Publications (20)94.35 Total impact
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Article: Association of serum sclerostin with bone mineral density, bone turnover, steroid and parathyroid hormones, and fracture risk in postmenopausal women: the OFELY study.
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ABSTRACT: Sclerostin is a key regulator of bone formation. In a population of 572 postmenopausal women (mean age, 67 years) followed prospectively for a median of 6 years, there was no significant association between baseline levels of serum sclerostin and incidence of all fractures which occurred in 64 subjects. INTRODUCTION: Sclerostin, an osteocyte soluble factor, is a major negative regulator of osteoblastic activity. Circulating sclerostin levels were reported to increase with age and to be modestly associated with bone mineral density (BMD) and bone turnover, but there are no data on the association with fracture risk. METHODS: We investigated 572 postmenopausal women (mean age, 67 ± 8.5 years) from the OFELY population-based cohort. The associations of serum sclerostin measured with a new two-site ELISA and spine and hip BMD by DXA, serum β-isomerized C-terminal crosslinking of type I collagen (CTX), intact N-terminal propeptide of type I collagen (PINP), intact PTH, 25-hydroxyvitamin D [25(OH)D], estradiol, testosterone, and fracture risk were analyzed. At the time of sclerostin measurements, 98 postmenopausal women had prevalent fractures. After a median of 6 years (interquartile range, 5-7 years) follow-up, 64 postmenopausal sustained an incident fracture. RESULTS: Serum sclerostin correlated positively with spine (r = 0.35, p < 0.0001) and total hip (r = 0.25, <0.0001) BMD. Conversely, serum sclerostin was weakly negatively associated with the bone markers PINP (r = -0.10, p = 0.014) and CTX (r = -0.13, p = 0.0026) and with intact PTH (r = -0.13, p = 0.0064). There was no significant association of serum sclerostin with 25(OH)D, estradiol, free estradiol index, or testosterone. Serum sclerostin considered as a continuous variable or in quartiles was not significantly associated with the risk of prevalent or incident fracture. CONCLUSION: Serum sclerostin is weakly correlated with BMD, bone turnover, and PTH in postmenopausal women. It was not significantly associated with the risk of all fractures, although the number of incident fractures recorded may not allow detecting a modest association.Osteoporosis International 04/2012; · 4.58 Impact Factor -
Article: Age determines longitudinal changes in body composition better than menopausal and bone status: the OFELY study.
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ABSTRACT: Long-term body composition (BC) changes and their determinants have been rarely explored. We aimed to evaluate BC changes in French women from the Os des Femmes de Lyon (OFELY) cohort and to explore several determinants of those changes. At baseline, premenopausal (PreM) women (n = 145) had lower fat body mass (FM) and greater lean body mass (LM), relative skeletal muscle mass index (RASM), and total body bone mineral content (TBBMC) compared with untreated postmenopausal (PostM) women (n = 412). During a 6-year follow-up, LM and RASM did not change, whereas a significant increase of FM and a decrease of TBBMC were observed in PreM (n = 88) and PeriM women (n = 44; women who became PostM during the follow-up). In untreated PostM women, FM increased, whereas LM, RASM, and TBBMC decreased (p < 0.0001). Age was a significant determinant of the changes in BC. After controlling for age, menopausal status was still a significant determinant only for changes in TBBMC. FM, LM, RASM, and TBBMC were higher in women with normal bone mineral density (BMD) compared with women with osteopenia or osteoporosis (p < 0.0001), but after adjusting for age, changes of BC were not significantly different according to the bone status. After controlling for age and menopausal status, levels of P1NP in the highest quartile were associated with a greater decrease of LM and RASM compared with lower levels. In conclusion, BC changes in French women over a 6-year follow-up showed a high interindividual variability. Aging may be the most important determinant of changes in body composition, rather than menopausal and bone status.Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 11/2011; 27(3):628-36. · 6.04 Impact Factor -
Article: Association of bone microarchitecture with parathyroid hormone concentration and calcium intake in men: the STRAMBO study.
