Magnesium whitlockite – omnipresent in pathological mineralisation of soft tissues but not a significant inorganic constituent of bone

Abstract

Whitlockite is a calcium phosphate that was first identified in minerals collected from the Palermo Quarry, New Hampshire. The terms magnesium whitlockite [Mg-whitlockite; Ca18Mg2(HPO4)2(PO4)12] and beta-tricalcium phosphate [β-TCP; β-Ca3(PO4)2] are often used interchangeably since Mg-whitlockite is not easily distinguished from β-Ca3(PO4)2 by powder X-ray diffraction although their crystalline structures differ significantly. Being both osteoconductive and bioresorbable, Mg-whitlockite is pursued as a synthetic bone graft substitute. In recent years, advances in development of synthetic Mg-whitlockite have been accompanied by claims that Mg-whitlockite is the second most abundant inorganic constituent of bone, occupying as much as 20–35 wt% of the inorganic fraction. To find evidence in support of this notion, this review presents an exhaustive summary of Mg-whitlockite identification in biological tissues. Mg-whitlockite is mainly found in association with pathological mineralisation of various soft tissues and dental calculus, and occasionally with enamel and dentine. With the exception of high-temperature treated tumoural calcified deposits around interphalangeal and metacarpal joints and rhomboidal Mg-whitlockite crystals in post-apoptotic osteocyte lacunae in human alveolar bone, this unusual mineral has never been detected in the extracellular matrix of mammalian bone. Characterisation techniques capable of unequivocally distinguishing between different calcium phosphate phases, such as high-resolution imaging, crystallography, and/or spectroscopy have exclusively identified bone mineral as poorly crystalline, ion-substituted, carbonated apatite. The idea that Mg-whitlockite is a significant constituent of bone mineral remains unsubstantiated. Contrary to claims that such biomaterials represent a bioinspired/biomimetic approach to bone repair, Mg-whitlockite remains, exclusively, a pathological biomineral. Statement of significanceMagnesium whitlockite (Mg-whitlockite) is a unique calcium phosphate that typically features in pathological calcification of soft tissues; however, an alarming trend emerging in the synthetic bioceramics community claims that Mg-whitlockite occupies 20–35 wt% of bone mineral and therefore synthetic Mg-whitlockite represents a biomimetic approach towards bone regeneration. By providing an overview of Mg-whitlockite detection in biological tissues and scrutinising a diverse cross-section of literature relevant to bone composition analysis, this review concludes that Mg-whitlockite is exclusively a pathological biomineral, and having never been reported in bone extracellular matrix, Mg-whitlockite does not constitute a biomimetic strategy for bone repair.