| 1. |
- Johansson, Peter, et al.
(författare)
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Increased Risk of Hip Fracture in Patients with Lymphoma, a Swedish Population Study of 37,236 Lymphoma Patients.
- 2020
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Ingår i: Calcified tissue international. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 106, s. 591-598
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Tidskriftsartikel (refereegranskat)abstract
- Increased bone loss has been noted in lymphoma patients; however, the incidence of hip fracture is not known. The aim of our study was to explore the risk for hip fracture in patients with lymphoma compared with the entire Swedish population. The risk of hip fracture was determined in a retrospective population cohort study of adult Swedish lymphoma patients (n=37,236), diagnosed 1995-2015 and compared with the entire Swedish population during the same period. The incidence of hip fracture in lymphoma patients was higher in women than in men, increased by age, and decreased by calendar year as also demonstrated in the total population. 2.2% of the men and 4.7% of women with lymphoma sustained a hip fracture. For the total group of females, the hazard ratio (HR) was 1.19 (95% CI 1.11-1.28) and for men, the hazard ratio was 1.06 (95% CI 0.97-1.17) compared with the Swedish population. The HR for hip fracture (2016) was 2.80 (95% CI 1.20-6.53), 2.04 (95% CI 1.30-3.20), 1.56 (95% CI 1.21-2.01), 1.08 (95% CI 0.89-1.30), and 1.07 (95% CI 0.92-1.25) in females aged 40, 50, 60, 70, and 80years, respectively. Corresponding figures for men were not significant in 2016. Unmarried men with lymphoma had a two times higher risk for hip fracture (HR 2.02 95% CI 1.63-2.50) compared with married men. Patients with lymphoma had an increased risk of hip fracture, especially younger women and unmarried men. The incidence of hip fracture is decreased by calendar year in the lymphoma patients and the entire Swedish population.
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| 2. |
- Kristjansdottir, Hallgerdur Lind, et al.
(författare)
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Anemia is associated with increased risk of non-vertebral osteoporotic fractures in elderly men: the MrOS Sweden cohort
- 2022
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Ingår i: Archives of Osteoporosis. - : Springer Science and Business Media LLC. - 1862-3522 .- 1862-3514. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- This study includes 1005 men from the Gothenburg part of the Osteoporotic Fracture in Men Study (MrOS). Included are 66 men with anemia (hemoglobin < 130 g/L). The follow-up time was up to 16 years, and the main results are that anemia is associated with all fractures and non-vertebral osteoporotic fractures. Introduction Anemia and osteoporotic fractures are conditions that are associated with increased morbidity and mortality. Clinical studies have suggested that anemia can be used as a predictor of future osteoporotic fractures. Method Men from the Osteoporotic Fractures in Men Study (MrOS) Sweden, Gothenburg, with available hemoglobin (Hb) values (n = 1005, median age 75.3 years (SD 3.2)), were included in the current analyses. Of these, 66 suffered from anemia, defined as Hb < 130 g/L. Median follow-up time for fracture was 10.1 years and the longest follow-up time was 16.1 years. Results Men with anemia had, at baseline, experienced more falls and had a higher prevalence of diabetes, cancer, prostate cancer, hypertension, and stroke. Anemia was not statistically significantly associated with bone mineral density (BMD). Men with anemia had higher serum levels of fibroblast growth factor 23 (iFGF23) (p < 0.001) and phosphate (p = 0.001) and lower serum levels of testosterone (p < 0.001) and estradiol (p < 0.001). Moreover, men with anemia had an increased risk of any fracture (hazard ratio (HR) 1.97, 95% CI 1.28-3.02) and non-vertebral osteoporotic fracture (HR 2.15, 95% CI 1.18-3.93), after adjustment for age and total hip BMD, in 10 years. The risk for any fracture was increased in 10 and 16 years independently of falls, comorbidities, inflammation, and sex hormones. The age-adjusted risk of hip fracture was increased in men with anemia (HR 2.32, 95% CI 1.06-5.12), in 10 years, although this was no longer statistically significant after further adjustment for total hip BMD. Conclusions Anemia is associated with an increased risk for any fracture and non-vertebral osteoporotic fracture in elderly men with a long follow-up time. The cause is probably multifactorial and our results support that anemia can be used as a predictor for future fracture.