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ABSTRACT: OBJECTVIE: In the elderly, vitamin D deficit, low calcium intake, and impaired bone microarchitecture are associated with higher risk of hip fracture. We assessed the association of bone microarchitecture with calcium intake and serum concentrations of 25-hydroxycholecalciferol (25OHD) and parathyroid hormone (PTH) in men. Cross-sectional analysis was performed in 1064 men aged 20-87 years not taking vitamin D or calcium supplements. Daily calcium intake was assessed using a food frequency questionnaire. Bone microarchitecture was assessed at distal radius and tibia by high-resolution peripheral quantitative computed tomography. We measured serum and urinary levels of biochemical bone turnover markers (BTMs). Statistical models were adjusted for age, weight, height, and glomerular filtration rate. In 500 men aged <65 years, lower 25OHD levels and low calcium intake were associated with lower trabecular volumetric bone mineral density (Dtrab) at the distal tibia, due to lower trabecular number (Tb.N). Low calcium intake was associated with lower cortical thickness (Ct.Th). Higher PTH level was associated with higher BTM levels. In 563 men aged ≥65 years, the highest PTH quartile was associated with lower Ct.Th (tibia), lower Dtrab (both sites), and lower Tb.N (radius) compared with the lowest quartile. Low calcium intake was associated with lower Tb.N and more heterogenous trabecular distribution. BTM positively correlated with the PTH concentration. In older men, elevated PTH concentration is associated with high bone turnover, poor trabecular microarchitecture (radius and tibia), and, at the distal tibia, lower Ct.Th. Low calcium intake is associated with lower Tb.N and more heterogenous trabecular distribution.European Journal of Endocrinology 07/2011; 165(1):151-9. · 3.42 Impact Factor -
Article: The FRAX tool in French women: How well does it describe the real incidence of fracture in the OFELY cohort?
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ABSTRACT: The FRAX tool estimates an individual's fracture probability over 10 years from clinical risk factors with or without bone mineral density (BMD) measurement. The aim of our study was to compare the predicted fracture probabilities and the observed incidence of fracture in French women during a 10-year follow-up. The probabilities of fracture at four major sites (hip, clinical spine, shoulder, or wrist) and at the hip were calculated with the FRAX tool in 867 women aged 40 years and over from the Os des Femmes de Lyon (OFELY) cohort.The incidence of fracture was observed over 10 years. Thus 82 women sustained 95 incident major osteoporotic (OP) fractures including 17 fractures at the hip. In women aged at least 65 years (n = 229), the 10-year predicted probabilities of fracture with BMD were 13% for major OP fractures and 5% for hip fractures, contrasting with 3.6% and 0.5% in women younger than 65 years (p < .0001). The predicted probabilities of both major OP and hip fractures were significantly higher in women with osteoporosis (n = 77, 18% and 10%) and osteopenia (n = 390, 6% and 2%) compared with women with normal BMD (n = 208, 3% and <1%; p < .0001. The predicted probabilities of fracture were two and five times higher in women who sustained an incident major OP fracture and a hip fracture compared with women who did not (p < .0001). Nevertheless, among women aged at least 65 years with low BMD values (T-score < or = -1; n = 199), the 10-year predicted probability of major OP fracture with BMD was 48% lower than the observed incidence of fractures (p < .01). A 10-year probability of major OP fracture higher than 12% identified more women with incident fractures than did BMD in the osteoporotic range (p < .05). In French women from the OFELY cohort, the observed incidence of fragility fractures over 10 years increased with age following a pattern similar to the predicted probabilities given by the FRAX tool. However, in women aged at least 65 years with low BMD, the observed incidence of fractures was substantially higher than the predicted probability.Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 04/2010; 25(10):2101-7. · 6.04 Impact Factor -
Article: Association between collagen cross-links and trabecular microarchitecture properties of human vertebral bone.
