Biodistribution of strontium and barium in the developing and mature skeleton of rats

Abstract

Bone acts as a reservoir for many trace elements. Understanding the extent and pattern of elemental accumulation in the skeleton is important from diagnostic, therapeutic, and toxicological perspectives. Some elements are simply adsorbed to bone surfaces by electric force and are buried under bone mineral, while others can replace calcium atoms in the hydroxyapatite structure. In this article, we investigated the extent and pattern of skeletal uptake of barium and strontium in two different age groups, growing, and skeletally mature, in healthy rats. Animals were dosed orally for 4 weeks with either strontium chloride or barium chloride or combined. The distribution of trace elements was imaged in 3D using synchrotron K-edge subtraction micro-CT at 13.5 µm resolution and 2D electron probe microanalysis (EPMA). Bulk concentration of the elements in serum and bone (tibiae) was also measured by mass spectrometry to study the extent of uptake. Toxicological evaluation did not show any cardiotoxicity or nephrotoxicity. Both elements were primarily deposited in the areas of active bone turnover such as growth plates and trabecular bone. Barium and strontium concentration in the bones of juvenile rats was 2.3 times higher, while serum levels were 1.4 and 1.5 times lower than adults. In all treatment and age groups, strontium was preferred to barium even though equal molar concentrations were dosed. This study displayed spatial co-localization of barium and strontium in bone for the first time. Barium and strontium can be used as surrogates for calcium to study the pathological changes in animal models of bone disease and to study the effects of pharmaceutical compounds on bone micro-architecture and bone remodeling in high spatial sensitivity and precision.

Graphical abstract

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Abbreviations

3D:

3-Dimensional

ANOVA:

Analysis of variance

BMIT:

Biomedical imaging and therapy

CLS:

Canadian light source

ECG:

Electrocardiogram

ELISA:

Enzyme-linked immunosorbent assay

EPMA:

Electron probe micro analysis

GLM:

General linear model

ICP-MS:

Inductively coupled plasma mass spectrometry

ICP-OES:

Inductively coupled plasma optical emission spectrometry

KES:

K-edge subtraction

Micro-CT:

Micro-computed tomography

PET:

Positron emission tomography

SPECT:

Single-photon-emission computed tomography

XRF:

X-ray fluorescence imaging

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Acknowledgements

This study was supported by the Sylvia Fedoruk Canadian Centre for Nuclear Innovation. DMLC and LDC are supported, in part, by the Canada Research Chairs program. AP is a Saskatchewan Health Research Foundation (SHRF) fellow as well as a fellow in the Canadian Institutes of Health Research Training Grant in Health Research Using Synchrotron Techniques (CIHR-THRUST). NS is a CIHR-THRUST fellow. The research described in this paper was performed at the Canadian Light Source, which is supported by the Canada Foundation for Innovation, Natural Sciences and Engineering Research Council of Canada, the University of Saskatchewan, the Government of Saskatchewan, Western Economic Diversification Canada, the National Research Council Canada, and the Canadian Institutes of Health Research.

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Contributions

Conception and design: AP and DMLC. Collection and assembly of data: AP and NS. Analysis and interpretation of the data: AP, LDC, LW, and DMLC. Statistical expertise: AP and DMLC. Obtaining of funding: LDC and DMLC. Drafting of the article: AP. Revising manuscript content: AP, LDC, LW, NS, and DMLC. Final approval of the article: AP, LDC, LW, NS, and DMLC. AP and DMLC take responsibility for the integrity of the data analysis.

Corresponding author

Correspondence to Arash Panahifar.

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Panahifar, A., Chapman, L.D., Weber, L. et al. Biodistribution of strontium and barium in the developing and mature skeleton of rats. J Bone Miner Metab 37, 385–398 (2019). https://doi.org/10.1007/s00774-018-0936-x

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Keywords

  • Bone
  • Synchrotron
  • Barium
  • Strontium
  • K-edge subtraction imaging