Effect of dietary protein on bone loss in elderly men and women: the Framingham Osteoporosis Study.

Few studies have evaluated protein intake and bone loss in elders. Excess protein may be associated with negative calcium balance, whereas low protein intake has been associated with fracture. We examined the relation between baseline dietary protein and subsequent 4-year change in bone mineral density (BMD) for 391 women and 224 men from the population-based Framingham Osteoporosis Study. BMD (g/cm2) was assessed in 1988-1989 and in 1992-1993 at the femur, spine, and radius. Usual dietary protein intake was determined using a semiquantitative food frequency questionnaire (FFQ) and expressed as percent of energy from protein intake. BMD loss over 4 years was regressed on percent protein intake, simultaneously adjusting for other baseline factors: age, weight, height, weight change, total energy intake, smoking, alcohol intake, caffeine, physical activity, calcium intake, and, for women, current estrogen use. Effects of animal protein on bone loss also were examined. Mean age at baseline (+/-SD) of 615 participants was 75 years (+/-4.4; range, 68-91 years). Mean protein intake was 68 g/day (+/-24.0; range, 14-175 g/day), and mean percent of energy from protein was 16% (+/-3.4; range, 7-30%). Proportional protein intakes were similar for men and women. Lower protein intake was significantly related to bone loss at femoral and spine sites (p < or = 0.04) with effects similar to 10 lb of weight. Persons in the lowest quartile of protein intake showed the greatest bone loss. Similar to the overall protein effect, lower percent animal protein also was significantly related to bone loss at femoral and spine BMD sites (all p < 0.01) but not the radial shaft (p = 0.23). Even after controlling for known confounders including weight loss, women and men with relatively lower protein intake had increased bone loss, suggesting that protein intake is important in maintaining bone or minimizing bone loss in elderly persons. Further, higher intake of animal protein does not appear to affect the skeleton adversely in this elderly population.     

The effect of smoking at different life stages on bone mineral density in elderly men and women

To assess the effect of smoking on bone mineral density (BMD) at different life stages, to examine whether the effect of smoking differs between men and women, and to discover whether its effect in women differs according to history of estrogen use, a cohort study was carried out with single cross-section measurement of BMD by single and dual photon absorptiometry. The setting was the Framingham Study, a population-based cohort study with over 40 years prospectively collected data on smoking. Subjects (n=1164) consisted of cohort members participating in the 20th biennial Framingham examination (1988–1989). The measurements included in the study were BMD measured at the hip, spine and radius, smoking history ascertained at all Framingham Study examinations since 1948, and other factors affecting BMD (age, weight, estrogen use, caffeine use, alcohol use and physical activity). Neither current smoking, recent (last 10 years) smoking, nor early adulthood smoking resulted in significantly lower BMD at any skeletal site among women who had not taken estrogen. Among women who had taken estrogen, BMD at most sites was lower among current or recent smokers, although the small numbers of smokers made it difficult to find significant differences at all skeletal sites. Among men, a consistently lower BMD at all skeletal sites was observed for smokers regardless of when in their life they smoked (4–15.3% lower), although the effect of smoking during early adulthood was of a lesser magnitude (4–8% lower). Former male smokers who had quit <10 years ago had lower BMD than men who had quit 10 years ago. In conclusion, in women who had used estrogen, BMD was lower in current or recent smokers than it was in non-smokers. In men, smoking at any stage of life had adverse effects on the skeleton that was independent of weight, alcohol or caffeine use, implying other mechanisms for smoking's effect on bone.     

Radial bone mineral density in pre- and perimenopausal women: a prospective study of rates and risk factors for loss.

Radial bone mineral density (BMD) of 217 white women aged 22-54 years from a single rural community was evaluated in 1984 using single-photon absorptiometry. BMD was measured at a site one-third the distance from the wrist to the elbow, a site that represents predominantly cortical bone tissue. Most of these women (181; 83%) were reexamined 5 years later. The overall average 5 year radial BMD loss was -5.6%. The average rate of loss was -4.5% for women retaining positive estrogen status at follow-up (n = 108) and -7.4% for women who were in negative estrogen status at follow-up (n = 73). Baseline radial BMD measures were highly predictive of the follow-up BMD values (r = 0.80). Women with positive estrogen status and greater baseline BMD also had less BMD change. Greater baseline BMD did not predict the amount of change in women with negative estrogen status. The bone turnover markers osteocalcin and bone-specific alkaline phosphatase were significantly associated with BMD change in women with negative, but not positive estrogen status. There was no conclusive evidence of a "peak age" in the baseline and follow-up BMD measures. Based on rates of BMD change, "peak" bone mineral content appears to occur before age 25 years. Factors significantly associated with lower levels of BMD were menopause without estrogen replacement, nulliparity, smoking, and age at first pregnancy. Factors associated with more bone loss were menopause without estrogen replacement, smoking, shorter duration of oral contraceptive use, and older age. Quetelet index, muscle area, number of lost pregnancies, ever breast-feeding, or calcium intake were not associated with BMD level or its 5 year rate of loss. Physical activity and alcohol intake were not associated with BMD level or change after data were adjusted for age or estrogen status.     

