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Modifying the osteoblastic niche with zoledronic acid in vivo-potential implications for breast cancer bone metastasis.

Haider MT, Holen I, Dear TN, Hunter K, Brown HK - Bone (2014)

Bottom Line: The associated cancer-induced bone disease is treated with bone-sparing agents like zoledronic acid.The effects on growth plate cartilage were visualised by toluidine blue staining.The number of circulating tumour cells was reduced in ZOL treated animals.

View Article: PubMed Central - PubMed

Affiliation: CR-UK/YCR Cancer Research Centre, University of Sheffield, Sheffield, UK. Electronic address: mhaider1@sheffield.ac.uk.

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Related in: MedlinePlus

Zoledronic acid-induced effects on osteoclasts and osteoblasts.(A) Tartrate-resistant alkaline phosphatase (TRAP) and (B) N-terminal propeptide of type I procollagen (PINP) concentration in serum samples of 6-week old female balb/c mice treated with a single dose of 100 μg/kg ZOL or PBS were analysed 1, 3, 5 and 10 days after injection in order to determine osteoclast and osteoblast activity, respectively (n = 5/time point and treatment group). (C) Osteoclasts (Oc) per mm trabecular bone surface and (G) osteoclast size in mm2 were scored on TRAP-stained histological sections. (D) Osteoblasts (Ob) per mm trabecular bone surface were scored on H&E stained sections of the right tibia. (E) Representative images of TRAP stained sections of proximal tibias. Scale bar = 100 μm, 20 × magnification. Example images for osteoclast size difference post ZOL vs. PBS treatment are illustrated in (F). Scale bar = 50 μm. Arrows indicate rows of osteoblasts; stars indicate TRAP-positive osteoclasts (red). Day 1: n = 7, day 3: n = 6, day 5: n = 7, day 10: n = 6 for PBS and n = 5 for all time points for ZOL. Two-way ANOVA and Bonferroni post-test: ****p ≤ 0.0001, ***p ≤ 0.001, **p ≤ 0.01, *p ≤ 0.05. All graphs show mean ± SEM.
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f0015: Zoledronic acid-induced effects on osteoclasts and osteoblasts.(A) Tartrate-resistant alkaline phosphatase (TRAP) and (B) N-terminal propeptide of type I procollagen (PINP) concentration in serum samples of 6-week old female balb/c mice treated with a single dose of 100 μg/kg ZOL or PBS were analysed 1, 3, 5 and 10 days after injection in order to determine osteoclast and osteoblast activity, respectively (n = 5/time point and treatment group). (C) Osteoclasts (Oc) per mm trabecular bone surface and (G) osteoclast size in mm2 were scored on TRAP-stained histological sections. (D) Osteoblasts (Ob) per mm trabecular bone surface were scored on H&E stained sections of the right tibia. (E) Representative images of TRAP stained sections of proximal tibias. Scale bar = 100 μm, 20 × magnification. Example images for osteoclast size difference post ZOL vs. PBS treatment are illustrated in (F). Scale bar = 50 μm. Arrows indicate rows of osteoblasts; stars indicate TRAP-positive osteoclasts (red). Day 1: n = 7, day 3: n = 6, day 5: n = 7, day 10: n = 6 for PBS and n = 5 for all time points for ZOL. Two-way ANOVA and Bonferroni post-test: ****p ≤ 0.0001, ***p ≤ 0.001, **p ≤ 0.01, *p ≤ 0.05. All graphs show mean ± SEM.

Mentions: As early as three days after administration there was a significant reduction in osteoclast activity in ZOL treated animals compared to control, measured by serum TRAP concentration (PBS: 7.26 U/L vs. ZOL: 3.22 U/L; p ≤ 0.01; Fig. 3A). This effect was transient and TRAP levels in the ZOL group started to increase again by day 5. The effect of the bisphosphonate on osteoclasts was further confirmed with the detection of a significant reduction in the osteoclast number on trabecular bone surfaces 3 days after ZOL injection compared to control (PBS: 4.97 vs. ZOL: 1.20; p ≤ 0.01; Fig. 3C). The osteoclast number started to normalise to control levels on day 5. We also detected an increase in osteoclast size as early as 24 h after ZOL administration when compared to mice receiving PBS, which reached significance at day 3 (PBS: 7.99 × 10− 05 mm2 vs. ZOL: 1.89 × 10− 04 mm2, p ≤ 0.001, Fig. 3F and G).


