Ghrelin and bone: is there an association in older adults?: the Rancho Bernardo study.

Laboratory studies suggest that ghrelin is involved in bone metabolism, but studies of ghrelin and bone in humans are limited. We studied sex-specific associations of ghrelin with BMD, NTX, and bone loss. Ghrelin was not associated with BMD or bone loss in either sex. There was a significant inverse association with NTX in men but not in women. INTRODUCTION: Ghrelin is a gastric hormone recently shown to be associated with bone metabolism in animal and in vitro studies. Studies in humans are limited. We investigated the association of ghrelin with BMD, the bone resorption marker N-telopeptide (NTX), and bone loss in older men and women. MATERIALS AND METHODS: Participants were 977 community-dwelling men and non-estrogen-using postmenopausal women, 50-91 years of age. Plasma ghrelin was measured by radioimmunoassay from blood obtained between 1984 and 1987. Between 1988 and 1991, BMD was measured at the midshaft radius by single photon absorptiometry and at the femoral neck, total hip, and lumbar spine by DXA. Axial BMD measurements were repeated an average of 4 years later in 544 participants. Bone turnover was assessed by NTX in urine obtained at the same time as the initial BMD. Multiple regression analyses were used to test sex-specific associations of ghrelin with BMD, NTX, and bone loss in both sexes. RESULTS: No significant ghrelin-BMD or ghrelin-bone loss associations were observed in either sex, after adjusting for age and body mass index (BMI). Ghrelin was inversely associated with NTX in men and positively associated with NTX in women, independent of age. After adjusting for both age and BMI, this association reached statistical significance in men and was weakened in women. CONCLUSIONS: Ghrelin may be associated with bone turnover, but there is no evidence for an association with BMD or short-term change in BMD in older adults.     

Osteoporosis and Apolipoprotein E Genotype in Older Adults: The Rancho Bernardo Study

Recent studies reported an association between apolipoprotein E (ApoE) 4 and osteoporosis. We examined the association of ApoE 4 genotype with bone mineral density (BMD), bone loss and fracture risk in 596 men and 332 community-dwelling women aged 45–95 years. Women were postmenopausal and not using estrogen. At the baseline visit, BMD was measured at the ultradistal and midshaft radius using single photon densitometry, and at the hip and lumbar spine using dual-energy X-ray absorptiometry. Hip and lumbar spine BMD levels were remeasured 4 years later. Self-reported fractures were confirmed by radiology reports in 95% of cases. ApoE allele distribution did not vary by age; 25% of men and 20% of women had one ApoE 4 allele. There were no differences in BMD at the lumbar spine, total hip, ultradistal or midshaft radius in men or women with the ApoE 4 allele compared with men or women without the ApoE 4 allele. After an average 4 year interval, there were also no differences in the annualized percent change in BMD at the hip or lumbar spine in men or women with or without an ApoE 4 allele. One or more clinical fractures were reported by 55 men and 109 women. Fewer, not more, clinical fractures were reported in men and women with an ApoE 4 allele; these differences were not statistically significant (p= 0.21 and p= 0.62, respectively). These data do not support the hypotheses that there is an association between ApoE genotype and BMD, bone loss or osteoporotic fractures in older community-dwelling men or women. Received: 26 July 2000 / Accepted: 13 October 2000     

Sex Differences in the Association Between Adiponectin and BMD,Bone Loss,and Fractures: The Rancho Bernardo Study

We evaluated sex differences in the prospective association between adiponectin with BMD, bone loss, and fractures. Adiponectin, an adipose‐derived protein with insulin‐sensitizing properties, is also expressed in bone‐forming cells. Conflicting results and sex differences in the adiponectin‐BMD association have been reported in cross‐sectional studies. Serum adiponectin was measured in fasting blood samples obtained in 1984–1987 in 447 postmenopausal women (mean age: 76 yr) and 484 men (mean age: 75 yr). Four years later, BMD was measured at the midshaft radius by single photon absorptiometry and at the femoral neck, total hip, and lumbar spine by DXA. In 1992–1996, axial BMD was remeasured in 261 women and 264 men. Multivariable analysis adjusted for age, weight, calcium intake, type 2 diabetes, alcohol intake, and exercise. Among women, adiponectin was inversely associated with BMD at the femoral neck (β = ?0.002, p = 0.007), total hip (β = ?0.002, p = 0.009), lumbar spine (β = ?0.003, p = 0.008), and midshaft radius (β = ?0.002, p = 0.01) after 4.4 yr and at the femoral neck and total hip 8.6 yr later. Among men, adiponectin was inversely associated with BMD at the femoral neck, (β = ?0.002, p = 0.03), total hip (β = ?0.004, p < 0.001), and midshaft radius (β = ?0.003, p < 0.001) after 4.4 yr and at the hip 8.6 yr later. Adiponectin was not associated with 4‐yr bone loss in either sex but was associated with vertebral fractures (adjusted OR: 1.13; 95% CI: 1.08–1.23; p = 0.009) among men only. Adiponectin was inversely associated with BMD; however, sex differences were observed by anatomical site and with regards to vertebral fractures.     

