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REVIEW article
Front. Endocrinol.
Sec. Clinical Diabetes
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1480838
This article is part of the Research Topic The Prevention and Treatment of Diabetic Osteoporosis View all 6 articles
The potential role of nitrate, a nitric oxide donor, in the prevention and treatment of diabetic osteoporosis
Provisionally accepted- 1 Shahid Beheshti University, Tehran, Tehran, Iran
- 2 School of Medicine, City University of New York, New York City, United States
- 3 Endocrine Physiology Research Center, Shahid Beheshti University, Tehran, Tehran, Iran
Approximately 28% of individuals with diabetes have osteoporosis. Diabetoporosis, which refers to the diabetes-related decrease in bone quality and quantity, increases the risk of osteoporotic fractures by 600-700% in individuals with type 1 diabetes (T1D) and by 38-70% in those with type 2 diabetes (T2D) compared to non-diabetic individuals. Decreased nitric oxide (NO) bioavailability contributes to diabetoporosis. This review summarizes the potential role of nitrate as a NO donor in preventing and treating diabetic osteoporosis. Evidence suggests that organic and inorganic nitrates have anti-osteoporotic effects in animal models of osteoporosis, as demonstrated by increasing bone mineral density (BMD, 3-42%) and bone weight (6-160%). Observational human studies indicate a lower fracture risk (6-17%) and a higher BMD (3-5%) following organic nitrate administration. Similar protective effects (7-74% reduction in fracture risk and 8-84% increase in BMD) have been observed with nitrate-rich diets. Randomized controlled trials have also shown that nitrate increases circulating bone formation markers; however, no effect on fracture risk has been reported, and increased BMD (8.8%) was reported only in one study. Nitrate converts to nitrite and then to NO (exogenous NO), increasing NO bioavailability in bone. In addition, nitrate increases the expression of endothelial NO synthase (eNOS), thereby increasing the endogenous NO in bone. Nitrate-derived NO promotes bone formation and reduces bone resorption via the NO/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signaling pathway. In addition to increasing NO availability, nitrate may enhance plasma insulin levels, reduce hyperglycemia, and improve insulin resistance in diabetes, further contributing to nitrates' anti-osteoporotic effects in diabetic bone. In conclusion, NO-based interventions such as nitrate may have a potential role in preventing and treating diabetoporosis.
Keywords: Diabetoporosis, Fracture risk, Nitric Oxide, nitrate, Osteoporosis
Received: 14 Aug 2024; Accepted: 21 Feb 2025.
Copyright: © 2025 Jeddi, Kashfi and Ghasemi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Khosrow Kashfi, School of Medicine, City University of New York, New York City, United States
Asghar Ghasemi, Endocrine Physiology Research Center, Shahid Beheshti University, Tehran, 1983963113, Tehran, Iran
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.