| 1. |
- Bokrantz, Tove, et al.
(författare)
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The association between peripheral arterial disease and risk for hip fractures in elderly men is not explained by low hip bone mineral density. Results from the MrOS Sweden study
- 2022
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 33, s. 2607-2617
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Tidskriftsartikel (refereegranskat)abstract
- In this prospective study in Swedish elderly men, PAD based on an ABI < 0.9 was associated with an increased risk of hip fracture, independent of age and hip BMD. However, after further adjustments for comorbidity, medications, physical function, and socioeconomic factors, the association diminished and was no longer statistically significant. Introduction To examine if peripheral arterial disease (PAD) is associated with an increased risk for hip fracture in men independent of hip BMD. Methods Ankle-brachial index (ABI) was assessed in the Swedish MrOS (Osteoporotic Fractures in Men) study, a prospective observational study including 3014 men aged 69-81 years at baseline. PAD was defined as ABI < 0.90. Incident fractures were assessed in computerized X-ray archives. The risk for hip fractures was calculated using Cox proportional hazard models. At baseline, BMD was assessed using DXA (Lunar Prodigy and Hologic QDR 4500) and functional measurements and blood samples were collected. Standardized questionnaires were used to collect information about medical history, falls, and medication. Results During 10 years of follow-up, 186 men had an incident hip fracture. The hazard ratio (HR) for hip fracture in men with PAD was 1.70 (95% CI 1.14-2.54), adjusted for age and study site. Additional adjustment for total hip BMD marginally affected this association (HR 1.64; 95% CI 1.10-2.45). In a final multivariate model, the HR attenuated to a non-significant HR 1.38 (95% CI 0.91-2.11) adjusted for age, site, hip BMD, BMI, falls, smoking, eGFR, handgrip strength, walking speed, former hip fracture, antihypertensive treatment, diabetes, education, and history of cardiovascular disease. Conclusion This study suggests that PAD is associated with an increased risk for hip fracture independently of hip BMD in elderly Swedish men. However, the high frequency of comorbidity and lower physical performance among men with PAD might partly explain this association.
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| 2. |
- Cawthon, Peggy M, et al.
(författare)
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What Cut-Point in Gait Speed Best Discriminates Community-Dwelling Older Adults With Mobility Complaints From Those Without? A Pooled Analysis From the Sarcopenia Definitions and Outcomes Consortium.
- 2021
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Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press (OUP). - 1758-535X .- 1079-5006. ; 76:10
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Tidskriftsartikel (refereegranskat)abstract
- Cut-points to define slow walking speed have largely been derived from expert opinion.Study participants (13 589 men and 5043 women aged ≥65years) had walking speed (m/s) measured over 4-6 m (mean ± SD: 1.20 ± 0.27 m/s in men and 0.94 ± 0.24 m/s in women.) Mobility limitation was defined as any self-reported difficulty with walking approximately 1/4 mile (prevalence: 12.6% men, 26.4% women). Sex-stratified classification and regression tree (CART) models with 10-fold cross-validation identified walking speed cut-points that optimally discriminated those who reported mobility limitation from those who did not.Among 5043 women, CART analysis identified 2 cut-points, classifying 4144 (82.2%) with walking speed ≥0.75 m/s, which we labeled as "fast"; 478 (9.5%) as "intermediate" (walking speed ≥0.62 m/s but <0.75 m/s); and 421 (8.3%) as "slow" (walking speed <0.62 m/s). Among 13 589 men, CART analysis identified 3 cut-points, classifying 10 001 (73.6%) with walking speed ≥1.00 m/s ("very fast"); 2901 (21.3%) as "fast" (walking speed ≥0.74 m/s but <1.00 m/s); 497 (3.7%) as "intermediate" (walking speed ≥0.57 m/s but <0.74 m/s); and 190 (1.4%) as "slow" (walking speed <0.57 m/s). Prevalence of self-reported mobility limitation was lowest in the "fast" or "very fast" (11% for men and 19% for women) and highest in the "slow" (60.5% in men and 71.0% in women). Rounding the 2 slower cut-points to 0.60 m/s and 0.75 m/s reclassified very few participants.Cut-points in walking speed of approximately 0.60 m/s and 0.75 m/s discriminate those with self-reported mobility limitation from those without.
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| 3. |
- 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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| 4. |
- Grassi, Lorenzo, et al.
