-
Dirk Vanderschueren,
Stephen R Pye,
Terence W O'Neill,
David M Lee,
Ivo Jans,
Jaak Billen,
Evelien Gielen,
Michaël Laurent,
Frank Claessens,
Judith E Adams, [......],
Gianni Forti,
Aleksander Giwercman,
Thang S Han,
Ilpo T Huhtaniemi,
Krzysztof Kula,
Michael E J Lean,
Neil Pendleton,
Margus Punab,
Frederick C W Wu,
Steven Boonen
[show abstract]
[hide abstract]
ABSTRACT: Context:There is little information on the potential impact of serum 1,25-dihydroxyvitamin D [1,25(OH)(2)D] on bone health including turnover.Objective:The objective of the study was to determine the influence of 1,25(OH)(2)D and 25-hydroxyvitamin D [25(OH)D] on bone health in middle-aged and older European men.Design, Setting, and Participants:Men aged 40-79 years were recruited from population registers in 8 European centers. Subjects completed questionnaires that included questions concerning lifestyle and were invited to attend for quantitative ultrasound (QUS) of the heel, assessment of height and weight, and a fasting blood sample from which 1,25(OH)(2)D, 25(OH)D, and PTH were measured. 1,25(OH)(2)D was measured using liquid chromatography tandem mass spectrometry. Bone markers serum N-terminal propeptide of type 1 procollagen (P1NP) and crosslinks (β-cTX) were also measured. Dual-energy x-ray absorptiometry (DXA) of the hip and lumbar spine was performed in 2 centers.Main Outcome Measure(s):QUS of the heel, bone markers P1NP and β-cTX, and DXA of the hip and lumbar spine were measured.Results:A total of 2783 men, mean age 60.0 years (SD 11.0) were included in the analysis. After adjustment for age and center, 1,25(OH)(2)D was positively associated with 25(OH)D but not with PTH. 25(OH)D was negatively associated with PTH. After adjustment for age, center, height, weight, lifestyle factors, and season, 1,25(OH)(2)D was associated negatively with QUS and DXA parameters and associated positively with β-cTX. 1,25(OH)(2)D was not correlated with P1NP. 25(OH)D was positively associated with the QUS and DXA parameters but not related to either bone turnover marker. Subjects with both high 1,25(OH)(2)D (upper tertile) and low 25(OH)D (lower tertile) had the lowest QUS and DXA parameters and the highest β-cTX levels.Conclusions:Serum 1,25(OH)(2)D is associated with higher bone turnover and poorer bone health despite being positively related to 25(OH)D. A combination of high 1,25(OH)(2)D and low 25(OH)D is associated with the poorest bone health.
The Journal of clinical endocrinology and metabolism 02/2013; · 6.50 Impact Factor
-
Stephen R. Pye,
Vinodh Devakumar,
Steven Boonen,
Herman Borghs,
Dirk Vanderschueren,
Judith E. Adams, Kate A. Ward,
Gyorgy Bartfai,
Felipe F. Casanueva,
Joseph D. Finn, [......],
Thang S. Han,
Ilpo T. Huhtaniemi,
Krzysztof Kula,
Michael E. J. Lean,
Neil Pendleton,
Margus Punab,
Alan J. Silman,
Frederick C. W. Wu,
Terence W. O’Neill,
EMAS Study Group
[show abstract]
[hide abstract]
ABSTRACT: We examined the distribution of quantitative heel ultrasound (QUS) parameters in population samples of European men and looked
at the influence of lifestyle factors on the occurrence of these parameters. Men aged between 40 and 79years were recruited
from eight European centers and invited to attend for an interviewer-assisted questionnaire, assessment of physical performance,
and quantitative ultrasound (QUS) of the calcaneus (Hologic; Sahara). The relationships between QUS parameters and lifestyle
variables were assessed using linear regression with adjustments for age, center, and weight. Three thousand two hundred fifty-eight
men, mean age 60.0years, were included in the analysis. A higher PASE score (upper vs. lower tertile) was associated with
a higher BUA (β coefficient=2.44dB/Mhz), SOS (β=6.83m/s), and QUI (β=3.87). Compared to those who were inactive, those
who walked or cycled more than an hour per day had a higher BUA (β=3.71dB/Mhz), SOS (β=6.97m/s), and QUI (β=4.50).
A longer time to walk 50ft was linked with a lower BUA (β=−0.62dB/Mhz), SOS (β=−1.06m/s), and QUI (β=−0.69). Smoking
was associated with a reduction in BUA, SOS, and QUI. There was a U-shaped association with frequency of alcohol consumption.
