Low width of tubular bones is associated with increased risk of fragility fracture in elderly men--the MINOS study.

The risk of fragility fractures in elderly men is only partly explained by areal bone mineral density (aBMD) measured by dual X-ray absorptiometry (DXA). Several studies suggest the importance of bone morphology for the risk of fracture. The aim of this study was to assess the value of bone size and estimated structural parameters for the prediction of incident fractures in a large cohort of men. This study was made in 759 men aged 50-85 from the MINOS cohort. During a 90-month follow-up, 74 men sustained incident vertebral and peripheral fractures. Areal BMD was measured by DXA at femoral neck, distal radius and distal ulna. Estimates of structural bone parameters and volumetric BMD (vBMD) were derived from aBMD measured by DXA. Given the limited number of fractures, the predictive value of investigated parameters was assessed for peripheral and vertebral fractures jointly by using logistic regression. Men who sustained the fractures had, at baseline, lower aBMD (3.5-6.5%), lower bone mineral content (BMC 5.4-8.7%) and lower cortical thickness (3.5-6.9%) compared with the men without fracture. At all the three skeletal sites, aBMD, BMC, width, cortical area and thickness, cross-sectional moment of inertia (CSMI), and section modulus predicted incident fractures (O.R. = 1.28-1.92 per 1 SD decrease, P < 0.05-0.0001). Fracture risk was weakly associated with vBMD for ulna (O.R. = 1.25 per 1 SD decrease, P < 0.05) but not for femoral neck or radius. After adjustment for aBMD, bone width remained a significant predictor of fractures (O.R. = 1.37-1.48 per 1 SD decrease, P < 0.02-0.01). Men with osteopenia (BMD T score < -1) and low bone width (T score < -1) had the fracture incidence similar to that observed in men with BMD T score < -2. Bone width and aBMD of the femoral neck and radius were predictive of fractures in 49 men with the incident peripheral fractures, whereas their O.R. did not attain the level of statistical significance in 25 men with the incident vertebral fractures. Men, who had both low aBMD and low CSMI ( both T scores < -1), had the fracture risk 3.8 to 4.2 higher than the reference group (both T scores >or= -1). Men, who had both low aBMD and low section modulus (both T scores < -1), had the fracture risk 2.1 to 4.1 higher than the reference group (both T scores >or= -1). In conclusion, men who sustained a fragility fracture during a 90-month follow-up had, at baseline, lower BMC because they had narrower bones but not necessarily less dense. In elderly men, small bone width, low BMC and poor resistance to bending may increase bone fragility. Low bone width seems to be associated with an increased fracture risk in elderly men regardless of aBMD.

Low skeletal muscle mass is associated with poor structural parameters of bone and impaired balance in elderly men--the MINOS study.

UNLABELLED: In 796 men, 50-85 years of age, decreased relative skeletal muscle mass index was associated with narrower bones, thinner cortices, and a consequent decreased bending strength (lower section modulus), as well as with impaired balance and an increased risk of falls. INTRODUCTION: In men, appendicular skeletal muscle mass (ASM) is correlated positively with BMC and areal BMD (aBMD). In elderly men, low muscle mass and strength (sarcopenia) is associated with difficulties in daily living activities. The aim of this study was to evaluate if ASM is correlated with bone size, mechanical properties of bones, balance, and risk of falls in elderly men. MATERIALS AND METHODS: This study used 796 men, 50-85 years of age, belonging to the MINOS cohort. Lifestyle factors were evaluated by standardized questionnaires. Estimates of mechanical bone properties were derived from aBMD measured by DXA. ASM was estimated by DXA. The relative skeletal muscle mass index (RASM) was calculated as ASM/(body height)(2.3). RESULTS: After adjustment for age, body size, tobacco smoking, professional physical activity, and 17beta-estradiol concentration, RASM was correlated positively with BMC, aBMD, external diameter, and cortical thickness (r = 0.17-0.34, p < 0.0001) but not with volumetric BMD. Consequently, RASM was correlated with section modulus (r = 0.29-0.39, p < 0.0001). Men in the lowest quartile of RASM had section modulus of femoral neck and distal radius lower by 12-18% in comparison with men in the highest quartile of RASM. In contrast, bone width was not correlated with fat mass, reflecting the load of body weight (except for L(3)), which suggests that the muscular strain may exert a direct stimulatory effect on periosteal apposition. After adjustment for confounding variables, a decrease in RASM was associated with increased risk of falls and of inability to accomplish clinical tests of muscle strength, static balance, and dynamic balance (odds ratio per 1 SD decrease in RASM, 1.31-2.23; p < 0.05-0.001). CONCLUSIONS: In elderly men, decreased RASM is associated with narrower bones and thinner cortices, which results in a lower bending strength. Low RASM is associated with impaired balance and with an increased risk of falls in elderly men. It remains to be studied whether low RASM is associated with decreased periosteal apposition and with increased fracture risk in elderly men, and whether the difference in skeletal muscle mass between men and women contributes to the between-sex difference in fracture incidence.

