 226-231
- ISSN
- 0009-921X (ISSN-L)
- OpenAlex
- W2077169253
- Cited by
- 32
- References
- 27
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 2 · 2021: 3 · 2019: 1 · 2018: 1 · 2015: 1 · 2014: 2 · 2013: 2 · 2012: 1
- FWCI
- 2.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Orthopaedics and Related Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- nitric oxide, nitroglycerin, osteoporosis, ovariectomy, estrogen deficiency, bone mineral density, bone loss, estradiol, dose-dependent effects, bone calcium content
- MeSH terms
- Analysis of Variance, Animals, Estradiol, Female, Nitroglycerin, Osteoporosis, Ovariectomy, Random Allocation, Bone Density, Rats, Sprague-Dawley, Nitric Oxide Donors, Rats
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