Fractures In Elderly Men Research Articles

Prediction of new clinical vertebral fractures in elderly men using finite element analysis of CT scans

Vertebral strength, as estimated by finite element analysis of computed tomography (CT) scans, has not yet been compared against areal bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) for prospectively assessing the risk of new clinical vertebral fractures. To do so, we conducted a case-cohort analysis of 306 men aged 65 years and older, which included 63 men who developed new clinically-identified vertebral fractures and 243 men who did not, all observed over an average of 6.5 years. Nonlinear finite element analysis was performed on the baseline CT scans, blinded to fracture status, to estimate L1 vertebral compressive strength and a load-to-strength ratio. Volumetric BMD by quantitative CT and areal BMD by DXA were also evaluated. We found that, for the risk of new clinical vertebral fracture, the age-adjusted hazard ratio per standard deviation change for areal BMD (3.2; 95% confidence interval [CI], 2.0-5.2) was significantly lower (p < 0.005) than for strength (7.2; 95% CI, 3.6-14.1), numerically lower than for volumetric BMD (5.7; 95% CI, 3.1-10.3), and similar for the load-to-strength ratio (3.0; 95% CI, 2.1-4.3). After also adjusting for race, body mass index (BMI), clinical center, and areal BMD, all these hazard ratios remained highly statistically significant, particularly those for strength (8.5; 95% CI, 3.6-20.1) and volumetric BMD (9.4; 95% CI, 4.1-21.6). The area-under-the-curve for areal BMD (AUC = 0.76) was significantly lower than for strength (AUC = 0.83, p = 0.02), volumetric BMD (AUC = 0.82, p = 0.05), and the load-to-strength ratio (AUC = 0.82, p = 0.05). We conclude that, compared to areal BMD by DXA, vertebral compressive strength and volumetric BMD consistently improved vertebral fracture risk assessment in this cohort of elderly men.

High serum adiponectin predicts incident fractures in elderly men. Mr OS Sweden

High serum adiponectin predicts incident fractures in elderly men. Mr OS Sweden

Risk factors for fracture in elderly men: a population-based prospective study

Risk factors for fractures were assessed in a random sample of 4,696 elderly men followed for 5.4 years. Results highlighted the importance of assessment of falls and dizziness as well as novel risk factors including frequent urination and erectile dysfunction. Knowledge about risk factors for fracture in men is limited. The aim of this study was to evaluate factors potentially associated with fracture risk in men. A questionnaire enquiring about potential risk factors for fractures in men was posted to a random sample of 9,314 men aged 60-74 years. A completed questionnaire was returned by 4,696 (50.4%). Follow-up on incident fractures over 5.4 years was performed using public registries. During the study, 203 individuals experienced a first clinical fracture, of which 85 patients were considered osteoporotic (9 in humerus, 10 vertebral, 32 in the hip and 34 in the forearm). Cox proportional hazard regression models were used to evaluate risk factors for any and osteoporotic fractures. The following variables were found to be associated with increased risk of any fracture in adjusted models family history of a hip fracture (HR; 95%CI: 1.56; 1.05-2.33), falls (2-4/year: 2.10; 1.35-3.27, >4/year: 2.46; 1.12-5.41, both compared to no falls), dizziness (2.36; 1.51-3.71), erectile dysfunction (1.41; 1.06-1.87) and frequent urination (2.06; 1.26-3.39). Similarly, falls (2.36; 1.45-3.86), dizziness (2.83; 1.52-5.25), erectile dysfunction (2.01; 1.30-3.09) and pulmonary illness (1.90; 1.03-3.53) were associated with increased risk of osteoporotic fractures in adjusted models. These results underline the importance of assessment of dizziness, falls and those with a family history of hip fracture. Frequent urination and erectile dysfunction were independently associated with increased fracture risk. Although the mechanism of association is unknown, these variables are likely to be indicators of frailty or hypogonadism.