Modification of lifestyle, including increasing physical activity and stopping smoking, may help optimize bone strength and
reduce the risk of fracture in middle-aged and elderly European men.
KeywordsEpidemiology-Ultrasound-Bone mineral density-Risk factors-Exercise
Calcified Tissue International 04/2012; 86(3):211-219. · 2.38 Impact Factor
-
Delnaz Roshandel,
Kate L Holliday,
Stephen R Pye, Kate A Ward,
Steven Boonen,
Dirk Vanderschueren,
Herman Borghs,
Ilpo T Huhtaniemi,
Judith E Adams,
Gyorgy Bartfai, [......],
Aleksander Giwercman,
Thang S Han,
Krzysztof Kula,
Michael E Lean,
Neil Pendleton,
Margus Punab,
Alan J Silman,
Frederick C Wu,
Wendy Thomson,
Terence W ONeill
[show abstract]
[hide abstract]
ABSTRACT: We sought to determine the influence of single-nucleotide polymorphisms (SNPs) in RANKL, RANK, and OPG on volumetric bone mineral density (vBMD) and bone geometry at the radius in men. Pairwise tag SNPs (r (2) ≥ 0.8) for RANKL (n = 8), RANK (n = 44), and OPG (n = 22) and five SNPs near RANKL and OPG strongly associated with areal BMD in genomewide association studies were previously genotyped in men aged 40-79 years in the European Male Ageing Study (EMAS). Here, these SNPs were analyzed in a subsample of men (n = 589) who had peripheral quantitative computed tomography (pQCT) performed at the distal (4%) and mid-shaft (50%) radius. Estimated parameters were total and trabecular vBMD (mg/mm(3)) and cross-sectional area (mm(2)) at the 4% site and cortical vBMD (mg/mm(3)); total, cortical, and medullary area (mm(2)); cortical thickness (mm); and stress strain index (SSI) (mm(3)) at the 50% site. We identified 12 OPG SNPs associated with vBMD and/or geometric parameters, including rs10505348 associated with total vBMD (β [95% CI] = 9.35 [2.12-16.58], P = 0.011), cortical vBMD (β [95% CI] = 5.62 [2.10-9.14], P = 0.002), cortical thickness (β [95% CI] = 0.08 [0.03-0.13], P = 0.002), and medullary area (β [95% CI] = -2.90 [-4.94 to -0.86], P = 0.005) and rs2073618 associated with cortical vBMD (β [95% CI] = -4.30 [-7.78 to -0.82], P = 0.015) and cortical thickness (β [95% CI] = -0.08 [-0.13 to -0.03], P = 0.001). Three RANK SNPs were associated with vBMD, including rs12956925 associated with trabecular vBMD (β [95% CI] = -7.58 [-14.01 to -1.15], P = 0.021). There were five RANK SNPs associated with geometric parameters, including rs8083511 associated with distal radius cross-sectional area (β [95% CI] = 8.90 [0.92-16.88], P = 0.029). No significant association was observed between RANKL SNPs and pQCT parameters. Our findings suggest that genetic variation in OPG and RANK influences radius vBMD and geometry in men.
Calcified Tissue International 10/2011; 89(6):446-55. · 2.38 Impact Factor
-
Steven Boonen,
Stephen R Pye,
Terence W O'Neill,
Pawel Szulc,
Evelien Gielen,
Herman Borghs,
Sabine Verschueren,
Frank Claessens,
Judith E Adams, Kate A Ward, [......],
Ilpo T Huhtaniemi,
Krzysztof Kula,
Fernand Labrie,
Michael E J Lean,
Neil Pendleton,
Margus Punab,
Alan J Silman,
Abdelouahid Tajar,
Frederick C W Wu,
Dirk Vanderschueren
[show abstract]
[hide abstract]
ABSTRACT: To assess the influence of sex hormones on markers of bone turnover and to explore the association between these markers and bone health in middle-aged and elderly European men.
A cross-sectional population-based survey.
Men aged 40-79 years were recruited from population registers in eight European centres. Subjects completed a postal questionnaire which included questions concerning lifestyle and were invited to undergo quantitative ultrasound (QUS) of the calcaneus and to provide a fasting blood sample from which the bone markers serum N-terminal propeptide of type 1 procollagen (P1NP) and crosslinks (β C-terminal cross-linked telopeptide (β-cTX)), total testosterone, total oestradiol (E(2)), sex hormone-binding globulin (SHBG) and insulin-like growth factor 1 (IGF1) were measured. Dual-energy X-ray absorptiometry (DXA) of the hip and lumbar spine was performed in two centres.
