Friday, October 5, 2012

Bones, Energy Metabolism, and Vitamin K

Skeletal physiology and that of the rest of the body is intricately and inseparably intertwined. We have talked about the need to address the health of the whole body if we are going to achieve long term bone health improvement. In a 2011 perspective  in the Journal of Bone and Mineral Research, Clemens and Karsenty explain how the whole-body approach has brought new insights to the complexity of bone. Researchers have discovered that bone acts as an endocrine organ by releasing the hormone osteocalcin. Insulin, secreted by the pancreas, has long been viewed as the most important hormone for blood glucose regulation, but we now find that osteocalcin, made by the bone-forming osteoblast cells, is also a key player in energy metabolism.

Clemens and Karsenty explain that the skeleton's involvement in energy regulation may have evolved in the Devonian Period (400 million years ago) when the first amphibians crawled out of the calcium rich seas and on to terra firma. Compared to mineral rich ocean water, the terrestrial environment was scarce in calcium necessitating biological adaptation if these animals were to survive. Evolutionary change, through the development of parathyroid glands, helped control blood calcium levels. Today, all land loving animals, including humans, are able to survive and grow strong, mineral-dense bones because the parathyroid glands help control calcium levels through their hormonal influence on osteoclastic bone remodeling activity, as well as promoting calcium absorption from the gut and limiting calcium losses in the urine. In addition to the necessity to conserve calcium, Clemens and Karsenty explain that these "early land dwellers also needed a way to manage fuel production and expenditure more efficiently to survive in their less abundant terrestrial environment. For this job, skeletal muscle and fat evolved into robust factories for acquiring, burning, and storing fuel, as did elaborate endocrine networks that could inventory and report the fuel status accurately among these tissues. It seems logical, therefore, that the osteoblast [bone building cells], whose cellular ancestry is common to fat and muscle, also evolved mechanisms for partnering in the fuel production and maintenance business."

A series of mouse experiments have helped researchers understand bone's relationship to energy metabolism. We know that osteoblasts secrete osteocalcin which is important for bone formation and specifically for the formation of the hydroxyapatite crystal. Before osteocalcin is able to form bone crystals it must first be activated (a process called carboxylation) by vitamin K. This is why vitamin K is so important to bone health. Without vitamin K, osteocalcin would not be carboxylated, bone crystals would not form, and the collagen matrix produced by the osteoblasts would not be mineralized. Osteocalcin is therefore vital to bone health, but now we are seeing that this hormone has a second job outside of the bone.

When carboxylated (activated) osteocalcin is secreted by osteoblasts into a resorption pit that has been newly excavated by osteoclasts it forms bone crystals. But a percentage of this carboxylated osteocalcin becomes uncarboxylated (it returns to its inactive, but still obviously important, biological state). This deactivated osteocalcin then makes it's way into the blood stream and stimulates pancreatic insulin production.

Understanding the importance of osteocalcin for glucose regulation is important. It is also important to question extremely high doses of vitamin K therapy for osteoporosis. Could it be that taking 45 mg of vitamin K2 (which has been studied in Japan as being beneficial for patients with osteoporosis) is too much? Could this high amount of vitamin K sway the ratio of carboxylated to uncarboxylated osteocalcin too far in the direction of the carboxylated form and cause a disruption in insulin/glucose regulation? In our supplements at OsteoNaturals we have tried to strike a balance, providing effective, but not what could be excessive dosages of ingredients. Concern about excessive intake of vitamin K is a case in point. Our products, OsteoSustain and OsteoStim, have what we feel are effective, but not excessive, dosages of vitamin K. 

Bones are clearly not functionally nor metabolically separate from the rest of our body. Glucose regulation is just one more aspect of bone biology that we need to keep in mind when we are working with osteoporosis.
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