The value of intermittent slow release
sodium fluoride treatment in the management of
osteoporosis was studied by a comprehensive metabolic and clinical assessment during a long term trial. Its effect was compared with that of a large dose of
1,25-dihydroxyvitamin D [1,25-(
OH)2D] given for a short period preceding each
fluoride treatment period in another group of randomly selected patients. The 24 patients in group I (3 idiopathic and 21 postmenopausal) received cyclic treatment in repeated 5-month cycles; each cycle was initiated by 1,25-(OH)2D (2 micrograms/day) for 2 weeks, followed for 3 months by
sodium fluoride (slow release, 25 mg twice daily) with
25-hydroxyvitamin D (50 micrograms twice weekly) and
calcium supplements (to bring total
calcium intake to 1500 mg/day), and was concluded by 6 weeks of
25-hydroxyvitamin D and
calcium supplementation without
sodium fluoride. The 21 patients in group II (3 idiopathic and 18 postmenopausal) received the same treatment, except for the omission of 1,25-(OH)2D. In both groups, the serum
fluoride level was maintained within 5-10 mumol/L (95-190 ng/mL) during
fluoride treatment, and serum
osteocalcin concentrations correlated positively with the
duration of treatment. However, vertebral bone mineral content (L2-L4) did not increase significantly in group I, whereas it rose significantly in group II (fractional change, +0.031/2.4 yr in group I vs. + 0.118/2.9 yr in group II; P less than 0.005). Although bone histomorphometric analyses disclosed overall improvement in both groups, only group II had significant increases in the
mineral apposition rate [0.5 +/- 0.2 (+/- SE) to 1.4 +/- 0.2 micron/day; P less than 0.05] and the adjusted apposition rate (0.2 +/- 0.1 to 0.7 +/- 0.1 micron/day; P = 0.04). The vertebral fracture rate significantly declined in both groups, but more so in group II. Excluding the first year of treatment, the fracture rate during treatment in group II of 0.03/patient yr was significantly lower than that of 0.28/patient yr in group I (P less than 0.05). The treatment was well tolerated in both groups; only 16% of patients had either gastrointestinal or rheumatic complications. We conclude that intermittent
sodium fluoride treatment without 1,25-(OH)2D provides safe and effective treatment of
osteoporosis, marked by formation of new adequately mineralized bone, a rise in vertebral bone mass, and reduced frequency of vertebral fractures. The addition of 1,25-(OH)2D treatment before initiation of each
fluoride phase yielded a less favorable response.