A total of 3120, mean age 59.9 years (s.d.=11.0) were included. After adjustment for centre, age, height, weight, lifestyle factors, season and other hormones, total and free E(2) were negatively associated with β-cTX but not P1NP while SHBG, IGF1 and parathyroid hormone (PTH) were positively associated with both β-cTX and P1NP. Total or free testosterone was not independently associated with either bone marker. After the same adjustments, higher levels of both bone markers were significantly associated with lower QUS parameters and lower DXA-assessed bone density at the total hip and lumbar spine.
E(2), SHBG, IGF1 and PTH contribute significantly to the regulation/rate of bone turnover in middle-aged and older European men. Higher rates of bone remodelling are negatively associated with male bone health.
European Journal of Endocrinology 09/2011; 165(6):977-86. · 3.42 Impact Factor
-
Stephen R Pye,
Bader Almusalam,
Steven Boonen,
Dirk Vanderschueren,
Herman Borghs,
Evelien Gielen,
Judith E Adams, Kate A Ward,
Gyorgy Bartfai,
Felipe F Casanueva, [......],
Thang S Han,
Ilpo T Huhtaniemi,
Krzysztof Kula,
Fernand Labrie,
Michael E J Lean,
Neil Pendleton,
Margus Punab,
Alan J Silman,
Frederick C W Wu,
Terence W O'Neill
[show abstract]
[hide abstract]
ABSTRACT: The aim of this study was to determine the influence of insulin-like growth factor binding protein (IGFBP)-1, IGFBP-3, and IGF-I on calcaneal ultrasound parameters in middle-aged and elderly European men. Men aged 40-79 years were recruited from population registers for participation in the European Male Ageing Study (EMAS). Subjects were invited by letter to complete a postal questionnaire and to attend for an interviewer-assisted questionnaire, quantitative ultrasound (QUS) of the calcaneus, and a fasting blood sample from which serum levels of IGFBP-1, IGFBP-3, IGF-I, estradiol (E(2)), and SHBG were assayed. The questionnaires included the Physical Activity Scale for the Elderly (PASE) and questions about smoking and alcohol consumption. Estimated bone mineral density (eBMD) was derived as a function of the QUS parameters speed of sound and broadband ultrasound attenuation. Height and weight were measured in all subjects. 3057 men, mean age 59.7 years (standard deviation 11.0) were included in the analysis. After adjusting for age, center, and BMI, higher levels of IGFBP-1 were associated with lower eBMD. Higher levels of both IGFBP-3 and IGF-I were associated with higher eBMD. After further adjustment for PASE score, current smoking, alcohol consumption, free E(2), and SHBG, IGFBP-3 and IGF-I, though not IGFBP-1, remained significantly associated with eBMD. IGFBP-1 was associated with bone health, though the effect could be explained by other factors. IGFBP-3 and IGF-I were independent determinants of bone health in middle-aged and elderly European men.
Calcified Tissue International 06/2011; 88(6):503-10. · 2.38 Impact Factor
-
Delnaz Roshandel,
Wendy Thomson,
Stephen R Pye,
Steven Boonen,
Herman Borghs,
Dirk Vanderschueren,
Ilpo T Huhtaniemi,
Judith E Adams, Kate A Ward,
Gyorgy Bartfai, [......],
Gianni Forti,
Aleksander Giwercman,
Thang S Han,
Krzysztof Kula,
Michael E Lean,
Neil Pendleton,
Margus Punab,
Frederick C Wu,
Kate L Holliday,
Terence W O'Neill
[show abstract]
[hide abstract]
ABSTRACT: In this study, we aimed to investigate the association between single nucleotide polymorphisms (SNPs) within two genes involved in the NF-κB cascade (GPR177 and MAP3K14) and bone mineral density (BMD) assessed at different skeletal sites, radial geometric parameters and bone turnover.
Ten GPR177 SNPs previously associated with BMD with genome-wide significance and twelve tag SNPs (r(2)≥0.8) within MAP3K14 (±10 kb) were genotyped in 2359 men aged 40-79 years recruited from 8 centres for participation in the European Male Aging Study (EMAS). Measurement of bone turnover markers (PINP and CTX-I) in the serum and quantitative ultrasound (QUS) at the calcaneus were performed in all centres. Dual energy X-ray absorptiometry (DXA), at the lumbar spine and hip, and peripheral quantitative computed tomography (pQCT), at the distal and midshaft radius, were performed in a subsample (2 centres). Linear regression was used to test for association between the SNPs and bone measures under an additive genetic model adjusting for study centre.