Testosterone and the Male Skeleton: A Dual Mode of Action

Testosterone is an important hormone for both bone gain and maintenance in men. Hypogonadal men have accelerated bone turnover and increased fracture risk. In these men, administration of testosterone inhibits bone resorption and maintains bone mass. Testosterone, however, is converted into estradiol via aromatization in many tissues including male bone. The importance of estrogen receptor alpha activation as well of aromatization of androgens into estrogens was highlighted by a number of cases of men suffering from an inactivating mutation in the estrogen receptor alpha or in the aromatase enzyme. All these men typically had low bone mass, high bone turnover and open epiphyses. In line with these findings, cohort studies have confirmed that estradiol contributes to the maintenance of bone mass after reaching peak bone mass, with an association between estradiol and fractures in elderly men. Recent studies in knock-out mice have increased our understanding of the role of androgens and estrogens in different bone compartments. Estrogen receptor activation, but not androgen receptor activation, is involved in the regulation of male longitudinal appendicular skeletal growth in mice. Both the androgen and the estrogen receptor can independently mediate the cancellous bone-sparing effects of sex steroids in male mice. Selective KO studies of the androgen receptor in osteoblasts in male mice suggest that the osteoblast in the target cell for androgen receptor mediated maintenance of trabecular bone volume and coordination of bone matrix synthesis and mineralization. Taken together, both human and animal studies suggest that testosterone has a dual mode of action on different bone surfaces with involvement of both the androgen and estrogen receptor.

Lower Hip Bone Mass and Proximal Femur Fractures in Elderly Patients: More Valuable than Lumbar Vertebrae Bone Mineral Density

A decreased bone mineral density, such as osteoporosis, has been considered a factor closely associated with proximal femur fractures. We studied the relationship between osteoporosis and proximal femur fractures. Dual energy radiograph absorptiometry was used to measure the bone mineral density of 121 patients with a femur neck fracture and 134 patients with an intertrochanteric fracture. The bone density of the femoral neck, Ward's triangle, and the trochanteric region were measured. Two hundred seventeen normal patients who had undergone a bone mineral density test and were found to have no proximal femur fracture were used as the control group. Comparative analysis was performed after the patients were subdivided into different groups depending on sex and fracture type. The bone mineral density of the lumbar vertebra in patients with a proximal femur fracture was not significantly different from that of the control group, but the bone mineral density of the proximal femur in patients with a proximal femur fracture was significantly less than that of the control group. The bone mineral density of the group with an intertrochanteric fracture was lower than that of the femur neck fracture group. However, the difference was statistically insignificant. In bone mineral density comparisons, no significant differences were observed between the displaced and undisplaced femur neck fracture group and between the stable and the unstable intertrochanteric fracture group. The bone mineral density of elderly patients with a proximal femur fracture was significantly less than that of normal individuals. However, femur neck fractures in elderly men were less likely to be associated with a decreased bone mineral density. Little correlation between bone mineral densities of the proximal femur and fracture location (neck vs intertrochanter) and type (nondisplaced vs displaced neck, stable vs unstable intertrochanter) was found.

Fall mechanisms, bone strength, and hip fractures in elderly men and women in Taiwan

Three modifiable factors of fall direction, poor bone strength, and depression were associated with an increased risk of hip fractures for elderly men and women; fall direction was a much stronger predictor than the other two. When a fall occurs, changing fall direction may be most effective to prevent hip fractures. A matched case-control study was conducted to identify risk factors for hip fractures in elderly men and women in Taiwan. Cases were defined as persons who visited the emergency room due to a fall and were diagnosed with a first hip fracture. For each case, a control was matched by gender and time of falling, selected from persons who sought care at the same emergency room due to a fall resulting in injury other than a hip fracture. In total, 85 paired men and 221 paired women were included. For men, backward, straight-down, and sideways falls were associated with 10.8-, 13.6-, and 15.2-fold increased risks of hip fractures, respectively, compared with forward falls. Poor bone strength and depression were associated with 2.27- and 2.85-fold increased risks of hip fractures, respectively, while dependence in ≥3 activities of daily living was associated with a fivefold lower risk. For women, compared with forward falls, backward, straight-down, and sideways falls were associated with 10.2-, 9.86-, and 12.8-fold increased risks of hip fractures, respectively. Living in a rented house, poor bone strength, depression, and use of antidiabetics were associated with 1.65-, 2.78-, 1.89-, and 1.92-fold increased risks of hip fractures, respectively. Hormone replacement therapy was associated with a fivefold lower risk of hip fractures. While bone strength and depression can be risk factors for hip fractures in elderly people, the direction of the fall was the strongest predictor. Some risk factors differed between elderly men and women.