Bone loss, weight loss, and weight fluctuation predict mortality risk in elderly men and women.

Low baseline BMD, rate of BMD loss, weight loss, and weight fluctuation are significant predictors of all-cause mortality in elderly men and women, independent of each other and of age, incident fracture, and concomitant diseases. INTRODUCTION: Although low BMD has been shown to be associated with mortality in women, the effect of BMD is affected by weight and weight change and the contribution of these factors to mortality risk, particularly in men, is not known. This study examined the association between baseline BMD, rate of bone loss, weight loss, and weight fluctuation and all-cause mortality risk in elderly men and women. MATERIALS AND METHODS: Data from 1059 women and 644 men, >or=60 years of age (as of 1989), of white background who participated in the Dubbo Osteoporosis Epidemiology Study were analyzed. All-cause mortality was recorded annually between 1989 and 2004. BMD at the femoral neck was measured by DXA (GE-LUNAR) at baseline and at approximately every 2 yr afterward. Data on incident osteoporotic fractures and concomitant diseases, including cardiovascular diseases, all types of cancer, and type I/II diabetes mellitus, was also recorded. RESULTS: In the multivariable Cox's proportional hazards model with adjustment for age, incident fractures, and concomitant diseases, the following variables were independent risk factors of all-cause mortality in men: rate of BMD loss of at least 1%/yr, rate of weight loss of at least 1%/yr, and weight fluctuation (defined by the CV) of at least 3%. In women, in addition to the significant factors observed in men, lower baseline BMD was also an independent risk factor of mortality. In both sexes, baseline weight was not an independent and significant predictor of mortality risk. Approximately 36% and 22% of deaths in women and men, respectively, were attributable to the four risk factors. CONCLUSIONS: These data suggest that, although low BMD was a risk factor of mortality in women, it was not a risk factor of mortality in men. However, high rates of BMD loss, weight loss, and weight fluctuation were also independent predictors of all-cause mortality in elderly men and women, independent of age, incident fracture, and concomitant diseases.     

Retinol intake and bone mineral density in the elderly: the Rancho Bernardo Study.

Retinol is involved in bone remodeling, and excessive intake has been linked to bone demineralization, yet its role in osteoporosis has received little evaluation. We studied the associations of retinol intake with bone mineral density (BMD) and bone maintenance in an ambulatory community-dwelling cohort of 570 women and 388 men, aged 55-92 years at baseline. Regression analyses, adjusted for standard osteoporosis covariates, showed an inverse U-shaped association of retinol, assessed by food-frequency questionnaires in 1988-1992, with baseline BMD, BMD measured 4 years later, and BMD change. Supplemental retinol use, reported by 50% of women and 39% of men, was an effect modifier in women; the associations of log retinol with BMD and BMD change were negative for supplement users and positive for nonusers at the hip, femoral neck, and spine. At the femoral neck, for every unit increase in log retinol intake, supplement users had 0.02 g/cm2 (p = 0.02) lower BMD and 0.23% (p = 0.05) greater annual bone loss, and nonusers had 0.02 g/cm2 (p = 0.04) greater BMD and 0.22% (p = 0.19) greater bone retention. However, among supplement users, retinol from dietary and supplement sources had similar associations with BMD, suggesting total intake is more important than source. In both sexes, increasing retinol became negatively associated with skeletal health at intakes not far beyond the recommended daily allowance (RDA), intakes reached predominately by supplement users. This study suggests there is a delicate balance between ensuring that the elderly consume sufficient vitamin A and simultaneously cautioning against excessive retinol supplementation.     

