Volume 67, Issue 3, Pages 920-930 (March 2005) Time-evolution and reversibility of strontium-induced osteomalacia in chronic renal failure rats  Line Oste, An R. Bervoets, Geert J. Behets, Geert Dams, Rita L. Marijnissen, Hilde Geryl, Ludwig V. Lamberts, Steven C. Verberckmoes, Viviane O. Van Hoof, Marc E. De Broe, Patrick C. D'Haese  Kidney International  Volume 67, Issue 3, Pages 920-930 (March 2005) DOI: 10.1111/j.1523-1755.2005.00156.x Copyright © 2005 International Society of Nephrology Terms and Conditions

Figure 1 Time scheme of the experimental study setup. CRF is chronic renal failure; WO is washout. Kidney International 2005 67, 920-930DOI: (10.1111/j.1523-1755.2005.00156.x) Copyright © 2005 International Society of Nephrology Terms and Conditions

Figure 2 Effect of strontium (Sr) loading and subsequent washout (WO) period on (A) phosphaturia and (B) calciuria. Values are expressed as mean ± SEM. aP < 0.05 versus controls; bP < 0.05 versus strontium-loading without washout. Kidney International 2005 67, 920-930DOI: (10.1111/j.1523-1755.2005.00156.x) Copyright © 2005 International Society of Nephrology Terms and Conditions

Figure 3 Strontium (Sr) concentration during 2, 6, and 12 weeks of strontium loading and serum strontium concentration after washout (WO) of 2, 4, or 8 weeks. (A) Mean serum strontium concentration. (B) Mean urinary strontium concentration. (C) Bulk strontium concentration in bone. Values are expressed as mean ± SEM. aP < 0.05 versus controls; bP < 0.05 versus strontium loading without washout. Kidney International 2005 67, 920-930DOI: (10.1111/j.1523-1755.2005.00156.x) Copyright © 2005 International Society of Nephrology Terms and Conditions

Figure 4 Effect of renal failure, strontium (Sr) loading, and washout (WO) on parathyroid hormone (PTH) concentration. Values are expressed as mean ± SEM. aP < 0.05 versus controls; bP < 0.05 versus strontium-loading without washout; cP < 0.05 versus pre-chronic renal failure (CRF). Kidney International 2005 67, 920-930DOI: (10.1111/j.1523-1755.2005.00156.x) Copyright © 2005 International Society of Nephrology Terms and Conditions

Figure 5 Serum alkaline phosphatase (ALP) isoenzymes. (A) Total serum ALP activity. (B) Bone ALP activity. (C) Liver ALP activity. (D) Intestinal ALP activity. Values are expressed as mean ± SEM. aP < 0.05 versus controls; bP < 0.05 versus strontium (Sr) loading without washout (WO). Kidney International 2005 67, 920-930DOI: (10.1111/j.1523-1755.2005.00156.x) Copyright © 2005 International Society of Nephrology Terms and Conditions

Figure 6 Histologic data of the various study groups. Data are as mean ± SEM. aP < 0.05 versus controls; bP < 0.05 versus strontium (Sr) loading without washout (WO). Kidney International 2005 67, 920-930DOI: (10.1111/j.1523-1755.2005.00156.x) Copyright © 2005 International Society of Nephrology Terms and Conditions

Figure 7 Goldner-stained histologic bone samples and tetracycline labeling. (A) Normal bone histology in a 12-week control chronic renal failure (CRF) rat with large, cuboidal osteoblasts lining the osteoid tissue. (B) Bone histology of CRF rat after 12 weeks of strontium loading. There is an increased amount of osteoid tissue without the presence of active osteoblasts. (C) Bone histology of a CRF rat after 12 weeks of strontium loading, followed by a washout period of 2 weeks. Large amounts of osteoid tissue are still present but osteoblasts have reappeared. (D) Bone histology of a CRF rat after 12 weeks of strontium loading, followed by a washout period of 4 weeks. Active osteoblasts are lining a normal amount of osteoid tissue. (E) Fluorescent tetracycline labeling in a CRF rat after 12 weeks of strontium loading. No labels are incorporated, which indicates the development of a mineralization defect. (F) Tetracycline labeling in a 12-week control CRF rat. Normal double labels are present. Kidney International 2005 67, 920-930DOI: (10.1111/j.1523-1755.2005.00156.x) Copyright © 2005 International Society of Nephrology Terms and Conditions