Predictive values of pQCT for non-vertebral fractures in elderly men

Predictive values of pQCT for non-vertebral fractures in elderly men

Diffuse idiopathic skeletal hyperostosis (DISH): relation to vertebral fractures and bone density

SummaryRadiographs and spinal bone mineral density (BMD) were evaluated from 342 elderly men regarding possible effects of diffuse idiopathic skeletal hyperostosis (DISH) on vertebral fractures and densitometry measurements. Prevalent vertebral fractures were more frequent among men with DISH compared to men with no DISH even after fracture prevalence was adjusted for BMD. Paravertebral calcifications should be considered in patients with DISH when interpreting BMD measurements because both dual X-ray absorptiometry (DXA) and quantitative CT (QCT) densitometry may not be reliable.IntroductionThe purpose of this study is to evaluate the prevalence of DISH in older men and its association with vertebral fractures and with BMD determined by DXA and QCT.MethodsLateral radiographs of the spine were analyzed in a sample of 342 men aged ≥65 years participating in the MrOS Study concerning the presence and grade of DISH and vertebral fractures. Lumbar BMD was measured by both DXA (areal, grams per square centimeter) and QCT (volumetric, grams per cubic centimeter). The association between DISH, BMD, and presence of fractures was studied using χ 2 and t tests.ResultsDISH was present in 52% (178/342) of the men. Men with DISH were older (mean, 75.1 vs 73.3, p < 0.05) and more likely to have prevalent fractures (28% vs 20%, p < p = 0.09). BMD assessed with DXA (1.08 vs 1.00 g/cm2, p ≤ 0.0001), but not with QCT (0.11 vs 0.11 g/cm3, p = 0.65), was significantly higher in men with DISH compared to men without DISH. Significantly lower BMD of men with both DISH and fractures compared to men with DISH but without fractures was only detected by QCT (−25%, 0.09 vs 0.12, p < 0.05). Both DXA BMD and QCT BMD were significantly higher in severe lumbar DISH (+22% and +31%, p < 0.0001), respectively.ConclusionDISH was associated with a higher prevalence of vertebral fractures in elderly men. Lumbar ossifications related to DISH should be considered when interpreting BMD measurements to predict their fracture risk.

Smoking predicts incident fractures in elderly men: Mr OS Sweden

The aim of this study was to investigate the association between smoking and bone mineral density (BMD) and radiographically verified prevalent vertebral fractures and incident fractures in elderly men. At baseline 3003 men aged 69 to 80 years of age from the Swedish Mr Os Study completed a standard questionnaire concerning smoking habits and had BMD of the hip and spine measured using dual-energy X-ray absorptiometry (DXA); 1412 men had an X-ray of the thoracic- and lumbar spine. Radiologic registers were used to confirm reported new fractures after the baseline visit. At baseline, 8.4% were current smokers. Current smokers had a 6.2% lower BMD at the total hip and a 5.4% lower BMD at the lumbar spine (p < .001). Current smoking remained independently inversely associated with BMD at the hip and lumbar spine after adjusting for age, height, weight, calcium intake, physical activity, and centers as covariates. Prevalent vertebral fractures among current smokers were increased in unadjusted analyses [odds ratio (OR) = 1.90, 95% confidence interval (CI) 1.26-2.87] and after adjustment for lumbar BMD (OR = 1.67, 95% CI 1.09-2.55). Smokers had a high risk for two or more prevalent vertebral fractures (OR = 3.18, 95% CI 1.88-5.36). During the average follow-up of 3.3 years, 209 men sustained an X-ray-verified fracture. Incident fracture risk among smokers was calculated with Cox proportional hazard models. Current smokers had an increased risk of all new fractures [hazard ratio (HR) = 1.76, 95% CI 1.19-2.61]; nonvertebral osteoporotic fractures, defined as humerus, radius, pelvis, and hip fractures (HR = 2.14, 95% CI 1.18-3.88); clinical and X-ray-verified vertebral fractures (HR = 2.53, 95% CI 1.37-4.65); and hip fractures (HR = 3.16, 95% CI 1.44-6.95). After adjustment for BMD, including other covariates, no significant association between smoking and incident fractures was found. Current tobacco smoking in elderly men is associated with low BMD, prevalent vertebral fractures, and incident fractures, especially vertebral and hip fractures.