Body size,estrogen use and thiazide diuretic use affect 5-year radial bone loss in postmenopausal women

Understanding factors associated with more rapid bone mineral loss among aging women is important for establishing preventive strategies for intervention. This study reports factors associated with the 5-year change in radial bone mineral density (BMD) determined prospectively in 435 women aged 55–80 years at baseline. The baseline study included measurement of radial BMD (gm/cm²) by single photon densitometry and personal interview. The baseline protocol was replicated 5 years later in a follow-up study. Women with a lower baseline weight or Quetelet index, smaller triceps skinfold and less arm muscle area had significantly greater 5-year bone loss (p=0.001). Current users of estrogens had less radial bone loss (2.8% vs 7.3%,p=0.0005) than women not currently using estrogens. Current users of estrogen had significantly less 5-year loss if use had been for 5 years or longer (–1.0% vs –6.9%,p=0.05). Current users of the thiazide class of medications had less 5-year radial bone loss (5.0% vs 7.4%,p=0.0035) than women without current thiazide use. Baseline dietary calcium, alcohol consumption and smoking were not associated with BMD change. This suggests that greater body size, and current use of estrogens or thiazide antihypertensives are associated with less radial bone mass loss in a 5-year period among postmenopausal women.     

Effects of current and discontinued estrogen replacement therapy on hip structural geometry: the study of osteoporotic fractures.

It is assumed that estrogen influences bone strength and risk of fractures by affecting bone mineral density (BMD). However, estrogen may influence the mechanical strength of bones by altering the structural geometry in ways that may not be apparent in the density. Repeated dual energy X-ray absorptiometry (DXA) hip scan data were analyzed for bone density and structural geometry in elderly women participating in the Study of Osteoporotic Fractures (SOF). Scans were studied with a hip structural analysis program for the effects of estrogen replacement therapy (ERT) on BMD and structural geometry. Of the 3,964 women with ERT-use data, 588 used ERT at both the start and end of the approximately 3.5-year study, 1,203 had past use which was discontinued by clinic visit 4, and 2,163 women had never used ERT. All groups lost BMD at the femoral neck, but the reduced BMD among users of ERT was entirely due to subperiosteal expansion and not bone loss, whereas both bone loss and expansion occurred in past or nonusers. BMD increased 0.8%/year at the femoral shaft among ERT users but decreased 0.8%/year among nonusers. Section moduli increased at both the neck and shaft among ERT users but remained unchanged in past and nonusers. Current, but not past, use of estrogen therapy in elderly women seems to increase mechanical strength of the proximal femur by improving its geometric properties. These effects are not evident from changes in femoral neck BMD.     

Body Weight Change Since Menopause and Percentage Body Fat Mass are Predictors of Subsequent Bone Mineral Density Change of the Proximal Femur in Women Aged 75 Years and Older: Results of a 5 Year Prospective Study

Few studies have evaluated risk factors for bone loss in elderly women. We examined risk factors associated with a 5-year longitudinal change in bone mineral density (BMD) at the hip in healthy women aged 75 years and older. The BMD of 276 women from the French EPIDOS (Epidémiologie des Osteoporoses) study was assessed in Montpellier from 1992 to 1993 and again from 1997 to 1998. BMD was measured at the femoral neck, trochanter, and Wards area using the same Lunar densitometer. We examined the relationship between clinical and behavioral factors at baseline and their variations during follow-up, with percentage BMD change adjusted for baseline BMD. Depending on the femur subregion studied, a significant decrease in BMD (exceeding the least significant difference, i.e., >2.8 CV) was observed in 36.2% to 51.1% of women. Multivariate analysis showed that both postmenopausal weight change before baseline and baseline percentage of fat mass were positively correlated with BMD change at the Wards triangle and the trochanter. Yearly absolute and relative weight changes over the follow-up period were significantly associated with change of trochanter and femoral neck BMD. Our results show that maintenance of body weight throughout the postmenopause period and body fat mass play protective roles against bone loss at the proximal femur in women aged 75 years and older and suggest the value in including assessment of weight change throughout postmenopause and percentage body fat mass in screening programs for elderly women who are at higher risk of accelerated bone loss.Members of the EP1DOS (Epidémiologie des Osteoporoses) Study Group. Coordinators: G. Brèart, P. Dargent-Molina (epidemiology); P.J. Meunier, A.M. Schott (clinical aspects); D. Hans (bone densitometry and ultrasound quality control); and P.D. Delmas (biochemistry). Principal Investigators(C enter): C. Baudoin, J.L. Sebert (Amiens); M.C. Chapuy, A.M. Schott (Lyon); F. Favier, C. Marcelli (Montpellier); E. Hausherr, C.J. Menkes, C. Cormier (Paris); and H. Grandjean, C. Ribot (Toulouse).     

