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P Szulc

Publications and source records attributed to P Szulc.

At least 19 recordsLinked to original sources
PubMed2006

Bone width is correlated positively with the upper to the lower segment ratio in elderly men--the MINOS study.

Before puberty, limbs grow more rapidly than the spine. During puberty, lengthening of the spine and increase in bone width accelerate. Correlation of parameters with lengths of the upper and lower segments and with the upper/lower segment ratio may indicate the period of growth critical for their determination. We assessed the association of bone mineral and width with the upper/lower segment ratio in 542 elderly men from the MINOS cohort. Areal bone mineral density (aBMD) was measured at the lumbar spine and right hip using pencil-beam dual-energy X-ray absorptiometry and at the distal forearm using single energy X-ray absorptiometry. Upper/lower segment ratio correlated positively with bone mineral content (BMC), aBMD and width of third lumbar vertebra (L3), femoral neck and distal radius. Men in the highest quartile of the upper/lower segment ratio had larger bones by 2.5 to 5.0% (0.3-0.4 SD, p<0.02-0.002) compared with the lowest quartile. Bone width correlated more strongly with the upper segment length than with that of the lower one. Volumetric BMD (vBMD) did not correlate with the upper/lower segment ratio nor with the lengths of the body segments. At the femoral neck and distal radius, men in the highest quartile of the upper/lower segment ratio had higher estimated cortical thickness (5.3%, 0.41 SD, p<0.01 and 4.0%, 0.31 SD, p<0.03), bigger cortical area (8.0%, 0.54 SD and 6.8%, 0.52 SD, p<0.0001) and higher estimated bending strength (9.3 to 13.3%, 0.46 to 0.54 SD, p<0.0001). Elderly men with the higher upper/lower segment ratio had higher BMC and bending strength because they had wider bones, not higher vBMD. The bone size correlated positively with the length of the upper segment, not negatively with that of the lower segment. Our data may suggest an important role of pubertal growth for both bone width and strength in men but do not establish the determinants of this association. Given methodological limitations, these results need to be confirmed in a younger and more representative group of men.

Absorptiometry, Photon↗
PubMed2005

Structural determinants of hip fracture in elderly women: re-analysis of the data from the EPIDOS study.

Hip fracture is the most disastrous osteoporotic fracture, characterized by high mortality, morbidity and institutionalization for the patient and by high economic costs for the health care system. The morphology of the upper part of the femur can influence the risk of hip fracture, e.g., a longer femoral neck is associated with a higher risk of cervical fractures, but not trochanteric ones. In this study, we evaluated the prediction of hip fracture risk by morphological parameters estimated from DXA measurements, and we compared their predictive value for cervical and trochanteric fractures in elderly women by reanalyzing previously published data (Duboeuf et al. J Bone Miner Res 1997 12 1895). This nested case-control study was performed in 232 elderly community-dwelling women from the EPIDOS cohort, including 65 women who sustained a hip fracture. After adjustment for confounding variables, women who sustained a cervical fracture had lower areal bone mineral density (aBMD), lower cortical thickness and a higher average buckling ratio (P<0.005 for all) as well as longer femoral neck (P<0.01) than controls. Women who sustained a trochanteric fracture had lower aBMD, lower cortical thickness and higher buckling ratio than controls (P<0.0001) and than women who sustained a cervical fracture (P<0.05). Their bending resistance (cross-sectional moment of inertia-CSMI, section modulus) was significantly lower in comparison with controls (P<0.05-0.001). A decrease in aBMD, cortical thickness, CSMI and section modulus as well as an increase in buckling ratio were predictive of all hip fractures (OR -1.42-2.46 per 1 SD, P<0.05-0.0001), but the ORs for all structural parameters were markedly higher for trochanteric than for cervical fractures. CSMI and section modulus were predictive of trochanteric, but not cervical fractures. However, aBMD was strongly correlated with the CSA, cortical thickness and buckling ratio (r2>0.74), which suggests that they convey the same information. CSMI and section modulus correlated with aBMD more weakly, but their OR lost statistical significance after adjustment for aBMD. In conclusion, low femoral neck aBMD, CSA and cortical thickness as well as a high buckling ratio are associated with the higher risk of hip fracture, especially trochanteric ones. These indices are highly correlated with aBMD and convey the same message. The calculated CSMI and section modulus predict trochanteric fractures, but not cervical fractures, and their statistical significance is lost after adjustment for aBMD, indicating that they reflect mainly aBMD, not mechanical properties. Thus, the independent contribution of the external diameter of the femoral neck to the risk of hip fracture cannot be reliably estimated by this technique.

