| 1. |
- Brembeck, Petra, 1977, et al.
(författare)
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Changes in cortical volumetric bone mineral density and thickness, and trabecular thickness in lactating women postpartum.
- 2015
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 100:2, s. 535-543
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Tidskriftsartikel (refereegranskat)abstract
- Context: Lactation is associated with decreased areal bone mineral density (aBMD). Replenishment occurs especially after ceased lactation. Changes in volumetric BMD (vBMD), microstructure and dimensional parameters are unknown and may clarify the role of lactation for skeletal health. Objective: and main outcomes: To test the hypothesis that lactation is associated with changes in aBMD, vBMD, microstructure and dimensional parameters. Design: At baseline (0.5 months after delivery) and 4, 12 and 18 months thereafter bone was assessed using dual energy x-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT). Participants: and setting: Eighty-one fair-skinned postpartum women and 21 controls aged 25-40 years were recruited. Completion ratio was 73%. Postpartum women were categorized depending on duration of lactation; 0-3.9, 4-8.9 and ≥9 months. Results: During the first 4 months, aBMD decreased at several sites (geometric mean±SE; -0.73±0.21% to -3.98±0.76%) in women lactating at least 4 months. During the same time, cortical vBMD at ultra-distal tibia decreased in women lactating 4-8.9 months (-0.26±0.08%) and ≥9 months (-0.49±0.10%). At 12 months postpartum, also cortical thickness (≥9 months, -2.48±0.41%) and trabecular thickness (4-8.9 months, -2.14±0.92%; ≥9 months, -2.56±1.21%) were lower than baseline. No decreases were found in women lactating less than 4 months or in controls in these parameters. At 18 months postpartum, both cortical vBMD (≥9 months, -0.77±0.17%) and trabecular thickness (4-8.9 months, -2.25±1.25%; ≥9 months, -3.21±1.41%) were lower in women with long lactation. Conclusions: Decreases in cortical vBMD, thickness, and trabecular thickness at ultra-distal tibia were found in women lactating 4 months or longer. Longer follow-up is needed to confirm whether women with extended lactation recover fully, or whether the changes could potentially lead to increased risk of fracture in later life.
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| 2. |
- Darelid, Anna, et al.
(författare)
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Bone turnover markers predict bone mass development in young adult men: a five-year longitudinal study.
- 2015
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 100:4, s. 1460-8
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Tidskriftsartikel (refereegranskat)abstract
- Peak bone mass is an important factor for the lifetime risk of developing osteoporosis. Ways to predict bone development in young adulthood are lacking. Objective and Main Outcome Measures: The aim of this study was to investigate whether baseline measurements of bone turnover markers could predict bone development in early adulthood in men.
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| 3. |
- Eriksson, Anna-Lena, 1971, et al.
(författare)
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Genetic Determinants of Circulating Estrogen Levels and Evidence of a Causal Effect of Estradiol on Bone Density in Men.
- 2018
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 103:3, s. 991-1004
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Tidskriftsartikel (refereegranskat)abstract
- Serum estradiol (E2) and estrone (E1) levels exhibit substantial heritability.To investigate the genetic regulation of serum E2 and E1 in men.Genome-wide association study in 11,097 men of European origin from nine epidemiological cohorts.Genetic determinants of serum E2 and E1 levels.Variants in/near CYP19A1 demonstrated the strongest evidence for association with E2, resolving to three independent signals. Two additional independent signals were found on the X chromosome; FAMily with sequence similarity 9, member B (FAM9B), rs5934505 (P = 3.4 × 10-8) and Xq27.3, rs5951794 (P = 3.1 × 10-10). E1 signals were found in CYP19A1 (rs2899472, P = 5.5 × 10-23), in Tripartite motif containing 4 (TRIM4; rs17277546, P = 5.8 × 10-14), and CYP11B1/B2 (rs10093796, P = 1.2 × 10-8). E2 signals in CYP19A1 and FAM9B were associated with bone mineral density (BMD). Mendelian randomization analysis suggested a causal effect of serum E2 on BMD in men. A 1 pg/mL genetically increased E2 was associated with a 0.048 standard deviation increase in lumbar spine BMD (P = 2.8 × 10-12). In men and women combined, CYP19A1 alleles associated with higher E2 levels were associated with lower degrees of insulin resistance.Our findings confirm that CYP19A1 is an important genetic regulator of E2 and E1 levels and strengthen the causal importance of E2 for bone health in men. We also report two independent loci on the X-chromosome for E2, and one locus each in TRIM4 and CYP11B1/B2, for E1.
