Wimalawansa Sunil J
Regional Osteoporosis Center, Division of Endocrinology, Metabolism and Nutrition, Department of Medicine, Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA.
Expert Opin Pharmacother. 2008 Dec;9(17):3025-44. doi: 10.1517/14656560802197162.
Relative nitric oxide (NO) deficiency is responsible for many pathophysiological processes, including in postmenopausal women providing a plausible biological basis for use of NO replacement therapy in humans. Excess or inappropriate local production of NO aggravates bone destruction in some diseases such as septic shock, rheumatoid and other inflammatory arthropathies.
A variety of in vitro and in vivo data have revealed the efficacy of nitroglycerin and nitrates on bone cells. Since some part of the beneficial effects of estrogen on bone is mediated via the NO-cGMP pathway, NO donor therapy is an attractive alternative to estrogen therapy to prevent and treat osteoporosis. When the body cannot generate adequate amounts of NO for biological homeostasis, administration of exogenous NO or prolongation of the actions of endogenous NO are practical ways to supplement NO, especially in postmenopausal women.
Postmenopausal NO deficiency is rectified with hormone replacement therapy, which enhances local production of NO. Declining local NO production secondary to estrogen deficiency in postmenopausal women, and perhaps in older men, could be one of the key reasons for age-related increased incidences of cardiovascular events, sexual dysfunction as well as osteoporosis. Thus, in addition to supplementation of NO compounds in acute situations such as alleviating angina and erectile dysfunction, it could be a valuable addition to the armamentarium of therapies for chronic conditions such as osteoporosis.
相对一氧化氮（NO）缺乏与许多病理生理过程有关，包括在绝经后女性中，这为人类使用NO替代疗法提供了合理的生物学基础。在某些疾病如脓毒症休克、类风湿性关节炎和其他炎症性关节病中，NO的过量或不适当局部产生会加重骨破坏。
各种体外和体内数据揭示了硝酸甘油和硝酸盐对骨细胞的作用。由于雌激素对骨的部分有益作用是通过NO-环磷酸鸟苷（cGMP）途径介导的，NO供体疗法是预防和治疗骨质疏松症的一种有吸引力的雌激素疗法替代方案。当身体无法产生足够量的NO以维持生物稳态时，给予外源性NO或延长内源性NO的作用是补充NO的实用方法，尤其是在绝经后女性中。
绝经后NO缺乏可通过激素替代疗法纠正，该疗法可增强NO的局部产生。绝经后女性以及可能老年男性中因雌激素缺乏导致的局部NO产生下降，可能是心血管事件、性功能障碍以及骨质疏松症与年龄相关发病率增加的关键原因之一。因此，除了在缓解心绞痛和勃起功能障碍等急性情况下补充NO化合物外，它可能是骨质疏松症等慢性疾病治疗手段中的一项有价值补充。
