Osteopenia in genetically diabetic DB/DB mice and effects of 1alpha-hydroxyvitamin D3 on the osteopenia. Basic Research Group.
To explore the pathogenesis of non-insulin-dependent diabetes mellitus associated osteopenia, we examined age-related changes of the femur metaphyseal bone mineral density in genetically diabetic (db/db) mice and non-diabetic (+/+) mice of the same strain using single photon absorptiometry and characterized the osteopenia pharmacologically and biochemically. Bone mineral density increased with age in the +/+ mice from 5 to 16 weeks of age, but reached a plateau in the db/db mice at 8 weeks of age, and significant differences between the two groups were observed after 12 weeks of age. Ash weight (A) and dry weight (D) of the femur and A/D ratio were significant lower in the db/db mice than in the +/+ mice after 8 weeks of age. Significant elevations of serum calcium and parathyroid hormone (PTH) were observed after 8 weeks and 12 weeks of age, respectively. Serum 1alpha,25-dihydroxyvitamin D levels were significantly decreased in the db/db mice compared to the +/+ mice. Daily oral treatment with 1alpha-hydroxyvitamin D3 (1alpha-(OH)D3) for 4 weeks starting from 8 weeks of age significantly attenuated the bone loss in the db/db mice. These results suggest that an impaired bone mineralization probably by insufficient vitamin D activity and high PTH levels are involved in the osteopenia in the db/db mice. 1alpha-(OH)D3 exerted beneficial effects on the bone loss.
Takeshita
N
N
Tsukuba Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., Ibaraki, Japan.
Mutoh
S
S
Yamaguchi
I
I
D015502:Absorptiometry, Photon; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D015519:Bone Density / Q000187:drug effects*; D001851:Bone Diseases, Metabolic / Q000188:drug therapy* / Q000209:etiology; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005269:Femur / Q000502:physiology; D006887:Hydroxycholecalciferols / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D010281:Parathyroid Hormone / Q000097:blood
D001786:Blood Glucose; D006887:Hydroxycholecalciferols; D007328:Insulin; D010281:Parathyroid Hormone; D002117:Calcitriol; D002118:Calcium; C008088:alfacalcidol