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| 4. |
- Eriksson, Anna-Lena, 1971, et al.
(författare)
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Genetic variations in sex steroid-related genes as predictors of serum estrogen levels in men.
- 2009
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 94:3, s. 1033-41
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: The risk of many conditions, including prostate cancer, breast cancer, and osteoporosis, is associated with serum levels of sex steroids. OBJECTIVE: The aim of the study was to identify genetic variations in sex steroid-related genes that are associated with serum levels of estradiol (E2) and/or testosterone in men. DESIGN: Genotyping of 604 single nucleotide polymorphisms in 50 sex steroid-related candidate genes was performed in the Gothenburg Osteoporosis and Obesity Determinants (GOOD) study (n = 1041 men; age, 18.9 +/- 0.6 yr). Replications of significant associations were performed in the Osteoporotic Fractures in Men (MrOS) Sweden study (n = 2568 men; age, 75.5 +/- 3.2 yr) and in the MrOS US study (n = 1922 men; age, 73.5 +/- 5.8 yr). Serum E2, testosterone, and estrone (E1) levels were analyzed using gas chromatography/mass spectrometry. RESULTS: The screening in the GOOD cohort identified the single nucleotide polymorphism rs2470152 in intron 1 of the CYP19 gene, which codes for aromatase, responsible for the final step of the biosynthesis of E2 and E1, to be most significantly associated with serum E2 levels (P = 2 x 10(-6)). This association was confirmed both in the MrOS Sweden study (P = 9 x 10(-7)) and in the MrOS US study (P = 1 x 10(-4)). When analyzed in all subjects (n = 5531), rs2470152 was clearly associated with both E2 (P = 2 x 10(-14)) and E1 (P = 8 x 10(-19)) levels. In addition, this polymorphism was modestly associated with lumbar spine BMD (P < 0.01) and prevalent self-reported fractures (P < 0.05). CONCLUSIONS: rs2470152 of the CYP19 gene is clearly associated with serum E2 and E1 levels in men.
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| 5. |
- Eriksson, Anna L, et al.
(författare)
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Serum Glycine Levels Are Associated With Cortical Bone Properties and Fracture Risk in Men.
- 2021
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 106:12
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Tidskriftsartikel (refereegranskat)abstract
- In a recent study a pattern of 27 metabolites, including serum glycine, associated with bone mineral density (BMD).To investigate associations for serum and urinary glycine levels with BMD, bone microstructure, and fracture risk in men.In the population-based Osteoporotic Fractures in Men (MrOS) Sweden study (men, 69-81 years) serum glycine and BMD were measured at baseline (n=965) and 5-year follow-up (n=546). Cortical and trabecular bone parameters of the distal tibia were measured at follow-up using high-resolution peripheral quantitative computed tomography. Urinary (n=2682) glycine was analyzed at baseline. X-ray-validated fractures (n=594) were ascertained during a median follow-up of 9.6 years. Associations were evaluated using linear regression (bone parameters) or Cox regression (fractures).Circulating glycine levels were inversely associated with femoral neck (FN)-BMD. A meta-analysis (n=7543) combining MrOS Sweden data with data from 3 other cohorts confirmed a robust inverse association between serum glycine levels and FN-BMD (P=7.7×10-9). Serum glycine was inversely associated with the bone strength parameter failure load in the distal tibia (P=0.002), mainly as a consequence of an inverse association with cortical cross-sectional area and a direct association with cortical porosity. Both serum and urinary glycine levels predicted major osteoporotic fractures (serum: hazard ratio [HR] per SD increase=1.22, 95% CI, 1.05-1.43; urine: HR=1.13, 95% CI, 1.02-1.24). These fracture associations were only marginally reduced in models adjusted by FRAX with BMD.Serum and urinary glycine are indirectly associated with FN-BMD and cortical bone strength, and directly associated with fracture risk in men.
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| 6. |
- Eriksson, Anna-Lena, 1971, et al.
(författare)
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SHBG gene promoter polymorphisms in men are associated with serum sex hormone-binding globulin, androgen and androgen metabolite levels, and hip bone mineral density.
- 2006
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 91:12, s. 5029-37
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: SHBG regulates free sex steroid levels, which in turn regulate skeletal homeostasis. Twin studies have demonstrated that genetic factors largely account for interindividual variation in SHBG levels. Glucuronidated androgen metabolites have been proposed as markers of androgenic activity. OBJECTIVE: Our objective was to investigate whether polymorphisms in the SHBG gene promoter [(TAAAA)(n) microsatellite and rs1799941 single-nucleotide polymorphism] are associated with serum levels of SHBG, sex steroids, or bone mineral density (BMD) in men. DESIGN AND STUDY SUBJECTS: We conducted a population-based study of two cohorts of Swedish men: elderly men (MrOS Sweden; n congruent with 3000; average age, 75.4 yr) and young adult men (GOOD study; n = 1068; average age, 18.9 yr). MAIN OUTCOME MEASURES: We measured serum levels of SHBG, testosterone, estradiol, dihydrotestosterone, 5alpha-androstane-3alpha,17beta-diol glucuronides, androsterone glucuronide, and BMD determined by dual-energy x-ray absorptiometry. RESULTS: In both cohorts, (TAAAA)(n) and rs1799941 genotypes were associated with serum levels of SHBG (P < 0.001), dihydrotestosterone (P < 0.05), and 5alpha-androstane-3alpha,17beta-diol glucuronides (P < 0.05). In the elderly men, they were also associated with testosterone and BMD at all hip bone sites. The genotype associated with high levels of SHBG was also associated with high BMD. Interestingly, male mice overexpressing human SHBG had increased cortical bone mineral content in the femur, suggesting that elevated SHBG levels may cause increased bone mass. CONCLUSIONS: Our findings demonstrate that polymorphisms in the SHBG promoter predict serum levels of SHBG, androgens, and glucuronidated androgen metabolites, and hip BMD in men.
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| 7. |
- Grahnemo, Louise, et al.
(författare)
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Low Circulating Valine Associate With High Risk of Hip Fractures
- 2023
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Ingår i: Journal of Clinical Endocrinology & Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 108:11
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Tidskriftsartikel (refereegranskat)abstract
- Context Hip fractures constitute a major health concern. An adequate supply of amino acids is crucial to ensure optimal acquisition and remodeling of bone. Circulating amino acid levels have been proposed as markers of bone mineral density, but data on their ability to predict incident fractures are scarce. Objectives To investigate the associations between circulating amino acids and incident fractures. Methods We used UK Biobank (n = 111 257; 901 hip fracture cases) as a discovery cohort and the Umea Fracture and Osteoporosis (UFO) hip fracture study (hip fracture cases n = 2225; controls n = 2225) for replication. Associations with bone microstructure parameters were tested in a subsample of Osteoporotic Fractures in Men Sweden (n = 449). Results Circulating valine was robustly associated with hip fractures in the UK Biobank (HR per SD increase 0.79, 95% CI 0.73-0.84), and this finding was replicated in the UFO study (combined meta-analysis including 3126 incident hip fracture cases, odds ratio per SD increase 0.84, 95% CI 0.80-0.88). Detailed bone microstructure analyses showed that high circulating valine was associated with high cortical bone area and trabecular thickness. Conclusion Low circulating valine is a robust predictor of incident hip fractures. We propose that circulating valine may add information for hip fracture prediction. Future studies are warranted to determine whether low valine is causally associated with hip fractures.
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| 8. |
- Jaiswal, Raju, et al.
(författare)
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Hemoglobin Levels Improve Fracture Risk Prediction in Addition to FRAX Clinical Risk Factors and Bone Mineral Density
- 2023
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Ingår i: The Journal of clinical endocrinology and metabolism. - : Endocrine Society. - 1945-7197 .- 0021-972X. ; 108:12
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Anemia and decreasing levels of hemoglobin (Hb) have previously been linked to increased fracture risk, but the added value to FRAX, the most utilized fracture prediction tool worldwide, is unknown. OBJECTIVE: To investigate the association between anemia, Hb levels, bone microstructure, and risk of incident fracture and to evaluate whether Hb levels improve fracture risk prediction in addition to FRAX clinical risk factors (CRFs). METHODS: A total of 2778 community-dwelling women, aged 75-80 years, and part of a prospective population-based cohort study in Sweden were included. At baseline, information on anthropometrics, CRFs, and falls was gathered, blood samples were collected, and skeletal characteristics were investigated using dual-energy x-ray absorptiometry and high-resolution peripheral quantitative computed tomography. At the end of follow-up, incident fractures were retrieved from a regional x-ray archive. RESULTS: The median follow-up time was 6.4 years. Low Hb was associated with worse total hip and femoral neck bone mineral density (BMD), and lower tibia cortical and total volumetric BMD, and anemia was associated with increased risk of major osteoporotic fracture (MOF; hazard ratio 2.04; 95% CI 1.58-2.64). Similar results were obtained for hip fracture and any fracture, also when adjusting for CRFs. The ratio between 10-year fracture probabilities of MOF assessed in models with Hb levels included and not included ranged from 1.2 to 0.7 at the 10th and 90th percentile of Hb, respectively. CONCLUSION: Anemia and decreasing levels of Hb are associated with lower cortical BMD and incident fracture in older women. Considering Hb levels may improve the clinical evaluation of patients with osteoporosis and the assessment of fracture risk.
