Preventive effects of nitroglycerine on glucocorticoid-induced osteoporosis in growing rats

Abstract

The preventive effects of nitroglycerine (NG) on glucocorticoid-induced osteoporosis in growing rats were studied. Three-month-old female Wistar rats were randomly divided into control group (CON), dexamethasone group (DXM), DXM plus a low dose NG group (NG-L), DXM plus a middle dose NG group (NG-M) and DXM plus a high dose NG group (NG-H), 8 rats in each group. The rat model of osteoporosis was developed by intramuscular injection of dexamethasone twice a week. NG 0.2, 0.4 and 1.0 mg/kg was administered by oral gavages to the treatment groups every day for 12 weeks. Rats in CON group and DXM group were treated with normal saline of the same amount. After the treatment, the bone mineral density (BMD) and bone metabolism-associated biochemical markers were determined. Compared with CON group, BMD of lumbar spine and femur in DXM group was decreased significantly (P<0.05 and P<0.01 respectively), blood BGP levels and NO levels reduced (both P<0.01), and TRAP level increased (P<0.05). As compared with DXM group, BMD, serum BGP and NO were increased, and TRAP decreased in NG-L group and NG-M group, but had no significant difference in comparison to CON group. All the markers other than serum NO and TRAP levels had no significant difference between NG-H group and DXM group. It was concluded that low or middle doses of NG could prevent glucocorticoid-induced bone loss in growing rats, but high dose of NG could not. Supplement with NO donor could be considered as a preventive treatment for glucocorticoid-induced osteoporosis in a developing skeleton.

Keywords

glucocorticoid-induced osteoporosis / nitroglycerin / nitric oxide / nitric oxide donor

References

[1] ErbenR. G.. Trabecular and endocortical bone surfaces in the rat: modeling or remodeling?. Anat Rec, 1966, 246: 39-46

[2] IwamotoJ., ShimamuraC., TakedaT., et al.. Effects of treadmill exercise on bone mass, bone metabolism, and calciotropic hormones in young growing rats. J Bone Miner Metab, 2004, 22: 26-31

[3] Lafage-ProustM. H., BoudignonB., ThomasT., et al.. Glucocorticoid-induced osteoporosis: pathophysiological data and recent treatments. Joint Bone Spine, 2003, 70(2): 109-118

[4] WeinsteinR. S., JilkaR. L., ParfittA. M., et al.. Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone. J Clin Invest, 1998, 102(2): 274-282

[5] HelfrichM. H., EvansD. E., GrabowskiP. S., et al.. Expression of nitric oxide synthase isoforms in bone and bone cell cultures. J Bone Miner Res, 1997, 12(7): 1108-1115

[6] FoxS. W., ChowJ. W.. Nitric oxide synthase expression in bone cells. Bone, 1998, 23: 1-6

[7] RalstonS. H., HoL. P., HelfrichM. H., et al.. Nitric oxide: a cytokine-induced regulator of bone resorption. J Bone Miner Res, 1995, 10: 1040-1049

[8] KoyamaA., OtsukaE., InoueA., et al.. Nitric oxide accelerates the ascorbic acid-induced osteoblastic differentiation of mouse stromal ST2 cells by stimulating the production of prostaglandin E (2). Eur J Pharmacol, 2000, 391: 225-231

[9] ManciniL., Moradi-BidhendiN., BecheriniL., et al.. The biphasic effects of nitric oxide in primary rat osteoblasts are cGMP dependent. Biochem Biophys Res Comm, 2000, 274: 477-481

[10] WimalawansaS. J., ChapaM. T., YallampalliC., et al.. Prevention of corticosteroid-induced bone loss with nitric oxide donor nitroglycerin in male rats. Bone, 1997, 21(3): 275-280

[11] WallerathT., WitteK., SchaferS. C., et al.. Down-regulation of the expression of endothelial NO synthase is likely to contribute to glucocorticoid-mediated hypertension. Proc Natl Acad Sci U S A, 1999, 96(23): 13 357-13-362

[12] WimalawansaS., ChapaT., FangL., et al.. Frequency-dependent effect of nitric oxide donor nitroglycerin on bone. J Bone Miner Res, 2000, 15(6): 1119-1125