Plasma 25-Hydroxyvitamin D Levels and Fracture Risk in a Community-Based Cohort of Elderly Men in Sweden

Blood levels of 25-hydroxyvitamin D [25(OH)D] is the generally accepted indicator of vitamin D status, but no universal reference level has been reached. The objective of the study was to determine the threshold at which low plasma 25(OH)D levels are associated with fractures in elderly men and clarify the importance of low levels on total fracture burden. In the Uppsala Longitudinal Study of Adult Men, a population-based cohort (mean age, 71 yr, n = 1194), we examined the relationship between 25(OH)D and risk for fracture. Plasma 25(OH)D levels were measured with high-pressure liquid chromatography-mass spectrometry. The study was conducted in the municipality of Uppsala in Sweden, a country with a high fracture incidence. Time to fracture was measured. During follow-up (median 11 yr), 309 of the participants (26%) sustained a fracture. 25(OH)D levels below 40 nmol/liter, which corresponded to the fifth percentile of 25(OH)D, were associated with a modestly increased risk for fracture, multivariable-adjusted hazard ratio 1.65 (95% confidence interval 1.09-2.49). No risk difference was detected above this level. Approximately 3% of the fractures were attributable to low 25(OH)D levels in this population. Vitamin D insufficiency is not a major cause of fractures in community-dwelling elderly men in Sweden. Despite the fact that cutaneous synthesis of previtamin D during the winter season is undetectable at this northern latitude of 60 degrees, only one in 20 had 25(OH)D levels below 40 nmol/liter, the threshold at which the risk for fracture started to increase. Genetic adaptations to limited UV light may be an explanation for our findings.

Independent from muscle power and balance performance, a creatinine clearance below 65 ml/min is a significant and independent risk factor for falls and fall-related fractures in elderly men and women diagnosed with osteoporosis

We assessed in a cross-sectional study in elderly men and women with osteoporosis, the association between the creatinine clearance (CrCl) and the performance in different balance and muscle power and function tests and found that a decreasing creatinine clearance was significantly associated with lower balance and muscle power. To determine if a creatinine clearance of <65 ml/min is significantly associated with decreasing muscle power and balance and an increased risk for falls and fractures. We assessed in a cross-sectional-study in 1781 German osteoporotic patients, the association between the CrCl, the physical performance, and the number of falls and fractures. Controlling for age, gender, BMI, and osteoporosis treatment (fracture analysis only), a decreasing CrCl was associated with lower physical performance in the timed-up-and-go test (corr -0.2337, P < 0.0001), chair-rising test (corr -0.1706, P < 0.001), and tandem-stand test (corr 0.2193, P < 0.0001), and a CrCl of <65 ml/min was associated with a significantly higher risk for falls (47.7% vs. 36.2%, P = 0.0008) and fall-related fractures (33.1% vs. 22.9%, P = 0.0003) compared with a CrCl of >or=65 ml/min. In this study, we found a significant gender-independent correlation between decreasing CrCl and lower performance in balance and muscle power tests. Reduced muscle power and balance may therefore be involved in the low creatinine clearance associated increased risk for falls and fall-related fractures. Furthermore, we found that a CrCl <65 ml/min., independent from the performance in muscle power, muscle function, and balance tests, is a significant risk factor for falls and fractures.