Absorptiometry, Photon↗
PubMed2004

Biochemical markers of bone formation reflect endosteal bone loss in elderly men--MINOS study.

In the skeleton of elderly men, two opposite activities occur: bone loss at the endosteal envelope, which increases bone fragility, and periosteal apposition, which improves bending strength of bone. Both may contribute to serum bone formation markers although they have an opposite effect on bone fragility. The aim of this study was to determine if circulating bone formation markers reflect periosteal bone formation and endosteal bone remodelling in 640 men aged 55-85 years belonging to the MINOS cohort. We measured biochemical markers of bone formation (osteocalcin, bone alkaline phosphatase, N-terminal extension propeptide of type I collagen) and bone resorption (urinary and serum beta-isomerised C-terminal telopeptide of collagen type I, total and free deoxypyridinoline). Parameters of bone size (cross-sectional surface of third lumbar vertebral body measured by X-ray, projected areas of total hip, femoral neck, radius and ulna measured by dual-energy X-ray absorptiometry) increased with age (r = 0.20-0.32, P < 0.0001). In contrast, parameters related to bone loss (areal bone mineral density [aBMD], volumetric bone mineral density [vBMD] and cortical thickness) and determined mainly by bone resorption, decreased with ageing (r = -0.14 to -0.23, P < 0.005-0.0001). Men in the highest quartile of bone resorption markers had lower aBMD (3.8-10.2%, P < 0.05-0.0001), lower vBMD (3.9-13.0%, P < 0.05-0.0001), and lower cortical thickness (1.5-9.6%, P < 0.05-0.0001) than men in the lowest quartile. Markers of bone resorption were not significantly associated with estimates of bone size at any skeletal site. Markers of bone formation were not associated with estimates of periosteal formation after adjustment for covariates. In contrast, men in the highest quartile of the bone formation markers had significantly lower aBMD (4.0-11.7%, P < 0.05-0.0001), lower vBMD (4.2-16.3, P < 0.05-0.0001) and lower cortical thickness (4.0-7.4%, P < 0.05-0.0001) than men in the lowest quartile. In summary, serum levels of bone formation markers are negatively correlated with the estimates of endosteal bone loss. In contrast, they disclose no association with parameters reflecting periosteal apposition. Thus, in elderly men, bone formation markers reflect endosteal bone remodelling, probably because of the coupling between resorption and formation activities. In contrast, they do not reflect the periosteal bone formation, probably because the periosteal surface is smaller and has a slower remodelling rate than the endosteal surface.

Absorptiometry, Photon↗
PubMed2004

Role of sex steroids in the regulation of bone morphology in men. The MINOS study.

In ageing men, skeletal fragility is associated with reduced cortical thickness and decreased bone density. To better understand the role of testosterone and 17beta-estradiol regarding these characteristics of skeletal fragility, we correlated their circulating levels with the estimates of mechanical bone properties derived from areal bone mineral density (aBMD) measured by DXA. External diameter and BMD were used to estimate cortical thickness, cross-sectional area (CSA), section modulus, buckling ratio and strength index of the femoral neck and distal radius on 760 men aged 40-85 years. The 17beta-estradiol level was an independent positive determinant of CSA, aBMD and estimated cortical thickness of both bones. In multivariate models adjusted for age, body weight, height, lean body mass and testosterone concentration, men in the lowest quartile of 17beta-estradiol had lower CSA at the femoral neck (4.8%, P<0.001) and distal radius (3.6%, P<0.01) compared with men in the highest quartile. They had also thinner cortical bone at the femoral neck and distal radius (4.8%, P<0.001 and 4.6%, P<0.001, respectively). Furthermore 17beta-estradiol had a negative association with indices of cortical instability (buckling ratio) and a positive association with bending strength (section modulus, strength index) both at femoral neck and radius. Men in the lowest quartile of 17beta-estradiol had higher buckling ratios (femoral neck 4.8%, P<0.002; radius 5.1%, P<0.005), lower strength index (femoral neck 8.5%, P<0.001, radius 6.1%, P<0.01) and greater section modulus at the femoral neck. However, there were no between-quartile differences in external diameter in any bone sites. Similar, even though somewhat smaller, between-quartile differences were found for bioavailable 17beta-estradiol. Neither total testosterone nor apparent free testosterone concentration was associated with any bone variables after adjusting for age, body weight, body height, and lean body mass and 17beta-estradiol level. In conclusion, in elderly men, low concentration of 17beta-estradiol (total and bioavailable) was associated with a decreased cortical thickness and with a deterioration of biomechanical parameters of long bones (lower section modulus and strength index, higher buckling ratio).