The effects of adiponectin and leptin on changes in bone mineral density

Summary

We tested the hypothesis that low leptin and high adiponectin levels are associated with higher rates of bone mineral density (BMD) loss among 3,075 men and women, aged 70–79, from the Health Aging and Body Composition Study. Results suggest that adiponectin, but not leptin, is a risk factor for bone loss in women.

Introduction

Adiponectin and leptin are hormones secreted by adipose cells that may impact BMD. Few studies have evaluated the longitudinal association of leptin and adiponectin levels with rates of BMD change.

Methods

Hip and whole-body areal BMD (aBMD) were measured five times using dual-energy X-ray absorptiometry over 10?years (average follow-up time, 7.95 ± 1.92 years). Trabecular lumbar spine volumetric BMD (vBMD) was measured using quantitative computed topography at baseline and year?6 in the Pittsburgh cohort only. Random slope and intercept models were used to account for within person correlation as a result of repeated measures of hip and whole-body aBMD. Linear regression was used to model changes in spine trabecular vBMD.

Results

Among women, the annualized rate of hip aBMD loss in the highest tertile of adiponectin was ?0.67% (95% CI ?0.77, ?0.58) compared to [?0.43% (95% CI ?0.51, ?0.35)] in the lowest tertile (p trend?=?0.019) after adjusting for age, race, BMI, diabetes, baseline hip aBMD, and weight change. In men, hip aBMD loss was greatest in the high adiponectin group (tertile 3), however this association was not significant (p trend?=?0.148). After adjusting for weight change in women, the association between higher leptin and lower hip aBMD loss was attenuated and no longer significant (p trend?=?0.134). Leptin and adiponectin levels were not associated with whole-body aBMD or trabecular lumbar spine vBMD loss.

Conclusions

Adiponectin was associated with increased hip aBMD loss in women only, supporting evidence that adiponectin may have an important role in bone health.     

Adipokines and the risk of fracture in older adults

Adiponectin and leptin are adipokines that influence bone metabolism in vitro and in animal models. However, less is known about the longitudinal association of leptin and adiponectin with fracture. We tested the hypothesis that low leptin and high adiponectin levels are each individually associated with fracture risk in a prospective cohort study in Memphis and Pittsburgh among 3075 women and men aged 70 to 79 years from the Health Aging and Body Composition (Health ABC) study. There were 406 incident fractures (334 nonvertebral and 72 vertebral) over a mean of 6.5 ± 1.9 years. Cox regression was used to estimate the hazard ratios for fracture. Sex modified the association between adiponectin and fracture (p = .025 for interaction). Men with the highest adiponectin level (tertile 3) had a 94% higher risk of fracture [hazard ratio (HR) = 1.94; 95% confidence interval (CI) 1.20–3.16] compared with the lowest tertile (tertile 1; p = .007 for trend) after adjusting age, race, body mass index (BMI), education, diabetes, weight change, and hip bone mineral density (BMD). Among women, after adjusting for age and race, this association was no longer significant (p = .369 for trend). Leptin did not predict fracture risk in women (p = .544 for trend) or men (p = .118 for trend) in the multivariate models. Our results suggest that adiponectin, but not leptin, may be a novel risk factor for increased fracture risk independent of body composition and BMD and that these relationships may be influenced by sex. More research is needed to understand the physiologic basis underlying these sex differences. © 2011 American Society for Bone and Mineral Research.     

BMD and risk of hip and nonvertebral fractures in older men: a prospective study and comparison with older women.