Prevalence of vertebral fracture in elderly men and women with osteopenia

The objective of our cross-sectional, not population-based, observational study was to determine the prevalence of patients with osteopenia in relation to bone mineral density (BMD) and vertebral fractures and to identify risk factors for vertebral fractures above the osteoporotic BMD T-score threshold of -2.5. A total of 698 consecutive hospitalized and ambulatory white patients with T-scores between -1.0 and -2.5 were investigated in an academic medical center in Austria between January 2005 and June 2006. Measurements of BMD (T-score at spine and hip) by DXA, spinal X-ray, laboratory data of bone metabolism and vitamin D, and sex-specific data were assessed. A multivariate general linear model was used to calculate vertebral and non-vertebral fractures, age, BMI and lowest T-score at measured anatomic sites. Overall, 218 patients (31.2%) with a mean age of 72.2 years and mean BMI of 26.0 presented with vertebral fractures; in comparison, patients with non-vertebral fractures had a mean age of 62.6 years and BMI 24.6, and patients without fractures had a mean age of 61.3 years and BMI 24.0 (P < 0.001). Serum markers of bone resorption and formation had no influence on fracture occurrence but 73% of the patients had vitamin D deficiency (25.2 +/- 9.8 ng/ml). The lowest T-score in all fracture patients was found at the femoral neck. At this site 64.3% patients with vertebral fractures had a T-score within the range -1.0 to -2.0 (95% CI 57.3-70.8). The prevalence of vertebral fractures increased stepwise (P < 0.05) and at T-scores between -1.5 and -2.0 the increase was linear. We conclude that a significant proportion of non-osteoporotic elderly men and women with mean age 72 years, BMI 26.0 and a threshold T-score above -2.0 are susceptible to osteoporotic vertebral fractures. These patients are not adequately detected by BMD measurements based on WHO thresholds. Early assessment, prior to their first fracture, is important for identifying individuals with clinical risk factors.

Fractures Halved With Vitamin C

MONTREAL — Consumption of vitamin C at sufficiently high levels is associated with nearly a 50% decrease in the risk of hip and nonvertebral osteoporotic fractures in elderly men and women, according to a 15- to 17-year follow-up of participants in the Framingham Osteoporosis Study. Previous studies of menopausal and postmenopausal women have shown that dietary intake of vitamin C is associated with increased bone mineral density (BMD) and that a high vitamin C serum level is associated with a decreased prevalence of fracture, Marian T. Hannan, DSc, said at the annual meeting of the American Society for Bone and Mineral Research. Vitamin C, an antioxidant, plays an important role in the formation of collagen. Published evidence suggests that oxidative stress may result in increased osteoclast formation, resulting in greater bone resorption, said Dr. Hannan, who presented the study on behalf of Shivani Sahni of Tufts University, Boston. Of 5,209 men and women in the original Framingham Heart Study cohort, the investigators identified 958 individuals who had participated in the beginning of the osteoporosis study in 1988–1989, had answered a food-frequency questionnaire, and had no history of a hip fracture. These individuals had a mean age of 75 years and experienced 100 hip fractures and 180 nonvertebral osteoporotic fractures during the follow-up period, Dr. Hannan reported. For the study, participants were divided into three groups based on their intake of vitamin C. The relative risk of hip fracture was significantly lower for individuals who had the highest total intake of both dietary and supplemental vitamin C (a median of 305 mg/day) than it was for people with the lowest total intake (median of 97 mg/day). This translated into a 44% decrease in relative risk of hip fracture, according to Dr. Hannan of Harvard Medical School's Institute for Aging Research, Boston. Those with the highest total intake of vitamin C also had a 36% lower relative risk of having a nonvertebral osteoporotic fracture than did individuals with the lowest total intake. When the investigators looked at supplemental vitamin C intake alone, the highest users (median of 260 mg/day) had a 70% lower relative risk of hip fracture than did nonusers. Supplements accounted for about 28% of the individuals' total vitamin C intake, Dr. Hannan said. The investigators found no effect for dietary intake of vitamin C alone. All of the comparisons were adjusted for age, sex, body mass index, height, smoking status, estrogen use in women, physical activity, alcohol use, multivitamin use, femoral neck BMD, and total intake of energy, calcium, vitamin D, and potassium. One audience member suggested that the discrepancy between the effects of supplemental and dietary vitamin C intake could mean that there are residual confounding effects from factors that were not accounted for in the study, such that supplemental use of vitamin C may be a marker for people who care more about their health and take better care of themselves. This is a problem that can only be answered with a randomized, controlled trial, Dr. Hannan noted. “We were intrigued by the lack of a BMD effect on [the association between] vitamin C and fracture, and we believe that it implies that vitamin C may affect a different pathway or other fracture risk factors, for example, fall risk factors or mobility risk factors,” Dr. Hannan said Jeff Evans is a senior writer with Elsevier Global Medical News.

