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Restoration of ovariectomy-induced osteopenia by nitroglycerin
1Department of Internal Medicine, General Medicine and Endocrinology, 8.104, Medical Research Building, The University of Texas Medical Branch at Galveston, 77555-1065, TX, USA. 77555-1065, USA.
Abstract:
Nitric oxide (NO) is known to inhibit osteoclastic bone resorption. Previously, we demonstrated that the NO donor nitroglycerin (NG) prevented ovariectomy (OVX)-induced bone loss. The current study shows that NG restores ovariectomy-induced osteopenia. Twenty-four female Sprague-Dawley rats, 36 weeks of age, underwent OVX, and a further six rats were sham-operated. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometric (DXA) scanning prior to OVX, at 6 weeks postsurgery, and at 6 weeks posttreatment. OVX rats were then assigned to four groups and treated with either (1) vehicle, (2) 17-beta-estradiol, (3) NG (0.2 mg/kg/day), or (4) a combination of estrogen and NG (n = 6/group). During the first 6-week post-OVX period, there was a significant decrease in the BMD in all ovariectomized (OVXed) rats (-11.0%, P < 0.001). There were no significant changes in BMD during the entire 12-week period in sham-operated rats. During the second 6-week period (after developing bone loss), there was no further significant loss of BMD in OVXed controls. BMD loss and loss of femur weight produced by OVXed were restored by treatment with estrogen, NG, or the two agents together during the second 6-week period (P < 0.01). The effects of estrogen and NG together, however, were not additive. The BMD of rats treated with NG alone, at 12 weeks, was similar to that of animals treated with estrogen alone or with estrogen and NG, and was comparable to that of sham-operated rats. The increased urinary excretion of deoxypyridinolines caused by OVX was negated by estrogen, NG, and estrogen together with NG (P < 0.01). In contrast to estrogen, NG did not decrease the post-OVX-induced increase of serum osteocalcin levels, suggesting that NG may also have a positive effect on bone formation. In summary, the results suggest that the NO donor, NG, reverses the OVX-induced bone loss in rats, and these effects are likely due to decreased bone resorption and, perhaps, increased bone formation.
Insights
Nitroglycerin (NG), a nitric oxide (NO) donor, reverses bone loss caused by ovariectomy (OVX) in rats. This study shows NG treatment restored bone mineral density and femur weight, suggesting potential for treating osteoporosis.
Area of Science:
- Bone Biology and Metabolism
- Pharmacology
- Endocrinology
Background:
- Nitric oxide (NO) is recognized for its inhibitory effect on osteoclastic bone resorption.
- Previous research indicated that the NO donor nitroglycerin (NG) could prevent bone loss induced by ovariectomy (OVX).
- Ovariectomy in rats is a common model for studying postmenopausal osteoporosis.
Purpose of the Study:
- To investigate whether NG can restore bone loss in established ovariectomy-induced osteopenia.
- To compare the effects of NG with 17-beta-estradiol and a combination of both on bone parameters.
- To explore the mechanisms underlying NG's effects on bone resorption and formation markers.
Main Methods:
- Twenty-four female Sprague-Dawley rats underwent OVX, with six serving as sham-operated controls.
- Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry (DXA) at baseline, 6 weeks post-surgery, and 6 weeks post-treatment.
- OVX rats were treated for 6 weeks with vehicle, 17-beta-estradiol, NG (0.2 mg/kg/day), or a combination of estrogen and NG.
Main Results:
- OVX induced significant bone loss (11.0% decrease in BMD) within 6 weeks, which was restored by estrogen, NG, or combined treatment during the subsequent 6 weeks.
- NG treatment negated the OVX-induced increase in urinary deoxypyridinolines, a marker of bone resorption.
- Unlike estrogen, NG did not decrease serum osteocalcin levels, suggesting a potential positive effect on bone formation.
Conclusions:
- The nitric oxide donor, nitroglycerin, effectively reverses ovariectomy-induced bone loss and osteopenia in rats.
- NG's therapeutic effects appear to stem from reduced bone resorption and possibly enhanced bone formation.
- NG demonstrates potential as a therapeutic agent for osteoporosis, comparable in efficacy to estrogen.