Monofluorophosphate Physiology: The Effects of Fluoride on Bone

Abstract

Fluoride is an effective agent in the treatment of osteoporosis and is the only available agent that is capable of producing a large increment in bone mass. Fluoride stimulates bone formation largely through its action to increase osteoblast number. In vitro work suggests that the effect of fluoride to increase osteoblast number is due to a direct action of fluoride to stimulate the proliferation of osteoblast precursors. In fluoride-treated patients the increase in bone formation leads to an increase in bone mass as manifested by an increase in X-ray density, which in turn leads to a decrease in bone pain and a decrease in fracture rate. These positive effects are limited to the axial skeleton and are not observed in the appendicular skeleton in the dose used. The increase in bone formation is reflected by an increase in serum total alkaline phoshatase activity, which is due to an increase in the bone isoenzyme and which can be used to assess serially the action of fluoride on bone. Serum total alkaline phosphatase activity measurements indicate that, during 2 years of fluoride treatment, about 80% of patients respond and that the magnitude of the response is quite variable. The major disadvantages of fluoride in the treatment of osteoporosis include: (1) All patients do not exhibit a response. (2) Fluoride treatment causes gastric and joint side effects in a significant proportion of patients.