Vitamin C supplementation for the treatment of osteoarthritis: perspectives on the past, present, and future.

According to the US Centers for Disease Control and Prevention (CDC), an estimated 14% of adults in the United States have either been diagnosed with osteoarthritis (OA) or have symptoms suggestive of the disease. The CDC also points out that the incidence of OA has been gradually increasing over the past 30 years. What is more worrisome is that this trend is going to accelerate due to the aging demographics of the United States and the increasing prevalence of obesity seen in the country. The need for better preventive treatments and efficacious therapeutics are direly needed to combat this public health crisis. Among the possible treatments being hypothesized, antioxidant supplementation has become one of the most widely studied over the past decade due to its ability to attenuate reactive oxygen species (ROS) formation within chondrocytes, a critical step in the pathogenesis of this disease. Vitamin C has emerged as among the most promising of the antioxidant group, with many animal and human studies having been conducted in recent years. Although many of the studies have shown encouraging results in terms of preventing OA, others have reached opposite conclusions, thus making the data controversial. However, after reviewing several of these studies, we hypothesize that certain parameters may not have been properly considered during data collection. In the end, more randomized placebo-controlled trials in humans are desperately needed in order to fully understand whether vitamin C therapy is efficacious in treating and/or preventing OA.

Enteroendocrine K Cells Exert Complementary Effects to Control Bone Quality and Mass in Mice.

The involvement of a gut-bone axis in controlling bone physiology has been long suspected, although the exact mechanisms are unclear. We explored whether glucose-dependent insulinotropic polypeptide (GIP)-producing enteroendocrine K cells were involved in this process. The bone phenotype of transgenic mouse models lacking GIP secretion (GIP-GFP-KI) or enteroendocrine K cells (GIP-DT) was investigated. Mice deficient in GIP secretion exhibited lower bone strength, trabecular bone mass, trabecular number, and cortical thickness, notably due to higher bone resorption. Alterations of microstructure, modifications of bone compositional parameters, represented by lower collagen cross-linking, were also apparent. None of these alterations were observed in GIP-DT mice lacking enteroendocrine K cells, suggesting that another K-cell secretory product acts to counteract GIP action. To assess this, stable analogues of the known K-cell peptide hormones, xenin and GIP, were administered to mature NIH Swiss male mice. Both were capable of modulating bone strength mostly by altering bone microstructure, bone gene expression, and bone compositional parameters. However, the two molecules exhibited opposite actions on bone physiology, with evidence that xenin effects are mediated indirectly, possibly via neural networks. Our data highlight a previously unknown interaction between GIP and xenin, which both moderate gut-bone connectivity. © 2020 American Society for Bone and Mineral Research.