Variations of stroking parameters associated with 200 m competitive performance improvement in top-standard front crawl swimmers.

The aim of this study was to analyse the variations of stroking parameters (speed, stroke length, stroke rate, and stroke index) associated with the 200 m front crawl competitive performance improvement. Two races completed by 17 top swimmers were analysed in the 200 m freestyle final of French or European championships, each final being separated by two years. All the swimmers' performances were bettered in the second race (mean +/- SD: 113.44 +/- 2.50 vs 111.78 +/- 2.71 s; p < 0.01) and were associated with a significant increase of stroke rate without variation of average stroke length and stroke index values (p > 0.05). Swimmers emphasized the first part of the race, with higher speed in the first three lengths, higher stroke rate in the first two lengths and lower stroke length in the first one. Stroke length and stroke rate variations were highly correlated (r = 0.98; p < 0.05). In 11 of the 17 swimmers, the improvement was concomitant with a decrease in stroke length and an increase in stroke rate. Only one swimmer's improvement was associated with a substantial increase in stroke length. These results highlighted that stroke length and stroke index cannot be considered as the only parameters linked to improvement in a 200 m crawl in adult swimmers competing at high standard. Moreover, an increase in stroke rate associated with a slight decrease in stroke length should not be considered as ineffective, especially at top standard.

Hormonal and lifestyle determinants of appendicular skeletal muscle mass in men: the MINOS study.

BACKGROUND: Aging-related sarcopenia is characterized by a loss of muscle mass and strength and increased fatigability. However, studies of its determinants in elderly men are scarce. OBJECTIVE: We investigated risk factors for sarcopenia in a large cohort of men. DESIGN: We analyzed 845 men aged 45-85 y who belonged to the MINOS cohort. Lifestyle factors (physical activity, tobacco smoking, alcohol intake, caffeine intake) were evaluated by using a standardized questionnaire. Appendicular skeletal muscle mass (ASM) was estimated by using dual-energy X-ray absorptiometry. The relative appendicular skeletal muscle mass index (RASM) was calculated as ASM/body height(2.3). Apparent free testosterone concentration (AFTC) and free testosterone index (FTI) were calculated on the basis of concentrations of total testosterone and sex hormone-binding globulin. RESULTS: RASM decreased with age (r = -0.29, P < 0.0001). Current smokers had lower RASM than did subjects who never smoked (-3.2%; P < 0.003). RASM increased with the intensity of physical activity at work (P for trend < 0.001). Men who participated in regular exercise during leisure time had 2.2% higher RASM than did those who did not (P < 0.03). Men whose values for AFTC, FTI, or 25-hydroxycholecalciferol [25(OH)D] were >2 SDs below the mean for young men had significantly lower RASM than did men with higher values. Men with sarcopenia, defined as the lowest quartile of RASM in the studied cohort (<6.32 kg/m(2.3)), were significantly older than men with normal RASM, weighed significantly less, smoked more, and spent significantly less time on leisure-time activities. Sarcopenic men also had lower values for testosterone, AFTC, FTI, and 25(OH)D. CONCLUSION: In elderly men, low physical activity, tobacco smoking, thinness, low testosterone (AFTC and FTI), and decreased 25(OH)D concentrations are risk factors for sarcopenia.

Factors predicting long-term efficacy of Hylan GF-20 viscosupplementation in knee osteoarthritis.