In a prospective study of 5384 older men, hip BMD was a very strong predictor of hip fracture, much stronger than spine BMD. The relationship between hip BMD and hip fracture risk seemed to be stronger than observed in a large prospective study of women. Hip BMD is an excellent test for predicting fracture risk in men. INTRODUCTION: There have been few studies of the relationship between BMD and risk of fractures in men and none for the association between lumbar spine BMD and risk of hip and nonvertebral fractures. There is also controversy about whether the associations between BMD and risk of fracture are the same in men and women. MATERIALS AND METHODS: We measured proximal femur and lumbar spine BMD in 5384 men, 5384 men, >or= 65 years of age. We compared the results to the very similar cohort of 7871 women >or=65 of age. During 4.4 years of 99% complete follow-up, we validated 317 nonvertebral (59 hip) fractures in men and 1169 nonvertebral (208 hip) fractures in women. RESULTS: Total hip BMD was very strongly associated with risk hip fracture in men (3.2-fold increased risk per sex-specific SD decrease in BMD; 95% CI, 2.4-4.1). The association was stronger than observed in SOF (2.1; 95% CI, 1.8, 2.4; p < 0.001 for interaction). Among the men, lumbar spine BMD was weakly associated with risk of hip fracture (relative risk [RR] per sex-specific SD decrease in BMD: 1.5; 95% CI, 1.2, 2.0). The association between total hip BMD and risk of nonvertebral fractures was somewhat stronger for men (RR = 1.6; 95% CI, 1.5, 1.8) than found for women (p = 0.01 for interaction). The risk of nonvertebral fracture was substantially higher in women than in men for all T scores of hip BMD, regardless of whether sex-specific or female reference values were used. CONCLUSIONS: Hip BMD is strongly associated with risk of nonvertebral, and especially hip fracture, in older men. These associations are at least as strong as in women. As in women, lumbar spine BMD in men is only weakly associated with risk of hip fracture. Regardless of whether sex-specific or female reference values were used, T scores indicated different risks of fractures in men than in women.     

Serum insulin-like growth factor binding protein-1 levels and bone mineral density in older adults: The Rancho Bernardo Study

Insulin-like growth factor-I (IGF-I) stimulates osteoblast function, inhibits collagen matrix degradation, and is positively associated with bone mineral density in most but not all studies. We previously reported that IGF-I was positively associated with BMD at the spine and hip in women but not men. Insulin-like growth factor binding protein-1 (IGFBP-1), a potent modulator of IGF-I, is expressed in normal osteoblasts and inhibits collagen gene expression in bone, but little is known about the relationship between IGFBP-1 and bone mineral density (BMD). We report a cross-sectional study of serum IGFBP-1 levels and BMD in 1,139 community-dwelling men and postmenopausal women (not using estrogen), aged 44–98. In both sexes, IGFBP-1 levels increased linearly with age (p<0.001) and decreased with body mass index (BMI) quartile (p<0.001). After adjusting for age and BMI, there was no significant association between IGFBP-1 and BMD at the hip or spine. IGF-I and IGFBP-1 were weakly and inversely associated with each other. These findings suggest that if there is an important role for IGFBP-1 in bone metabolism, it is mediated or confounded by weight. Studies are needed to further investigate the relationship between inhibitory components of IGF-1 and bone loss.     

A potentially deleterious role of IGFBP-2 on bone density in aging men and women.