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ABSTRACT: It has been suggested that age-related deterioration in trabecular microarchitecture and changes in collagen cross-link concentrations may contribute to skeletal fragility. To further explore this hypothesis, we determined the relationships among trabecular bone volume fraction (BV/TV), microarchitecture, collagen cross-link content, and bone turnover in human vertebral trabecular bone. Trabecular bone specimens from L2 vertebrae were collected from 51 recently deceased donors (54-95 years of age; 20 men and 30 women). Trabecular bone volume and microarchitecture was assessed by microCT and bone formation, reflected by osteoid surface (OS/BS, %), was measured by 2D histomorphometry. Pyridinoline (PYD), deoxypyridinoline (DPD), pentosidine (PEN) and collagen content in the cancellous bone were analysed by high-performance liquid chromatography. Associations between variables were investigated by Pearson correlations and multiple regression models, which were constructed with BV/TV and collagen cross-links as explanatory variables and microarchitecture parameters as the dependent variables. RESULTS: Microarchitecture parameters were modestly to strongly correlated with BV/TV (r(2)=0.10-0.71). The amount of mature enzymatic PYD and DPD cross-links were not associated with the microarchitecture, either before or after adjustment for BV/TV. However, there was a positive correlation between PEN content and trabecular number (r=0.45, p=0.001) and connectivity density (r=0.40, p=0.004), and a negative correlation between PEN content and trabecular separation (r=-0.29, p=0.04). In the multiple regression models including BV/TV, age and PEN content was still significantly associated with several of the microarchitecture variables. In summary, this study suggests a link between trabecular microarchitecture and the collagen cross-link profile. As PEN reflects non-enzymatic glycation of collagen and generally increases with bone age, the association between PEN and trabecular architecture suggests that the preserved trabeculae may contain mainly old bone and have undergone little remodeling. Thus, vertebral fragility may not only be due to alterations in bone architecture but also to modification of collagen cross-link patterns thereby influencing bone's mechanical behavior.Bone 10/2009; 46(2):342-7. · 4.02 Impact Factor -
Article: Cortical and trabecular architecture are altered in postmenopausal women with fractures.
Osteoporosis International 09/2009; 20(8):1291-7. · 4.58 Impact Factor -
Article: Urinary levels of pentosidine and the risk of fracture in postmenopausal women: the OFELY study.
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ABSTRACT: The aim of the study was to investigate prospectively whether the levels of urinary pentosidine could predict fractures in postmenopausal women from the OFELY cohort. The results of the study suggest that urine pentosidine concentration is not an independent risk factor for fractures in postmenopausal women from a French cohort. Pentosidine has been described as an independent risk factor for hip and vertebral fracture in postmenopausal Japanese women. We investigated the prediction of urinary pentosidine on all fragility fracture risk in healthy untreated postmenopausal women from the OFELY cohort. Urinary pentosidine was assessed at baseline in 396 healthy untreated postmenopausal women aged 63.3 +/- 8.4 years from the OFELY cohort using high-performance liquid chromatography method. Incident clinical fractures were recorded during annual follow-up and confirmed by radiographs, and vertebral fractures were assessed on radiographs performed every 4 years. Multivariate Cox's regression analysis was used to calculate the risk of urinary pentosidine levels after adjustment for age, prevalent fractures, and total hip bone mineral density (BMD). During a mean follow-up of 10 years, 88 of the 396 postmenopausal women have undergone incident vertebral (n = 28) and peripheral (n = 60) fractures. Fracture risk was higher in postmenopausal women with pentosidine in the highest quartile (p = 0.02), but it did not remain significant after adjustment for age, BMD, and prevalent fracture. Urine pentosidine concentration is not an independent risk factor of osteoporotic fracture in healthy postmenopausal women from the OFELY cohort.Osteoporosis International 06/2009; 21(2):243-50. · 4.58 Impact Factor -
Article: Effects of yearly zoledronic acid 5 mg on bone turnover markers and relation of PINP with fracture reduction in postmenopausal women with osteoporosis.