Diabetes and bone loss at the hip in older black and white adults.

Type 2 diabetes may be associated with elevated fracture risk, but the impact on bone loss is unknown. Analysis of 4-year change in hip BMD data from a cohort of white and black well-functioning men and women 70-79 years of age found that white women with diabetes had more rapid bone loss at the femoral neck than those with normal glucose metabolism. INTRODUCTION: Type 2 diabetes may be associated with elevated fracture risk in older adults. Although type 2 diabetes is not associated with lower BMD, older diabetic adults have a higher prevalence of other risk factors for fracture, including more frequent falls, functional limitations, and diabetic complications. With this burden of risk factors, loss of BMD could place older adults with diabetes at higher risk of sustaining a fracture. MATERIALS AND METHODS: To determine if bone loss is increased with type 2 diabetes, we analyzed data from the Health, Aging, and Body Composition Study of white and black well-functioning men and women 70-79 years of age. Hip BMD was measured at baseline and 4 years later in 480 (23%) participants with diabetes, 439 with impaired glucose metabolism, and 1172 with normal glucose homeostasis (NG). RESULTS: Those with diabetes had higher baseline hip BMD and weight, but among white women, had more weight loss over 4 years. White women with diabetes lost more femoral neck and total hip BMD than those with NG in age-adjusted models. After multivariable adjustment, diabetes was associated with greater loss of femoral neck BMD (-0.32%/year; 95% CI: -0.61, -0.02) but not total hip BMD. In men and black women, change in hip BMD was similar for participants with diabetes and NG. CONCLUSIONS: Despite having higher baseline BMD, diabetic white women, but not men or black women, had more rapid bone loss at the femoral neck than those with NG. This increased bone loss may contribute to the higher fracture risk observed in older diabetic women.     

Cigarette Smoking, Alcohol and Caffeine Consumption, and Bone Mineral Density in Postmenopausal Women

The aim of this analysis was to compare the effects of different measures of cigarette, alcohol and caffeine consumption upon bone mineral density (BMD). Five hundred and eighty postmenopausal women aged 45–59 years at recruitment completed a risk factor questionnaire that contained detailed sections on cigarette, alcohol and caffeine consumption. BMD was measured using dual-energy X-ray absorptiometry. Measurements taken at five bone sites were used: anterior-posterior spine, femoral neck, greater trochanter, radius/ulna and whole body. The data were analyzed using multiple linear regression, adjusting for a number of established BMD risk factors. BMD was more strongly related to the number of months spent smoking than to pack-years of smoking at all five sites (p <0.05 at four of the five sites). There were significant reductions in BMD when comparing smokers with non-smokers at ages 20, 30 and 40 years, but not for current smoking. Lifetime alcohol consumption and current alcohol consumption did not have an independent association with BMD. However, the heaviest beer drinkers in the sample had a particularly low bone density. Caffeine consumption at various ages was not associated with BMD. The results of these analyses suggest that for predicting BMD a simple history of smoking duration is as good as trying to obtain more detailed smoking information, but that only 25% of the variation in BMD is explained by personal characteristics, family history and lifestyle factors. Received: 30 June 1997 / Accepted: 23 December 1997     

Bone mineral density measured by dual-energy X-ray absorptiometry in healthy finnish women

Summary A cross-sectional study of 351 healthy Finnish women aged 20–76 years was done to establish reference values of bone mineral density (BMD) using dual-energy X-ray absorptiometry (DEXA). The effects of age and of several physical and lifestyle factors on BMD of the lumbar spine and proximal femur (femoral neck, trochanter, and Ward's triangle area) were investigated. Altogether 58 women were excluded from the final analysis due to significant spinal osteoarthritis or other diseases or drugs known to influence calcium or bone metabolism. The precision of the method was 0.9, 1.2, 2.7, and 2.4% in the lumbar, femoral neck, Ward's triangle and trochanter area, respectively. Lumbar BMD was increased by 30% (P<0.001) in 15 patients with osteoarthritis (21% of women 50 years or older), but it was apparently unaffected in 5 cases with aortic calcification. Except for the trochanter area, BMD diminished along with age, and this was significant after the menopause. The peak of mean BMD was observed at the age of 31–35 years in the spine and at the age of 20–25 years in the femoral neck and Ward's triangle. BMD was in a positive relationship to weight both in premenopausal and postmenopausal women and to the use of oral contraceptives in premenopausal women and to that of estrogen replacement therapy in postmenopausal women. Labors and pregnancies had a weak positive effect on BMD in premenopausal women. As compared with nonusers premenopausal women who had used alcohol showed a slightly decreased BMD of Ward's triangle. In postmenopausal women there was a positive correlation between alcohol intake and BMD.     