We validated the associations between SNPs in GPR177 and BMD(a) previously reported and also observed evidence of pleiotrophic effects on density and geometry. Rs2772300 in GPR177 was associated with increased total hip and LS BMD(a), increased total and cortical vBMD at the radius and increased cortical area, thickness and stress strain index. We also found evidence of association with BMD(a), vBMD, geometric parameters and CTX-I for SNPs in MAP3K14. None of the GPR177 and MAP3K14 SNPs were associated with calcaneal estimated BMD measured by QUS.
Our findings suggest that SNPs in GPR177 and MAP3K14 involved in the NF-κB signalling pathway influence bone mineral density, geometry and turnover in a population-based cohort of middle aged and elderly men. This adds to the understanding of the role of genetic variation in this pathway in determining bone health.
PLoS ONE 01/2011; 6(11):e28031. · 4.09 Impact Factor
-
Kate L Holliday,
Stephen R Pye,
Wendy Thomson,
Steven Boonen,
Herman Borghs,
Dirk Vanderschueren,
Evelien Gielen,
Ilpo T Huhtaniemi,
Judith E Adams, Kate A Ward, [......],
Gianni Forti,
Aleksander Giwercman,
Thang S Han,
Krzysztof Kula,
Fernand Labrie,
Michael E J Lean,
Neil Pendleton,
Margus Punab,
Frederick C W Wu,
Terence W O'Neill
[show abstract]
[hide abstract]
ABSTRACT: Genome-wide association studies (GWAS) have identified 6q25, which incorporates the oestrogen receptor α gene (ESR1), as a quantitative trait locus for areal bone mineral density (BMD(a)) of the hip and lumbar spine. The aim of this study was to determine the influence of this locus on other bone health outcomes; calcaneal ultrasound (QUS) parameters, radial peripheral quantitative computed tomography (pQCT) parameters and markers of bone turnover in a population sample of European men.
Eight single nucleotide polymorphisms (SNP) in the 6q25 locus were genotyped in men aged 40-79 years from 7 European countries, participating in the European Male Ageing Study (EMAS). The associations between SNPs and measured bone parameters were tested under an additive genetic model adjusting for centre using linear regression.
2468 men, mean (SD) aged 59.9 (11.1) years had QUS measurements performed and bone turnover marker levels measured. A subset of 628 men had DXA and pQCT measurements. Multiple independent SNPs showed significant associations with BMD using all three measurement techniques. Most notably, rs1999805 was associated with a 0.10 SD (95%CI 0.05, 0.16; p = 0.0001) lower estimated BMD at the calcaneus, a 0.14 SD (95%CI 0.05, 0.24; p = 0.004) lower total hip BMD(a), a 0.12 SD (95%CI 0.02, 0.23; p = 0.026) lower lumbar spine BMD(a) and a 0.18 SD (95%CI 0.06, 0.29; p = 0.003) lower trabecular BMD at the distal radius for each copy of the minor allele. There was no association with serum levels of bone turnover markers and a single SNP which was associated with cortical density was also associated with cortical BMC and thickness.
Our data replicate previous associations found between SNPs in the 6q25 locus and BMD(a) at the hip and extend these data to include associations with calcaneal ultrasound parameters and radial volumetric BMD.
PLoS ONE 01/2011; 6(7):e22037. · 4.09 Impact Factor
-
Delnaz Roshandel,
Wendy Thomson,
Stephen R Pye,
Steven Boonen,
Herman Borghs,
Dirk Vanderschueren,
Ilpo T Huhtaniemi,
Judith E Adams, Kate A Ward,
Gyorgy Bartfai, [......],
Aleksander Giwercman,
Thang S Han,
Krzysztof Kula,
Michael E Lean,
Neil Pendleton,
Margus Punab,
Alan J Silman,
Frederick C Wu,
Kate L Holliday,
Terence W O'Neill
[show abstract]
[hide abstract]
ABSTRACT: A number of single nucleotide polymorphisms (SNPs) have been associated with broadband ultrasound attenuation (BUA) and speed of sound (SOS) as measured by quantitative ultrasound (QUS) at the calcaneus in the Framingham 100K genome-wide association study (GWAS) but have not been validated in independent studies. The aim of this analysis was to determine if these SNPs are associated with QUS measurements assessed in a large independent population of European middle-aged and elderly men. The association between these SNPs and bone mineral density (BMD) measured using dual-energy X-ray absorptiometry (DXA) was also tested.
