Ling-Ling Zhu, Jay Cao, Merry Sun, Tony Yuen, Raymond Zhou, Jianhua Li, Yuanzhen Peng, Surinder S. Moonga, Lida Guo, Jeffrey I. Mechanick, Jameel Iqbal, Liu Peng, Harry C. Blair, Zhuan Bian, Mone Zaidi

Epidemiologic studies correlate low vitamin C intake with bone loss. The genetic deletion of enzymes involved in de novo vitamin C synthesis in mice, likewise, causes severe osteoporosis. However, very few studies have evaluated a protective role of this dietary supplement on the skeleton. Here, we show that the ingestion of vitamin C prevents the low-turnover bone loss following ovariectomy in mice. We show that this prevention in areal bone mineral density and micro-CT parameters results from the stimulation of bone formation, demonstrable in vivo by histomorphometry, bone marker measurements, and quantitative PCR. Notably, the reductions in the bone formation rate, plasma osteocalcin levels, and ex vivo osteoblast gene expression 8 weeks post-ovariectomy are all returned to levels of sham-operated controls. The study establishes vitamin C as a skeletal anabolic agent.