Long-term effects of serum cholesterol on bone mineral density in women and men: the Framingham Osteoporosis Study

Laboratory studies have suggested a role for cholesterol in the pathogenesis of both osteoporosis and atherosclerosis. The purpose of this prospective study was to assess whether cholesterol levels, repeatedly measured over three decades in young and middle-aged adult women and men, predicted bone mineral density (BMD) at advanced age. Study participants included 712 women and 450 men enrolled in the Framingham Osteoporosis Study, aged 32-61 years at baseline (1953-55) who underwent bone densitometry 34 years later (1988-1989). BMD was measured at the proximal femur (neck, trochanter, and Ward's triangle) and lumbar spine using dual-photon absorptiometry and at the one-third radial shaft and ultradistal radius using single-photon absorptiometry. Sex-specific multivariable linear regression was used to model each BMD site as a function of total cholesterol level, adjusted for age, cigarette smoking, alcohol consumption, body mass index, systolic blood pressure, diabetes, and estrogen use (women). No significant association between total cholesterol and BMD was found in women for any of the bone sites considered. For example, adjusted mean BMD at the lumbar spine was similar in women from the lowest to highest quartile of total cholesterol, respectively, 1.07, 1.08, 1.06, 1.07 g/cm2; P for trend=0.98. Similarly, the findings in men largely showed no association between cholesterol and BMD, although there was an isolated finding of a statistically significant trend in decreasing mean radial shaft BMD with increasing total cholesterol, 0.73, 0.72, 0.72, 0.70 g/cm2, lowest to highest quartile, P for trend=0.02. Cholesterol levels in women and men from young adulthood to middle age years do not appear to have long-term clinical implications for osteoporosis later in life.     

Overweight postmenopausal women lose bone with moderate weight reduction and 1 g/day calcium intake.

Overweight postmenopausal women may be more susceptible to bone loss with weight reduction than previously studied obese women. The influence of energy restriction and Ca intake on BMD was assessed in 66 individuals. Weight reduction resulted in bone loss at several sites in women consuming 1 g Ca/day and was mitigated with higher calcium intake at 1.7 g/day. INTRODUCTION: Bone loss is associated with weight loss in obese postmenopausal women and can be prevented with calcium (Ca) supplementation. However, because bone loss caused by weight loss may be greater in overweight than obese women, it is not clear whether Ca supplementation is also beneficial in overweight women. MATERIALS AND METHODS: We assessed the influence of caloric restriction at two levels of Ca intake on BMD and BMC in 66 overweight postmenopausal women (age, 61 +/- 6 years; body mass index, 27.0 +/- 1.8 kg/m2). Subjects completed either a 6-month energy-restricted diet (WL, n = 47) and lost 9.3 +/- 3.9 % weight or maintained weight (WM; 1 g Ca/day, n = 19). Participants in the WL group were randomly assigned to either normal (1 g/day; WL NL-Ca) or high (1.7 g/day; WL Hi-Ca) Ca intake. Regional BMD and BMC were measured at baseline and after 6 months. RESULTS: During normal Ca intake, trochanter BMD and BMC and total spine BMD were decreased more in WL than WM women (p < 0.05). The WL NL-Ca group lost more trochanter BMD (-4.2 +/- 4.1%) and BMC (-4.8 +/- 7.1%) than the WL Hi-Ca group (-1.4 +/- 5.6% and -1.1 +/- 8.1%, respectively; p < 0.05). There were no significant changes in BMD or BMC at the femoral neck in any group. Weight loss correlated with trochanter BMD loss (r = 0.687, p < 0.001) in the WL NL-Ca group. CONCLUSION: Despite an intake of 1 g Ca/day, bone loss occurred at some sites because of weight loss. Calcium intake of 1.7 g/day will minimize bone loss during weight loss in postmenopausal overweight women.     

