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.

Teeth reveal juvenile diet, health and neurotoxicant exposure retrospectively: What biological rhythms and chemical records tell us

“…This is consistent with experimental work showing that barium from ingested liquids is rapidly incorporated into hydroxyapatite, and cleared from the bloodstream within a day of dosing. [ 34 ] Thus, sustained decreases of Ba/Ca in tooth enamel are likely to correspond to the withdrawal of enriched milk‐products or the cessation of nursing within days of the actual event.…”

“…Figure 3D also shows a Sr/Ca transition at the end of artificial formula consumption, but it is slightly less defined compared to Ba and Pb, an observation that may reflect a more diffuse or delayed mineralization process for Sr, or longer retention in the bloodstream than Ba. [ 34 ] A study of postnatal Sr/Ca bands in an orangutan canine also found only a minor amount of elemental modification after initial secretion of the enamel and dentine. [ 23 ] These authors suggested that Sr overprinting may occur for approximately 1 to 2 months in each tissue, although the outermost enamel showed prolonged changes in Sr values that were not numerically quantified.…”

“…These double charged ions (M 2+ ) may substitute for one another in cellular transport processes, and with Ca 2+ sites in the hydroxyapatite mineral of bones and teeth, which store more than 90% of their total amounts retained in the body. [32][33][34] Considerations of non-essential metals further illustrate the complex relationship between elemental chemistry and physiology. Barium (Ba) can be absorbed via GI uptake with lethal effect when bound to soluble salts, [35,36] but when bound to sulfate it forms insoluble barium sulfate and is excreted.…”

“…These double charged ions (M 2+ ) may substitute for one another in cellular transport processes, and with Ca 2+ sites in the hydroxyapatite mineral of bones and teeth, which store more than 90% of their total amounts retained in the body. [ 32–34 ]…”

Evaluation of La(XT), a novel lanthanide compound, in an OVX rat model of osteoporosis

“…Nonetheless, alkaline earth metal ions such as barium and strontium exhibit high binding affinities to hydroxyapatite (HAP), resulting in an increased bone mineral density and an improvement in bone strength. It has been demonstrated that both barium and strontium target to bone where active bone formation and bone remodeling are taking place; this has been elucidated using 3D synchrotron K-edge subtraction micro-CT imaging ( Panahifar et al, 2018 ). Barium is highly toxic to the cardiovascular system due to potassium channel blockade, thus it is highly unlikely to be developed as a therapeutic bone-seeking agent ( Bhoelan et al, 2014 ).…”