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| 3. |
- Kristjansdottir, Hallgerdur Lind
(författare)
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Blood and Bone - Epidemiological studies on the association between blood and bone
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Preclinical and clinical studies have suggested that blood- and bone cells are interconnected. Aims: To study the association between hematological variables, specifically serotonin, erythropoietin (EPO), hemoglobin (Hb), neutrophil-, lymphocyte-, and platelet count, and bone mineral density (BMD), and/or risk for fractures (paper I-III). To study the risk for hip fractures in patients with lymphoma (paper IV). Methods: In paper I-III data from MrOS (The Osteoporotic Fractures in Men Study), a prospective, population-based study, was used. Men in the ages 69-81 years were randomly selected from Gothenburg (n=1010), 2002-2004. In the second part of paper I, additional cohorts from Uppsala and Malmö were used. Baseline data included blood tests (serotonin, EPO, Hb, neutrophil-, lymphocyte-, and platelet count) and dual x-ray absorptiometry (DXA). Subjects were followed until the end of 2013. In paper IV adults ≥18 years diagnosed with lymphoma between 1995 and 2015 were identified in the Swedish Cancer Register. Data on the Swedish population and lymphoma patients was retrieved from Statistiska Centralbyrån, and hip fractures were identified via the Inpatient Register. The risk for hip fractures in patients with lymphoma was compared with that of the Swedish population. Results: Serotonin was negatively associated with total hip BMD. Men with serotonin in quintile 5 had an increased risk for all fractures, nonvertebral osteoporotic fractures and hip fractures. In men with normal renal function EPO was positively associated with total hip BMD, inflammation, and comorbidities, as well as increased risk for all fractures and major osteoporotic fractures. Platelet- and neutrophil count, and not Hb and lymphocyte count, were negatively associated with total hip BMD. Women with lymphoma had increased risk for hip fracture compared with the Swedish population. Conclusions: The results support the hypothesis that blood and bone are interconnected. Serotonin and EPO both predict for fractures in elderly men. Platelet- and neutrophil count are associated with BMD. Physicians treating lymphoma patients should be aware of the increased risk for hip fractures in women.
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| 4. |
- Kristjansdottir, Hallgerdur Lind, et al.
(författare)
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High Plasma Erythropoietin Predicts Incident Fractures in Elderly Men with Normal Renal Function : The MrOS Sweden Cohort
- 2020
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Ingår i: Journal of Bone and Mineral Research. - : WILEY. - 0884-0431 .- 1523-4681. ; 35:2, s. 298-305
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Tidskriftsartikel (refereegranskat)abstract
- Preclinical studies on the role of erythropoietin (EPO) in bone metabolism are contradictory. Regeneration models indicate an anabolic effect on bone healing, whereas models on physiologic bone remodeling indicate a catabolic effect on bone mass. No human studies on EPO and fracture risk are available. It is known that fibroblast growth factor 23 (FGF23) affects bone mineralization and that serum concentration of FGF23 is higher in men with decreased estimated glomerular filtration rate (eGFR). Recently, a direct association between EPO and FGF23 has been shown. We have explored the potential association between EPO and bone mineral density (BMD), fracture risk, and FGF23 in humans. Plasma levels of EPO were analyzed in 999 men (aged 69 to 81 years), participating in the Gothenburg part of the population-based Osteoporotic Fractures in Men (MrOS) study, MrOS Sweden. The mean +/- SD EPO was 11.5 +/- 9.0 IU/L. Results were stratified by eGFR 60 mL/min. For men with eGFR >= 60 mL/min (n = 728), EPO was associated with age (r = 0.13, p < 0.001), total hip BMD (r = 0.14, p < 0.001), intact (i)FGF23 (r = 0.11, p = 0.004), and osteocalcin (r = -0.09, p = 0.022). The association between total hip BMD and EPO was independent of age, body mass index (BMI), iFGF23, and hemoglobin (beta = 0.019, p < 0.001). During the 10-year follow-up, 164 men had an X-ray-verified fracture, including 117 major osteoporotic fractures (MOF), 39 hip fractures, and 64 vertebral fractures. High EPO was associated with higher risk for incident fractures (hazard ratio [HR] = 1.43 per tertile EPO, 95% confidence interval [CI] 1.35-1.63), MOF (HR = 1.40 per tertile EPO, 95% CI 1.08-1.82), and vertebral fractures (HR = 1.42 per tertile EPO, 95% CI 1.00-2.01) in a fully adjusted Cox regression model. In men with eGFR<60 mL/min, no association was found between EPO and BMD or fracture risk. We here demonstrate that high levels of EPO are associated with increased fracture risk and increased BMD in elderly men with normal renal function.
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| 5. |
- Kristjansdottir, Hallgerdur Lind, et al.
(författare)
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High platelet count is associated with low bone mineral density: The MrOS Sweden cohort.
- 2021
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Ingår i: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 32:5, s. 865-871
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Tidskriftsartikel (refereegranskat)abstract
- In elderly ambulatory men, high platelet and high neutrophil counts are related to low bone mineral density (BMD), after adjustment for relevant covariates. Low hemoglobin (hgb) is even associated with low BMD, but this relationship seems to be dependent on estradiol and osteocalcin.Blood and bone cells exist in close proximity to each other in the bone marrow. Accumulating evidence, from both preclinical and clinical studies, indicates that these cell types are interconnected. Our hypothesis was that BMD measurements are associated with blood count variables and bone remodeling markers.We analyzed blood count variables, bone remodeling markers, and BMD, in subjects from the MrOS cohort from Gothenburg, Sweden. Men with at least one blood count variable (hgb, white blood cell count, or platelet count) analyzed were included in the current analysis (n=1005), median age 75.3years (range 69-81years).Our results show that high platelet counts were related to low BMD at all sites (total hip BMD; r=-0.11, P=0.003). No statistically significant association was seen between platelet counts and bone remodeling markers. Neutrophil counts were negatively associated with total body BMD (r=-0.09, P=0.006) and total hip BMD (r=-0.08, P=0.010), and positively related to serum ALP (r=0.15, P<0.001). Hgb was positively related to total hip BMD (r=0.16, P<0.001), and negatively to serum osteocalcin (r=-0.13, P<0.001). The association between platelet and neutrophil counts and total hip BMD was statistically significant after adjustments for other covariates, but the association between hgb and total hip BMD was dependent on estradiol and osteocalcin.Our observations support the hypothesis of an interplay between blood and bone components.
