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Bone degeneration and recovery after early and late bisphosphonate treatment of ovariectomized wistar rats assessed by in vivo micro-computed tomography.

Brouwers JE, Lambers FM, Gasser JA, van Rietbergen B, Huiskes R - Calcif. Tissue Int. (2008)

Bottom Line: Late ZOL treatment significantly improved bone microstructure, although the structure did not recover to original levels.Early ZOL treatment resulted in a significantly better microstructure than late treatment.However, late treatment was still significantly better than no treatment.

View Article: PubMed Central - PubMed

Affiliation: Eindhoven University of Technology, P.O. Box 513, 5600MB Eindhoven, The Netherlands. j.e.m.brouwers@tue.nl

ABSTRACT
Bisphosphonates are antiresorptive drugs commonly used to treat osteoporosis. It is not clear, however, what the influence of the time point of treatment is. Recently developed in vivo micro-computed tomographic (CT) scanners offer the possibility to study such effects on bone microstructure in rats. The aim of this study was to determine the influence of early and late zoledronic acid treatment on bone in ovariectomized rats, using in vivo micro-CT. Twenty-nine female Wistar rats were divided into the following groups: ovariectomy (OVX, n = 5), OVX and zoledronic acid (ZOL) at week 0 (n = 8), OVX and ZOL at week 8 (n = 7), and sham (n = 9). CT scans were made of the proximal tibia at weeks 0, 2, 4, 8, 12, and 16; and bone structural parameters were determined in the metaphysis. Two fluorescent labels were administered to calculate dynamic histomorphometric parameters. At week 16, all groups were significantly different from each other in bone volume fraction (BV/TV), connectivity density, and trabecular number (Tb.N), except for the early ZOL and control groups which were not significantly different for any structural parameter. After ZOL treatment at week 8, BV/TV, structure model index, Tb.N, and trabecular thickness significantly improved in the late ZOL group. The OVX and ZOL groups showed, respectively, higher and lower bone formation rates than the control group. Early ZOL treatment inhibited all bone microstructural changes seen after OVX. Late ZOL treatment significantly improved bone microstructure, although the structure did not recover to original levels. Early ZOL treatment resulted in a significantly better microstructure than late treatment. However, late treatment was still significantly better than no treatment.

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Same slice of an unprocessed CT scan of the same rat in the OVX group taken at weeks 0 (a), 2 (b), 4 (c), 8 (d), 12 (e), and 16 (f). Images show typical trabecular bone loss due to OVX in the metaphysis. Green line shows the analyzed metaphyseal bone
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Fig2: Same slice of an unprocessed CT scan of the same rat in the OVX group taken at weeks 0 (a), 2 (b), 4 (c), 8 (d), 12 (e), and 16 (f). Images show typical trabecular bone loss due to OVX in the metaphysis. Green line shows the analyzed metaphyseal bone

Mentions: Based on the uterine weight, we determined seven unsuccessful OVXs. The rats concerned were removed from further analyses, which left nine rats in the control group, five in the OVX group, seven in the OVX and late ZOL group, and eight in the OVX and early ZOL group. For each animal, we determined the percentage change in structural parameters compared to the values at week 0. Figure 1 shows the average percentage change and upper standard deviation for all groups for BV/TV, Conn.D, SMI, Tb.N, Tb.Th, and Tb.Sp. The OVX group without treatment showed large changes in structural parameters, indicating the development of OVX-induced bone loss (Figs. 1 and 2). Paired Student’s t-test indicated significant changes within 2 weeks after OVX for all structural parameters. BV/TV, Conn.D, and Tb.N decreased during the experiment and SMI and Tb.Sp increased. Both Tb.Th and Tb.N decreased within 2 weeks, indicating that both thinning and complete resorption of trabeculae started directly after OVX. The initial rapid loss of bone and connectivity was largely accompanied by trabecular thinning, while secondary, slower loss of bone was concomitant with a decrease in Tb.N. While BV/TV, Conn.D, SMI, Tb.N, and Tb.Sp showed continuous changes in the same direction throughout the experiment, Tb.Th initially decreased significantly until 4 weeks after OVX and then increased again until after 16 weeks Tb.Th was significantly higher than in the control group.Fig. 1


Bone degeneration and recovery after early and late bisphosphonate treatment of ovariectomized wistar rats assessed by in vivo micro-computed tomography.

