Vitamin C, or ascorbate, plays an important role in maintaining bone mass – promoting the balance between old bone resorption and new bone formation, said researchers from Baylor College of Medicine and Lexicon Pharmaceuticals in a report that appears online in the Journal of Biological Chemistry.

"The assumption is that everyone gets enough vitamin C in their diet," said Dr. Kenneth Gabbay, professor of pediatrics – molecular diabetes and metabolism at BCM. "However, multiple studies of large groups of people show that higher intakes of vitamin C are associated with higher bone mass and lower fracture rates. Our study shows that vitamin C or ascorbate is critical to maintaining the homeostasis necessary for healthy bone mass."

In particular, he referred to the Framingham Osteoporosis study and the Women's Health Initiative, both of which involved thousands of participants.

Gabbay and his colleagues built on the fact that mice can actually synthesize vitamin C, an ability that is lacking in humans. They identified two enzymes critical to this process by providing the building material for vitamin C – aldehyde reductase and aldose reductase. Aldehyde reductase is responsible for 85 percent of vitamin C production and aldose reductase, the remaining 15 percent. Mice bred to lack both enzymes cannot make any vitamin C and develop scurvy, a condition that affects many organ systems including bone.

However, if mice lack only aldehyde reductase, they and their skeletons develop and grow normally on the 15 percent ascorbate or vitamin X generated through aldose reductase until they face a stressor that requires more vitamin C, such as pregnancy or the loss of sex hormones that accompany menopause and aging.

"Then they fall off a cliff and develop early profound osteoporosis," said Gabbay.

Bone formation

His studies (in mice) show that ascorbate or vitamin C both suppresses osteoclasts, which promote bone resorption, and stimulates the development of osteoblasts that make new bone, thus enhancing new bone formation. The constant renewal of bone is crucial to healthy bone architecture.

Many treatments for osteoporosis, including bisphosphonates such as Fosamax and Actonel, suppress the function of osteoclasts, and hence blocks bone resorption and mechanisms of bone repair. Unfortunately, these treatments do not stimulate osteoblast formation and new bone is not made. Many anti-oxidants such as resveratrol (found in red wine) and pycnogenol do the same thing. Only vitamin C affects both sides of the equation – osteoclast suppression and osteoblast development, said Gabbay.

Important as vitamin D, calcium

Most experts recommend vitamin D, calcium, exercise and bisphosphonates to keep bones healthy, said Gabbay.

"Vitamin C is never mentioned, whereas it's likely an equally important element for maintaining strong healthy bones" he said. "Our studies necessitate formal studies in patients to evaluate the usefulness of vitamin C therapy in susceptible populations."

Others who took part in this work include: Kurt M. Bohren, Roy Morello, Terry Bertin, all of BCM, and Jeff Liu and Peter Vogel of Lexicon Pharmaceuticals in the Woodlands. Morello is now at the University of Arkansas for Medical Sciences in Little Rock, Ark.

Funding for this work came from the Harry & Aileen Gordon Foundation, the Jacob & Louise Gabbay Foundation, the Agar Organization, the U.S. Department of Agriculture and the Children's Nutrition Research Center at Baylor College of Medicine and Texas Children's Hospital. The authors also thank the Rolanette and Berdon Lawrence Bone Disease Program of Texas.