OBJECTIVES: To describe the long-term effects of Hylan GF-20 viscosupplementation in patients with knee osteoarthritis and to identify factors predicting efficacy. METHODS: One hundred and fifty-five patients (80 women and 75 men; mean age, 69 years) with symptomatic knee osteoarthritis each received three intraarticular Hylan GF-20 injections. Effectiveness, safety, and satisfaction were evaluated 7-14 months later based on a physician's examination and a five-item questionnaire. Radiological data (distribution and degree of joint space loss), size of the effusion (none, moderate, large), injection route (anterior, medial to the patella, or lateral to the patellar), and side effects were recorded. Factors predicting effectiveness were looked for by univariate analysis followed by multivariable analysis with adjustments on age, body mass index, gender, and time from treatment to questionnaire administration. RESULTS: Satisfaction was good in 78% and 58.9% of the patients according to the physician examination and questionnaire, respectively. Safety was considered excellent or good in 96.2% of the patients. Factors significantly (P < 0.05) associated with a good outcome were a moderate effusion, injection lateral to the patella, joint space loss in a single compartment, and radiological meniscal calcinosis. CONCLUSION: The factors predictive of a good response to Hylan GF-20 in this study need to be confirmed, and their impact quantitated, in prospective studies.

Predictive parameters of accelerated muscle loss in men-MINOS study.

BACKGROUND: Aging-related muscle loss is a public health problem. We investigated the association of lifestyle and hormonal factors with a prospectively assessed muscle loss in older men. METHODS: Among 608 home-dwelling men, aged 60-85 (mean 68) years, lifestyle and health status were evaluated through a questionnaire. Appendicular skeletal muscle mass was estimated using dual-energy x-ray absorptiometry and calculated as the sum of lean mass of the 4 limbs. Free testosterone concentration was calculated using concentrations of total testosterone and sex hormone-binding globulin. Longitudinal data were analyzed by hierarchical models. RESULTS: Average muscle loss was 0.63 ± 0.05%/year. The results of our multivariable adjusted analyses showed that muscle loss was higher in men whose leisure physical activity was <15 hours/week versus ≥15 hours/week (-0.76 vs -0.57%/year). Age-related acceleration of muscle loss was greater in men with lower total testosterone levels (<10 vs ≥10 nmol/L: -0.10 vs -0.07%/year/year of age at baseline [age]). Men with lower free testosterone (<75 vs ≥75 pmol/L) had greater age-related acceleration of muscle loss (-0.12 vs -0.08%/year/age). Higher parathyroid hormone concentrations were associated with greater age-related acceleration of muscle loss (≥45 vs <45 pg/mL -0.14 vs -0.12%/year/age). Men with type 2 diabetes had higher age-related acceleration of muscle loss versus men without diabetes (-0.08 vs -0.03%/year/age) (All P values are <.05). CONCLUSION: In elderly men, low leisure physical activity, type 2 diabetes, low total and free testosterone, and elevated parathyroid hormone concentrations are associated with greater age-related acceleration of muscle loss. These factors are likely to represent real determinants of aging-related muscle loss in men.

Lower fracture risk in older men with higher sclerostin concentration: a prospective analysis from the MINOS study.

Sclerostin is synthesized by osteocytes and inhibits bone formation. We measured serum sclerostin levels in 710 men aged 50 years and older. Bone mineral density (BMD) was measured at the lumbar spine, hip, and distal forearm. Serum sclerostin increased with age (unadjusted r = 0.30, p < 0.001). After adjustment for age, weight, and bioavailable 17ß-estradiol, serum sclerostin correlated positively with BMD (r = 0.24 to 0.35, p < 0.001) and negatively with the levels of bone turnover markers (r = - 0.09 to - 0.23, p < 0.05 to 0.001). During a 10-year follow-up, 75 men sustained fragility fractures. Fracture risk was lower in the two upper quintiles of sclerostin combined versus three lower quintiles combined (6.1 versus 13.5%, p < 0.01). We compared fracture risk in the two highest quintiles combined versus three lower quintiles combined using the Cox model adjusted for age, weight, leisure physical activity, BMD, bone width (tubular bones), prevalent fracture, prevalent falls, ischemic heart disease, and severe abdominal aortic calcification. Men with higher sclerostin concentration had lower fracture risk (adjusted for hip BMD, hazard ratio [HR] = 0.55, 95% confidence interval [CI] 0.31 to 0.96, p < 0.05). The results were similar in 47 men with major fragility fractures (adjusted for lumbar spine BMD: HR = 0.39, 95% CI 0.17 to 0.90, p < 0.05). Men who had higher sclerostin and higher BMD (two highest quintiles) had lower risk of fracture compared with men who had lower BMD and lower sclerostin levels (three lower quintiles) (HR = 0.24, 95% CI 0.10 to 0.62, p < 0.005). Circulating sclerostin was not associated with mortality rate or the incidence of major cardiovascular events. Thus, in older men, higher serum sclerostin levels are associated with lower risk of fracture, higher BMD, and lower bone turnover rate.

