6.7.2. Magnesium

Magnesium (Mg2+) is another mineral that inhibits the formation of apatite. In healthy individuals, serum magnesium concentrations are carefully balanced in a narrow range [190]. The kidneys are the main organs controlling systemic Mg2+ homeostasis, where its transport is highly regulated by hormonal and other intrarenal factors [191]. Bones are the main reservoir of Mg2+, holding ~60% of the total body content. Mg2+ in bones is primarily embedded at the surface of the apatite crystals [192]. Because of its inhibitory properties towards calcification and oral bioavailability, Mg2+ supplementation appeared to be a good option to decrease soft tissue calcification in pathologies with calcification such as chronic kidney disease (CKD) [193], but also in PXE, as both share some phenotypical characteristics [194]. Preliminary testing in *Abcc6*−/<sup>−</sup> mice with increased dietary Mg2+ showed results [138,139] encouraging enough that a prospective human clinical trial was initiated (NCT01525875). However, the translation to humans proved to be inconclusive [129], probably because the dosages used in animal models exceeded what could actually be tolerated in humans and/or as a result of the method for phenotype evaluation methodology (*Cf.* Section 6.1). Therefore, Mg2+ supplementation is probably not a viable treatment strategy, at least on its own.