The role of the IGFs and IGFBPs on age-related changes in BMD in adult men and women is not well understood. Studying an age-stratified community based sample of 344 men and 276 women, we found higher IGFBP-2 levels to be associated with lower BMD. IGFBP-2, which increases with age in both men and women, was the strongest, most consistent predictor of BMD among the IGF/IGFBPs studied. INTRODUCTION: Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are important regulators of tissue growth and metabolism, but their association with BMD in adult men and women is controversial. MATERIALS AND METHODS: In an age-stratified, random sample of the community population, we examined the role of serum levels of IGF-I, IGF-II, and IGFBP-1, -2, and -3 on BMD of the proximal femur (total hip), lateral spine, midshaft, and ultradistal radius as measured by DXA. We explored the association before and after adjustment for potential confounders, including age, bioavailable estradiol and testosterone, sex hormone binding globulin (SHBG), and measures of total fat and skeletal muscle mass. RESULTS: We studied 344 men (age, 23-90 years) and 276 women (age, 21-93 years; 166 postmenopausal) not on hormone replacement or oral contraceptives. In both men and women, IGF-I and IGFBP-3 levels fell with advancing age, whereas IGFBP-2 levels tended to rise with age. There was an inverse association of IGFBP-2 with BMD at most skeletal sites in men and both premenopausal and postmenopausal women, whereas lower IGF-I and IGFBP-3 were associated with lower BMD in men and postmenopausal women only. Lower IGF-II was associated with lower BMD in men only. There were no associations between IGFBP-1 and BMD in either sex. After adjustment for age, in most cases, we found no further associations between IGF-I, IGF-II, or IGFBP-3 and BMD. In contrast, after age adjustment, higher IGFBP-2 remained a predictor of lower BMD in men and postmenopausal women at all sites except for the lateral spine (for men: r = -0.21, -0.20, and -0.19, all p < 0.001; and for postmenopausal women: r = -0.34, -0.24, and -0.25, all p < 0.01, for the total hip, midshaft, and ultradistal radius, respectively). IGFBP-2 remained an independent negative predictor of BMD in men, postmenopausal women, and all women combined after additional adjustment for bioavailable sex steroids, but not at all sites after adjustment for SHBG and muscle mass. In premenopausal women, IGFBP-2 had similar associations as seen in postmenopausal women, but they were weaker and not statistically robust. CONCLUSIONS: Among the IGF/IGFBPs in our study, IGFBP-2 was a key negative predictor of BMD among men and women, particularly postmenopausal women. Our findings suggest a potential role of the IGF/IGFBP system in regulating bone loss in aging men and women and identify a previously under-recognized, potentially deleterious role for IGFBP-2, a known inhibitor of IGF action that increases with age in both sexes. Whether the action of the IGF/IGFBP system on bone metabolism is mediated partly through its effects on muscle mass or SHBG deserves further study.     

A comparison between peripheral BMD and central BMD measurements in the prediction of spine fractures in men

Introduction: Most of the research on osteoporosis has been conducted on women. Few studies have compared central and peripheral densitometry and their association with vertebral fractures in men. The present study was designed to compare peripheral bone mineral density (BMD) measurements with central BMD measurements, and to examine their association with radiographic spine fracture in men. Methods: We studied 402 community-dwelling men aged 45–92 years (mean: 70 years) from the Rancho Bernardo Study cohort who attended a clinic visit between 1988 and 1992 when BMD measurements of the midshaft radius, ultradistal wrist, lumbar spine, and total hip were obtained, and who returned for lateral X-rays of the thoracic and lumbar spine an average of 4 years later. Logistic regression, T-scores, and quintiles were used to analyze BMD and its association with vertebral fractures. Results: The prevalence of osteoporosis defined by the National Osteoporosis Foundation criteria (for women) was 14.2% at the spine and 13% at the hip. Because there are no validated definitions of osteoporosis based on the ability to predict fracture risk for peripheral densitometry, the frequency of overlap by bone site was calculated among men in the lowest quintile of each site. Of the 402 men, 82 men (20.3%) had at least two sites with BMD measurements in the lowest quintile. After an average of 4 years, 33 (8.2%) men had at least one radiographic vertebral fracture, and ten (2.5%) men had at least two vertebral fractures. Low BMD at the spine (with and without covariate adjustment) was associated with having one or more vertebral fractures, whether using NOF T-score-defined osteoporosis [Odds ratio (OR): 3.81; confidence interval (CI): 1.52, 9.57] or the lowest quintile versus all others (OR: 2.53; CI: 1.03, 6.19). After age and/or other covariate adjustments, neither BMD at the total hip nor at the peripheral sites was associated with spine fractures using either NOF women-based criteria or male quintiles from this cohort. Conclusion: Although different men had osteoporosis defined by quintiles at different sites, only low BMD at the spine was associated with vertebral fracture.     

