Vitamin C (VitC) is essential for bone health, and low VitC serum levels increase the risk for skeletal fractures. If and how VitC affects bone mineralization is unclear. Using micro-computed tomography (μCT), histologic staining, as well as quantitative backscattered electron imaging (qBEI), we assessed the effects of VitC on femoral structure and microarchitecture, bone formation, and bone mineralization density distribution (BMDD) in the VitC incompetent Gulo^−/− mouse model and wild-type mice. In particular, VitC-supplemented, 20-week-old mice were compared with age-matched counterparts where dietary VitC intake was excluded from week 15. VitC depletion in Gulo^−/− mice severely reduced cortical thickness of the diaphyseal shaft and bone volume around the growth plate (eg, bone volume of the primary spongiosa −43%, p < 0.001). Loss of VitC also diminished the amount of newly formed bone tissue as visualized by histology and calcein labeling of the active mineralization front. BMDD analysis revealed a shift to higher calcium concentrations upon VitC supplementation, including higher average (~10% increase in female VitC deficient mice, p < 0.001) and peak calcium concentrations in the epiphyseal and metaphyseal spongiosa. These findings suggest higher bone tissue age. Importantly, loss of VitC had significantly more pronounced effects in female mice, indicating a higher sensitivity of their skeleton to VitC deficiency. Our results reveal that VitC plays a key role in bone formation rate, which directly affects mineralization. We propose that low VitC levels may contribute to the higher prevalence of bone-degenerative diseases in females and suggest leveraging this vitamin against these conditions. © 2023 American Society for Bone and Mineral Research (ASBMR).

中文翻译：

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维生素 C 缺乏会以性别特异性方式恶化成年小鼠的骨微结构和矿化

维生素 C (VitC) 对于骨骼健康至关重要，血清 VitC 水平低会增加骨骼骨折的风险。VitC 是否以及如何影响骨矿化尚不清楚。使用微计算机断层扫描 (μCT)、组织学染色以及定量背散射电子成像 (qBEI)，我们评估了 VitC 对 VitC 功能不全患者的股骨结构和微结构、骨形成和骨矿化密度分布 (BMDD) 的影响Gulo ^−/−小鼠模型和野生型小鼠。特别是，将补充 VitC 的 20 周龄小鼠与年龄匹配的小鼠进行比较，其中从第 15 周开始排除膳食 VitC 摄入。Gulo − / ⁻小鼠的 VitC 消耗严重降低了骨干轴的皮质厚度和周围的骨量生长板（例如，初级海绵体的骨体积-43%，p  < 0.001）。VitC 的损失还减少了新形成的骨组织的数量，如活性矿化前沿的组织学和钙黄绿素标记所示。BMDD 分析显示，补充 VitC 后钙浓度发生转变，包括 骨骺和干骺端海绵体的平均钙浓度升高（雌性 VitC 缺乏小鼠增加约 10%， p < 0.001）和峰值钙浓度。这些发现表明骨组织年龄较高。重要的是，VitC 的丧失对雌性小鼠的影响更为明显，表明其骨骼对 VitC 缺乏的敏感性更高。我们的结果表明，VitC 在骨形成率中起着关键作用，直接影响矿化。我们认为，低 VitC 水平可能会导致女性骨退行性疾病的患病率更高，并建议利用这种维生素来对抗这些疾病。© 2023 美国骨与矿物质研究学会 (ASBMR)。