Plasma B Vitamins, Homocysteine, and Their Relation with Bone Loss and Hip Fracture in Elderly Men and Women

Elevated homocysteine is a strong risk factor for osteoporotic fractures among elders, yet it may be a marker for low B-vitamin status. Our objective was to examine the associations of plasma concentrations of folate, vitamin B12, vitamin B6, and homocysteine with bone loss and hip fracture risk in elderly men and women. This was a longitudinal follow-up study of the Framingham Osteoporosis Study. Community dwelling residents of Framingham, MA, were included in the study. A total of 1002 men and women (mean age 75 yr) was included in the study. Baseline (1987-1989) blood samples were used to categorize participants into plasma B-vitamin (normal, low, deficient) and homocysteine (normal, high) groups. Femoral neck bone mineral density (BMD) measured at baseline and 4-yr follow-up was used to calculate annual percent BMD change. Incident hip fracture was assessed from baseline through 2003. Multivariable-adjusted mean bone loss was inversely associated with vitamin B6 (P for trend 0.01). Vitamins B12 and B6 were inversely associated with hip fracture risk (all P for trend < 0.05), yet associations were somewhat attenuated and not significant after controlling for baseline BMD, serum vitamin D, and homocysteine. Participants with high homocysteine (>14 micromol/liter) had approximately 70% higher hip fracture risk after adjusting for folate and vitamin B6, but this association was attenuated after controlling for vitamin B12 (hazard ratio = 1.49; 95% confidence interval 0.91, 2.46). Low B-vitamin concentration may be a risk factor for decreased bone health, yet does not fully explain the relation between elevated homocysteine and hip fracture. Thus, homocysteine is not merely a marker for low B-vitamin status.

Weight Cycling and Risk of Forearm Fractures: A 28-Year Follow-up of Men in the Oslo Study

Weight cycling may lead to fractures in non-weight-bearing bone. The authors investigated the association between self-reported episodes of weight loss and forearm fracture in a cohort of elderly Norwegian men (n = 4,601; mean age = 71.6 years). Men initially examined in 1972-1973 as part of the population-based Oslo Study were reexamined in 2000. Weight and height were measured both times; histories of weight cycling (amount and frequency) and fracture and information on covariates were elicited by questionnaire. Irrespective of amount of weight loss, 35-43% of men reporting four or more weight loss episodes at ages 25-50 years had experienced a forearm fracture, as compared with 17-18% of men without weight loss episodes. For weight loss episodes that had occurred after age 50 years, associations were weaker. In an analysis limited to men whose last fracture had occurred after the weight loss episodes, the adjusted odds ratio for forearm fracture was 2.91 (95% confidence interval: 1.10, 7.64) for four or more weight loss episodes versus none. These findings suggest that weight cycling may predict forearm fracture in elderly men and indicate that the potentially harmful effects of weight cycling are related to the number of episodes occurring at ages 25-50 years.

Osteoporosis in the aging male: treatment options.

In elderly women, loss in bone mass and micro-architectural changes are generally attributed to the onset of menopause. Men do not experience menopause, they do, however, experience age-related acceleration in bone loss and micro-architecture deterioration. The incidence of osteoporotic fractures in elderly men, just as in aged women, increases exponen-tially with age; the rise in men, however, is some 5-10 years later than in women. Up to 50% of male osteoporotics have no identifiable etiology; however elderly males have much higher likelihood of having an identifiable secondary cause than younger men. Therefore, clinical and laboratory evaluation of aged male osteoporotics must be thorough and should be aimed at identifying lifestyle or conditions contributing to bone loss and fragility. It is essential to identify and treat secondary causes and ensure adequate vitamin D and calcium intake before embarking upon treatment with pharmacological agents. The evidence from a limited number of trials suggests that bisphosphonates, especially alendronate and risedronate, are effective in improving BMD, and seem to be the treatments of choice in aged men with osteoporosis. In cases where bisphosphonates are contra-indicated or ineffective, teriparatide or alternatives such as strontium should be considered.