The effect of age and menopause on bone mineral density of the proximal femur

Although the menopause has been associated with increased bone loss at several skeletal sites, it has not previously been noted in the hip, yet estrogen therapy has been reported to reduce the incidence of hip fractures. We investigated the effect of age and menopause on bone loss in the proximal femur by measuring bone mineral density (BMD) of the femoral neck, Ward's triangle, and trochanter by dual-photon absorptiometry in 263 normal women aged 20-84. Multiple regression analyses revealed a significant decrease in BMD of the femoral neck and Ward's triangle with age in both pre- and postmenopausal women (p less than 0.001). In the trochanter the decrease with age was significant only in postmenopausal women (p less than 0.001). Further analysis revealed that BMD decreased faster at all sites in the early postmenopausal years. During the first 6 years postmenopause, the decrease in BMD of the femoral neck and trochanter was 3-10 times higher than the change in the decade prior to menopause. About 20% of the lifetime femoral neck loss and 30% of the trochanteric loss occurred in the early postmenopausal period. It is concluded that both age and menopause are major determinants of BMD in the proximal femur. These findings could explain why estrogen therapy has been reported to prevent hip fracture. The rapid early postmenopausal loss in BMD of the proximal femur demonstrates the importance of starting estrogen replacement therapy immediately after menopause for maximum effect.     

Association between a functional interleukin-6 gene polymorphism and peak bone mineral density and postmenopausal bone loss in women: the OFELY study

Genetic factors play an important role in determining bone mass and several genes are involved in this process. Interleukin-6 (IL-6) is a candidate gene for regulation of bone mineral density (BMD) and it has been suggested recently that novel IL-6 -174 G/C allelic variants may be associated with peak BMD in young men and with bone resorption in elderly women. In this study, we assessed the relationships between IL-6 gene polymorphism, peak BMD, rate of postmenopausal BMD loss, and bone turnover in women. BMD was measured by dual-energy X-ray absorptiometry in 255 healthy premenopausal women, aged 31-57 years. BMD loss at the forearm was measured over 4 years in 298 healthy untreated postmenopausal women, 50-88 years (mean 64 years). We also measured levels of serum osteocalcin, bone alkaline phosphatase, and N-propeptide of type I collagen for bone formation and three markers of bone resorption, including urinary and serum C-terminal cross-linking telopeptide of type I collagen and urinary N-terminal telopeptide of type I collagen, in both pre- and postmenopausal women at baseline. In premenopausal women we found a significant association between IL-6 genotypes and BMD at the whole body (analysis of variance [ANOVA], p = 0.03), femoral neck (p = 0.03), trochanter (p = 0.014), Ward's triangle (p = 0.03), and total hip (p = 0.006), with subjects having the CC genotype showing 3%-7% higher BMD levels than their GG counterparts. However, after matching women with CC and GG genotypes for body height the differences decreased (2%-4%), and were no longer significant (p = 0.10-0.23). In postmenopausal women the mean rate of loss at the ultradistal radius was significantly associated with IL-6 genotypes (ANOVA, p = 0.049), with women having the CC genotype showing a significantly greater rate of bone loss (p < 0.05) compared with their GC and GG counterparts. After adjustment for weight changes, the difference in the rate of ultradistal radius bone loss between genotypes decreased and was not significant (p = 0.06 for CC vs. GG). A similar trend was observed for distal radius bone loss (p = 0.10, ANOVA), but not for the middle radius. We found no significant association between genotypes, bone turnover markers in premenopausal women, and either bone turnover or BMD in postmenopausal women. We conclude that this new functional IL-6 polymorphism was weakly associated with level of peak BMD and the rate of forearm trabecular postmenopausal bone loss in this cohort of healthy French women. IL-6 genotypes accounted only for a small proportion of the interindividual variation of both peak BMD and rate of bone loss and were not significant after adjustment for height and changes in body weight, respectively, suggesting that part of the effect may have been due to the differences in body size. Larger long-term studies are necessary to assess adequately the relationships between IL-6 genotype, rate of bone loss, and risk of fracture.     

Interactions of interleukin-6 promoter polymorphisms with dietary and lifestyle factors and their association with bone mass in men and women from the Framingham Osteoporosis Study.

