Metabolic acids impact bone mineral maturation

Bone mineral has a complex 3D architecture that is essential to its mechanical properties. It is a complex calcium phosphate phase related to hydroxyapatite that also contains significant quantities of cell respiration metabolites, in particular: carbonate, citrate and lactate. An as-yet unanswered question is what, if any, role do these metabolites collectively play in determining the 3D architecture of bone mineral? Here we synthesize apatitic materials by transformation from precursor mineral phases containing citrate, lactate or carbonate so that the synthesis environment mimics the densely-packed ionic environment within which bone mineral forms in vivo, and so that we can understand the mineral factors that may direct bone mineral 3D architecture. We show that incorporating citrate and lactate leads to complex mineral architectures reminiscent of those in bone mineral, including curvature of the mineral crystals. Our results suggest that metabolic acids may assist the moulding of bone mineral to restricted spaces available for mineral in in vivo bone. We find that the incorporation of lactate creates a softer material and inhibits the transformation towards apatitic structures, which may help to explain why foetal bone - necessarily soft - contains considerable quantities of lactate. High levels of plasma citrate have been previously found to correlate with high bone mineral density. Here we find that citrate incorporation leads to mineral crystal curvature modelling that in in vivo bone mineral suggesting its importance in mineral morphology. We conclude that metabolic anions may play an important role in controlling bone mineral physicochemical properties and 3D architecture.