Men aged 40-79 years (N = 2960) were recruited from population registers in seven European centres for participation in an observational study of male ageing, the European Male Ageing Study (EMAS). QUS at the calcaneus was measured in all subjects and blood was taken for genetic analysis. Lumbar spine (LS), femoral neck (FN) and total hip (TH) BMD were measured by DXA in a subsample of 620 men in two centres. SNPs associated with BUA or SOS in the Framingham study with p < 10-4 were selected and genotyped using SEQUENOM technology. Linear regression was used to test for the association between SNPs and standardised (SD) bone outcomes under an additive genetic model adjusting for centre. The same direction of effect and p < 0.05 indicated replication.
Thirty-four of 38 selected SNPs were successfully genotyped in 2377 men. Suggestive evidence of replication was observed for a single SNP, rs3754032, which was associated with a higher SOS (β(SD) = 0.07, p = 0.032) but not BUA (β(SD) = 0.02, p = 0.505) and is located in the 3'UTR of WDR77 (WD repeat domain 77) also known as androgen receptor cofactor p44. A single SNP, rs238358, was associated with BMD at the LS (β(SD) = -0.22, p = 0.014), FN (β(SD) = -0.31,p = 0.001) and TH (β(SD) = -0.36, p = 0.002) in a locus previously associated with LS BMD in large-scale GWAS, incorporating AKAP11 and RANKL.
We found suggestive evidence of association between a single SNP located in the 3'UTR of WDR77 with calcaneal ultrasound parameters. The majority of SNPs, associated with QUS parameters in the Framingham Study, were not replicated in an independent population sample of European men.
BMC Medical Genetics 01/2011; 12:19. · 2.33 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To determine the influence of disease-related variables on hand cortical bone loss in women with early inflammatory arthritis (IA), and whether hand cortical bone mass predicts subsequent joint damage.
Adults aged ≥ 16 years with recent onset of IA were recruited to the Norfolk Arthritis Register between 1990 and 1998, and followed prospectively. At baseline, patients had their joints examined for swelling and tenderness and had CRP and disease activity 28-joint assessment score (DAS-28) measured. Radiographs of the hands were performed in a subgroup of patients at Year 1 and at follow-up, which were assessed using digital X-ray radiogrammetry (DXR). They were also evaluated for the presence of erosions using Larsen's method. Linear mixed models were used to investigate whether disease-related factors predicted change in DXR-areal bone mineral density (BMD(a)). We also evaluated whether DXR-BMD(a) predicted the subsequent occurrence of erosive disease.
Two hundred and four women, mean (s.d.) age 55.1 (14.0) years, were included. Median follow-up between radiographs was 4 years. The mean within-subject change in BMD(a) was 0.024 g/cm(2) equivalent to 1% decline per year. After adjustment for age, height and weight, compared with those within the lower tertile for CRP, those in the upper tertile had greater subsequent loss of bone. This was true also for DAS-28 and Larsen score. Among those without erosions on the initial radiograph (121), DXR-BMD(a) at baseline did not predict the new occurrence of erosions.
Increased disease activity and severity are associated with accelerated bone loss. However, lower BMD(a) did not predict the new occurrence of erosive disease.
Rheumatology (Oxford, England) 10/2010; 49(10):1943-8. · 4.24 Impact Factor
-
Stephen R Pye,
Vinodh Devakumar,
Steven Boonen,
Herman Borghs,
Dirk Vanderschueren,
Judith E Adams, Kate A Ward,
Gyorgy Bartfai,
Felipe F Casanueva,
Joseph D Finn, [......],
Aleksander Giwercman,
Thang S Han,
Ilpo T Huhtaniemi,
Krzysztof Kula,
Michael E J Lean,
Neil Pendleton,
Margus Punab,
Alan J Silman,
Frederick C W Wu,
Terence W O'Neill
[show abstract]
[hide abstract]
ABSTRACT: We examined the distribution of quantitative heel ultrasound (QUS) parameters in population samples of European men and looked at the influence of lifestyle factors on the occurrence of these parameters. Men aged between 40 and 79 years were recruited from eight European centers and invited to attend for an interviewer-assisted questionnaire, assessment of physical performance, and quantitative ultrasound (QUS) of the calcaneus (Hologic; Sahara). The relationships between QUS parameters and lifestyle variables were assessed using linear regression with adjustments for age, center, and weight. Three thousand two hundred fifty-eight men, mean age 60.0 years, were included in the analysis. A higher PASE score (upper vs. lower tertile) was associated with a higher BUA (beta coefficient = 2.44 dB/ Mhz), SOS (beta = 6.83 m/s), and QUI (beta = 3.87). Compared to those who were inactive, those who walked or cycled more than an hour per day had a higher BUA (beta = 3.71 dB/Mhz), SOS (beta = 6.97 m/s), and QUI (beta = 4.50). A longer time to walk 50 ft was linked with a lower BUA (beta = -0.62 dB/ Mhz), SOS (beta = -1.06 m/s), and QUI (beta = -0.69). Smoking was associated with a reduction in BUA, SOS, and QUI. There was a U-shaped association with frequency of alcohol consumption. Modification of lifestyle, including increasing physical activity and stopping smoking, may help optimize bone strength and reduce the risk of fracture in middle-aged and elderly European men.
