Elizabeth A. Krall

Effect of Calcium and Vitamin D Supplementation on Bone Density in Men and Women 65 Years of Age or Older

BACKGROUND Inadequate dietary intake of calcium and vitamin D may contribute to the high prevalence of osteoporosis among older persons. METHODS We studied the effects of three years of dietary supplementation with calcium and vitamin D on bone mineral density, biochemical measures of bone metabolism, and the incidence of nonvertebral fractures in 176 men and 213 women 65 years of age or older who were living at home. They received either 500 mg of calcium plus 700 IU of vitamin D3 (cholecalciferol) per day or placebo. Bone mineral density was measured by dual-energy x-ray absorptiometry, blood and urine were analyzed every six months, and cases of nonvertebral fracture were ascertained by means of interviews and verified with use of hospital records. RESULTS The mean (+/-SD) changes in bone mineral density in the calcium-vitamin D and placebo groups were as follows: femoral neck, +0.50+/-4.80 and -0.70+/-5.03 percent, respectively (P=0.02); spine,+2.12+/-4.06 and +1.22+/-4.25 percent (P=0.04); and total body, +0.06+/-1.83 and -1.09+/-1.71 percent (P<0.001). The difference between the calcium-vitamin D and placebo groups was significant at all skeletal sites after one year, but it was significant only for total-body bone mineral density in the second and third years. Of 37 subjects who had nonvertebral fractures, 26 were in the placebo group and 11 were in the calcium-vitamin D group (P=0.02). CONCLUSIONS In men and women 65 years of age or older who are living in the community, dietary supplementation with calcium and vitamin D moderately reduced bone loss measured in the femoral neck, spine, and total body over the three-year study period and reduced the incidence of nonvertebral fractures.

A controlled trial of the effect of calcium supplementation on bone density in postmenopausal women.

Background. The effectiveness of calcium in retarding bone loss in older postmenopausal women is unclear. Earlier work suggested that the women who were most likely to benefit from calcium supplementation were those with low calcium intakes. Methods. We undertook a double-blind, placebo-controlled, randomized trial to determine the effect of calcium on bone loss from the spine, femoral neck, and radius in 301 healthy postmenopausal women, half of whom had a calcium intake lower than 400 mg per day and half an intake of 400 to 650 mg per day. The women received placebo or either calcium carbonate or calcium citrate malate (500 mg of calcium per day) for two years. Results. In women who had undergone menopause five or fewer years earlier, bone loss from the spine was rapid and was not affected by supplementation with calcium. Among the women who had been postmenopausal for six years or more and who were given placebo, bone loss was less rapid in the group with the higher dietary calcium intake. In those with the lower calcium intake, calcium citrate malate prevented bone loss during the two years of the study; its effect was significantly different from that of placebo (P less than 0.05) at the femoral neck (mean change in bone density [+/- SE], 0.87 +/- 1.01 percent vs. -2.11 +/- 0.93 percent), radius (1.05 +/- 0.75 percent vs. -2.33 +/- 0.72 percent), and spine (-0.38 +/- 0.82 percent vs. -2.85 +/- 0.77 percent). Calcium carbonate maintained bone density at the femoral neck (mean change in bone density, 0.08 +/- 0.98 percent) and radius (0.24 +/- 0.70 percent) but not the spine (-2.54 +/- 0.85 percent). Among the women who had been postmenopausal for six years or more and who had the higher calcium intake, those in all three treatment groups maintained bone density at the hip and radius and lost bone from the spine. Conclusions. Healthy older postmenopausal women with a daily calcium intake of less than 400 mg can significantly reduce bone loss by increasing their calcium intake to 800 mg per day. At the dose we tested, supplementation with calcium citrate malate was more effective than supplementation with calcium carbonate.

Effect of vitamin D supplementation on wintertime and overall bone loss in healthy postmenopausal women.