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ABSTRACT: In patients with osteoporosis treated with antiresorptive agents, reduction in bone turnover explains much of the observed fracture risk reduction. Lower levels of bone turnover markers (BTMs) appear to be associated with a lower risk of fracture in bisphosphonate-treated patients. BTMs were measured in a subset of subjects in the HORIZON Pivotal Fracture Trial. Annual infusions of zoledronic acid 5 mg significantly reduced BTMs: median decrease of 50% for beta-C-terminal telopeptides of type 1 collagen (beta-CTX), 30% for bone alkaline phosphatase (ALP), and 56% for procollagen type 1 amino-terminal propeptide (PINP). The mean level of BTMs decreased in treated patients but remained within the premenopausal range before the next injection. The percentage of zoledronic acid-treated patients with values below the premenopausal reference range at all time points was 1.7%, 17.8%, and 19% for bone ALP, CTX, and PINP, respectively. The third injection of zoledronic acid resulted in 60% reduction of beta-CTX within 9-11 days, followed by a gradual increase, indicating the persistence of osteoclastic bone resorption. The association between changes in BTMs and fracture incidence was assessed in 1132 patients who had PINP measurements at baseline and 1 yr. There was no association between low PINP levels at 1 yr and increased fracture incidence. In summary, (1) annual injections of zoledronic acid reduced BTMs in the premenopausal range, with a significant response persisting after the third infusion; and (2) low levels of PINP were not associated with increased fracture risk.Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 05/2009; 24(9):1544-51. · 6.04 Impact Factor -
Article: An in vitro model to test the contribution of advanced glycation end products to bone biomechanical properties.
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ABSTRACT: We developed an in vitro model which provides the ability to test the effects of advanced glycation end products (AGEs), specifically pentosidine (PEN) and one of its inhibitors, the aminoguanidine (AMG), on cortical bone. This model allows modification of the extent of collagen cross-linking, while controlling other factors known to influence bone strength. In this in vitro model, young bovine cortical bone specimens were incubated in phosphate-buffered saline (PBS)+/-ribose (RIB, an inducer of AGEs formation)+/-AMG for 15 days at 37 degrees C. The mineral and organic matrix as well as biomechanical properties were examined. We found that (i) incubation+/-treatments did not induce collagen denaturation compared to specimens that were not incubated; (ii) neither treatment or incubation time effected the concentration of trivalent enzymatic cross-links pyridinoline and deoxypyridinoline. The non-enzymatic cross-link PEN was undetectable in specimens that were not incubated or that were incubated in PBS or AMG alone. However, PEN concentration increased significantly in specimens incubated with RIB, whereas ribose-induced PEN formation was markedly inhibited by AMG. (iii) Incubation+/-treatments did not change the mineral maturity, crystallinity or microhardness assessed by X-ray diffraction, X-ray microscopy analyses, FTIRM and micro-indentation tests. (iv) PEN concentration was not associated with biomechanical properties assessed by 3-point bending. In conclusion, this in vitro incubation model of young bovine cortical bone induced physiologic concentrations of PEN in the RIB+AMG group and is the first to show that AMG inhibits ribose-induced formation of PEN cross-links in bone while not affecting the organic and mineral phases. AGE concentration did not influence bending mechanical properties; however, the simple 3-point bending test we used was likely inadequate to demonstrate effects of AGEs on mechanical properties.Bone 02/2008; 42(1):139-49. · 4.02 Impact Factor -
Article: Homocysteine and fracture risk in postmenopausal women: the OFELY study.