Calcified Tissue International 03/2010; 86(3):211-9. · 2.38 Impact Factor
-
Delnaz Roshandel,
Kate L Holliday,
Stephen R Pye,
Steven Boonen,
Herman Borghs,
Dirk Vanderschueren,
Ilpo T Huhtaniemi,
Judith E Adams, Kate A Ward,
Gyorgy Bartfai, [......],
Aleksander Giwercman,
Thang S Han,
Krzysztof Kula,
Michael E Lean,
Neil Pendleton,
Margus Punab,
Alan J Silman,
Frederick C Wu,
Wendy Thomson,
Terence W O'Neill
[show abstract]
[hide abstract]
ABSTRACT: The aim of this study was to determine if single-nucleotide polymorphisms (SNPs) in RANKL, RANK, and OPG influence bone turnover and bone mineral density (BMD) in men. Pairwise tag SNPs (r(2) > or = 0.8) were selected for RANKL, RANK, and OPG and their 10-kb flanking regions. Selected tag SNPs plus five SNPs near RANKL and OPG, associated with BMD in published genome-wide association studies (GWAS), were genotyped in 2653 men aged 40 to 79 years of age recruited for participation in a population-based study of male aging, the European Male Ageing Study (EMAS). N-terminal propeptide of type I procollagen (PINP) and C-terminal cross-linked telopeptide of type I collagen (CTX-I) serum levels were measured in all men. BMD at the calcaneus was estimated by quantitative ultrasound (QUS) in all men. Lumbar spine and total-hip areal BMD (BMD(a)) was measured by dual-energy X-ray absorptiometry (DXA) in a subsample of 620 men. Multiple OPG, RANK, and RANKL SNPs were associated with bone turnover markers. We also identified a number of SNPs associated with BMD, including rs2073618 in OPG and rs9594759 near RANKL. The minor allele of rs2073618 (C) was associated with higher levels of both PINP (beta = 1.83, p = .004) and CTX-I (beta = 17.59, p = 4.74 x 10(-4)), and lower lumbar spine BMD(a) (beta = -0.02, p = .026). The minor allele of rs9594759 (C) was associated with lower PINP (beta = -1.84, p = .003) and CTX-I (beta = -27.02, p = 6.06 x 10(-8)) and higher ultrasound BMD at the calcaneus (beta = 0.01, p = .037). Our findings suggest that genetic variation in the RANKL/RANK/OPG signaling pathway influences bone turnover and BMD in European men.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 03/2010; 25(8):1830-8. · 6.04 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Teenage pregnancy occurs during a time when the maternal skeleton may still be accruing mineral. We hypothesized that teenage mothers would have reduced amounts of bone mineral and altered bone geometry compared with controls. This cross-sectional, observational compared teenage mothers (n=18) to age- and ethnicity-matched controls (n=52). The main outcomes were peripheral quantitative computed tomography and dual-energy X-ray absorptiometry to measure bone geometry, bone mineral density (BMD) at radius, lumbar spine and hip, and whole body bone mineral content (WBBMC). In teenage mothers, cortical BMD was reduced at the radial diaphysis (mean difference: -1.3%; p=0.03). Size-adjusted WBBMC was reduced (mean difference: -4.0%; p=0.004) and was lower for a given amount of lean mass (mean difference: -5.8%; p=0.02). No other significant differences between groups were found. The recruitment and retention of participants to this study were extremely difficult and disappointing. Teenage mothers had lower BMD at cortical sites compared with age-matched controls. These data suggest that pregnancy might have a detrimental effect on teenage mothers' future skeletal health. The results of this study require confirmation and provide pilot data for further investigations.
Journal of Clinical Densitometry 03/2009; 12(2):219-23. · 1.29 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: There has been a resurgence of vitamin D deficiency among infants, toddlers, and adolescents in the United Kingdom. Myopathy is an important clinical symptom of vitamin D deficiency, yet it has not been widely studied.
Our objective was to investigate the relationship of baseline serum 25 hydroxyvitamin D [25(OH)D] concentration and PTH with muscle power and force.