Modifying the osteoblastic niche with zoledronic acid in vivo-potential implications for breast cancer bone metastasis.

Haider MT, Holen I, Dear TN, Hunter K, Brown HK - Bone (2014)

Zoledronic acid-induced effects on osteoclasts and osteoblasts.(A) Tartrate-resistant alkaline phosphatase (TRAP) and (B) N-terminal propeptide of type I procollagen (PINP) concentration in serum samples of 6-week old female balb/c mice treated with a single dose of 100 μg/kg ZOL or PBS were analysed 1, 3, 5 and 10 days after injection in order to determine osteoclast and osteoblast activity, respectively (n = 5/time point and treatment group). (C) Osteoclasts (Oc) per mm trabecular bone surface and (G) osteoclast size in mm2 were scored on TRAP-stained histological sections. (D) Osteoblasts (Ob) per mm trabecular bone surface were scored on H&E stained sections of the right tibia. (E) Representative images of TRAP stained sections of proximal tibias. Scale bar = 100 μm, 20 × magnification. Example images for osteoclast size difference post ZOL vs. PBS treatment are illustrated in (F). Scale bar = 50 μm. Arrows indicate rows of osteoblasts; stars indicate TRAP-positive osteoclasts (red). Day 1: n = 7, day 3: n = 6, day 5: n = 7, day 10: n = 6 for PBS and n = 5 for all time points for ZOL. Two-way ANOVA and Bonferroni post-test: ****p ≤ 0.0001, ***p ≤ 0.001, **p ≤ 0.01, *p ≤ 0.05. All graphs show mean ± SEM.
© Copyright Policy - CC BY-NC-SA
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4127787&req=5

f0015: Zoledronic acid-induced effects on osteoclasts and osteoblasts.(A) Tartrate-resistant alkaline phosphatase (TRAP) and (B) N-terminal propeptide of type I procollagen (PINP) concentration in serum samples of 6-week old female balb/c mice treated with a single dose of 100 μg/kg ZOL or PBS were analysed 1, 3, 5 and 10 days after injection in order to determine osteoclast and osteoblast activity, respectively (n = 5/time point and treatment group). (C) Osteoclasts (Oc) per mm trabecular bone surface and (G) osteoclast size in mm2 were scored on TRAP-stained histological sections. (D) Osteoblasts (Ob) per mm trabecular bone surface were scored on H&E stained sections of the right tibia. (E) Representative images of TRAP stained sections of proximal tibias. Scale bar = 100 μm, 20 × magnification. Example images for osteoclast size difference post ZOL vs. PBS treatment are illustrated in (F). Scale bar = 50 μm. Arrows indicate rows of osteoblasts; stars indicate TRAP-positive osteoclasts (red). Day 1: n = 7, day 3: n = 6, day 5: n = 7, day 10: n = 6 for PBS and n = 5 for all time points for ZOL. Two-way ANOVA and Bonferroni post-test: ****p ≤ 0.0001, ***p ≤ 0.001, **p ≤ 0.01, *p ≤ 0.05. All graphs show mean ± SEM.
Mentions: As early as three days after administration there was a significant reduction in osteoclast activity in ZOL treated animals compared to control, measured by serum TRAP concentration (PBS: 7.26 U/L vs. ZOL: 3.22 U/L; p ≤ 0.01; Fig. 3A). This effect was transient and TRAP levels in the ZOL group started to increase again by day 5. The effect of the bisphosphonate on osteoclasts was further confirmed with the detection of a significant reduction in the osteoclast number on trabecular bone surfaces 3 days after ZOL injection compared to control (PBS: 4.97 vs. ZOL: 1.20; p ≤ 0.01; Fig. 3C). The osteoclast number started to normalise to control levels on day 5. We also detected an increase in osteoclast size as early as 24 h after ZOL administration when compared to mice receiving PBS, which reached significance at day 3 (PBS: 7.99 × 10− 05 mm2 vs. ZOL: 1.89 × 10− 04 mm2, p ≤ 0.001, Fig. 3F and G).

Bottom Line: The associated cancer-induced bone disease is treated with bone-sparing agents like zoledronic acid.The effects on growth plate cartilage were visualised by toluidine blue staining.The number of circulating tumour cells was reduced in ZOL treated animals.

View Article: PubMed Central - PubMed

Affiliation: CR-UK/YCR Cancer Research Centre, University of Sheffield, Sheffield, UK. Electronic address: mhaider1@sheffield.ac.uk.

Show MeSH
Related in: MedlinePlus