Adult↗
PubMed2004

Insulin-like growth factor I is a determinant of hip bone mineral density in men less than 60 years of age: MINOS study.

Several studies show that in elderly men bone mineral density (BMD) is not correlated with the insulin-like growth factor (IGF-I) level, but data are scanty in young men. Results of studies correlating insulin-like growth factor binding protein 3 (IGFBP-3) and BMD in men are discordant. As different hypotheses can explain the discordant results, we evaluated the correlation of BMD with serum IGF-I, IGFBP-3, and IGF-I/IGFBP-3 index in a large cohort of 721 men aged 19-85 years taking into account age, body weight, 17beta-estradiol, free testosterone, and parathyroid hormone. Serum IGF-I and IGFBP-3 decreased with age (r = -0.44 and r = -0.36, P = 0.0001). After adjustment for confounding variables, IGF-I correlated weakly positively with BMD and with bone mineral apparent density (BMAD) of hip as well as with cortical thickness of femoral neck, both of which are determined mainly by bone resorption, but not with bone size determined by periosteal apposition. IGF-I correlated weakly positively with BMD at the whole body and at the third lumbar vertebra IGFBP-3 and IGF-I/IGFBP-3 index did not correlate with densitometric parameters. In men aged 19-60 years, IGF-I correlated with BMD and BMAD of total hip and with cortical thickness of femoral neck positively and more strongly than in the entire cohort but not with the size of proximal femur. BMD of total hip was 6% higher in men in the highest quartile of IGF-I than in men in the lowest quartile. IGF-I, IGFBP-3, and IGF-I/IGFBP-3 index did not correlate with densitometric parameters of other sites. In the men aged more than 60 years, neither IGF-I nor IGFBP-3 nor IGF-I/IGFBP-3 index correlated with BMD, BMAD, or bone size. In men aged 19-60 years, the most significant hormonal determinants of BMD and BMAD of the hip and of the cortical thickness of femoral neck were 17beta-estradiol and IGF-I (P < 0.05-0.0001). In men aged more than 60 years, the most significant determinants of hip BMD were 17beta-estradiol and PTH. In conclusion, IGF-I seems to contribute to the inhibition of bone resorption and to maintaining bone mass of the proximal femur during the phase of slow bone loss in men aged less than 60 years. IGFBP-3 and IGF-I/IGFBP-3 index were not correlated with BMD or bone size.

Adult↗
PubMed2003

Role of vitamin D and parathyroid hormone in the regulation of bone turnover and bone mass in men: the MINOS study.

We investigated the role of vitamin D and of parathyroid hormone (PTH) in the regulation of bone mineral density (BMD), tone dimensions and seasonal variation of bone turnover in 881 men aged 19-85 years. Bone mineral content (BMC) and BMD of the lumbar spine, hip and whole body were measured with HOLOGIC 1000W and those of distal forearm with an OSTEOMETER DTX 100 device. Bone formation was evaluated using osteocalcin, bone alkaline phosphatase and N-terminal extension propeptide of type I collagen (PINP). Bone resorption was evaluated by 24-hour excretion of deoxypyridinoline and of C-terminal telopeptide of collagen type I. In young men (< 55 yrs) PTH level decreased with age (r = -0.18, P < 0.005) whereas 25-hydroxyvitamin D (25OHD) concentration was stable. In older men (> 55 years) 25OHD decreased whereas PTH increased with age (r = -0.27 and r = 0.21, P = 0.0001). In young men, 25OHD level varied with season but not PTH, biochemical markers of bone turnover nor BMD. In young men, 25OHD, but not PTH, was a significant determinant of BMC, cortical thickness and of biomechanical properties of the femoral neck. Biochemical bone markers and BMD were not correlated with PTH nor with 25OHD. In elderly men, winter levels of 25OHD were lowest whereas those of PTH, bone resorption markers and PINP were highest. After adjustment for age, body weight and season, biochemical markers of bone turnover were correlated with PTH. In elderly men, 25OHD and PTH were significant determinants of BMC, cortical thickness and of biomechanical parameters of the femoral neck. Men with vertebral deformities had lower concentrations of 25OHD, higher PTH levels and slightly elevated urinary excretion of biochemical markers of bone resorption compared with men without vertebral deformities. In conclusion, in young men, 25OHD discloses a seasonal variability in contrast to PTH and biochemical bone markers. In this group, 25OHD is a significant determinant of BMC and BMD but not of bone size. In elderly men, seasonal variation of 25OHD and PTH concentrations result in seasonal variation of bone resorption. In this group, both 25OHD and PTH are determinants of BMC and cortical thickness of the femoral neck and, consequently, of its mechanical parameters.