Femoral Neck BMD Is a Strong Predictor of Hip Fracture Susceptibility in Elderly Men and Women Because It Detects Cortical Bone Instability: The Rotterdam Study

We studied HSA measurements in relation to hip fracture risk in 4,806 individuals (2,740 women). Hip fractures (n = 147) occurred at the same absolute levels of bone instability in both sexes. Cortical instability (propensity of thinner cortices in wide diameters to buckle) explains why hip fracture risk at different BMD levels is the same across sexes. Despite the sexual dimorphism of bone, hip fracture risk is very similar in men and women at the same absolute BMD. We aimed to elucidate the main structural properties of bone that underlie the measured BMD and that ultimately determines the risk of hip fracture in elderly men and women. This study is part of the Rotterdam Study (a large prospective population-based cohort) and included 147 incident hip fracture cases in 4,806 participants with DXA-derived hip structural analysis (mean follow-up, 8.6 yr). Indices compared in relation to fracture included neck width, cortical thickness, section modulus (an index of bending strength), and buckling ratio (an index of cortical bone instability). We used a mathematical model to calculate the hip fracture distribution by femoral neck BMD, BMC, bone area, and hip structure analysis (HSA) parameters (cortical thickness, section modulus narrow neck width, and buckling ratio) and compared it with prospective data from the Rotterdam Study. In the prospective data, hip fracture cases in both sexes had lower BMD, thinner cortices, greater bone width, lower strength, and higher instability at baseline. In fractured individuals, men had an average BMD that was 0.09 g/cm(2) higher than women (p < 0.00001), whereas no significant difference in buckling ratios was seen. Modeled fracture distribution by BMD and buckling ratio levels were in concordance to the prospective data and showed that hip fractures seem to occur at the same absolute levels of bone instability (buckling ratio) in both men and women. No significant differences were observed between the areas under the ROC curves of BMD (0.8146 in women and 0.8048 in men) and the buckling ratio (0.8161 in women and 0.7759 in men). The buckling ratio (an index of bone instability) portrays in both sexes the critical balance between cortical thickness and bone width. Our findings suggest that extreme thinning of cortices in expanded bones plays a key role on local susceptibility to fracture. Even though the buckling ratio does not offer additional predictive value, these findings improve our understanding of why low BMD is a good predictor of fragility fractures.

The COMT val158met polymorphism is associated with prevalent fractures in Swedish men

Introduction Sex steroids are important for growth and maintenance of the skeleton. Catechol- O-methyltransferase (COMT) is an estrogen degrading enzyme. The COMT val158met polymorphism results in a 60–75% difference in enzyme activity between the val (high activity = H) and met (low activity = L) variants. We have previously reported that this polymorphism is associated with bone mineral density (BMD) in young men. The aim of this study was to investigate associations between COMT val158met, BMD and fractures in elderly men. Methods Population-based study of Swedish men 75.4, SD 3.2, years of age. Fractures were reported using standardized questionnaires. Fracture and genotype data were available from 2822 individuals. Results Total number of individuals with self-reported fracture was 989 (35.0%). Prevalence of ≥ 1 fracture was 37.2% in COMT LL, 35.7% in COMT HL and 30.4% in COMT HH ( p < 0.05). Early fractures (≤ 50 years of age) were less common in COMT HH than in the combined COMT LL + HL genotype, OR 0.78 (95% CI 0.63–0.97). No associations were found for late fractures (> 50 years of age). The OR for fracture of the non-weight bearing skeleton in COMT HH compared with COMT LL + HL was 0.74 (95% CI 0.59–0.92). No associations between COMT val158met and BMD were found in this cohort of elderly men. Conclusions The COMT val158met polymorphism is associated with life time fracture prevalence in elderly Swedish men. This association is mainly driven by early fractures (≤ 50 years of age).