This was a cross-sectional study.
The study was community based in a secondary school.
A total of 99 post-menarchal 12- to 14-yr-old females was included in the study.
Jumping mechanography to measure muscle power, velocity, jump height, and Esslinger Fitness Index from a two-legged counter movement jump and force from multiple one-legged hops was performed. Body height, weight, and serum concentrations of 25(OH)D, PTH, and calcium were measured.
Median serum 25(OH)D concentration was 21.3 nmol/liter (range 2.5-88.5) and PTH 3.7 pmol/liter (range 0.47-26.2). After correction for weight using a quadratic function, there was a positive relationship between 25(OH)D and jump velocity (P = 0.002), jump height (P = 0.005), power (P = 0.003), Esslinger Fitness Index (P = 0.003), and force (P = 0.05). There was a negative effect of PTH upon jump velocity (P = 0.04).
From these data we conclude that vitamin D was significantly associated with muscle power and force in adolescent girls.
Journal of Clinical Endocrinology & Metabolism 12/2008; 94(2):559-63. · 6.50 Impact Factor
-
Ilpo T Huhtaniemi,
Stephen R Pye,
Kate L Limer,
Wendy Thomson,
Terence W O'Neill,
Hazel Platt,
Debbie Payne,
Sally L John,
Min Jiang,
Steven Boonen, [......],
Joseph D Finn,
Gianni Forti,
Aleksander Giwercman,
Thang S Han,
Krzysztof Kula,
Michael E J Lean,
Neil Pendleton,
Margus Punab,
Alan J Silman,
Frederick C W Wu
[show abstract]
[hide abstract]
ABSTRACT: The individual variability in the waning androgenic-anabolic functions of aging men may be influenced by the CAG repeat polymorphism in exon 1 of the androgen receptor (AR), affecting androgen sensitivity. However, findings on its phenotypic effects are inconclusive. Objective: The aim was to investigate the relationships between health status, various reproductive hormones, and the AR CAG repeat length.
We conducted a multinational prospective cohort observational study with cross-sectional baseline data.
This was a population survey of community-dwelling men. Participants: Men (40-79 yr old; n = 3369) were randomly recruited from centers in eight European countries; CAG repeat analysis was performed in 2878 men.
We measured the correlations of the CAG repeat length with selected endocrine, metabolic, and phenotypic parameters related to aging and sex hormone action.
Only minor differences were found in CAG repeat lengths between the eight European countries. They showed significant positive association with total, free, and bioavailable levels of testosterone (T) and estradiol. FSH but not LH correlated inversely with CAG repeat length. Significant associations were found with bone ultrasound parameters at the calcaneus. Negative correlation was found with triglycerides, but not with other blood lipids or with anthropometry, blood pressure, hemoglobin, insulin sensitivity, or sexual and prostatic functions.
The AR CAG repeat length correlates significantly with serum T and estradiol of aging men. Weaker transcriptional activity of the AR with longer CAG-encoded polyglutamine repeats appears to be totally or nearly totally compensated for by higher T levels. The residual phenotypic correlations may reflect differences in estrogen levels/actions after aromatization of the higher T levels.
Journal of Clinical Endocrinology & Metabolism 11/2008; 94(1):277-84. · 6.50 Impact Factor
-
Kate L Limer,
Stephen R Pye,
Wendy Thomson,
Steven Boonen,
Herman Borghs,
Dirk Vanderschueren,
Ilpo T Huhtaniemi,
Judith E Adams, Kate A Ward,
Hazel Platt, [......],
Gianni Forti,
Aleksander Giwercman,
Thang S Han,
Krzysztof Kula,
Michael E Lean,
Neil Pendleton,
Margus Punab,
Alan J Silman,
Frederick C Wu,
Terence W O'Neill
[show abstract]
[hide abstract]
ABSTRACT: Genes involved in sex hormone pathways are candidates for influencing bone strength. Polymorphisms in these genes were tested for association with heel quantitative ultrasound (QUS) parameters in middle-aged and elderly European men. Men 40-79 yr of age were recruited from population registers in eight European centers for the European Male Aging Study (EMAS). Polymorphisms were genotyped in AR, ESR1, ESR2, CYP19A1, CYP17A1, SHBG, SRD5A2, LHB, and LHCGR. QUS parameters broadband ultrasound attenuation (BUA) and speed of sound (SOS) were measured in the heel and used to derive BMD. The relationships between QUS parameters and polymorphisms were assessed using linear regression adjusting for age and center. A total of 2693 men, with a mean age of 60.1 +/- 11.1 (SD) yr were included in the analysis. Their mean BUA was 80.0 +/- 18.9 dB/Mhz, SOS was 1550.2 +/- 34.1 m/s, and BMD was 0.542 +/- 0.141 g/cm(2). Significant associations were observed between multiple SNPs in a linkage disequilibrium (LD) block within CYP19A1, peaking at the TCT indel with the deletion allele associating with reduced ultrasound BMD in heterozygotes (beta =-0.016, p = -0.005) and homozygotes (beta = -0.029, p = 0.001). The results for BUA and SOS were similar. Significant associations with QUS parameters were also observed for the CAG repeat in AR and SNPs in CYP17A1, LHCGR, and ESR1. Our data confirm evidence of association between bone QUS parameters and polymorphisms in CYP19A1, as well as modest associations with polymorphisms in CYP17A1, ESR1, LHCGR, and AR in a population sample of European men; this supports a role for genetically determined sex hormone actions in influencing male bone health.