(författare)
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3D Finite Element Models Reconstructed From 2D Dual-Energy X-Ray Absorptiometry (DXA) Images Improve Hip Fracture Prediction Compared to Areal BMD in Osteoporotic Fractures in Men (MrOS) Sweden Cohort
- 2023
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Ingår i: Journal of Bone and Mineral Research. - : John Wiley & Sons. - 0884-0431 .- 1523-4681. ; 38:9, s. 1258-1267
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Tidskriftsartikel (refereegranskat)abstract
- Bone strength is an important contributor to fracture risk. Areal bone mineral density (aBMD) derived from dual-energy X-ray absorptiometry (DXA) is used as a surrogate for bone strength in fracture risk prediction tools. 3D finite element (FE) models predict bone strength better than aBMD, but their clinical use is limited by the need for 3D computed tomography and lack of automation. We have earlier developed amethod to reconstruct the 3D hip anatomy froma 2D DXA image, followed by subject-specific FE-based prediction of proximal femoral strength. In the current study, we aim to evaluate the method's ability to predict incident hip fractures in a populationbased cohort (Osteoporotic Fractures in Men [MrOS] Sweden). We defined two subcohorts: (i) hip fracture cases and controls cohort: 120men with a hip fracture (<10 years frombaseline) and two controls to each hip fracture case, matched by age, height, and body mass index; and (ii) fallers cohort: 86men who had fallen the year before their hip DXA scan was acquired, 15 of which sustained a hip fracture during the following 10 years. For each participant, we reconstructed the 3D hip anatomy and predicted proximal femoral strength in 10 sideways fall configurations using FE analysis. The FE-predicted proximal femoral strength was a better predictor of incident hip fractures than aBMD for both hip fracture cases and controls (difference in area under the receiver operating characteristics curve, Delta AUROC = 0.06) and fallers (Delta AUROC = 0.22) cohorts. This is the first time that FE models outperformed aBMD in predicting incident hip fractures in a population-based prospectively followed cohort based on 3D FE models obtained from a 2D DXA scan. Our approach has potential to notably improve the accuracy of fracture risk predictions in a clinically feasible manner (only one single DXA image is needed) and without additional costs compared to the current clinical approach.
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| 5. |
- Grassi, Lorenzo, et al.
(författare)
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3d Finite Element Models Reconstructed From 2d Dxa Images Improve Hip Fracture Prediction Compared to Areal Bmd in Mros Sweden Cohort
- 2023
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Ingår i: Journal of Bone and Mineral Research. - 1523-4681. ; 38:9, s. 1258-1267
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Tidskriftsartikel (refereegranskat)abstract
- Bone strength is an important contributor to fracture risk. Areal bone mineral density (aBMD) derived from dual-energy X-ray absorptiometry (DXA) is used as a surrogate for bone strength in fracture risk prediction tools. 3D finite element (FE) models predict bone strength better than aBMD, but their clinical use is limited by the need for 3D computed tomography and lack of automation. We have earlier developed a method to reconstruct the 3D hip anatomy from a 2D DXA image, followed by subject-specific FE-based prediction of proximal femoral strength. In the current study, we aim to evaluate the method's ability to predict incident hip fractures in a population-based cohort (MrOS Sweden). We defined two sub-cohorts: (i) hip fracture cases and controls cohort: 120 men with a hip fracture (<10 years from baseline) and 2 controls to each hip fracture case, matched by age, height, and body mass index; (ii) fallers cohort: 86 men who had fallen the year before their hip DXA scan was acquired, 15 of which sustained a hip fracture during the following 10 years. For each participant, we reconstructed the 3D hip anatomy and predicted proximal femoral strength in 10 sideways fall configurations using FE analysis. The FE-predicted proximal femoral strength was a better predictor of incident hip fractures than aBMD for both hip fracture cases and controls (difference in area under the receiver operating characteristics curve, ΔAUROC = 0.06) and fallers (ΔAUROC = 0.22) cohorts. This is the first time that FE models outperform aBMD in predicting incident hip fractures in a population-based prospectively followed cohort based on 3D FE models obtained from a 2D DXA scan. Our approach has potential to notably improve the accuracy of fracture risk predictions in a clinically feasible manner (only one single DXA image is needed) and without additional costs compared to the current clinical approach.
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| 6. |
- Khamisi, Selwan, et al.
