The bioinorganic chemistry of the early transition metals in bone: distribution and uptake mechanisms

Early transition metals (ETMs) have a complex aqueous chemistry and are widely dispersed in the environment in a number of forms and oxidation states. Due to their unique properties, these metals are used in a variety of applications, including bone implants. Upon environmental or medical exposure, ETMs have been found to accumulate primarily in bone, a well-known storage site for both essential and toxic metals in the body. Though the effects of early transition metals on bone function have been well documented, the role of metal speciation on toxicity as well the mechanism for metal uptake/release in bone is poorly understood. Accurately determining ETM distribution and speciation in bone is essential for understanding potential toxicological implications of metal accumulation. This review focuses on the literature addressing metal distribution and speciation in bone, and the need to expand this research to biomimetic systems and in vivo studies. Furthermore, by evaluating the interplay between ETM chemistry under physiological conditions, bone composition and biology, and metal distribution, this review aims to provide a context through which to untangle the complexity of ETM accumulation in bone.