Lifestyle and dietary factors may influence the association of IL-6 polymorphisms with bone mass. In 1574 unrelated men and women from the Framingham Offspring Cohort, we observed significant hip BMD differences between IL-6 -174 genotypes only in older women, those without estrogens, and those with a poor calcium intake. Hence, association of IL-6 polymorphisms with BMD may be limited to discrete population subgroups. INTRODUCTION: Interleukin (IL)-6 plays a central role in the pathogenesis of osteoporosis. Two functional variants in the IL-6 promoter have previously been associated with IL-6 expression, bone resorption levels, and BMD in late postmenopausal women, but results were conflicting in different populations. We hypothesized that the association between IL-6 promoter alleles and BMD may be affected by interactions with lifestyle and dietary factors known to influence bone turnover. MATERIALS AND METHODS: Among the Offspring Cohort of the Framingham Heart Study, 1574 unrelated men and women were genotyped for IL-6 -572 and -174 alleles. Interaction analyses with years since menopause, estrogen status, physical activity, smoking, dietary calcium, vitamin D, and alcohol intake were based on BMD measurements at the hip. RESULTS AND CONCLUSIONS: In models that considered only the main effects of IL-6 polymorphisms, no significant association with BMD was observed in either gender. In contrast, p values (0.003-0.096 by ANOVA) suggestive of an interaction between IL-6 -174 genotypes and years since menopause, estrogen status, dietary calcium, and vitamin D intake were observed in women (n = 819). In turn, BMD was significantly lower with genotype -174 GG compared with CC, and intermediate with GC, in women who were more than 15 years past menopause and in those without estrogens or with calcium intake <940 mg/day. In estrogen-deficient women with poor calcium intake, BMD differences between genotypes CC and GG were 10.2% at femoral neck (p = 0.012), 12.0% at trochanter (p = 0.012), and 16.8% at Ward's area (p = 0.0014). In contrast, no such interactions were observed in men (n = 755). In conclusion, IL-6 genetic variation was prominently associated with hip BMD in late postmenopausal women, those without estrogen replacement therapy, and those with inadequate calcium intake. In contrast, IL-6 polymorphisms are unlikely to be significant determinants of bone mass in other women or men.     

Risk factors for incident vertebral fractures in men and women: the Rotterdam Study.

Low BMD and prevalent vertebral fractures are known risk factors for incident vertebral fractures. In 3001 men and women from the Rotterdam Study, prevalent nonvertebral fractures, early menopause, current smoking, and walking aid use were also strong risk factors for incident vertebral fractures. INTRODUCTION: Thus far, age, low BMD, and prevalent vertebral fractures are the only well-known risk factors for incident vertebral fractures. Therefore, our aim was to investigate other potential risk factors for incident vertebral fractures in the elderly. MATERIALS AND METHODS: This study was based on the Rotterdam Study, a large prospective population-based cohort study among men and women > or =55 years of age. For 3001 subjects, spinal radiographs were obtained at baseline and again approximately 6.3 years later. These follow-up radiographs were scored for vertebral fractures using the McCloskey-Kanis method. Whenever a vertebral fracture was detected, the radiograph was compared with the baseline radiograph. If this fracture was not already present at baseline, it was considered incident. At baseline, information on potential risk factors was obtained. RESULTS: Low BMD and prevalent vertebral fractures were strong risk factors for incident vertebral fractures in both men and women (RR 2.3 [1.6-3.3] and 2.2 [0.9-5.0] for men and RR 2.1 [1.6-2.6] and 4.1 [2.5-6.7] for women, respectively). For women, age, early menopause (< or =45 years of age; RR 1.0 [1.1-3.5]), current smoking (2.1 [1.2-3.5]), and walking aid use (2.5 [1.1-5.5]) were additional independent risk factors. For men, only a history of nonvertebral fractures was a significant independent risk factor (OR 2.4 [1.2-4.8]). CONCLUSION: Apart from low BMD and prevalent vertebral fractures, prevalent nonvertebral fractures are associated with an increased incident vertebral fracture risk in men. In women, early menopause, current smoking, and walking aid use are additional independent risk factors for incident vertebral fractures.     

Racial differences in rate of decline in bone mass in older men: the Baltimore men's osteoporosis study.