(författare)
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Comparison between thyroid stimulating immunoglobulin and TSH-receptor antibodies in management of Graves' orbitopathy
- 2023
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Ingår i: Experimental and clinical endocrinology & diabetes. - : Georg Thieme Verlag KG. - 0947-7349 .- 1439-3646. ; 131:04, s. 236-241
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Tidskriftsartikel (refereegranskat)abstract
- Objectives TSH-receptor antibodies (TRAb) targeting the TSH receptor (TSH-R) induce hyperthyroidism in Graves´ disease (GD). Graves´ orbitopathy (GO) is influenced by stimulation of the TSH-R in the orbita. GO has been, among other factors, linked to high TRAb levels. Thyroid stimulating immunoglobulins (TSI) is a relatively new method for assessing TSH-receptor antibodies. The aim of this study was to investigate the role of TSI in the management of GO.Methods Patients with newly diagnosed GD (n=30, median age 55 years (range 35–72), 29 women) received pharmacological therapy (methimazole+++thyroxine) for up to 24 months. GO was identified by clinical signs and symptoms. Eleven patients had GO at diagnosis, and another six developed GO during treatment. Blood samples for TSI and other thyroidal biomarkers were obtained at baseline and on five occasions during the 24-month follow-up. Twenty-two subjects completed the drug regimen without surgery or radioiodine treatment.Results At baseline, TSI was highly correlated with TRAb (r s =0.64, p<0.001), and both assays similarly correlated to fT3 values. TSI and TRAb did not differ significantly between GO and non-GO patients for visit v1 (n=30, 17 GO during the whole study) or at follow-up (n=22, 12 GO during the whole study). During follow-up, levels of TSI and TRAb decreased and normalized in both groups.Conclusion The present study does not support any added benefit of TSI compared to TRAb for the prediction and management of GO.
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| 7. |
- Khamisi, Selwan, et al.
(författare)
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Fracture Incidence in Graves' Disease: A Population-Based Study.
- 2023
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Ingår i: Thyroid : official journal of the American Thyroid Association. - : Mary Ann Liebert. - 1557-9077 .- 1050-7256. ; 33:11, s. 1349-1357
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Tidskriftsartikel (refereegranskat)abstract
- Background: Population-based studies have indicated an increase in bone turnover in hyperthyroidism with a subsequent decrease in bone mineral density and an increased risk of fractures, especially in postmenopausal women. However, heterogeneity between studies prevents a definitive conclusion. Graves' disease (GD) is an autoimmune disease, and it is the most common cause of hyperthyroidism. The aim of this study was to investigate fracture risk in patients with GD. Methods: A total of 2134 patients with incident GD and 21,261 age, sex- and county-matched controls were included 16-18 years after diagnosis in a retrospective cohort study. Drug and patient national registries in Sweden were used to assess the risk of developing skeletal complications. Up to 10 years of age, sex- and county-matched controls per patient were selected from databases from the National Board of Health and Welfare and Statistics Sweden. Cox proportional hazards models were fitted to estimate hazard ratios (HR) and confidence intervals [CI]. Results: There were no significant differences in fracture rates between GD and controls but after adjustment for comorbidities, the data showed higher vertebral fracture rates in male GD patients aged >52 years compared to male controls, HR=2.83 [CI 1.05-7.64]. The rates of osteoporosis treatments as well as treatment with corticosteroids were higher in patients with GD. However, HR for the association between GD and fractures remained largely unchanged after adjustment for osteoporosis treatments and treatments with corticosteroids. Conclusions: There were no significant differences in total fracture rate between GD and the general population. However, men older than 52 years had a higher vertebral fracture rate. This study also shows that patients with treated GD receive more osteoporosis treatments compared to the general population.
