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Frequency-dependent effect of nitric oxide donor nitroglycerin on bone
S Wimalawansa1, T Chapa, L Fang
1Department of Internal Medicine, The University of Texas Medical Branch at Galveston, 77555-1065, USA.
Summary
Nitroglycerin (NG) prevents bone loss in ovariectomized rats, similar to estrogen. However, its bone-protective effects diminish with increased application frequency, highlighting the importance of dosing for nitric oxide (NO) therapy.
Area of Science:
- Endocrinology
- Bone Biology
- Pharmacology
Background:
- Estrogen deficiency, common after ovariectomy, leads to significant bone loss.
- Nitric oxide (NO) donors, like nitroglycerin (NG), have previously shown potential in mitigating bone loss.
- The efficacy of NG in angina treatment decreases with frequent application, raising questions about its bone-protective effects.
Purpose of the Study:
- To investigate the frequency-dependent effects of NG on bone mineral density (BMD) and bone mass in an ovariectomized rat model.
- To compare the efficacy of different NG application frequencies with estrogen therapy.
- To assess the impact of NG frequency on bone turnover markers and blood pressure.
Main Methods:
- Ovariectomized and sham-operated female Brown Norway rats were treated with vehicle, 17beta-estradiol (E2), or NG (0.2 mg, dermal) once, twice, or thrice daily for 10 weeks.
- BMD of the lumbar spine was measured using dual-energy X-ray absorptiometry (DXA).
- Femur weights, trabecular bone volumes (BV/TV), urinary deoxypyridinoline, serum osteocalcin, and bone-specific alkaline phosphatase were analyzed. Blood pressure was monitored.
Main Results:
- Once-daily NG application completely prevented ovariectomy-induced bone loss, comparable to E2 treatment.
- Increased NG application frequency (twice or thrice daily) significantly reduced its efficacy in preserving BMD.
- While once-daily NG maintained bone mass and reduced bone resorption markers, higher frequencies led to less favorable changes in bone turnover markers and a tendency to lower blood pressure.
Conclusions:
- NO supplementation via NG can effectively counteract estrogen deficiency-induced bone loss in rats.
- The bone-protective benefits of NG are frequency-dependent, with once-daily application being most effective.
- These findings suggest that careful consideration of dosing frequency is crucial for optimizing the therapeutic potential of NO donors in bone health.