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ABSTRACT: Homocysteine has recently been described as an independent risk factor for osteoporotic fractures in the elderly. We prospectively followed 671 postmenopausal women belonging to the OFELY study, mean age 62 years, during a mean follow-up of 10 years. After adjustment for age, there was no significant relation between the plasma level of homocysteine and the subsequent risk of fracture. Plasma homocysteine increases with age. Recent studies have described homocysteine as an independent risk factor for osteoporotic fractures in elderly. We investigated the role of plasma homocysteine in the subsequent risk of fractures in healthy ambulatory postmenopausal women. Homocysteine was measured at baseline in 671 postmenopausal women from the OFELY cohort (mean age 62.2 +/- 9 years). Incident clinical fractures were recorded during annual follow-up and vertebral fractures were evaluated with radiographs every four years. A cox proportional hazards model based on time to first fracture was used to calculate hazard ratios for quartiles of homocysteine values. Mean homocysteine was 10.6 +/- 3.4 mumol/l, increasing with age. After adjustment for age, homocysteine was significantly associated with physical activity, calcium intake, serum albumin and serum creatinine but not with bone turnover markers and bone mineral density. During a mean follow-up of 10 years, 183 fractures occurred among 134 women. After adjustment for age, the overall relative risk of fracture for each 1 SD increment of homocysteine was 1.03 (95%CI 0.87-1.31). Fracture risk was higher in women with homocysteine in the highest quartile without adjustment but no longer after adjustment for age. Homocysteine is not an independent risk factor of osteoporotic fractures in healthy postmenopausal women from the OFELY cohort with a broad age range.Osteoporosis International 11/2007; 18(10):1329-36. · 4.58 Impact Factor -
Article: Estrogen-dependent increase in bone turnover and bone loss in postmenopausal women with breast cancer treated with anastrozole. Prevention with bisphosphonates.
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ABSTRACT: Aromatase inhibitors have demonstrated their superiority to tamoxifen as adjuvant therapy for early breast cancer in postmenopausal women, but are associated with an increased risk of fractures. The aim of our study was to analyze bone loss, bone turnover and their determinants in postmenopausal women treated with anastrozole. We investigated bone loss and bone turnover markers (BTM) in a prospective open cohort study of 118 postmenopausal women treated with anastrozole for an early hormone-dependent breast cancer. Women without osteoporosis were not treated and compared with an age-matched control group of 114 healthy women. Osteoporotic patients (T-score<or=-2.5 S.D.) received weekly risedronate. Bone mineral density (BMD), and the BTM serum osteocalcin and serum C-terminal cross linking telopeptide of type I collagen (CTX) and 17beta-estradiol were measured at baseline and 1 year later. In the surveillance group, anastrozole induced after 1 year of treatment a marked bone loss at the spine (mean+/-S.E.M., [95% confidence interval]) -3.3+/-0.4% [-4.1 to -2.5]), and hip (2.8+/-0.4% [-3.6 to -2]) that was significantly greater than in controls (p<0.0001). Anastrozole induced an increase in bone remodelling: osteocalcin (+36.6%, p<0.0001) and CTX (+34%, p<0.0001). In univariate models, a recent menopause, a low body mass index, a complete chemotherapy (>or=6 courses) and a marked antiestrogenic response--defined by a level of 17beta-estradiol<or=2 pg/ml at 1 year or a decrease >50% between baseline and 1 year--were associated with greater bone loss. In multivariate model, women in the highest quartile of bone loss at the spine (>5.6% at 1 year) and hip (>4.9%) had a marked antiestrogenic response with OR of 10.4 [95% C.I. 1.9-57.2] (p=0.007) and 5.7 [1.3-25] (p=0.024) respectively. Among patients in the surveillance group, those with a normal T-score at both sites (n=46) had also a significant bone loss at spine -3.3+/-0.5% [-4.3 to -2.3], p<0.0001 and at the hip -2.9+/-0.6% [-4.1 to -1.7] p<0.0001. In osteoporotic women treated simultaneously with anastrozole and risedronate, bone loss was prevented at hip, and increased at the spine (+4.1+/-0.9% [2.3 to 5.9], p=0.008), and BTM decreased (-24%, -39% for CTX, p=0.003 and 0.001 vs. changes in the untreated group). Anastrozole increases bone turnover and induces an accelerated bone loss that is significantly related to the suppression of 17beta-estradiol production induced by aromatase inhibitor. The bisphosphonate risedronate prevents anastrozole induced bone loss.Bone 10/2007; 41(3):346-52. · 4.02 Impact Factor -
Article: Associations of vitamin D status with bone mineral density, bone turnover, bone loss and fracture risk in healthy postmenopausal women. The OFELY study.