Adult↗
PubMed2003

Similar prevalence of vertebral fractures despite different approaches to define reference data.

Morphometric detection of vertebral fractures requires the use of reference normal values. In previous studies, normal values were obtained in young healthy adults or in adults of various ages in whom abnormal radiographs were excluded using trimming algorithms. We established four sets of normal values defined according to different approaches. We used a group of 102 young healthy women with normal spine radiographs and a population-based cohort of 260 women 51 to 85 years old (EVOS study) to select those with normal spine radiographs based on the semiquantitative method of Genant, the trimming algorithm defined by Melton, and the trimming algorithm defined by Black. Using the four sets of reference data, we applied two diagnostic criteria, the mean - 3SD and the 0.85 x mean to detect prevalent vertebral fractures in two groups of women: the population-based cohort of 260 women recruited for the EVOS study and 176 osteoporotic women 54 to 88 years old with at least one vertebral fracture. In the population-based cohort, the number of vertebral fractures varied from 53 to 57 for the 0.85 x mean cutoff and from 93 to 115 for the mean - 3SD cutoff. In the osteoporotic women, the number of vertebral fractures varied from 255 to 273 for the 0.85 x mean cutoff and from 372 to 404 for the mean - 3SD cutoff. In both groups, the number of vertebral fractures detected with the 0.85 x mean cutoff was close to the number detected by the semiquantitative method of Genant, which does not require a reference population. For the 0.85 x mean cutoff, agreement of diagnosis using different reference values was excellent (kappa = 0.96-0.99). For the mean - 3SD cutoff, agreement of vertebral fracture detection based on the four reference sets was good (kappa = 0.79-0.93). Agreement of diagnosis was lower when two cutoffs were compared using the same set of reference values (kappa = 0.60-0.81). In conclusion, reference data derived using different approaches give similar rates of prevalence of vertebral fractures. Compared to the semiquantitative assessment, the prevalence of vertebral fractures is similar for the 0.85 x mean cutoff, whereas it is considerably higher for the mean - 3SD cutoff.

Aged↗
PubMed2003

Increased risk of falls and increased bone resorption in elderly men with partial androgen deficiency: the MINOS study.

The goal of this study was to identify the clinical and biological patterns of hypogonadism in a cohort of 1040 elderly men. Residual androgenic activity was estimated by total testosterone as well as the apparent free testosterone concentration (AFTC) and free testosterone index (FTI) calculated on the basis of concentrations of SHBG and total testosterone using appropriate formulae. The lower limit of the normal range defined by 2 SD below the mean in 150 healthy, nonobese, and nonsmoking men, aged 19-40 yr, was calculated for total testosterone (9.26 nmol/liter), AFTC (146 pmol/liter), and FTI (0.14 nmol/nmol). The prevalence of hypogonadism increased with ageing. Hypogonadal men were older and heavier (due to a higher fat body mass) and had lower concentrations of 17 beta-estradiol and androstenedione than men with normal androgenic activity. Men with decreased AFTC had a slightly lower bone mineral density (BMD) at certain sites. Men with decreased FTI had lower appendicular skeletal muscle mass and relative skeletal muscle index. For all three measures of androgenic activity, hypogonadal men had increased levels of the markers of bone resorption. In the multiple regression models including both 17 beta-estradiol and testosterone (total, AFTC, or FTI), 17 beta-estradiol was the only significant determinant of BMD. In the multiple regression models including 17 beta-estradiol and AFTC or FTI, only testosterone was a significant determinant of the variability in bone formation markers, whereas both 17 beta-estradiol and testosterone were significant determinants of the variability of the markers of bone resorption. Hypogonadism was associated with an increase in the risk of falls, an impairment of static and dynamic balance, as well as the inability to stand up from a chair and to perform the tandem walk. Decreased AFTC (<146 pmol/liter) discriminated best men with functional disabilities (odds ratio, 1.54-7.95; P < 0.05-0.0001). Hypogonadal elderly men had increased bone resorption that was not adequately matched by an increase in bone formation, lower muscle strength, impaired static and dynamic balance, a higher risk of falls, and, in men with low AFTC, a slightly lower BMD. Low AFTC seems to have the best discriminative power for densitometric, biochemical, and functional parameters, followed by FTI, whereas total testosterone was the least discriminative. In multiple regression models, 17 beta-estradiol was the strongest determinant of BMD, and AFTC and FTI were significant determinants of the variability in bone formation markers, whereas both 17 beta-estradiol and testosterone determined the variability in bone resorption markers.

