A randomized clinical trial of the effects of isosorbide mononitrate on bone formation and resorption in post-menopausal women: a pilot study.
BACKGROUND
Nitric oxide (NO) stimulates bone formation and inhibits bone resorption in vitro. NO donors (nitrates) are inexpensive and widely available, but their value for post-menopausal osteoporosis has never been evaluated in a randomized trial. The objective of this study was to compare the effects of 5 and 20 mg of isosorbide mononitrate (ISMO) on markers of bone turnover in post-menopausal women.


METHODS
A prospective randomized trial was carried out in the Department of Obstetrics & Gynecology, Ain Shams University, Egypt. The study included 50 healthy post-menopausal women with a hip bone mineral density T score between 0 and -2.5. Participants were randomly assigned to 5 or 20 mg/day of ISMO for 12 weeks. Urine N-telopeptide (NTx), a marker of bone resorption, and serum bone-specific alkaline phosphatase (BSALP), a marker of bone formation, were measured. Markers were measured immediately before randomization and after 12 weeks of treatment. The percent change in NTx and BSALP for each of the treatment groups (5 mg ISMO and 20 mg ISMO) was calculated. The main outcome measures were serum NTx and BSALP in the 5 and 20 mg ISMO groups after 12 weeks of treatment.


RESULTS
Women adhering to 20 mg of ISMO had a 42.03% (95% confidence interval (CI), 20.1-73.7) reduction in NTx and a 29.05% (95% CI, 10.8-48.4) increase in BSALP, and women adhering to 5 mg of ISMO had a 31.12% (95% CI, 8.3-68.2) reduction in NTx and a 28.4% (95% CI, 4.6-52.1) increase in BSALP.


CONCLUSIONS
ISMO, as a NO donor, may be useful for the prevention of post-menopausal osteoporosis.
Nabhan
Ashraf F I
AF
Department of Obstetrics & Gynecology, Ain Shams University, Cairo, Egypt. ashraf.nabhan@gmail.com
D000469:Alkaline Phosphatase / Q000097:blood; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015519:Bone Density / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects; D001862:Bone Resorption / Q000517:prevention & control*; D001842:Bone and Bones / Q000201:enzymology; D024042:Collagen Type I / Q000652:urine; D005260:Female; D006801:Humans; D007548:Isosorbide Dinitrate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008875:Middle Aged; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000627:therapeutic use*; D010012:Osteogenesis / Q000187:drug effects*; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control*; D010455:Peptides / Q000652:urine; D010865:Pilot Projects; D017698:Postmenopause
D015415:Biomarkers; D024042:Collagen Type I; D020030:Nitric Oxide Donors; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D000469:Alkaline Phosphatase; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate