Fluoride therapy for osteoporosis: A review of dose response, duration of treatment, and skeletal sites of action

Osteoporosis is a disease characterized by a reduction in bone density which predisposes to fracture after even minimal trauma. Fluoride, because it has consistently been shown to stimulate bone formation and increase trabecular bone density, has been widely studied for the treatment of osteoporosis. The article focuses on the dose response, duration of treatment, and skeletal sites of action of fluoride; we also include comments on the effect of fluoride on vertebral and appendicular fracture rates. The skeletal response to fluoride doses, ranging from 15 to 43 mg elemental fluoride per day, included a linear increase in spinal bone density at an average rate of 1.25±0.91 mg/cm³ per month. The rate of increase in spinal bone density was related to the dose of fluoride (r=0.34, P<0.03). Spinal bone density had increased above the fracture threshold in 44% of patients treated with fluoride for 32±10 months. The time required to achieve this goal was, however, influenced by the pretreatment spinal bone density and interpatient variation in response to fluoride treatment. Patients whose spinal bone density remained below the fracture threshold had lower pretreatment bone densities and/or slower rates of increase in spinal bone density (P<0.001). The osteogenic effect of fluoride was not limited to the spine. After 2 years of fluoride therapy, we found bone density in the femoral condyle (measured by QCT) to have increased by 13±2.6 mg/cm³ (n=38, P<0.001); bone density in the hip (measured by DPA) was increased by 0.0261±0.015 g/cm² (n=55, P<0.025). The efficacy of fluoride therapy to reduce fractures is not well established. Recently, investigators from the Mayo Clinic and Henry Ford Hospital reported fluoride had no effect on the vertebral fracture rate despite a significant increase in spinal bone density, but this finding has not been supported by findings in other studies. Moreover, our preliminary analysis of over 500 fluoride-treated patients found a time-dependent decrease in vertebral fracture rate related to a corresponding increase in spinal bone density. We conclude that these data, together with the many other positive international findings related to fluoride, justify continued investigation of this potent agent for the treatment of osteoporosis.