Accidental Falls↗
PubMed2002

Increased bone resorption in moderate smokers with low body weight: the Minos study.

Tobacco was found to be a risk factor for osteoporosis, mainly in postmenopausal women. We studied the effect of smoking on bone mineral density (BMD) and bone turnover in a cohort of 719 men, aged 51-85 yr, composed of 83 current smokers, 405 former smokers, and 231 men who never smoked. Most current and former smokers were moderate smokers (median, 10 cigarettes/d). Current smokers were younger, thinner, and drank more coffee and more alcoholic beverages. After adjustment for age, body weight, alcohol intake, and caffeine intake, current and former smokers had similar BMD, except at the forearm. Former smokers had lower BMD compared with never-smokers at most skeletal sites. Men who had smoked more than 7120 packs (third quartile) had lower BMD of total hip (P < 0.01) and distal forearm (P = 0.03) compared with men in the 2 lower tertiles. In the 3 groups, levels of bone formation markers did not differ. After adjustment for confounding variables, levels of urinary markers of bone resorption (beta-isomerized C-terminal telopeptide, free and total deoxypyridinoline) were higher in the current smokers than in former smokers and never-smokers. Concentrations of T, total 17beta-E2, and androstenedione were higher, whereas that of 25-hydroxyvitamin D was lower, in current smokers. When men were divided according to tertiles of body weight, increased bone resorption, decreased BMD and biochemical indexes of secondary hyperparathyroidism were observed in current smokers in the lowest tertile of body weight (<75 kg) compared with the never-smokers, but not in men in the two highest tertiles of body weight. Current smokers had a higher prevalence of vertebral deformities after adjustment for age and body weight (13% vs. 5%; P < 0.005). In summary, in moderate smokers with low body weight (<75 kg), increased bone resorption, not matched by increased bone formation, results in decreased BMD and an increased prevalence of vertebral deformities. In this group, low serum 25-hydroxyvitamin D and secondary hyperparathyroidism may explain, at least partly, the effect of tobacco on bone turnover. In former smokers, bone resorption is not increased, but BMD remains lower compared with that in never-smokers.

Aged↗
PubMed2001

Semiquantitative evaluation of prevalent vertebral deformities in men and their relationship with osteoporosis: the MINOS study.

Epidemiologic studies have shown a high prevalence of vertebral deformities in men without a steep increase with aging, suggesting that a substantial number of these deformities are not related to osteoporosis. To determine which vertebral deformities are likely to be osteoporotic fractures, we compared vertebral deformities and bone mineral density (BMD) in a cohort of 786 men aged 51-85 years (the MINOS study). Normal vertebral height ratios were defined in a group of 120 healthy men aged 21-50 years. We classified vertebral deformities by using the semiquantitative method described by Genant et al., which was slightly modified at the level of thoracic kyphosis (T6-T9). At that level, grade 1 wedge deformities were defined as a 25-30% decrease in anterior vertebral height and grade 2 by a 30-40% decrease. The same cutoff of 40% was used for grade 3 for all vertebrae from T4 to L4. BMD was measured with a Hologic 1500 device at the lumbar spine, hip and whole body and with an Osteometer DTX 100 device at the forearm. Z-scores were calculated in 10-year age groups. The prevalence of vertebral deformities increased significantly with age. After adjustment for age and body weight, BMD did not differ between those with and without vertebral deformities. In patients having grade 2 and 3 deformities, BMD was lower than in men having no deformities or only grade 1 deformities when adjusted for age and body weight. Using the age- and body-weight-adjusted test of linear trend for sextiles of BMD, prevalence of grade 2 and 3 vertebral deformities increased with a decrease in BMD at all the sites of measurement. Grade 1 deformities were not correlated with BMD at any site. Among 126 patients who had only grade 1 vertebral deformities, 32 deformities in 30 men were confirmed as vertebral fractures according to their morphology but their BMD did not differ from the nonfractured men. These findings were confirmed when vertebral deformities were measured by the conventional morphometric method in a subgroup of 131 men. Our data suggest that a cutoff of 30% for wedge deformities from T6 to T9 and of 25% for other deformities has a high specificity and a moderate sensitivity for identifying vertebral deformities related to low BMD in men. Grade 1 deformities are often either false positive or deformities related to nonosteoporotic disease of the spine.

