title: Prevention of corticosteroid-induced bone loss with nitric oxide donor nitroglycerin in male rats.
abstract: Nitric oxide (NO) has been reported to inhibit osteoclastic bone resorption. We examined the bone sparing effect of NO on prevention of corticosteroid-induced bone loss in older male rats. Recently, we demonstrated that NO donor nitroglycerin (NG) can alleviate ovariectomy-induced bone loss, and the protective effects of estrogens on bone are mediated through NO [Bone 18(4):301-304; 1996]. Therefore, we chose to study a different model (i.e., steroid-induced osteoporosis in males) to evaluate whether NG can inhibit the bone loss associated with corticosteroid therapy. Twenty-five 32-week-old male Wistar rats were randomly assigned to five groups (n = 5/group). They received either vehicle, methylprednisolone (7 mg/kg per week), NO synthase inhibitor L-NAME (25 mg/kg per day), NO donor nitroglycerin (NG, 0.2 mg twice daily), a combination of prednisolone+NG, or prednisolone plus L-NAME, respectively. Prior to treatment and at the end of the 6 week treatment period, bone mineral density (BMD) of the lumbar spine was measured by dual energy X-ray absorptiometry scanning. Administration of prednisolone significantly decreased BMD (-9.50%, p < 0.05). The group receiving NG with prednisolone (-2.34%) and the group treated with NG alone (-0.36%) were not statistically different from the control group (-0.11%). Similar to the changes in BMD, femur weights were also significantly lower in prednisolone-treated rats (1.09 +/- 0.01 g vs. 1.17 +/- 0.03 in controls; p < 0.05). However, the rats receiving prednisolone together with NG were able to maintain their femur weights (1.13 +/- 0.02). There was a reduction of 9.5% of BMD (p < 0.05) and 7.8% of femoral weight (p < 0.05) in rats treated with L-NAME. A 50%-70% reduction of the percentage trabecular bone volume in the proximal tibia and distal femur and a 50% reduction of the midshaft cortical area was seen after corticosteroid therapy, and these too were prevented by administration of NG. Here, we demonstrate, for the first time, that supplementation with a NO donor compound can counteract prednisolone-induced bone loss.
authors.affiliation: Department of Internal Medicine, University of Texas Medical Branch at Galveston 77555-1065, USA. swimalaw@impo1.utmb.edu
authors.forename: S J
authors.initials: SJ
authors.lastname: Wimalawansa
authors.forename: M T
authors.initials: MT
authors.lastname: Chapa
authors.forename: C
authors.initials: C
authors.lastname: Yallampalli
authors.forename: R
authors.initials: R
authors.lastname: Zhang
authors.forename: D J
authors.initials: DJ
authors.lastname: Simmons
mesh_terms: D015502:Absorptiometry, Photon; D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D001862:Bone Resorption / Q000139:chemically induced / Q000517:prevention & control*; D005269:Femur / Q000187:drug effects; D008297:Male; D008775:Methylprednisolone; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D005996:Nitroglycerin / Q000627:therapeutic use*; D015675:Osteocalcin / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000097:blood; D013977:Tibia / Q000187:drug effects
chemical_list: D015675:Osteocalcin; D009569:Nitric Oxide; D013739:Testosterone; D005996:Nitroglycerin; D019331:NG-Nitroarginine Methyl Ester; D008775:Methylprednisolone