OBJECTIVES To determine whether relative vitamin D deficiency during the winter months contributes to age-related bone loss and whether rates of change in hard- and soft-tissue mass vary during the year. DESIGN Double-blind, placebo-controlled, 1-year trial in 249 women in which equal numbers of women were randomized to either placebo or 400 IU of vitamin D daily. All women received 377 mg/d of supplemental calcium largely as calcium citrate malate. PATIENTS Healthy, ambulatory postmenopausal women with usual intakes of vitamin D of 100 IU/d. MEASUREMENTS Duplicate spine and whole-body scans were done by dual energy x-ray absorptiometry at 6-month intervals that were timed to periods when 25-hydroxyvitamin D levels were highest and lowest. Period 1 was June-July to December-January and period 2 was December-January to the next June-July. Serum parathyroid hormone and plasma 25-hydroxyvitamin D levels were measured during periods 1 and 2. MAIN RESULTS In the placebo group, spinal bone mineral density increased in period 1, decreased in period 2, and sustained no net change. Women treated with vitamin D had a similar spinal increase in period 1 (1.46% compared with 1.40% in placebo), less loss in period 2 (-0.54% compared with -1.22%, CI for the difference, 0.05% to 1.31%, P = 0.032) and a significant overall benefit (0.85% compared with 0.15%, CI for the difference, 0.03% to 1.37%, P = 0.04). In period 2, 25-hydroxyvitamin D levels were lower and parathyroid hormone levels were higher in the placebo than in the vitamin D group. Whole-body lean and fat tissue and bone mineral density varied during the year but did not change overall. CONCLUSIONS At latitude 42 degrees, healthy postmenopausal women with vitamin D intakes of 100 IU daily can significantly reduce late wintertime bone loss and improve net bone density of the spine over one year by increasing their intake of vitamin D to 500 IU daily. A long-term benefit of preventing vitamin D insufficiency in the winter seems likely although it remains to be shown. Observed changes in bone as well as in fat and lean tissue appear to be related to season.

Effect of vitamin D intake on seasonal variations in parathyroid hormone secretion in postmenopausal women.

Vitamin D intake should be sufficient to maintain calcium absorption and prevent increased parathyroid secretion throughout the year. To determine the level of intake that achieved the latter in elderly women, we studied the interrelations among vitamin D intake, serum 25-hydroxyvitamin D (25(OH)D) levels, and parathyroid hormone concentrations in a cross-sectional study of 333 healthy, white, postmenopausal women with low median calcium (408 mg a day) and vitamin D (112 IU a day) intakes who lived in Massachusetts. The overall inverse relation between serum parathyroid hormone and 25(OH)D levels was found to be dependent on vitamin D intake. In women whose estimated intake of vitamin D was less than or equal to 220 IU a day, the mean (+/- SD) serum parathyroid hormone values were lowest in those studied between August and October (30 +/- 11 ng per liter; n = 72) and highest in those studied between March and May (37 +/- 16 ng per liter; n = 54); the respective serum 25(OH)D levels were 93 +/- 32 and 63 +/- 21 nmol per liter. At vitamin D intakes of more than 220 IU a day, the mean serum parathyroid hormone and 25(OH)D levels did not vary with the season. The correlation between vitamin D intake and serum 25(OH)D concentration, although significant in all women (r = 0.29; P less than 0.001), was highest in those studied between March and May (r = 0.65; P less than 0.001) and lowest in those studied between August and October (r = 0.13; P greater than 0.10). The estimated serum 25(OH)D level associated with a vitamin D intake of 220 IU a day between March and May was 95 nmol per liter. Mean serum calcium values were similar at all times in both groups. We conclude that the dietary intake of more than 220 IU of vitamin D a day by postmenopausal women in Massachusetts may be sufficient to maintain constant serum 25(OH)D and parathyroid hormone concentrations throughout the year. Such an intake prevents a seasonal increase in parathyroid hormone secretion, with its possible deleterious skeletal effects.