Serum leptin as a determinant of bone resorption in healthy postmenopausal women

To examine the relationships between serum leptin and bone metabolism, we measured bone mineral density (BMD) at the spine and the hip, fasting serum leptin, and osteocalcin and urinary excretion of C-terminal crosslinking telopeptide of type I collagen (CTX), as markers of bone formation and resorption, respectively, in 121 postmenopausal women aged 54 +/- 5 years. These parameters were also assessed at 6 months and 2 years of treatment with either 2.5 mg tibolone (n = 34), 1.25 mg tibolone (n = 45), or 2 mg estradiol plus 1 mg norethindrone acetate (n = 42). At baseline, serum leptin correlated positively with spine (r = 0.21, P = 0.02) and total hip (r = 0.26, P = 0.0044) BMD and negatively with CTX (r = -0.38, P < 0.0001) and osteocalcin (r = 0.21, P = 0.025). After adjustment for BMI and for fat mass, the association between serum leptin and CTX persisted with a partial correlation coefficient of -0.18 (P = 0.046) and of -0.22 (P = 0.03), respectively. Women in the highest quartile of leptin levels had 11% higher total hip (P = 0.0039) and lumbar spine BMD (P = 0.016), 21% lower osteocalcin (P = 0.01), and 38% lower CTX (P = 0.0005) than women in the lowest quartile (P < 0.05). During treatment, serum leptin levels increased (+14.7 +/- 47.3%, P = 0.019), without significant difference between the groups. This increase correlated with the increase in body weight (r = 0.46, P < 10(-4)). No correlation was found between the changes in leptin and the changes in bone parameters. In conclusion, leptin may play a role as a determinant of bone resorption in healthy, untreated postmenopausal women, but the effect of estradiol or tibolone on bone are not mediated by leptin.     

Role of serum leptin, insulin, and estrogen levels as potential mediators of the relationship between fat mass and bone mineral density in men versus women

Although fat mass is related to bone mineral density (BMD), the potential mechanism(s) of this effect remain to be defined. Thus, we assessed the role of the candidate hormones, leptin, insulin, and estrogen in mediating fat mass effects on the skeleton. Specifically, we related these hormones and fat mass to BMD at the total hip, mid-lateral spine, and mid-distal radius in a sample of 137 premenopausal women (age range 21-54 years), 165 postmenopausal women (34-93 years), and 343 men (23-90 years) recruited from the general population. Fat mass and BMD were significantly related in pre- and postmenopausal women at multiple sites, whereas this relationship was only weakly present in men at the total hip. Serum leptin levels were also significantly related to BMD in the women, but not in the men. Insulin was associated with hip BMD in the women, and bioavailable estradiol (E2) was correlated with BMD at all sites in men and in postmenopausal women. In the women, adjusting for leptin reduced the strength of the association between fat mass and BMD, with further adjustments for insulin or bioavailable E2 having no additional effects. Adjusting for leptin in the men had no consistent effect on the relationship between fat mass and BMD. Collectively, these data suggest that there is a sexual dimorphism in the relationship of fat mass and leptin to BMD, with both being positively associated with BMD in women but not in men. In women, leptin may also mediate at least part of the protective effect of fat mass on the skeleton.     

The association of Parkinson’s disease with bone mineral density and fracture in older women

Among community-dwelling older women, compared to those without Parkinson's disease (PD), women with PD have 7.3% lower BMD and an increased risk for hip fracture (HR = 2.6). INTRODUCTION: Studies reporting an association of Parkinson's disease (PD) with low bone mineral density (BMD) and increased fracture risk often have been prone to selection bias, and have not accounted for potentially important explanatory variables, including recent weight loss. Further, little is known about the association between PD and non-hip fractures. Consequently, we investigated the independent association of PD with hip BMD and long-term fracture risk. METHODS: Associations of self-reported PD with hip BMD and incident hip and non-spine, non-hip fracture were analyzed using linear regression and Cox proportional hazards, respectively. This prospective cohort study analyzed 8,105 older women with known PD status (n = 73 with PD) at four US clinical centers of the Study of Osteoporotic Fractures. RESULTS: Compared to women without PD, age-adjusted mean total hip BMD was 7.3% lower in women with PD. Women with PD had a 2.6-fold higher age-adjusted risk for incident hip fracture. Parkinson's disease was not significantly associated with non-spine, non-hip fractures. CONCLUSIONS: In age-adjusted models, women with PD had lower hip BMD and increased hip fracture risk, associations that were no longer significant after further weight and multivariate adjustment. Older women with PD should be considered for evaluation and treatment to reduce their fracture risk.     

Relationship of serum leptin concentration with bone mineral density in the United States population.

