The effects of vanadium treatment on bone in diabetic and non-diabetic rats.
Vanadium-based drugs lower glucose by enhancing the effects of insulin. Oral vanadium drugs are being tested for the treatment of diabetes. Vanadium accumulates in bone, though it is not known if incorporated vanadium affects bone quality. Nine- to 12-month-old control and streptozotocin-induced diabetic female Wistar rats were given bis(ethylmaltolato)oxovanadium(IV) (BEOV), a vanadium-based anti-diabetic drug, in drinking water for 12 weeks. Non-diabetic rats received 0, 0.25 or 0.75 mg/ml BEOV. Groups of diabetic rats were either untreated or treated with 0.25-0.75 mg/ml BEOV as necessary to lower blood glucose in each rat. In diabetic rats, this resulted in a Controlled Glucose group, simulating relatively well-managed diabetes, and an Uncontrolled Glucose group, simulating poorly managed diabetes. Plasma insulin, glucose and triglyceride assays assessed the diabetic state. Bone mineral density (BMD), mechanical testing, mineral assessment and histomorphometry measured the effects of diabetes on bone and the effects of BEOV on non-diabetic and diabetic bone. Diabetes decreased plasma insulin and increased plasma glucose and triglycerides. In bone, diabetes decreased BMD, strength, mineralization, bone crystal length, and bone volume and connectivity. Treatment was effective in incorporating vanadium into bone. In all treated groups, BEOV increased osteoid volume. In non-diabetic bone, BEOV increased cortical bone toughness, mineralization and bone formation. In controlled glucose rats, BEOV lowered plasma glucose and improved BMD, mechanical strength, mineralization, bone crystal length and bone formation rate. In poorly controlled rats, BEOV treatment slightly lowered plasma glucose but did not improve bone properties. These results suggest that BEOV improves diabetes-related bone dysfunction primarily by improving the diabetic state. BEOV also appeared to increase bone formation. Our study found no negative effects of vanadium accumulation in bone in either diabetic or non-diabetic rats at the dose given.
Facchini
D M
DM
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Ave., Toronto, Canada M5G 1X5. facchini@mshri.on.ca
Yuen
V G
VG
Battell
M L
ML
McNeill
J H
JH
Grynpas
M D
MD
D015502:Absorptiometry, Photon; D000284:Administration, Oral; D000818:Animals; D001696:Biomechanical Phenomena; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D015519:Bone Density; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D007328:Insulin / Q000097:blood; D011863:Radioimmunoassay; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000097:blood; D014638:Vanadates / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D014961:X-Ray Diffraction
D001786:Blood Glucose; D007328:Insulin; D014280:Triglycerides; D014638:Vanadates