Rapid loss of appendicular skeletal muscle mass is associated with higher all-cause mortality in older men: the prospective MINOS study.

BACKGROUND: Changes in body composition underlying the association between weight loss and higher mortality are not clear. OBJECTIVE: The objective was to investigate the association between changes in body composition of the appendicular (4 limbs) and central (trunk) compartments and all-cause mortality in men. DESIGN: In men aged > or = 50 y, body composition was assessed every 18 mo for 7.5 y with a whole-body dual-energy X-ray absorptiometry scan. Mortality was assessed for 10 y. Data were analyzed by logistic regression and Cox model and adjusted for age, body mass index (BMI), educational level, lifestyle, physical performance, comorbidities, body composition, and serum concentrations of 17beta-estradiol and 25-hydroxycholecalciferol. RESULTS: Of 715 men who were followed up, 137 (19.2%) died. Mortality was higher in men with the fastest weight loss [lowest compared with middle tertile odds ratio (OR): 2.31; 99% CI: 1.05, 5.09]. Faster loss of appendicular skeletal muscle mass (ASMM) was predictive of mortality (lowest compared with middle tertile OR: 3.60; 99% CI: 1.64, 7.89). Faster loss in ASMM remained a strong predictor of mortality after adjustment for weight loss (OR: 3.41; 99% CI: 1.51, 7.71). Faster loss in ASMM was the strongest predictor of death in the stepwise procedures when it was analyzed jointly with changes in the mass of other compartments. Loss in ASMM calculated over 36 mo was also a stronger predictor of death than were changes in the mass of other compartments (hazard ratio: 1.33 per 1-SD decrease; 95% CI: 1.06, 1.66). CONCLUSION: The accelerated loss of ASMM is predictive of all-cause mortality in older men regardless of age, BMI, lifestyle, physical performance, health status, body composition, and serum 17beta-estradiol and 25-hydroxycholecalciferol.

Increased bone resorption is associated with higher mortality in community-dwelling men >or=50 years of age: the MINOS study.

Low BMD, high concentration of 17beta-estradiol (17betaE2), and decreased level of 25-hydroxycholecalciferol [25(OH)D] predict mortality. Our hypothesis is that high levels of biochemical bone turnover markers (BTMs) are independent predictors of mortality in home-dwelling men. In 781 men >or=50 yr of age followed up prospectively for 10 yr, we studied the association of BTMs with mortality after adjustment for confounders including BMD, major osteoporotic fractures, and concentrations of 17betaE2 and 25(OH)D. Men who died had lower BMD and higher BTM levels. In multivariate models, mortality was higher in men with low BMD (lowest quartile) at the total hip, whole body, and ultradistal radius (HR = 1.49-1.70, p < 0.05). After exclusion of the first 3 yr, higher levels (fourth quartile) of bone resorption markers (free and total deoxypyridinoline and urinary and serum type I collagen C-telopeptide) predicted mortality in multivariate models adjusted for age, BMI, smoking habits, alcohol intake, physical performance and activity, comorbidities, total hip BMD, major osteoporotic fractures, creatinine clearance, season, and concentrations of 17betaE2 and 25(OH)D (HR = 1.58-2.44, p < 0.05-0.001). In conclusion, in older community-dwelling men, increased bone resorption markers levels predicted mortality regardless of age and other confounders. Thus, in older men, high bone resorption may reflect poor current health status and poor aging.

Bone mineral density predicts osteoporotic fractures in elderly men: the MINOS study.