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ABSTRACT: Vitamin D status is considered as an important determinant of bone health but supplementation trials with vitamin D(3) have yielded conflicting results. The aim of this study was to investigate the associations between serum 25-hydroxyvitamin D (25-OH D), bone turnover markers, bone mineral density (BMD), radius bone loss and incidence of fracture in postmenopausal women. 669 postmenopausal women (mean age: 62.2 years) belonging to a population-based cohort were followed prospectively for a median of 11.2 years. At baseline, 25-OH D levels, BMD, bone turnover markers and clinical risk factors of osteoporosis were assessed. BMD loss at the radius was estimated by annual measurements of BMD and all incident fractures which occurred in 134 women were confirmed by radiographs. 73% and 35% of women had serum 25-OH D levels below 75 and 50 nmol/l which correspond respectively to the median and lowest optimal values recently proposed for fracture prevention. 11% of women had levels below 30 nmol/l. Serum 25-OH D correlated modestly with intact PTH (r(2)=0.023, p<0.0001), but not with bone turnover markers or BMD at the hip and radius after adjustment for age. When levels of 25-OH D were considered as a continuous variable, there was no significant association between 25-OH D levels and radius BMD loss or fracture risk. After adjustment for age, there was no significant difference in incidence of fracture, BMD, radius BMD loss, bone turnover markers, grip strength and the percentage of fallers in the previous year between women with 25-OH D levels below or above 75, 50 or 30 nmol/l. In a population of home-dwelling healthy postmenopausal women with few of them with severe vitamin D deficiency, vitamin D status may not be an important determinant of bone health.Bone 03/2007; 40(3):716-22. · 4.02 Impact Factor -
Article: Vitamin D receptor gene polymorphisms are associated with the risk of fractures in postmenopausal women, independently of bone mineral density.
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ABSTRACT: Osteoporosis is a systemic disease with a strong genetic component. Vitamin D receptor (VDR) gene polymorphisms explain only a small part of the genetic influence on the level of bone mineral density (BMD), whereas their effect on fracture remains uncertain. The objective of this study was to investigate the relationships between VDR genotypes and fracture risk. A prospective population-based cohort was studied. A total of 589 postmenopausal women (mean age, 62 yr) were followed prospectively during a median (interquartile) of 11 (1.1) yr. The study measured incidents of vertebral and nonvertebral fractures. VDR allele B was significantly and dose dependently overrepresented in women who fractured, including 34 and 86 women with first incident vertebral and nonvertebral fragility fractures, respectively. This corresponded to an odds ratio of 1.5 (95% confidence interval, 0.95-2.40) for heterozygous carriers (bB, n = 286) and 2.10 (95% confidence interval, 1.16-3.79) for homozygous carriers (BB, n = 90) of the B allele, compared with women with the bb genotype (n = 213). VDR genotype groups did not differ for demographics, physical activity, grip strength, personal and maternal history of fracture, and calcium intake. The association was independent of BMD of the spine, hip, and radius, and of the BMD loss at the radius. The relationship between VDR polymorphisms and fracture risk was not altered after adjustment for baseline circulating levels of bone turnover markers, estradiol, dehydroepiandrosterone sulfate, SHBG, IGF-I, intact PTH, and 25 hydroxyvitamin D. VDR genotypes are associated with the risk of fracture in postmenopausal women independently of BMD, rate of postmenopausal forearm BMD loss, bone turnover, and endogenous hormones. The mechanisms by which VDR genotypes influence bone strength remain to be determined.Journal of Clinical Endocrinology & Metabolism 09/2005; 90(8):4829-35. · 6.50 Impact Factor -
Article: Role of vitamin D and parathyroid hormone in the regulation of bone turnover and bone mass in men: the MINOS study.