Calcium and vitamin D supplements reduce tooth loss in the elderly

PURPOSE Oral bone and tooth loss are correlated with bone loss at nonoral sites. Calcium and vitamin D supplementation slow the rate of bone loss from various skeletal sites, but it is not known if intake of these nutrients affects oral bone and, in turn, tooth retention. SUBJECTS AND METHODS Tooth loss was examined in 145 healthy subjects aged 65 years and older who completed a 3-year, randomized, placebo-controlled trial of the effect of calcium and vitamin D supplementation on bone loss from the hip, as well as a 2-year follow-up study after discontinuation of study supplements. Teeth were counted at 18 months and 5 years. A comprehensive oral examination at 5 years included assessment of caries, oral hygiene, and periodontal disease. The odds ratio (OR) and 95% confidence interval (CI) of tooth loss were estimated by stepwise multivariate logistic regression. Initial age (mean +/- SD) of subjects was 71 +/- 5 years, and the number of teeth remaining was 22 +/- 7. RESULTS During the randomized trial, 11 of the 82 subjects (13%) taking supplements and 17 of the 63 subjects (27%) taking placebo lost one or more teeth (OR = 0.4; 95% CI: 0.2 to 0.9). During the 2-year follow-up period, 31 of the 77 subjects (40%) with total calcium intake of at least 1000 mg per day lost one or more teeth compared with 40 of the 68 subjects (59%) who consumed less (OR = 0.5; 95% CI: 0.2 to 0.9). CONCLUSION These findings suggest that intake levels of calcium and vitamin D aimed at preventing osteoporosis have a beneficial effect on tooth retention.

Increased risk of tooth loss is related to bone loss at the whole body, hip, and spine

Increased systemic bone loss may be a risk factor for tooth loss by contributing to the resorption of toothsupporting alveolar bone. Concurrent longitudinal associations between tooth loss and bone loss at the whole body, femoral neck, and spine were examined in 189 healthy, white, dentate, postmenopausal women who participated in three intervention trials conducted within a 7-year period. None of the subjects was taking estrogen. Bone mineral density (BMD) was measured by dual photon or dual energy X-ray absorptiometry. Teeth were counted at baseline; number and timing of teeth lost over the observation period were assessed by questionnaire. All analyses were controlled for years since menopause, body mass index, number of teeth at baseline, smoking status, and the assigned treatment during each study. These interventions were calcium (Ca) or placebo (P) in Study I, vitamin D+Ca or P+Ca in Study II, and 1 of 2 doses of vitamin D+Ca in Study III. Age at baseline (mean±SD) was 59±6 years and the number of teeth remaining was 23±7. Women who lost teeth during the 7-year follow-up (n=45) experienced less favorable changes in BMD at all sites compared with 144 women who lost no teeth (whole body mean±SE, -0.35±0.08%/year versus -0.11±0.05, P<0.01; femoral neck -0.48±0.38%/year versus -0.14±0.35, P<0.05; and spine, +0.05±0.21%/year versus +0.45±0.16, P<0.05). For each 1%/year decrement in BMD, relative risks (and 95% CI) of losing a tooth were significantly elevated at the whole body (RR=relative risks, CI=confidence interval) (RR=4.83, CI=1.72–13.52, n=180), femoral neck (1.50, 1.02 to 2.22, n=189), and spine (1.45, 1.00 to 2.11, n=167). These results provide support for a role of systemic bone loss in the development of tooth loss among postmenopausal women.

Tooth loss and skeletal bone density in healthy postmenopausal women

Associations between dental status and skeletal bone density were investigated in a group of 329 healthy postmenopausal women with normal bone density. Bone mineral density (BMD) of the lumbar spine, femoral neck and distal radius were measured by dual-or single-photon absorptiometry. Number of teeth remaining were counted and presence of complete dentures noted by a nurse practitioner. Forty-eight women (15%) wore a complete maxillary and/or mandibular denture: 22 (7%) were completely edentulous and an additional 26 (8%) had one edentulous ridge. Among women without complete dentures (n=281), significant positive linear relationships were observed between number of teeth and BMD at the spine (p<0.05) and radius (p<0.01), controlling for years since menopause, pack-years of smoking, education and body mass index. BMD did not differ between the groups with and without dentures. However, women who acquired dentures after the age of 40 years had significantly lower mean spinal and radial BMD than women who acquired dentures at age 40 years or earlier (at the radius, 0.584±0.015 v 0.630±0.017 g/cm2,p<0.05; at the spine, 1.043±0.031 v 1.124±0.029 g/cm2,p=0.05). In linear regression analysis, significant independent correlations were found among all women (n=329) between number of teeth and age (partialr=−0.19,p<0.001), pack-years of cigarette use (partialr=−0.23,p<0.001) and years of education (partialr=+0.11,p<0.05). These associations between dental status and BMD support the hypothesis that systemic bone loss may contribute to tooth loss.