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| 9. |
- Jakobsson, Jenny, et al.
(författare)
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Large differences in testosterone excretion in Korean and Swedish men are strongly associated with a UDP-glucuronosyl transferase 2B17 polymorphism.
- 2006
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 91:2, s. 687-93
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: The reproductive endocrinology in Asians and Caucasians is of great interest in view of large differences in prostate cancer rate and sensitivity to pharmacological male contraception. In addition, interpretation of certain antidoping tests is confounded by interethnic variation in androgen disposition. Uridine diphosphoglucuronosyl transferases have a key role in the homeostasis and metabolism of androgens. Recently a deletion polymorphism was detected in the UGT2B17 gene. OBJECTIVE: The objective of the study was to evaluate the contribution of the UGT2B17 deletion polymorphism to the interindividual and interethnic variation of androgen metabolism and excretion. METHODS AND RESULTS: Urine from 122 Swedish and 74 Korean healthy men was analyzed for several androgen glucuronides including testosterone. The distribution of the natural logarithms of urinary testosterone concentrations showed a distinct bimodal pattern in both groups, suggesting a monogenic inheritance. When the UGT2B17 genotypes were compared with urinary testosterone levels, all of the individuals of the UGT2B17 homozygous deletion/deletion genotype had no or negligible amounts of urinary testosterone. The deletion/deletion genotype was seven times more common in the Korean (66.7%) than the Swedish population (9.3%). In addition, the Swedes had significantly higher levels of serum testosterone, compared with the Koreans. CONCLUSIONS: Our results show that the UGT2B17 polymorphism is strongly associated with the bimodal distribution of the testosterone excretion and also with the large differences in testosterone excretion between Koreans and Swedes.
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| 10. |
- Larsson, Berit A M, et al.
(författare)
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Association between cortical bone microstructure and statin use in older women.
- 2019
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 104:2, s. 250-7
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Tidskriftsartikel (refereegranskat)abstract
- Treatment with statins has been associated with increased bone mineral density (BMD), but if this association depends on differences in cortical or trabecular volumetric bone microstructure is unknown.The aim of this study was to investigate if treatment with statins is associated with bone microstructure and geometry in older women.Older women were included in a population-based study of 3,028 women (mean age ± SD: 77.8 ± 1.6 years) from the greater Gothenburg area in Sweden. Information regarding medical history, medication and life-style factors was obtained from validated questionnaires.Bone geometry and microstructure were measured at the ultradistal and distal (14%) site of radius and tibia using high-resolution peripheral quantitative computed tomography (HR-pQCT; XtremeCT).The 803 women in the cohort who used statins had higher body weight, worse physical function and more frequently cardiovascular disease and diabetes than nonusers (p<0.05). Statin users had lower cortical porosity (radius 2.2± 1.9 vs. 2.5± 2.0%; tibia 5.2± 2.4 vs. 5.4± 2.5, p=0.01), higher cortical bone density (radius 1008 ± 39.1 vs. 1001 ± 38.4 mg/cm3; tibia 919 ± 42.6 vs. 914 ± 41.5, p<0.01), and greater cortical area (radius 60.5 ± 9.6 vs. 58.6 ± 9.7 mm2; tibia 150.0 ± 23.6 vs. 146.7 ± 23.8, p<0.01) than non-users, also after adjustment for a large number of confounders, including age, weight, smoking, other medications and prevalent diseases.Use of statins was associated with better cortical bone characteristics in older women.
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