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ABSTRACT: 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.Calcified Tissue International 01/2004; 73(6):520-30. · 2.38 Impact Factor -
Article: Similar prevalence of vertebral fractures despite different approaches to define reference data.
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ABSTRACT: 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.Bone 05/2003; 32(4):441-8. · 4.02 Impact Factor -
Article: Independent predictors of all osteoporosis-related fractures in healthy postmenopausal women: the OFELY study.
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ABSTRACT: Several epidemiological studies have identified clinical factors that predict the risk of hip fractures in elderly women independently of the level of bone mineral density (BMD), such as low body weight, history of fractures, and clinical risk factors for falls. Their relevance in predicting all fragility fractures in all postmenopausal women, including younger ones, is unknown. The objective of this study was to identify independent predictors of all osteoporosis-related fractures in healthy postmenopausal women. We prospectively followed for 5.3 +/- 1.1 years a cohort of 672 healthy postmenopausal women (mean age 59.1 +/- 9.8 years). Information on social and professional conditions, demographic data, current and past medical history, fracture history, medication use, alcohol consumption, caffeine consumption, daily calcium intake, cigarette smoking, family history of fracture, and past and recent physical activity was obtained. Anthropometric and total hip bone mineral density measurements were made. Incident falls and fractures were ascertained every year. We observed 81 osteoporotic fractures (annual incidence, 21 per 1000 women/year). The final model consisted of seven independent predictors of incident osteoporotic fractures: age > or = 65 years, odds ratio estimate (OR), 1.90 [95% confidence interval (CI) 1.04-3.46], past falls, OR, 1.76 (CI 1.00-3.09), total hip bone mineral density (BMD) < or = 0.736 g/cm(2), OR, 3.15 (CI 1.75-5.66), left grip strength < or = 0.60 bar, OR, 2.05 (CI 1.15-3.64), maternal history of fracture, OR, 1.77 (CI 1.01-3.09), low physical activity, OR, 2.08 (CI 1.17-3.69), and personal history of fragility fracture, OR, 3.33 (CI 1.75-5.66). In contrast, body weight, weight loss, height loss, smoking, neuromuscular coordination assessed by three tests, and hormone replacement therapy were not independent predictors of all fragility fractures after adjustment for all variables. We found that some--but not all--previously reported clinical risk factors for skeletal fragility predicted all fragility fractures independently of BMD in healthy postmenopausal women, although they differed somewhat from those predicting specifically hip fractures in elderly women. These risk factors appear to reflect quality of bone structure (previous fragility fracture), lifestyle habits (physical activity), muscle function and health status (grip strength), heredity (maternal history of fracture), falls, and aging. Measurements of these variables should be included in the clinical assessment of the risk of osteoporotic fractures in postmenopausal women.Bone 01/2003; 32(1):78-85. · 4.02 Impact Factor -
Article: Cross-sectional evaluation of bone metabolism in men.
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ABSTRACT: 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.Journal of Bone and Mineral Research 10/2001; 16(9):1642-50. · 6.37 Impact Factor -
Article: Semiquantitative evaluation of prevalent vertebral deformities in men and their relationship with osteoporosis: the MINOS study.
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ABSTRACT: 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.Osteoporosis International 02/2001; 12(4):302-10. · 4.58 Impact Factor -
Article: Bioavailable estradiol may be an important determinant of osteoporosis in men: the MINOS study.
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ABSTRACT: 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.Journal of Clinical Endocrinology & Metabolism 02/2001; 86(1):192-9. · 6.50 Impact Factor -
Article: Comparison of morphometric assessment of prevalent vertebral deformities in women using different reference data.
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ABSTRACT: 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.Bone 12/2000; 27(6):841-6. · 4.02 Impact Factor
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Institutions
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2007–2008
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Université de Lyon
Lyon, Rhone-Alpes, France
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2005
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Institut national de la santé et de la recherche médicale
Paris, Ile-de-France, France
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2003
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Université Claude Bernard Lyon 1
Villeurbanne, Rhone-Alpes, France
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