Glucocorticoid-induced osteoporosis in the rat is prevented by the tyrosine phosphatase inhibitor, sodium orthovanadate  P.A Hulley, M.M Conradie, C.R.

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Glucocorticoid-induced osteoporosis in the rat is prevented by the tyrosine phosphatase inhibitor, sodium orthovanadate  P.A Hulley, M.M Conradie, C.R Langeveldt, F.S Hough  Bone  Volume 31, Issue 1, Pages 220-229 (July 2002) DOI: 10.1016/S8756-3282(02)00807-4 Copyright © 2002 Elsevier Science Inc. Terms and Conditions

Figure 1 Rat weights. Rats were weighed two or three times per week throughout the 9 week course of the study. Weights on day 1 of each week are presented as an average of ten rats for each treatment group. Rats were given sham injections alone (C, solid line, open circles), daily subcutaneous injections of 3.5 mg/kg methylprednisolone (S, solid line, filled circles), daily subcutaneous injections of 3.5 mg/kg methylprednisolone plus 0.5 mg/mL sodium orthovanadate in pH 6–7 drinking water ad libitum (SV, dashed line, open triangles), or sham injection plus 0.5 mg/mL sodium orthovanadate in pH 6–7 drinking water ad libitum (V, dashed line, filled triangles). Bone 2002 31, 220-229DOI: (10.1016/S8756-3282(02)00807-4) Copyright © 2002 Elsevier Science Inc. Terms and Conditions

Figure 2 Effect of glucocorticoid and sodium orthovanadate on BMD and BMC. Rats (n = 10 per group) were given sham injections alone (C, open bars), daily subcutaneous injections of 3.5 mg/kg methylprednisolone (S, hatched bars), daily subcutaneous injections of 3.5 mg/kg methylprednisolone plus 0.5 mg/mL sodium orthovanadate in pH 6–7 drinking water ad libitum (SV, filled bars), or sham injection plus 0.5 mg/mL sodium orthovanadate in pH 6–7 drinking water ad libitum (V, stippled bars), for a period of 9 weeks. After killing, BMD and BMC of the right femur were determined using Hologic’s small animal program for dual-energy X-ray absorptiometry. (A) Mean ± SD BMD of femur. **p < 0.005 vs. S (steroid-treated group). (B) Mean ± SD BMC of femur. *p < 0.05 and **p < 0.005 vs. S (steroid-treated group). Bone 2002 31, 220-229DOI: (10.1016/S8756-3282(02)00807-4) Copyright © 2002 Elsevier Science Inc. Terms and Conditions

Figure 3 Effect of glucocorticoid and sodium orthovanadate treatment on static and dynamic parameters of bone formation in the proximal tibia. Rats (n = 10 per group) were given sham injections alone (C, open bars), daily subcutaneous injections of 3.5 mg/kg methylprednisolone (S, hatched bars), daily subcutaneous injections of 3.5 mg/kg methylprednisolone plus 0.5 mg/mL sodium orthovanadate in pH 6–7 drinking water ad libitum (SV, filled bars), or sham injection plus 0.5 mg/mL sodium orthovanadate in pH 6–7 drinking water ad libitum (V, stippled bars), for a period of 9 weeks. Rats were double tetracycline-labeled by injection 13 and 3 days before killing. The left tibias were fixed in Millonig solution, embedded in plastic, and processed for quantitative histomorphometry. (A) Dynamic formation parameters as determined by time-spaced tetracycline labeling. *p < 0.05 and **p < 0.001 vs. S (steroid-treated group). (B) Static formation parameters. *p < 0.05 vs. S (steroid-treated group). (C) Static resorptive parameters. *p < 0.05 vs. C (control group). Bone 2002 31, 220-229DOI: (10.1016/S8756-3282(02)00807-4) Copyright © 2002 Elsevier Science Inc. Terms and Conditions

Figure 4 Effect of glucocorticoid and sodium orthovanadate on mechanical strength of bones. Rats (n = 10 per group) were given sham injections alone (C, white bars), daily subcutaneous injections of 3.5 mg/kg methylprednisolone (S, hatched bars), daily subcutaneous injections of 3.5 mg/kg methylprednisolone plus 0.5 mg/mL sodium orthovanadate in pH 6–7 drinking water ad libitum (SV, filled bars), or sham injection plus 0.5 mg/mL sodium orthovanadate in pH 6–7 drinking water ad libitum (V, stippled bars), for a period of 9 weeks. (A) Tensile strength of long bones was tested by a three point bending test, with the tibia being clipped into a frame and incrementally loaded until the breaking point was reached. *p < 0.05 vs. C (control group). (B) Compressive strength of vertebrae was tested by incremental crushing of the fourth lumbar vertebra, with the breaking point being taken as the maximum force recorded before the collapse of the vertebral body. Both tests were performed in a compression cage attached to an Instron tensile tester with 50 kg load cell (n = 10 per group, ±SD). Bone 2002 31, 220-229DOI: (10.1016/S8756-3282(02)00807-4) Copyright © 2002 Elsevier Science Inc. Terms and Conditions