Osteocytes are contained within spaces called lacunae and play a central role in bone remodelling. Administered frequently to prevent osteoporotic fractures, antiresorptive agents such as bisphosphonates suppress osteocyte apoptosis and may be localized within osteocyte lacunae. Bisphosphonates also reduce osteoclast viability and thereby hinder the repair of damaged tissue. Osteocyte lacunae contribute to toughening mechanisms. Following osteocyte apoptosis, the lacunar space undergoes mineralization, termed “micropetrosis”. Hypermineralized lacunae are believed to increase bone fragility. Using nanoanalytical electron microscopy with complementary spectroscopic and crystallographic experiments, postapoptotic mineralization of osteocyte lacunae in bisphosphonate-exposed human bone was investigated. We report an unprecedented presence of ∼80 nm to ∼3 μm wide, distinctly faceted, magnesium whitlockite [Ca₁₈Mg₂(HPO₄)₂(PO₄)₁₂] crystals and consequently altered local nanomechanical properties. These findings have broad implications on the role of therapeutic agents in driving biomineralization and shed new insights into a possible relationship between bisphosphonate exposure, availability of intracellular magnesium, and pathological calcification inside lacunae.

中文翻译：

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微米级镁双晶镁晶体在双膦酸盐暴露的人牙槽骨微石化中的应用

骨细胞被包含在被称为腔的空间内，并且在骨重塑中起着核心作用。为预防骨质疏松性骨折而经常给药，抗吸收剂（如双膦酸盐）可抑制骨细胞凋亡，并且可能位于骨细胞腔内。双膦酸盐还降低破骨细胞的活力，从而阻碍受损组织的修复。骨细胞凹腔有助于增韧机制。骨细胞凋亡后，腔隙空间发生矿化作用，称为“微石化”。矿化度高的腔隙被认为会增加骨骼的脆弱性。使用具有互补光谱和晶体学实验的纳米分析电子显微镜，研究了双膦酸盐暴露的人骨中骨细胞腔的凋亡后矿化。₁₈ Mg ₂（HPO ₄）₂（PO ₄）₁₂ ]晶体，因此改变了局部纳米力学性能。这些发现对治疗剂在驱动生物矿化中的作用具有广泛的意义，并为双膦酸盐暴露，细胞内镁的可利用性以及腔隙内部的病理性钙化之间的可能关系提供了新的见解。