Age Distribution↗
PubMed2001

Biochemical markers of bone turnover in men.

Although osteoporosis in men has been recently recognized as a public health problem, the mechanisms leading to bone loss are still poorly understood. Longitudinal studies of bone mineral density suggest an acceleration of bone loss after 70 years of age. Histomorphometric data concerning age-related changes of bone turnover in men are limited, including few men over 70 years and have been restricted to the trabecular envelope of bone biopsies. Most measurements of biochemical markers of bone turnover have been performed in small cohorts of limited age range, and results obtained in large cohorts are scanty. Levels of markers of bone formation and of bone resorption are very high in men aged 20-30 years which corresponds to the late phase of formation of peak bone mass, and then declines, reaching their lowest levels between 50 and 60 years. Data on bone turnover markers in elderly men are discordant. Concentrations of bone formation markers remain stable, decrease slightly, or even increase marginally. Markers of bone resorption increase in some studies, mainly after 70 years of age, in line with acceleration of bone loss in this age range. This discordance between studies can result from different reasons. The increase of bone turnover may be limited to a subgroup of elderly men. In addition, urinary levels of bone resorption markers depend on the rate of bone turnover, on pre-renal and renal catabolism of peptides released from bone matrix, on glomerular filtration rate, as well as unit of expression of their results (per 24 hours per urinary creatinine mass, per glomerular filtrate volume). In elderly men, biochemical bone markers are negatively correlated with bone mineral density. Longitudinal studies are not yet available on the relationship among bone turnover markers, rate of bone loss, and fracture. In conclusion, in elderly men, age-related bone loss seems to result from increased bone resorption which is not matched by increased bone formation. Thus, antiresorptive therapy may be of interest in the prevention and treatment of osteoporosis in men. Further studies are necessary to determine if bone resorption markers predict the risk of fragility fractures in elderly men.

Adult↗
PubMed2001

Bioavailable estradiol may be an important determinant of osteoporosis in men: the MINOS study.

During recent years, experimental data, case reports, and epidemiological studies have suggested an important role for estradiol in bone metabolism in men. In a cohort of 596 men, aged 51-85 yr, we measured bone mineral density (BMD) of the lumbar spine, hip, total body, and forearm; serum levels of sex steroid hormones [total and free testosterone, total estradiol (17betaE(2)), bioavailable estradiol (bio-17betaE(2)), androstenedione, and sex hormone-binding globulin]; and markers of bone turnover [serum osteocalcin, bone alkaline phosphatase, N-terminal extension propeptide of type I collagen, and beta-isomerized C-terminal telopeptide of collagen type I (betaCTX)], as well as urinary excretion of betaCTX and deoxypyridinoline (DPyr). An age-related decrease was found for bio-17betaE(2) (r = -0.16; P < 0.001), free testosterone (r = -0.25; P < 0.001), free testosterone index (r = -0.32; P < 0.001), and androstenedione (r = -0.22; P < 0.001), but not for total 17betaE(2) or total testosterone. 17betaE(2) and bio-17betaE(2), but not other hormones, were correlated with BMD after adjustment for age and body weight. In men with a bio-17betaE(2) level in the lowest quartile, the average BMD was lower than in men having a bio-17betaE(2) level in the highest quartile by 6.6-8.7% according to the site of measurement, which corresponded to 0.45-0.65 SD. In age- and body weight-adjusted models, bio-17betaE(2), but not other hormones, was negatively correlated with bone markers (e.g., osteocalcin: r = -0.14; P < 0.001; urinary betaCTX: r = -0.20; P = 0.0001; DPyr: r = -0.14; P < 0.001). In men with the lowest concentration of bio-17betaE(2) (first quartile), the concentrations of markers of bone turnover were higher by 11-35% (or 0.4-0.7 SD) than in men having the highest bio-17betaE(2) level (upper quartile). In men in the lowest quartile for bio-17betaE(2) and in the highest quartile for urinary DPyr or betaCTX, the BMD of total hip and that of distal forearm were 8% and 10% lower than in men in the highest quartile for bio-17betaE(2) and in the lowest quartile for DPyr or ssCTX. In the age- and body weight-adjusted multiple regression models, bio-17betaE(2) contributed significantly to the explanation for the variability in all markers. In summary, we found in a cross-sectional analysis of a cohort of men that low levels of bio-17betaE(2) are associated with high bone turnover and low BMD. These data suggest that the age-related decrease in bio-17betaE(2) contributes to bone loss in elderly men by increasing bone turnover. Low 17betaE(2) levels may be an important risk factor for osteoporosis in men.