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 10/2008; 24(2):314-23. · 6.04 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This chapter provides an overview of the current densitometry techniques that are used in children. The strengths and limitations
of each of the techniques are discussed. Dualenergy x-ray absorptiometry (DXA) is discussed only briefly, as the remainder
of this book concentrates on this technique in detail. Table 1 provides a technical overview of costs, uses, precision, and
radiation exposure associated with densitometry methods. Radiation doses associated with other imaging modalities and with
natural background sources are provided for comparison in Table 2.
11/2007: pages 15-40;
-
[show abstract]
[hide abstract]
ABSTRACT: The use and correct interpretation of bone densitometry measurements in paediatric patients relies on the availability of appropriate reference data. Ideally, such data should be matched for sex, chronological age, height, weight, pubertal development and ethnicity.
To provide UK-specific reference data for the Hologic QDR Discovery dual-energy x ray absorptiometry (DXA) scanners.
Healthy, Caucasian children aged 5-18 years were recruited from local schools, colleges, general practitioner surgeries and staff from the University of Manchester, Manchester, UK. Suitable participants had DXA measurements taken of the lumbar spine, hip and total body. Sex-specific reference centile curves for bone mineral apparent density (BMAD; spine and femoral neck) are provided, using the approach suggested by Mølgaard et al. to interpret the scans. LMS (lambda, mu, varsigma) tables for calculation of individual standard deviation scores (SDSs) were produced; a weblink is provided to these tables to allow calculation of an individual child's SDSs.
The total study population consisted of 442 participants (239 male). The total numbers of scans available for analysis were 431 of the lumbar spine, 426 of the total body and 393 of the proximal femur. Data are provided for clinical interpretation of the spine and femoral neck scans based on BMAD (g/cm3), which reduces the size dependence of DXA areal bone mineral density (g/cm2). The spine and total-body data are also presented for interpretation of results using the approach suggested by Mølgaard et al.
This article provides the first sex-specific and ethnicity-specific reference databases for UK, which should allow the clinician to assess bone mineral density in paediatric patients, measured by the Hologic QDR Discovery DXA scanner.
Archives of Disease in Childhood 02/2007; 92(1):53-9. · 2.88 Impact Factor
-
Journal of the Royal Society of Medicine 02/2006; 99 Suppl 46:2-5. · 1.41 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: At birth, the fetus will contain 30 g of calcium; during the third trimester the calcium accrual can be up to 340 mg/day. Therefore, extremely high demands for calcium provision are placed upon the mother. This review aims to describe the adaptive mechanisms of the female skeleton to pregnancy and lactation, which ensure optimal fetal skeletal mineralization without compromise to maternal bone strength.
Descriptions of changes in bone status during pregnancy and lactation have been published. One of the only studies to measure pre-conception to post-weaning shows complete recovery of maternal spinal bone mineral density (BMD) and near recovery at the hip. Most studies describe trabecular bone loss, but there is evidence for endosteal resorption of the metacarpals. In a retrospective study of former teenage mothers those who breastfed had similar hip BMD to nulliparous age-matched women; those who did not breastfeed had lower hip BMD. Maternal response to low calcium intake differs from that of normal calcium intake.
Pregnancy and lactation do not have an overall negative effect upon the maternal skeleton. Retrospective evidence suggests no harmful effect of teenage pregnancy if the teenager breastfed, but this requires further investigation. The effects of other situations, for example low vitamin D status or low calcium intake, require further research to inform future clinical practice.
Current Opinion in Obstetrics and Gynecology 09/2005; 17(4):435-9. · 2.38 Impact Factor