Brouwers JE, Lambers FM, Gasser JA, van Rietbergen B, Huiskes R - Calcif. Tissue Int. (2008)

Same slice of an unprocessed CT scan of the same rat in the OVX group taken at weeks 0 (a), 2 (b), 4 (c), 8 (d), 12 (e), and 16 (f). Images show typical trabecular bone loss due to OVX in the metaphysis. Green line shows the analyzed metaphyseal bone
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2268729&req=5

Fig2: Same slice of an unprocessed CT scan of the same rat in the OVX group taken at weeks 0 (a), 2 (b), 4 (c), 8 (d), 12 (e), and 16 (f). Images show typical trabecular bone loss due to OVX in the metaphysis. Green line shows the analyzed metaphyseal bone
Mentions: Based on the uterine weight, we determined seven unsuccessful OVXs. The rats concerned were removed from further analyses, which left nine rats in the control group, five in the OVX group, seven in the OVX and late ZOL group, and eight in the OVX and early ZOL group. For each animal, we determined the percentage change in structural parameters compared to the values at week 0. Figure 1 shows the average percentage change and upper standard deviation for all groups for BV/TV, Conn.D, SMI, Tb.N, Tb.Th, and Tb.Sp. The OVX group without treatment showed large changes in structural parameters, indicating the development of OVX-induced bone loss (Figs. 1 and 2). Paired Student’s t-test indicated significant changes within 2 weeks after OVX for all structural parameters. BV/TV, Conn.D, and Tb.N decreased during the experiment and SMI and Tb.Sp increased. Both Tb.Th and Tb.N decreased within 2 weeks, indicating that both thinning and complete resorption of trabeculae started directly after OVX. The initial rapid loss of bone and connectivity was largely accompanied by trabecular thinning, while secondary, slower loss of bone was concomitant with a decrease in Tb.N. While BV/TV, Conn.D, SMI, Tb.N, and Tb.Sp showed continuous changes in the same direction throughout the experiment, Tb.Th initially decreased significantly until 4 weeks after OVX and then increased again until after 16 weeks Tb.Th was significantly higher than in the control group.Fig. 1

Bottom Line: Late ZOL treatment significantly improved bone microstructure, although the structure did not recover to original levels.Early ZOL treatment resulted in a significantly better microstructure than late treatment.However, late treatment was still significantly better than no treatment.

View Article: PubMed Central - PubMed

Affiliation: Eindhoven University of Technology, P.O. Box 513, 5600MB Eindhoven, The Netherlands. j.e.m.brouwers@tue.nl

ABSTRACT
Bisphosphonates are antiresorptive drugs commonly used to treat osteoporosis. It is not clear, however, what the influence of the time point of treatment is. Recently developed in vivo micro-computed tomographic (CT) scanners offer the possibility to study such effects on bone microstructure in rats. The aim of this study was to determine the influence of early and late zoledronic acid treatment on bone in ovariectomized rats, using in vivo micro-CT. Twenty-nine female Wistar rats were divided into the following groups: ovariectomy (OVX, n = 5), OVX and zoledronic acid (ZOL) at week 0 (n = 8), OVX and ZOL at week 8 (n = 7), and sham (n = 9). CT scans were made of the proximal tibia at weeks 0, 2, 4, 8, 12, and 16; and bone structural parameters were determined in the metaphysis. Two fluorescent labels were administered to calculate dynamic histomorphometric parameters. At week 16, all groups were significantly different from each other in bone volume fraction (BV/TV), connectivity density, and trabecular number (Tb.N), except for the early ZOL and control groups which were not significantly different for any structural parameter. After ZOL treatment at week 8, BV/TV, structure model index, Tb.N, and trabecular thickness significantly improved in the late ZOL group. The OVX and ZOL groups showed, respectively, higher and lower bone formation rates than the control group. Early ZOL treatment inhibited all bone microstructural changes seen after OVX. Late ZOL treatment significantly improved bone microstructure, although the structure did not recover to original levels. Early ZOL treatment resulted in a significantly better microstructure than late treatment. However, late treatment was still significantly better than no treatment.

Show MeSH
Related in: MedlinePlus