Effect of dietary B vitamins on BMD and risk of fracture in elderly men and women: The Rotterdam Study

A mildly elevated homocysteine (Hcy) level is a novel and potentially modifiable risk factor for age-related osteoporotic fractures. Elevated Hcy levels can have a nutritional cause, such as inadequate intake of folate, riboflavin, pyridoxine or cobalamin, which serve as cofactors or substrates for the enzymes involved in the Hcy metabolism. We examined the association between intake of Hcy-related B vitamin (riboflavin, pyridoxine, folate and cobalamin) and femoral neck bone mineral density BMD (FN-BMD) and the risk of fracture in a large population-based cohort of elderly Caucasians. We studied 5304 individuals aged 55 years and over from the Rotterdam Study. Dietary intake of nutrients was obtained from food frequency questionnaires. Incident non-vertebral fractures were recorded during a mean follow-up period of 7.4 years, and vertebral fractures were assessed by X-rays during a mean follow-up period of 6.4 years. We observed a small but significant positive association between dietary pyridoxine ( β = 0.09, p = 1 × 10 − 8 ) and riboflavin intake ( β = 0.06, p = 0.002) and baseline FN-BMD. In addition, after controlling for gender, age and BMI, pyridoxine intake was inversely correlated to fracture risk. As compared to the three lowest quartiles, individuals in the highest quartile of age- and energy-adjusted dietary pyridoxine intake had a decreased risk of non-vertebral fractures (HR = 0.77, 95% CI = 0.65–0.92, p = 0.005) and of fragility fractures (HR = 0.55, 95% CI = 0.40–0.77, p = 0.0004). Further adjustments for other dietary B vitamins (riboflavin, folate and cobalamin), dietary intake of calcium, vitamin D, vitamin A and vitamin K, protein and energy intake, smoking and BMD did not essentially modify these results. We conclude that increased dietary riboflavin and pyridoxine intake was associated with higher FN-BMD. Furthermore, we found a reduction in risk of fracture in relation to dietary pyridoxine intake independent of BMD. These findings highlight the importance of considering nutritional factors in epidemiological studies of osteoporosis and fractures.

Vitamin D Receptor 3′ Haplotypes Are Unequally Expressed in Primary Human Bone Cells and Associated With Increased Fracture Risk: The MrOS Study in Sweden and Hong Kong

The VDR is a prime candidate gene for osteoporosis. Here, we studied three common VDR haplotypes in relation to bone phenotypes in 5014 participants of the global MrOS Study. We also studied the relative expression of the haplotypes in human bone cells. One haplotype was associated with increased fracture risk and differently expressed in primary human bone cells. Vitamin D plays an essential role in skeletal metabolism by binding to its nuclear steroid receptor, the vitamin D receptor (VDR). The heritability of BMD is well established, and the VDR gene is considered a prime candidate suggested to partially account for genetically controlled BMD variance in the population. Here, we reconstructed common haplotypes in the VDR 3' untranslated region (UTR) and studied the association to BMD and risk of vertebral fractures in elderly men from Sweden (n = 3014) and Hong Kong (n = 2000), all participants of the global MrOS Study. To assess any functional implications of the VDR polymorphisms, we studied allele-specific expressions of the different VDR 3' UTR haplotypes in the normal chromosomal context of 70 unrelated human trabecular bone samples. This was performed by quantitative genotyping of coding polymorphisms in RNA samples and in corresponding DNA samples isolated from the bone samples. Three major haplotypes were reconstructed and in agreement with the previously well-defined baT, BAt, and bAT haplotypes, herein denoted Hap1, Hap2, and Hap3. The Hap1 haplotype was independently associated with increased risk of vertebral fractures in Swedish men (OR, 1.655; 95% CI, 1.146-2.391; p < 0.01) and with lower lumbar spine BMD in elderly men from Sweden (p < 0.01) and Hong Kong (p < 0.05). The VDR gene was also shown to exhibit a 3' UTR haplotype dependent allelic imbalance, indicating that the VDR Hap1 allele was overexpressed in human trabecular bone samples. The results indicate that the relatively overexpressed VDR Hap1 haplotype could be considered a risk allele for osteoporosis regardless of ethnicity.