Overweight is associated with both higher bone mineral density (BMD) and higher serum leptin concentrations. In humans, little is known about the relationship of leptin concentration and bone density. We studied this relationship in a large, national population-based sample. Participants included 5815 adults in the Third U.S. National Health and Nutrition Examination Survey (NHANES III; 1988-1994) who underwent DXA of the proximal femur and measurement of fasting serum leptin. Mean +/- SE BMD (gm/cm2) of the total hip was 1.01 +/- 0.005 in men, 0.94 +/- 0.004 in premenopausal women, and 0.78 +/- 0.007 in postmenopausal women. Bone density increased with increasing leptin concentration in men (p = 0.003), premenopausal women (p < 0.001), and postmenopausal women (p < 0.001). However, after adjusting for body mass index (BMI) and other bone density-related factors, an inverse association emerged in men (p < 0.001), being most evident among men < 60 years old. There was no association of leptin and BMD in premenopausal women (p = 0.66) or postmenopausal women (p = 0.69) in multivariate analysis. Controlling for leptin had no effect on the strong positive association of BMI and BMD in either men or women. Serum leptin concentration did not appear to affect directly BMD. If present, the association appeared to be limited to younger men who are at lower risk of osteoporosis.     

Risk factors for decreased bone density and effects of HIV on bone in the elderly

SUMMARY: Most studies of bone density in HIV-infected individuals focus on young men. This study compares differences in bone density in elderly HIV positive men and women to HIV negative controls. Bone density was lower in the lumbar spine and hip in the HIV-infected group. Antiretrovirals may be associated with decreased bone mineralization. INTRODUCTION: Individuals with human immunodeficiency virus (HIV) may be at increased risk for osteoporosis. Prolonged exposures to HIV and/or antiretroviral therapy are possible causes for this association. This study compares differences in bone mineral density (BMD) in elderly HIV positive men and women to HIV negative controls. METHODS: A cross-sectional study was conducted among 57 HIV-infected and 47 HIV negative subjects over age 55. BMD at the lumbar spine and total hip and markers of bone turnover were compared. RESULTS: BMD was borderline lower in the lumbar spine and significantly lower in the hip in the HIV-infected group. Controlling for age, sex, race and body mass index, differences between the groups were significant at both sites. There was no difference in markers of bone turnover between the groups. Tenofovir use was significantly associated with decreased BMD at the spine while protease inhibitor use was significantly associated with decreased BMD at the hip. CONCLUSION: Elderly men and women with HIV have lower bone mass than HIV negative controls. Decreased body mass index was the most important risk factor associated with decreased BMD. Bone demineralization was observed among HIV-infected subjects receiving either tenofovir or a protease inhibitor.     

Diabetes is associated independently of body composition with BMD and bone volume in older white and black men and women: The Health, Aging, and Body Composition Study.

The association between type 2 diabetes, BMD, and bone volume was examined to determine the effect of lean and fat mass and fasting insulin in the Health, Aging, and Body Composition Study, which included white and black well-functioning men and women 70-79 years of age (N = 2979). Diabetes predicted higher hip, whole body, and volumetric spine BMD, and lower spine bone volume, independent of body composition and fasting insulin. INTRODUCTION: The purpose of this study was to determine if the association between type 2 diabetes and higher BMD observed in older white women is seen in elderly white men and blacks and to evaluate if higher BMD in diabetic individuals is accounted for by lean mass, fat mass, or fasting insulin differences. MATERIALS AND METHODS: In the Health, Aging, and Body Composition Study, which included white and black well-functioning men and women 70-79 years of age (N = 2979), 19% of participants had diabetes at baseline. Of those with diabetes, 57% were men, and 62% were black. Multivariate linear regression models examined independent effects of diabetes, lean mass, fat mass, visceral fat, and fasting insulin on BMD and bone volume while adjusting for relevant covariates. RESULTS AND CONCLUSIONS: Fasting insulin, visceral fat, and volumetric spine BMD, assessed by CT, and lean mass, fat mass, and total hip and whole body BMD, assessed by DXA, were higher (p < or = 0.05 for all) for those with diabetes. Hip BMD was higher in white men (0.99 +/- 0.14 versus 0.93 +/- 0.14 g/cm2, p < 0.001), black men (1.06 +/- 0.17 versus 1.00 +/- 0.15 g/cm2, p < 0.001), white women (0.83 +/- 0.13 versus 0.76 +/- 0.13 g/cm2, p < 0.001), and black women (0.90 +/- 0.15 versus 0.85 +/- 0.15 g/cm2, p < 0.001) with diabetes compared with those without diabetes, although the relationship was attenuated by body composition. In multiple regression models, diabetes was an independent predictor of higher hip, whole body, and volumetric spine BMD in all participants (p < or = 0.001), but lower spine volume (p = 0.01) and higher hip BMD for each race-gender group (p < or = 0.01). Type 2 diabetes was associated with a 4-5% higher total hip BMD in all race-gender groups of elderly adults, independent of body composition and fasting insulin levels.     