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| 8. |
- Khamisi, Selwan
(författare)
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Graves' Disease; Aspects on Orbitopathy and Bone Metabolism
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Graves' disease (GD) is an autoimmune disorder that affects the thyroid gland, with an annual incidence of 21 in 100,000 individuals in Sweden. Graves' orbitopathy (GO) is relatively common in GD and affects 50% of all patients to varying degrees of severity, with severe forms affecting 3–5% of patients. Early diagnosis and treatment of GO are crucial to avoid developing complications from the severe forms of GO. Diagnosis and treatment of GO are still challenging in many complicated cases; thus, new biomarkers are required for improved management. Thyroglobulin (Tg) is a glycoprotein produced by the follicular cells in the thyroid gland whose connection to GO has not been clarified. Measurement of thyroid stimulating immunoglobulins (TSI) is described as a more precise method than the traditional third-generation immunoassay of TSH receptor antibodies (TRAb), for improved diagnosis and management of GD. Vitamin D and bone health in GD have been investigated in different studies with conflicting results. This thesis aimed to explore the role of new biomarkers in the management of GO and to study the impact of GD on bone health. In Papers I–III, we studied 30 consecutive patients with de novo GD. Our studies show that higher levels of Tg are associated with a higher risk of developing GO. However, TSI was highly correlated to TRAb in GD, and it was not more precise than TRAb in the management of GO. No vitamin D deficiency was observed, but data confirm that hyperthyroidism has a negative effect on bone health. During treatment of GD, bone health improved over a two-year follow-up period. In Paper IV, a total of 2,134 patients with GD were included in an investigation 16–18 years after inclusion regarding the risk of developing skeletal complications. There were no increased fracture rates in patients with GD compared to up to ten controls from the general population. However, male patients older than 52 years may have an increased risk of vertebral fractures.
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| 9. |
- Khamisi, Selwan, et al.
(författare)
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Increased plasma levels of soluble programmed death ligand 1 (sPD-L1) and fibroblast growth factor 23 (FGF-23) in patients with Graves' ophthalmopathy in comparison to hyperthyroid patients without Graves' ophthalmopathy.
- 2023
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Ingår i: Cytokine. - : Elsevier. - 1043-4666 .- 1096-0023. ; 169, s. 156269-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Management of Graves' ophthalmopathy (GO) is still a challenge in Graves' disease (GD). Moreover, 40% of GD patients show radiological muscle enlargement without clinically apparent GO. Delayed treatment of GO may lead to deterioration in prognosis.METHODS: Thirty GD patients with overt hyperthyroidism were included in this study, 17 of whom either had GO at diagnosis or developed GO during the study period. Samples were collected at the beginning of the study, at 6 months, and at 24 months. Plasma samples were analyzed for 92 cytokines using the Olink Target 96 inflammation panel.RESULTS: After adjustment for multiplicity testing using the false discovery rate approach, soluble programmed death ligand 1 (sPD-L1) and fibroblast growth factor 23 (FGF-23) were significantly elevated in GO patients.CONCLUSION: Using a broad cytokine panel we show that patients with Graves' ophthalmopathy have elevated PD-L1 and FGF-23 levels. The findings support previous suggestions that PD-L1 may serve as a treatment target.
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| 10. |
- Khamisi, Selwan, et al.
(författare)
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Vitamin D and bone metabolism in Graves’ disease : a prospective study
- 2023
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Ingår i: Journal of Endocrinological Investigation. - : Springer. - 0391-4097 .- 1720-8386. ; 46, s. 425-433
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Vitamin D and osteoporosis in Graves' disease (GD) have been examined in cross-sectional studies with divergent results. Here, we prospectively studied vitamin D metabolism and bone health in patients with newly diagnosed GD. Methods Thirty consecutive patients with de novo overt thyrotoxicosis diagnosed with GD were included. At diagnosis, none of the patients were treated with vitamin D or anti-osteoporotic drugs. All patients were initially treated with antithyroid drugs. Blood samplings were taken at baseline and at 6 weeks, 3, 6, 12 and 24 months after treatment start. Serum levels of 25OHD3, 1,25OH2D3, calcium, parathyroid hormone (PTH), and C-terminal telopeptides of Type I collagen (CTX-I) were analysed. Bone mineral density (BMD) was measured at baseline, and 1 and 2 years after treatment initiation. Results At diagnosis, patients with GD did not have vitamin D deficiency. There were no significant correlations between levels of 25OHD3 and thyrotoxicosis. Upon treatment of the thyrotoxicosis, serum calcium fell transiently, and PTH and 1,25OH2D3 increased. 25OHD3 fell within the normal range and stabilised at 6 months. CTX-I fell over 12 months, BMD increased significantly up to 2 years, p = 0.002, < 0.001 and 0.005 in the spine, left total hip and left femoral neck, respectively. Conclusions The present data underline that thyrotoxicosis has a negative impact on bone health and demonstrate fine-tuned dynamics in bone and vitamin D metabolism. Upon treatment, bone health improved over a follow-up period of 24 months despite rising PTH. Increased conversion of 25OHD3 to 1,25OH2D3 occurs during treatment of GD.
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