Smoking, Smoking Cessation, and Tooth Loss

Smoking is associated with an increased risk of tooth loss, but it is not known if this risk decreases significantly when individuals quit smoking. The objectives of this study were to describe the rates of tooth loss by smoking status in two populations of medically healthy men and women. Among the men, rates of tooth loss and edentulism in relation to smoking cessation were also evaluated. The subjects were drawn from a group of 584 women (aged 40 to 70) recruited from the Boston, MA, area and a separate population of 1231 male veterans (aged 21 to 75) who participated in the VA Dental Longitudinal Study in Boston. In cross-sectional baseline analyses, current cigarette smokers of either sex had significantly more missing teeth than never-smokers or former smokers. Former smokers and pipe or cigar smokers tended to have an intermediate number of missing teeth. Current male smokers had more teeth with calculus, but the differences in plaque, tooth mobility, probing depth > 2 mm, filled and decayed teeth, and bleeding on probing by smoking history were not significant. Prospective observations of 248 women (mean follow-up time = 6 ± 2 years) and 977 men (mean = 18 ± 7 years) indicated that individuals who continued to smoke cigarettes had 2.4-fold (men) to 3.5-fold risk (women) of tooth loss compared with non-smokers. The rates of tooth loss in men were significantly reduced after they quit smoking cigarettes but remained higher than those in non-smokers. Men who smoked cigarettes had a 4.5-fold increase in risk of edentulism, and this risk also decreased upon smoking cessation. These findings indicate that the risk of tooth loss is greater among cigarette smokers than among non-smokers. Smoking cessation significantly benefits an individuals likelihood of tooth retention, but it may take decades for the individual to return to the rate of tooth loss observed in non-smokers.

Three-dimensional reconstruction of fracture callus morphogenesis

Rat and mouse femur and tibia fracture calluses were collected over various time increments of healing. Serial sections were produced at spatial segments across the fracture callus. Standard histological methods and in situ hybridization to col1a1 and col2a1 mRNAs were used to define areas of cartilage and bone formation as well as tissue areas undergoing remodeling. Computer-assisted reconstructions of histological sections were used to generate three-dimensional images of the spatial morphogenesis of the fracture calluses. Endochondral bone formation occurred in an asymmetrical manner in both the femur and tibia, with cartilage tissues seen primarily proximal or distal to the fractures in the respective calluses of these bones. Remodeling of the calcified cartilage proceeded from the edges of the callus inward toward the fracture producing an inner-supporting trabecular structure over which a thin outer cortical shell forms. These data suggest that the specific developmental mechanisms that control the asymmetrical pattern of endochondral bone formation in fracture healing recapitulated the original asymmetry of development of a given bone because femur and tibia grow predominantly from their respective distal and proximal physis. These data further show that remodeling of the calcified cartilage produces a trabecular bone structure unique to fracture healing that provides the rapid regain in weight-bearing capacity to the injured bone. (J Histochem Cytochem 54:1215-1228, 2006)

Smoking relapse after 2 years of abstinence: findings from the VA Normative Aging Study

Little is known about the risk of cigarette smoking relapse after 2 or more years of abstinence. The rates and predictors of late smoking relapse were estimated in 483 men who participated in a prospective study for up to 35 years. Subjects are participants in the VA Normative Aging Study, a prospective observational study of aging in men that began in 1963. Subjects are evaluated approximately every 3 years with physical examinations and questionnaires. Smoking, alcohol use, caffeine consumption, and socioeconomic variables were obtained by questionnaire, and weight and height were measured at clinical examinations every 3 years since 1963. Predictors of smoking relapse were identified using proportional hazards regression models. The rate of smoking relapse in the 2nd-6th years of abstinence fluctuated between 2 and 4% per year, and fell to less than 1% only after 10 years of abstinence. In multivariate regression models, coffee and alcohol consumption, and use of cigars or pipes significantly increased the risk of smoking relapse. A small risk of smoking relapse remains for at least 10 years after smoking cessation. Use of other tobacco products, coffee and alcohol increased the risk of late relapse. These findings may be useful in identifying those at highest risk for late relapse and for motivating former smokers to continue long-term abstinence.