Abstract
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.
Highlights
The diligent search for small molecules and biologics to treat osteoporosis resonates with the expanding definition of osteoporosis and the implication that many more individuals worldwide have fragile bones
Harvested bone marrow stromal cells were cultured in the absence of ascorbic acid for 6 and 10 days, following which quantitative PCR (qPCR) was performed on the extracted RNA [13]
Minimal, statistically insignificant, decrements in tibial bone mineral density (BMD) were noted at 8 weeks; this change was prevented with vitamin C so that there was a statistically significant difference between tibial BMD in ovariectomized mice and ovariectomized mice treated with vitamin C (Figure 1C)
Summary
The diligent search for small molecules and biologics to treat osteoporosis resonates with the expanding definition of osteoporosis and the implication that many more individuals worldwide have fragile bones. Low vitamin C intake is associated with low bone mass and a high fracture risk [3,4]. Persuasive epidemiological evidence suggests that higher vitamin C intake is associated with higher bone mass [5], as well as reduced fracture risk over a 17-year follow-up [6]. The Women’s Health Initiative found a statistical relationship between total vitamin C intake and bone mineral density at both the hip and spine in women receiving hormone therapy [7]. It appears that, while adequate vitamin C prevents scurvy, higher doses might protect against skeletal loss
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