Aging↗
PubMed2001

Osteoprotegerin serum levels in men: correlation with age, estrogen, and testosterone status.

Previous studies have suggested an important role for androgens and estrogens in bone metabolism in men. However, their local mode of action has not been clearly established. Osteoprotegerin (OPG) is a secreted decoy receptor that inhibits osteoclast formation and activity by neutralizing its cognate ligand. To assess the role of OPG on bone metabolism in men, we conducted a study aimed at evaluating OPG serum levels and their correlation with age, bone mineral density, biochemical markers of bone turnover, and testosterone and estradiol levels in 252 men, aged 19-85 yr. Serum concentrations of OPG increased significantly with age (r = 0.41; P = 0.0001), and were positively correlated with free testosterone index and free estradiol index (r = 0.20; P < 0.002 and r = 0.15; P < 0.03, respectively) after adjustment for age and body weight. Beyond the age of 40 yr, OPG serum concentrations were negatively correlated with urinary excretion of total deoxypyridinoline (r = -0.20; P < 0.01) and PTH serum levels (r = -0.23; P < 0.01). In contrast, there was no correlation with biochemical markers of bone formation, 25-hydroxyvitamin D(3) levels, or bone mineral density at any site. Our data reveal that age as well as androgen and estrogen status are significant positive determinants, whereas PTH is a negative determinant, of OPG serum levels in men. These data suggest that OPG may be an important paracrine mediator of bone metabolism in elderly men and highlight the role of estrogens in the homeostasis of the male skeleton.

Adult↗
PubMed2001

Cross-sectional evaluation of bone metabolism in men.

There are relatively few data concerning age-related changes of bone turnover in men. The aim of the study was to evaluate age-related changes of the levels of serum and urinary biochemical markers of bone metabolism in a large cohort of 934 men aged 19-85 years and to investigate their association with bone mineral density (BMD). Bone formation was evaluated using serum levels of osteocalcin (OC), bone alkaline phosphatase (BAP), and N-terminal extension propeptide of type I collagen (PINP). Bone resorption was evaluated by measurement of urinary excretion of beta-isomerized C-terminal telopeptide of collagen type I beta-CTX) of free deoxypyridinoline (fDpyr) and total Dpyr (tDPyr) and of the serum level of beta-CTX. Levels of biochemical bone markers were very high in young men and decreased rapidly until the age of 40 years and then more slowly until 60 years of age. After the age of 60 years, markers of bone formation remained stable while resorption markers showed a moderate and variable increase with aging. Serum and urinary beta-CTX levels were elevated only in about 5% of elderly men. The age-related increase of urinary excretion of tDpyr and of its free and peptide-bound fractions was related to the presence of elevated levels in a subgroup of about 15% of elderly men. Before 60 years of age, levels of biochemical bone markers were not correlated with BMD, whereas after 60 years of age, they were correlated negatively with BMD. After adjustment for age and body weight, BMD in men with the highest levels of biochemical bone markers (i.e., in the upper quartile) was 1.8-12.5% (i.e., 0.25-0.89 SD) lower than in men with levels of biochemical bone markers in the lowest quartile. In conclusion, bone turnover in men is high in young adults and decreases to reach a nadir at 55-60 years of age. After the age of 60 years, bone resorption markers--but not bone formation markers--increase in some men and are associated with lower BMD, suggesting that this imbalance is responsible for increasing bone loss in elderly men.

Adult↗
PubMed2000

Biochemical measurements of bone turnover in children and adolescents.

Biochemical measurements of bone turnover are helpful in the study of the pathophysiology of skeletal metabolism and growth. However, interpretation of their results is difficult because they depend on age, pubertal stage, growth velocity, mineral accrual, hormonal regulation, nutritional status, circadian variation, day-to-day variation, method of expression of results of urinary markers, specificity for bone tissue, sensitivity and specificity of assays. Three markers of bone formation have been described including their bone specificity and age-related changes: osteocalcin, alkaline phosphatase and its skeletal isoenzyme, procollagen I extension peptides. Bone resorption markers (hydroxyproline; deoxypyridinoline; pyridinoline; peptides containing these crosslinks such as N-telopeptide to helix in urine (NTX), C-telopeptide-1 to helix in serum (ICTP) and C-telopeptide-2 in urine and serum (CTX); tartrate-resistant acid phosphatase; hydroxylysine and its glycosides) are described with special attention to methodologic issues, mainly ways of expression of their results. Changes of bone turnover during growth are described during four periods: infancy, prepubertal period, puberty and the postpubertal period. Pubertal changes of bone markers are described with special attention to gender differences and hormonal mechanisms of the growth spurt which determine differences related to the pubertal stage. Disturbances of bone turnover in four conditions are described to illustrate the impact of such diseases on growth and formation of peak bone mass: prematurity, malnutrition, growth hormone deficiency and corticosteroid-treated bronchial asthma. Available data suggest biochemical markers of bone remodeling may be useful in the clinical investigation of bone turnover in children in health and disease. However, their use in everyday clinical practice is not advised at present.

