Possible involvement of vitamin D3-deficiency and relatively enhanced bone resorption in the development of bone loss in streptozotocin-induced diabetic rats.

Abstract

To explore the pathogenesis of diabetes associated osteopenia, we characterized the osteopenia in streptozotocin (STZ)-diabetic rats pharmacologically and biochemically. The femur metaphyseal bone mineral density measured by single photon absorptiometry decreased time-dependently in the STZ rats compared with that in control, and the difference reached statistical significance from 2 weeks after treatment with STZ. Closely similar bone loss was obtained in ovariectomized (Ovx) and vitamin D deficient(D(-)) rats. Daily oral treatment with a bone resorption inhibitor, FR78844 (a bisphosphonate compound, 100 mg/kg), for 4 weeks significantly attenuated the osteopenia in the STZ and Ovx rats, but not in the D(-) rats, while 1 alpha-hydroxyvitamin D3 (1 alpha-(OH)D3) significantly attenuated the osteopenia in the STZ and D(-) rats in a dose of 0.1 microgram/kg/day, and that in the Ovx rats in 1 microgram/kg/day. The latter dose of 1 alpha-(OH)D3 significantly increased the metaphyseal bone mineral density of the femur in normal rats. Serum levels of 1 alpha, 25-dihydroxyvitamin D (1 alpha, 25-(OH)2D), the most active metabolite of vitamin D, hardly changed in the Ovx rats compared with that in control, but decreased to 24 and 76% that of control in the STZ and D(-) rats, respectively. Serum PTH levels in the STZ, Ovx and D(-) rats were comparable with those in controls, but serum calcitonin levels were reduced to 60 and 66% of control in the STZ and Ovx rats, respectively. Serum osteocalcin levels also decreased in the STZ rats compared to control. It is thus speculated that the predominance of bone resorption over bone formation and the reduction of 1 alpha, 25-(OH)2D are involved in the pathogenesis of diabetes associated osteopenia.

• Authors: N Takeshita, T Yoshino, S Mutoh, I Yamaguchi
• Journal: Life sciences (Life Sci) Vol. 55 Issue 4 Pg. 291-9 ( 1994) ISSN: 0024-3205 [Print] Netherlands
• PMID: 8028447 (Publication Type: Journal Article)

Chemical References

• Diphosphonates
• Hydroxycholecalciferols
• FR 78844
• Cholecalciferol
• Streptozocin

Topics

• Animals
• Bone Density
• Bone Diseases, Metabolic (etiology)
• Bone Resorption (complications, prevention & control)
• Cholecalciferol (deficiency)
• Diabetes Mellitus, Experimental (complications, physiopathology)
• Diphosphonates (therapeutic use)
• Female
• Hydroxycholecalciferols (blood, therapeutic use)
• Ovariectomy
• Rats
• Rats, Wistar
• Streptozocin
• Vitamin D Deficiency (complications, drug therapy)