Faculty of Medicine, Memorial University of Newfoundland, St. John's, Canada.
St. Vincent's Institute of Medical Research and the Department of Medicine at St. Vincent's Hospital, The University of Melbourne, Melbourne, Australia.
J Bone Miner Res. 2018 Jan;33(1):16-26. doi: 10.1002/jbmr.3217. Epub 2017 Aug 2.
We hypothesized that adaptation to calcium supply demands of pregnancy and lactation do not require calcitriol. Adult Cyp27b1 null mice lack calcitriol and have hypocalcemia, hypophosphatemia, and rickets. We studied wild-type (WT) and null sister pairs raised on a calcium-, phosphorus-, and lactose-enriched "rescue" diet that prevents hypocalcemia and rickets. Bone mineral content (BMC) increased >30% in pregnant nulls, declined 30% during lactation, and increased 30% by 4 weeks post-weaning. WT showed less marked changes. Micro-CT revealed loss of trabecular bone and recovery in both genotypes. In lactating nulls, femoral cortical thickness declined >30%, whereas endocortical perimeter increased; both recovered to baseline after weaning; there were no such changes in WT. Histomorphometry revealed a profound increase in osteoid surface and thickness in lactating nulls, which recovered after weaning. By three-point bend test, nulls had a >50% decline in ultimate load to failure that recovered after weaning. Although nulls showed bone loss during lactation, their milk calcium content was 30% lower compared with WT. Serum parathyroid hormone (PTH) was markedly elevated in nulls at baseline, reduced substantially in pregnancy, but increased again during lactation and remained high post-weaning. In summary, pregnant Cyp27b1 nulls gained BMC with reduced secondary hyperparathyroidism, implying increased intestinal calcium delivery. Lactating nulls lost more bone mass and strength than WT, accompanied by increased osteoid, reduced milk calcium, and worsened secondary hyperparathyroidism. This implies suboptimal intestinal calcium absorption. Post-weaning, bone mass and strength recovered to baseline, whereas BMC exceeded baseline by 40%. In conclusion, calcitriol-independent mechanisms regulate intestinal calcium absorption and trabecular bone metabolism during pregnancy and post-weaning but not during lactation; calcitriol may protect cortical bone during lactation. © 2017 American Society for Bone and Mineral Research.
我们假设适应妊娠和哺乳的钙供应需求不需要钙三醇。成年 Cyp27b1 基因缺失的小鼠缺乏钙三醇，患有低钙血症、低磷血症和佝偻病。我们研究了在富含钙、磷和乳糖的“挽救”饮食中饲养的野生型（WT）和基因缺失姐妹对，该饮食可预防低钙血症和佝偻病。妊娠基因缺失小鼠的骨矿物质含量（BMC）增加了 30%以上，哺乳期下降了 30%，断奶后 4 周增加了 30%。WT 表现出的变化不那么显著。微 CT 显示两种基因型的小梁骨丢失和恢复。哺乳期基因缺失小鼠的股骨皮质厚度下降了 30%以上，而皮质内周径增加；断奶后两者均恢复至基线；WT 没有这种变化。组织形态计量学显示哺乳期基因缺失小鼠的类骨质表面和厚度显著增加，断奶后恢复。通过三点弯曲试验，基因缺失小鼠的极限载荷失效下降了 50%以上，断奶后恢复。尽管基因缺失小鼠在哺乳期有骨丢失，但它们的乳汁钙含量比 WT 低 30%。基础状态下基因缺失小鼠的甲状旁腺激素（PTH）显著升高，妊娠时显著降低，但哺乳期再次升高，断奶后仍居高不下。总之，妊娠 Cyp27b1 基因缺失小鼠 BMC 增加，继发性甲状旁腺功能亢进症减轻，提示肠道钙供应增加。哺乳期基因缺失小鼠的骨量和强度损失比 WT 更多，伴随着类骨质增加、乳汁钙减少和继发性甲状旁腺功能亢进症恶化。这意味着肠道钙吸收不佳。断奶后，骨量和强度恢复到基线，而 BMC 比基线增加了 40%。总之，钙三醇非依赖性机制在妊娠和断奶后调节肠道钙吸收和小梁骨代谢，但在哺乳期不调节；钙三醇可能在哺乳期保护皮质骨。2017 年美国骨与矿物研究学会。