Oral daily ibandronate prevents bone loss in early postmenopausal women without osteoporosis.

Oral daily ibandronate was investigated for the prevention of bone loss in postmenopausal women without osteoporosis (n = 653). BMD at the lumbar spine and hip were significantly increased (3.1% and 1.8%, respectively; p < or = 0.0001 versus placebo) with 2.5 mg ibandronate after 24 months. Oral ibandronate is a promising option for the prevention of postmenopausal bone loss. INTRODUCTION: Further strategies to manage patients most at risk from developing postmenopausal osteoporosis are required. The objectives of this multicenter, double-blind, randomized, placebo-controlled study were to examine the efficacy, tolerability, and optimal dose of oral daily ibandronate in the prevention of bone loss in postmenopausal women. MATERIALS AND METHODS: In total, 653 women (mean bone mineral density [BMD] T-score > -2.5 at the lumbar spine), who had been postmenopausal for at least 1 year, were allocated to one of four strata based on time since menopause and baseline lumbar spine BMD. Women were randomized to receive calcium (500 mg daily) plus either placebo (n = 162) or ibandronate 0.5 mg (n = 162), 1 mg (n = 166), or 2.5 mg (n = 163) as once-daily oral treatment for 2 years. The primary endpoint was the mean percent change in lumbar spine BMD with ibandronate versus placebo. RESULTS AND CONCLUSIONS: After 2 years, oral daily ibandronate produced a dose-related and sustained maintenance or increase in BMD at the lumbar spine and hip (total hip, femoral neck, trochanter), together with a dose-related reduction in the rate of bone turnover. The greatest nominal increases in spinal and hip BMD were observed with the 2.5-mg dose, which produced statistically significant BMD gains compared with placebo at 6 months and all subsequent time-points at the spine and hip (3.1% and 1.8% increase in lumbar spine and total hip BMD, respectively, versus placebo; p < or = 0.0001 after 24 months). Oral daily ibandronate was well tolerated with an incidence of upper gastrointestinal adverse events similar to placebo. No safety concerns were identified. In summary, oral daily ibandronate 2.5 mg decreases bone turnover, preserves or increases BMD in the spine and proximal femur, and is well tolerated. Oral ibandronate provides a promising option for the prevention of bone loss in postmenopausal women.     

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.     

Posterior-anterior and lateral dual-energy x-ray absorptiometry for the assessment of vertebral osteoporosis and bone loss among older men.

Lateral spine dual-energy x-ray absorptiometry (DXA) selectively measures the trabecular-rich vertebral bodies without the contributions of the cortical-rich posterior elements of the spine and is less affected by spinal degenerative disease than posterior-anterior DXA. We tested whether lateral DXA detects vertebral osteoporosis more often and is more sensitive to age-related bone loss than posterior-anterior DXA in 193 healthy, community-dwelling men aged 51-81 years (mean +/- SD; 67 +/- 8 years). All men had supine lateral, posterior-anterior, and proximal femur DXA scans on a Hologic QDR 2000 densitometer. A subset (n = 102) had repeat scans after 4 years to determine annualized rates of change in bone mineral density (BMD). Age was inversely and significantly associated with BMD in the midlateral (r = -0.27) and lateral (r = -0.24) but not posterior-anterior (r = 0.04) projections. Midlateral (-1.43 +/- 3.48% per year; p = 0.0001), lateral (-0.27 +/- 1.68% per year; p = 0.12), and hip (-0.19 +/- 1.02% per year; p = 0.06) BMD decreased, whereas posterior-anterior BMD increased (0.73 +/- 1.11% per year; p = 0.0001) during follow-up. When compared with normal values in 43 men aged 21-42 years, mean T scores were significantly lower with lateral (-1.47 +/- 1.32) and midlateral (-1.57 +/- 1.36) than posterior-anterior (-0.12 +/- 1.30; p < 0.0001) DXA. Only 2.6% of the older men were considered osteoporotic (T score < or = -2.5) at the posterior-anterior spine, whereas 11.0% were osteoporotic at the femoral neck, 22.5% at the lateral spine, and 24.6% were osteoporotic at the midlateral spine. We conclude that supine lateral DXA identifies considerably more men as osteoporotic and is more sensitive to age-related bone loss than posterior-anterior DXA. Spinal osteoporosis may represent a substantially greater health problem among older men than previously recognized.     

