Although fluoride increases bone mass, the newly formed bone may have reduced strength. To assess the effect of fluoride treatment on the fracture rate in osteoporosis, we conducted a four-year prospective clinical trial in 202 postmenopausal women with osteoporosis and vertebral fractures who were randomly assigned to receive sodium fluoride (75 mg per day) or placebo. All received a calcium supplement (1500 mg per day). Sixty-six women in the fluoride group and 69 women in the placebo group completed the trial. As compared with the placebo group, the treatment group had increases in median bone mineral density of 35 percent (P less than 0.0001) in the lumbar spine (predominantly cancellous bone), 12 percent (P less than 0.0001) in the femoral neck, and 10 percent (P less than 0.0001) in the femoral trochanter (sites of mixed cortical and cancellous bone), but the bone mineral density decreased by 4 percent (P less than 0.02) in the shaft of the radius (predominantly cortical bone). The number of new vertebral fractures was similar in the treatment and placebo groups (163 and 136, respectively; P not significant), but the number of nonvertebral fractures was higher in the treatment group (72 vs. 24; P less than 0.01). Fifty-four women in the fluoride group and 24 in the placebo group had side effects sufficiently severe to warrant dose reduction; the major side effects were gastrointestinal symptoms and lower-extremity pain. We conclude that fluoride therapy increases cancellous but decreases cortical bone mineral density and increases skeletal fragility. Thus, under the conditions of this study, the fluoride-calcium regimen was not effective treatment for postmenopausal osteoporosis.

We report a 4-year randomized, double-blind, placebo-controlled clinical trial in 236 normal postmenopausal women (mean age ؎ SE, 66.3 ؎ 0.2 years) who were randomized to a calcium (1600 mg/day as the citrate) or placebo group. The women were seen every 6 months; 177 completed the trial. Net percentage changes in each group are given relative to baseline. The differences in net percentage changes (calcium group minus placebo group) in medians were: for lumbar spine bone density, 2.0% ( p < 0.001) at year 1 and 0.3% (not significant) at year 4; for proximal femur bone density, 1.3% ( p ‫؍‬ 0.003) at year 1 and 1.3% ( p ‫؍‬ 0.015) at year 4; and for total body bone mineral, 0.4% ( p ‫؍‬ 0.002) at year 1 and 0.9% ( p ‫؍‬ 0.017) at year 4. Similar differences at year 4 were: ؊18.9% ( p ‫؍‬ 0.002) for parathyroid hormone (PTH), ؊11.9% ( p ‫؍‬ 0.026) for serum osteocalcin, and ؊32.2% ( p ‫؍‬ 0.003) for urine free pyridinoline. We conclude that long-term administration of calcium supplements to elderly women partially reverses age-related increases in serum PTH level and bone resorption and decreases bone loss. However, the effects on bone loss were weaker than those reported for estrogen, bisphosphonates, or calcitonin therapy, indicating that calcium supplements alone cannot substitute for these in treating established osteoporosis. Nonetheless, because of their safety, high tolerance, and low expense, calcium supplements may be a useful preventive measure for elderly postmenopausal women whose bone mineral density values are normal for their age. (J Bone Miner Res 1998;13:168-174)

Bone mass and its mineral content are under genetic control. The vitamin D receptor (VDR) gene has been shown to be a major locus for genetic effects on bone mineral density (BMD), and polymorphisms in this gene accounted for a large proportion of genetic variance in BMD in an Australian population. In this study, we investigated whether similar associations are present in a North American population. We studied 139 normal healthy women (age 53.2 +/- 14.5, mean +/- SD) and 43 severely osteoporotic postmenopausal women (age 65.8 +/- 5.9). In the 127 of them with complete genetic studies, the distribution of genotypes, determined by polymerase chain reaction on leukocyte DNA samples, agreed closely with that in the Australian population. BMD was strongly related to age and weight, and, thus was adjusted for these parameters prior to genetic analysis. We found that age modulated the effect of VDR genotypes on femoral neck BMD (FN-BMD) (TaqI, p = 0.036; BsmI, p = 0.118; ApaI, p = 0.041) such that the effect of genotype was greatest among younger (premenopausal) women and declined with age so that there was no discernible difference by age 70. Among the younger women, a high FN-BMD was associated with the TT (or aa or bb) genotype while low FN-BMD was associated with the tt (or AA or BB) genotype.(ABSTRACT TRUNCATED AT 250 WORDS)

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The epidemiology of bone loss in populations of Asian heritage is still poorly known. This study compared the skeletal status of a convenience sample of 396 Southeast Asian immigrants (172 Vietnamese, 171 Cambodians and 53 Laotians) residing in Rochester, Minnesota in 1997 with 684 white subjects previously recruited from an age-stratified random sample of community residents. Areal bone mineral density (BMD, g/cm2) and volumetric bone mineral apparent density (BMAD, g/cm3) were determined for lumbar spine and proximal femur using the Hologic QDR 2000 instrument for the white population and the QDR 4500 for Southeast Asian subjects; the machines were cross-calibrated from data on 20 volunteers. Lumbar spine BMD was 7% higher in white than Southeast Asian women (p < 0.001), and similar results were observed for the femoral neck; lumbar spine BMD was 12% higher in white than nonwhite men (p < 0.001). Race-specific discrepancies were reduced by calculating BMAD: for premenopausal women, lumbar spine and femoral neck differences between whites and Southeast Asians were eliminated; for postmenopausal women the lumbar spine differences persisted (p < 0.0001), while femoral neck BMAD was actually higher for Southeast Asians. There were no race-specific differences in femoral neck BMAD among men of any age (p = 0.312), but lumbar spine BMAD was less for younger (p = 0.042) but not older (p = 0.693) Southeast Asian men. There were differences among the Southeast Asian subgroups, but no clear pattern emerged. Predictors of lumbar spine BMAD in Southeast Asian women were age (p < 0.001), weight (p = 0.015) and gravidity (p = 0.037). Even after adjusting for bone size using BMAD, 32% and 9% of Southeast Asian women and men, respectively, would be considered to have osteoporosis at the femoral neck and 25% and 4%, respectively, at the lumbar spine. These findings indicate a need for culturally sensitive educational interventions for Southeast Asians and for physicians to pursue diagnosis and treatment to prevent osteoporosis-related disabilities in this population.