AbstractSince osteoporosis is a disease of diminished bone density, and since osteoporotic fractures occur most commonly in the spine, the ideal therapeutic agent for osteoporosis is one which can increase spinal bone density and thereby reduce the risk for vertebral fractures. In the current study we sought to examine the effect of fluoride therapy on spinal bone density utilizing quantitative computed tomography to measure changes in vertebral trabecular bone density during treatment with fluoride. A group of 61 postmenopausal osteoporotic females, aged 70 ± 9 years, were treated with 34 ± 7 mg elemental fluoride/day (equivalent to 75 ± 15 mg NaF/day) and 1500 mg calcium/day for 19 ± 6 months. Spinal bone density was increased within the first 6 months of fluoride therapy by 42% or 10 ± 13 mg/cm3(p<0.001) and continued to increase throughout 2 years of observation. The skeletal response to fluoride therapy was also associated with an early increase in serum alkaline phosphatase activity (p<0.001), which was related to the increase in spinal bone density (r= .58,p<0.001). Large interpatient variation was observed in the spinal bone response to fluoride therapy, which was not explained by variations in the pretreatment spinal bone density (r= .04), age of the patient (r= .15), or dose of fluoride (r= .16). Results from these studies demonstrate (1) the therapeutic value of fluoride to increase trabecular bone density lineraly for 2 years in the osteoporotic spine and (2) the clinical value of measuring spinal bone density and/or serum alkaline phosphatase activity as indices of the skeletal response to fluo