Assessment of incident spine and hip fractures in women and men using finite element analysis of CT scans

Finite element analysis of computed tomography (CT) scans provides noninvasive estimates of bone strength at the spine and hip. To further validate such estimates clinically, we performed a 5‐year case‐control study of 1110 women and men over age 65 years from the AGES‐Reykjavik cohort (case = incident spine or hip fracture; control = no incident spine or hip fracture). From the baseline CT scans, we measured femoral and vertebral strength, as well as bone mineral density (BMD) at the hip (areal BMD only) and lumbar spine (trabecular volumetric BMD only). We found that for incident radiographically confirmed spine fractures (n = 167), the age‐adjusted odds ratio for vertebral strength was significant for women (2.8, 95% confidence interval [CI] 1.8 to 4.3) and men (2.2, 95% CI 1.5 to 3.2) and for men remained significant (p = 0.01) independent of vertebral trabecular volumetric BMD. For incident hip fractures (n = 171), the age‐adjusted odds ratio for femoral strength was significant for women (4.2, 95% CI 2.6 to 6.9) and men (3.5, 95% CI 2.3 to 5.3) and remained significant after adjusting for femoral neck areal BMD in women and for total hip areal BMD in both sexes; fracture classification improved for women by combining femoral strength with femoral neck areal BMD (p = 0.002). For both sexes, the probabilities of spine and hip fractures were similarly high at the BMD‐based interventional thresholds for osteoporosis and at corresponding preestablished thresholds for “fragile bone strength” (spine: women ≤ 4500 N, men ≤ 6500 N; hip: women ≤ 3000 N, men ≤ 3500 N). Because it is well established that individuals over age 65 years who have osteoporosis at the hip or spine by BMD criteria should be considered at high risk of fracture, these results indicate that individuals who have fragile bone strength at the hip or spine should also be considered at high risk of fracture. © 2014 American Society for Bone and Mineral Research.     

Effect of alendronate on bone mineral density and bone turnover markers in post-gastrectomy osteoporotic patients

Alendronate decreases the urinary levels of cross-linked N-terminal telopeptides of type I collagen (NTX; about 45% at 3 months) and serum levels of alkaline phosphatase (ALP; about 27% at 24 months), leading to an increase in lumbar spine bone mineral density (BMD; about 9% at 24 months) in postmenopausal Japanese women with osteoporosis. However, the effectiveness of oral bisphosphonates on osteoporosis remains to be established in patients who have undergone a gastrectomy. The objective of the present case series study was to examine the effect of alendronate on BMD and bone turnover markers in post-gastrectomy osteoporotic patients. Sixteen patients (3 men and 13 postmenopausal women) with osteoporosis, who had undergone a gastrectomy (mean age: 69.1 years), were recruited in our outpatient clinic. All the patients were treated with alendronate (5 mg daily or 35 mg weekly) for 24 months. The effects of alendronate on lumbar spine (women) or total hip (men) BMD and urinary NTX and serum ALP levels were examined. A total or partial gastrectomy had been performed for eight patients each. The mean duration after surgery was 16.0 years. With alendronate therapy, urinary NTX levels significantly decreased at 3 months (−27.0%). Serum ALP levels decreased (−12.1%) and lumbar spine BMD increased (+5.2%), but total hip BMD did not significantly change (+0.6%) at 24 months. No severe adverse events were observed, and alendronate therapy was well tolerated. These results suggest that alendronate mildly increases lumbar spine BMD by mildly reducing bone turnover in osteoporotic patients after a gastrectomy.