Older black men have higher adjusted BMD than older white men. Using data from a longitudinal cohort study of older men followed for a mean of 18.8 +/- 6.5 (SD) months, we found that older black men have a higher rate of decline in femoral neck and total hip BMD and femoral neck BMAD than older white men. INTRODUCTION: Older black men have higher adjusted BMD compared with older white men. The difference in BMD may be caused by having attained higher peak bone mass as young adults and/or having a slower rate of decline in bone mass as adults. There are few published longitudinal data on change in bone mass in older white men and no published data for older black men. MATERIALS AND METHODS: Three hundred forty-nine white men and 119 black men 65 of age (mean age, 75 +/- 5.7 and 72 +/- 5.6 years, respectively) who participated in the longitudinal component of the Baltimore Men's Osteoporosis Study returned for a second visit after a mean of 18.8 +/- 6.5 (SD) months and were not taking medications used to treat low bone mass at either visit. BMD was measured at the femoral neck and total hip by Hologic-certified technicians using a QDR 2000 at the baseline visit (V1) and QDR 4500 at the first follow-up visit (V2). Participants also completed self-administered and interviewer-administered questionnaires and underwent standardized clinic examinations. Bone mineral apparent density (BMAD) at the femoral neck was calculated as an estimate of volumetric BMD. Annual crude and multiple variable adjusted percent changes in BMD and BMAD were calculated. RESULTS: In univariate analyses, black men had lower percent decline in femoral neck and total hip BMD and femoral neck BMAD than white men. In addition, older age at baseline, lower baseline weight, current smoking, and lower baseline BMD were associated with greater percent decline per year in femoral neck BMD; older age at baseline, current smoking, and lower baseline BMD were associated with greater percent decline per year in total hip BMD; and older age at baseline and lower baseline femoral neck BMAD were associated with greater percent decline per year in femoral neck BMAD. Racial differences in bone loss persisted in multiple variable models that controlled for other factors associated with change in BMD and BMAD. CONCLUSIONS: Older black men seem to lose bone mass at a slower rate than older white men. These differences in the rate of bone loss may account, in part, for the racial disparities in BMD and BMAD and risk of osteoporotic fractures among older men.     

Skipping breakfast and less exercise are risk factors for bone loss in young Japanese adults: a 3-year follow-up study

Although bone loss contributes to osteoporosis (OP) in the elderly, little is known about changes in bone mineral density (BMD) in young adults that lead to bone loss. Here, we evaluated the rate of bone change and risk factors for bone loss in young men and women using data from a 3-year prospective study of Japanese medical students. The study included a self-administrated questionnaire survey, anthropometric measurements, and BMD measurements of the spine (L2–L4) and femoral neck (FN). After 3 years, the BMD of the participants was again measured at the same sites. In all, 458 students (95.4 %; 298 men and 160 women; age range, 18–29 years; mean age, 20.2 years) completed both the baseline and follow-up surveys. The mean L2–L4 BMD value at baseline increased significantly within 3 years. This tendency was also observed for the FN in men but not in women. The annual changes at L2–L4 were 1.78 % in men and 0.97 % in women per year; those for FN were 1.08 % in men and 0.08 % in women per year. However, 20.3 % and 38.5 % of the total freshmen lost BMD in the lumbar spine and FN, respectively. After adjustment for age and body mass index, logistic regression analysis revealed that bone loss in men at L2–L4 at the baseline was affected by skipping breakfast. In contrast, exercise (>2 h/week) increased lumbar spine BMD in both genders. These findings indicate that breakfast and exercise are important for maintaining BMD in young men and women.     

An Association Between Respiratory Function and Bone Mineral Density in Women from the General Community: A Cross Sectional Study

Respiratory function has been associated with bone mineral density (BMD) in patients with respiratory diseases. We examined the relationship between bone density measured at the hip and respiratory function in women from the general community. A total of 4830 women aged 45–76 years were recruited from general practice age – sex registers in Cambridge between 1991 and 1995. At baseline survey, data collection included health questionnaires, measures of anthropometry, respiratory function, as well as bone mineral density BMD measured using dual energy X ray absorptiometry. BMD at total hip, femoral neck and trochanter significantly and positively correlated with FEV₁. This association was independent of age, weight, height, smoking habit, history of respiratory diseases, corticosteroids and use of hormone replacement therapy. After adjustment for these factors, an increase in FEV₁ of 1 l/s was associated with 0.026, 0.021 and 0.026g/cm² increase in bone mineral density at total hip, femoral neck and trochanter respectively. The association was consistent and similar in magnitude among current smokers and current non-smokers and across all age groups. The magnitude of the association was comparable to that associated with an age difference of 6 years or weight difference of 5 kg. Women in the bottom compared to top quartile of respiratory function had about double the risk of low bone density independent of other factors. Respiratory function measured using FEV₁ is positively and independently related to BMD in these middle-aged and older women across the whole normal distribution of these physiologic measures. This may reflect underlying common determinants such as physical activity. Even in healthy women, respiratory function may be a marker for women at increased risk of osteoporosis and associated fractures. Received: 6 February 2002 / Accepted: 22 May 2002