Osteoporosis in men is becoming a public health problem in developed countries. Fracture incidence increases with age, and the number of fractures increases because of the ageing of the population. We assessed the predictive value of bone mineral density (BMD) for osteoporotic fractures evaluated prospectively in a large cohort of elderly men and assessed the sensitivity of the T-score =-2 to detect men who will sustain a fracture. Fracture incidence was evaluated for 90 months in 759 men from the MINOS cohort aged 50 and over at baseline. In 74 men, 77 incident vertebral and peripheral fractures occurred. BMD was measured at baseline at the lumbar spine, hip, whole body and distal forearm. The incidence of osteoporotic fractures increased with age and with decreasing body weight. In men with low BMD (T-score <-2), fracture incidence varied from 2.26 to 3.07 fractures per 100 person-years and was 2.1 to 3.6 times higher than in men with normal BMD. After adjustment for age, body weight and height, baseline BMD was 3.7 to 7.9% ( P <0.05-0.0001) lower at all the sites of measurement in men who sustained a fracture. After adjustment for age, weight and prevalent fractures, BMD was predictive of osteoporotic fractures at all the sites. Odds ratios varied from 1.28 to 1.89 per 1 SD decrease in BMD ( P <0.05-0.0001). The predictive accuracy of BMD for fractures (area under the curve of the receiving operator characteristics adjusted for age, weight and prevalent fractures) varied from 0.643 to 0.712 according to the skeletal site and was higher for the whole body than for other sites. Thus, BMD itself has a limited value for determining men at an increased risk for fracture. The percentage of incident fractures occurring in men with low BMD (T-score <-2) ranged from 13.7% at the trochanter to 44.6% at the ultradistal radius. Conversely, 27 to 45% of incident fractures occurred in men with mildly decreased BMD (T-score between -1 and -2). In conclusion, BMD predicts osteoporotic fractures in men independently of age, body weight and prevalent fractures. However, the sensitivity of BMD to detect men at high risk of fracture is low. More studies on the predictors of fractures in men, such as bone architecture, morphology, biochemical markers of bone turnover and hormonal levels, are necessary.

Assessment of the role of 17beta-oestradiol in bone metabolism in men: does the assay technique matter? The MINOS study.

OBJECTIVE: 17Beta-oestradiol (17beta-E2), mainly its bioavailable fraction (bio-17beta-E2), is a determinant of bone mineral density (BMD) and bone remodelling in men. As direct measurement of bio-17beta-E2 is time-consuming, we compared the value of directly measured bio-17beta-E2 and of calculated bio-17beta-E2 and free 17beta-E2 by studying their association with BMD and markers of bone turnover in a cohort of men (MINOS). DESIGN: A cross-sectional study in which the association between BMD and bone markers, on the one hand, and serum levels of 17beta-E2, on the other, was analysed according to the levels of measured and calculated bio-17beta-E2 and free 17beta-E2 in a cohort of men. SUBJECTS: Men from the MINOS cohort including 87 men aged 19-45 to establish the reference control normal range of hormones and 637 men aged 50-85 (studied group). MEASUREMENTS: Total 17beta-E2, testosterone, SHBG and albumin were measured by standard methods. bio-17beta-E2 was directly measured after the precipitation of SHBG by ammonium sulfate. bio-17beta-E2 and free 17beta-E2 were calculated using serum SHBG and albumin levels as described by Sodegard et al. (J. Steroid Biochem., 16 (1982) 801). RESULTS: Calculated bio-17beta-E2 and free 17beta-E2 were correlated with measured bio-17beta-E2 and between themselves (r = 0.90-1.00, P < 0.0001). Calculated bio-17beta-E2 and free 17beta-E2 disclosed a similar association with BMD (difference between lowest and highest quartiles of 17beta-E2: 2.6-6.8%, P < 0.05-0.005) to that of measured bio-17beta-E2 (3.6-6.1%, P < 0.005-0.001). The association between bone markers levels and measured vs. calculated 17beta-E2 were also similar. Predictive accuracy for lowered BMD and elevated levels of biochemical bone markers (evaluated using receiver operating characteristics) was relatively low (area under curve -0.582 to 0.709) but similar for different forms of bioavailable and free 17beta-E2. CONCLUSIONS: In elderly men, the concentrations of bioavailable and free 17beta-E2, calculated using equations including either the measured albumin concentration or the constant albumin concentration of 43 g/l, can be used, at least in clinical studies, instead of the bio-17beta-E2 concentrations measured after ammonium sulfate precipitation.