The Formation of Calcified Nanospherites during Micropetrosis Represents a Unique Mineralization Mechanism in Aged Human Bone

Osteocytes—the central regulators of bone remodeling—are enclosed in a network of microcavities (lacunae) and nanocanals (canaliculi) pervading the mineralized bone. In a hitherto obscure process related to aging and disease, local plugs in the lacuno‐canalicular network disrupt cellular communication and impede bone homeostasis. By utilizing a suite of high‐resolution imaging and physics‐based techniques, it is shown here that the local plugs develop by accumulation and fusion of calcified nanospherites in lacunae and canaliculi (micropetrosis). Two distinctive nanospherites phenotypes are found to originate from different osteocytic elements. A substantial deviation in the spherites' composition in comparison to mineralized bone further suggests a mineralization process unlike regular bone mineralization. Clearly, mineralization of osteocyte lacunae qualifies as a strong marker for degrading bone material quality in skeletal aging. The understanding of micropetrosis may guide future therapeutics toward preserving osteocyte viability to maintain mechanical competence and fracture resistance of bone in elderly individuals. Within the lacunae in aged and osteoporotic human bone, dying osteocytes release globular formations able to concentrate calcium, eventually turning into calcified nanospherites of various sizes with distinctive surface morphologies and specific composition patterns. When these numerous calcified nanospherites accumulate, fill up the lacunar cavities, and fuse, complete lacunar occlusion limits the mechanosensitive function of the bone lacuno‐canalicular network.