Adolescent↗
PubMed2000

Comparison of morphometric assessment of prevalent vertebral deformities in women using different reference data.

The semiquantitative assessment of vertebral deformities is based on visual evaluation. The quantitative approach is based on different morphometric criteria. This study is aimed at comparing the impact of different reference groups to define normal vertebral shape on the diagnosis of verterbral deformities. Reference normal values were obtained in three groups of women: French, mixed European, and Argentinian. All these women had normal lumbar spine bone mineral density and no vertebral deformities according to the semiquantitative assessment. In a group of 135 women having vertebral deformities according to Genant's semiquantitative assessment, three different morphometric criteria were applied. Morphometric diagnosis disclosed a good agreement with semiquantitative assessment. Agreement of diagnosis was higher for a given cutoff using thresholds obtained in different reference groups (kappa = 0.84-0.96) and lower when different criteria were compared using thresholds obtained in the same reference group (kappa = 0. 75-0.85). When fracture thresholds obtained in three different cohorts were compared separately for the three morphometric criteria, agreement was the highest when the cutoff was based only on the arithmetical mean of vertebral heights and was independent of its standard deviation (SD). Average vertebral height ratios did not differ between the three reference cohorts, whereas SDs of vertebral height ratios were the highest in the mixed European cohort and the lowest in the French cohort (F = 7.41, p < 0.001). In the three groups of women of different nationality, SDs of vertebral height ratios, but not the arithmetical means, were significantly higher in the radiographs of poor quality compared with those of good quality. Thus, the main source of difference of diagnosis was related to different SDs whereas average height ratios were not different. Differences in SDs between the three groups were found to be related, at least partly, to poor quality of radiographs. The impact of the differences between populations seems less important, however, only three countries were compared. These findings suggest that those techniques that take into account the SD of vertebral height ratios will provide different reference values for vertebral morphometry. Because differences in SDs depend mainly on the quality of radiographs, they can be reduced by improving the X-ray technique and by the use of standardized protocols. This variability will result in the identification of a variable number of vertebral deformities in osteoporotic women. These results may be of importance especially for multicentric studies.

Absorptiometry, Photon↗
PubMed2000

Cross-sectional assessment of age-related bone loss in men: the MINOS study.

There are few data on osteoporosis in men, but cross-sectional studies have shown that age-related bone loss in men is of lower magnitude than in women. To elucidate some controversies related partially to methodological aspects, we measured bone mineral density (BMD) by dual-energy X-ray absorptiometry (DEXA) at various skeletal sites (spine, hip, and whole body using a Hologic QDR-1500 device; forearm using an Osteometer DTX 100 device) in a large cohort of 1040 men, aged 19-85 years. The final investigation was performed on 934 men, aged 19-85 years, after exclusion of 106 men with disease or treatment known to affect bone metabolism. Peak BMD was achieved at 25 and 29 years at the lumbar spine and hip, respectively, but only at 40 and 37 years at the distal forearm and whole body, respectively. The magnitude of bone loss between peak bone mass and 80 years of age was linear at most sites and averaged 13%-18%; that is, SD of 1.1-1.8 from peak BMD, except for Ward's triangle, which showed a marked bone loss of 43% (i.e., 2.5 SD), and for the lumbar spine. In the entire cohort, increase of the average lumbar spine BMD after the age of 55 years was related to the development of osteoarthritis, because, in men without severe arthritis, lumbar spine BMD continued to decrease. Height-adjusted partial correlations indicate that both the mineral content and the area of long bones of the limbs increased with age up to 50 years, followed by a significant decrease of BMD without change of bone surface. SD of mean BMD increased significantly with age at most skeletal sites. In summary, age-related change of BMD varied according to skeletal site in men with peak bone mass achieved earlier at sites rich in trabecular bone than at those rich in cortical bone. Bone loss varied according to skeletal site from 14% to 43%. The variability of BMD increased with age, which may reflect interindividual variability of age-related bone loss.

Absorptiometry, Photon↗