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| 6. |
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| 7. |
- Kristjansdottir, Hallgerdur Lind, et al.
(författare)
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High Serum Serotonin Predicts Increased Risk for Hip Fracture and Nonvertebral Osteoporotic Fractures : The MrOS Sweden Study
- 2018
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431. ; 33:9, s. 1560-1567
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Tidskriftsartikel (refereegranskat)abstract
- Because several studies have implicated serotonin as a regulator of bone mass, we here explore its potential association on fracture risk and falls, as on bone mineral density (BMD) and muscle strength, in humans. Serum levels of serotonin were analyzed in 950 men (aged 69 to 81 years), participating in the Gothenburg part of the population-based study MrOS Sweden. Men taking selective serotonin reuptake inhibitors (SSRIs) had a mean value of 31.2 μg/L compared with 159.4 μg/L in those not taking SSRIs. SSRI users were excluded from further analysis. During 10-year follow-up, 224 men exhibited fractures, including 97 nonvertebral osteoporotic fractures (57 hip fractures), and 86 vertebral fractures. Serotonin was associated with hip fracture in linear analysis (hazard ratio [HR] = 1.27, 95% confidence interval [CI] 1.03–1.58) and to all fractures in a nonlinear manner, when quintiles of serotonin was included in quadratic terms (HR = 1.12, 95% CI 1.04–1.21). Men in serotonin quintile 5 had, in multivariable analysis, a HR of 2.30 (95% CI 1.31–4.02) for hip fracture and 1.82 (95% CI 1.17–2.85) for nonvertebral fractures compared with men in quintiles 1 to 4. Men in quintile 1 had, in multivariable analysis, a HR of 1.76 (95% CI 1.03–2.99) for nonvertebral fractures compared with men in quintiles 2 to 4. No association was found with vertebral fractures. Individuals in serotonin quintile 1 had higher prevalence of falls compared with quintiles 2 to 5 (odds ratio = 1.90, 95% CI 1.26–2.87). Serotonin was positively associated with hand-grip strength (r = 0.08, p = 0.02) and inversely with hip BMD (r = −0.10, p = 0.003). To assess the association between SSRIs and falls and fractures, the total MrOS Sweden cohort was examined (n = 3014). SSRI users (n = 90) had increased prevalence of falls (16% versus 33%, p = 0.0001) and increased rate of incident fractures (28.0 versus 44.7 per 1000 person-years, p = 0.018). We present novel data showing that high levels of serotonin predict an increased risk for hip fracture and nonvertebral osteoporotic fractures.
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| 8. |
- Wernig-Zorc, Sara, et al.
(författare)
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Global distribution of DNA hydroxymethylation and DNA methylation in chronic lymphocytic leukemia.
- 2019
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Ingår i: Epigenetics & chromatin. - : Springer Science and Business Media LLC. - 1756-8935. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Chronic lymphocytic leukemia (CLL) has been a good model system to understand the functional role of 5-methylcytosine (5-mC) in cancer progression. More recently, an oxidized form of 5-mC, 5-hydroxymethylcytosine (5-hmC) has gained lot of attention as a regulatory epigenetic modification with prognostic and diagnostic implications for several cancers. However, there is no global study exploring the role of 5-hydroxymethylcytosine (5-hmC) levels in CLL. Herein, using mass spectrometry and hMeDIP-sequencing, we analysed the dynamics of 5-hmC during B cell maturation and CLL pathogenesis.We show that naïve B-cells had higher levels of 5-hmC and 5-mC compared to non-class switched and class-switched memory B-cells. We found a significant decrease in global 5-mC levels in CLL patients (n=15) compared to naïve and memory B cells, with no changes detected between the CLL prognostic groups. On the other hand, global 5-hmC levels of CLL patients were similar to memory B cells and reduced compared to naïve B cells. Interestingly, 5-hmC levels were increased at regulatory regions such as gene-body, CpG island shores and shelves and 5-hmC distribution over the gene-body positively correlated with degree of transcriptional activity. Importantly, CLL samples showed aberrant 5-hmC and 5-mC pattern over gene-body compared to well-defined patterns in normal B-cells. Integrated analysis of 5-hmC and RNA-sequencing from CLL datasets identified three novel oncogenic drivers that could have potential roles in CLL development and progression.Thus, our study suggests that the global loss of 5-hmC, accompanied by its significant increase at the gene regulatory regions, constitute a novel hallmark of CLL pathogenesis. Our combined analysis of 5-mC and 5-hmC sequencing provided insights into the potential role of 5-hmC in modulating gene expression changes during CLL pathogenesis.
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