Anemia is associated with increased risk of non-vertebral osteoporotic fractures in elderly men : the MrOS Sweden cohort

Summary: 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

Vitamin B12 and folate depletion in the elderly Diagnosis, clinical correlates and causes

Subclinical vitamin B12 and folate deficiency is common in the elderly. The clinical significance remains unresolved. There is not a universally accepted set of laboratory criteria for diagnosis, however subclinical deficiency is important to diagnose since it is easy to treat. Currently available measures of vitamin concentrations are, except in pronounced deficiency, unreliable. Plasma tHcy and serum MMA are potentially more reliable markers of intracellular vitamin status. The overall aim was to estimate the prevalence of B-vitamin deficiency and atrophic gastritis, to calculate health related reference intervals for plasma tHcy/serum MMA, to explore the dependence of glomerular filtration rate on these metabolites, and to study the effect of oral B-vitamin therapy both on biochemical and clinical outcome. The thesis is based on a population-based study of 209 community-dwelling subjects, mean age 76 years. The study included a double-blind placebo controlled intervention with an oral daily combination of vitamin B12 (0.5mg), folic acid (0.8mg) and B6 (3mg) during four months. Elevated plasma tHcy and serum MMA was found in 53% and 11%. Vitamin B12 deficiency occurred in 7.2%, folate deficiency in 11%, atrophic gastritis in up to 14%. Health- related upper reference limits for the metabolites were higher than those commonly used. After adjustment for glomerular filtration rate also within it’s normal range, the fraction of subjects with elevated plasma tHcy diminished significantly. Plasma tHcy and serum MMA correlated inversely with movement and cognitive performance. Vitamin therapy significantly decreased plasma tHcy (32%) and serum MMA (14%) but failed to improve movement or cognitive performance. Atrophic gastritis did not cause reduced vitamin absorption. In conclusion, elevated levels of plasma tHcy and serum MMA were common and more frequent than actual B-vitamin deficiency. The prevalence of “elevated” plasma tHcy may be overestimated unless adjusted for glomerular filtration rate. Atrophic gastritis was not uncommon and correlated to inferior B-vitamin status. Short-term oral B vitamin treatment normalized plasma tHcy and serum MMA levels also in subjects with atrophic gastritis, but did not affect movement or cognitive performance

Diagnostic Outcomes and Treatment Modalities in Patients with Mycosis Fungoides in West Sweden&mdash;A Retrospective Register-Based Study

(1) Background: Mycosis fungoides (MF) is a variant of primary cutaneous T-cell lymphoma. The aim of this study was to describe the clinical features and epidemiological and diagnostic findings in addition to the treatment modalities and responses in patients with MF. Furthermore, comparisons between patients in the early stage and the advanced stage were evaluated. (2) Methods: A retrospective register-based study based on data collected from the primary cutaneous lymphoma register and medical records was performed at the Department of Dermatology and Venerology at Sahlgrenska University Hospital, Gothenburg, Sweden. (3) Results: Eighty-four patients with a median age of 55 years with MF were included. Most of the patients (n = 73) were diagnosed at the early stage of the disease (IA&ndash;IIA). Overall disease progression was seen in 12.5% (n = 9) of the patients. Nine (10.7%) patients were deceased, out of which four (4.8%) deaths were associated with MF-related causes. (4) Conclusions: This study contributes to the knowledge of the epidemiological and clinical features in addition to the diagnostic findings and treatment responses in patients with MF in Sweden

Increased risk of hip fracture in patients with lymphoma, a Swedish population study of 37,236 lymphoma patients

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 80 years, 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

Holotranscobalamin is not influenced by decreased renal function in elderly men: the MrOS Sweden study

Background Subclinical cobalamin deficiency is common in the elderly, but the sensitivity and specificity of serum total cobalamin for this diagnosis is poor. Serum holotranscobalamin (holoTC), a measure of biologically available cobalamin, is considered a better marker for early cobalamin depletion than total cobalamin. However, in elderly populations, health-related reference intervals for holoTC and correlations to renal function are not entirely clear. Methods HoloTC was determined with an automated microparticle enzyme immunoassay (AxSYM (R)) in 790 elderly non-vitamin-supplemented Swedish men, median age 75.3 years. Renal function was assessed with creatinine, cystatin C and estimated glomerular filtration rate (eGFR calculated from creatinine). Results Median holoTC was 51.8pmol/L, the health-related reference interval 19.6-132.3pmol/L. There was no significant difference in mean holoTC in probands with normal compared to high creatinine (P=0.80) and cystatin C (P=0.82). No significant differences between the quartiles of creatinine or cystatin C in mean of log holoTC were seen. HoloTC correlated strongly with total cobalamin (r=0.69, P<0.001), weaker with eGFR(creatinine) (r=-0.09, P<0.05) and creatinine (r=0.09, P<0.05), the latter correlation was only seen in subjects with creatinine <100 mu mol/L. HoloTC correlated negatively with plasma total homocysteine (r=-0.24, P<0.001), but not with cystatin C and age. Conclusions Serum holoTC in healthy elderly men shows the same distribution as earlier described for a younger reference population. In this group of elderly subjects, holoTC did not correlate to reduced renal function. Thus, holoTC appears to be a promising tool for evaluating cobalamin status also in elderly populations

Low serum iron is associated with high serum intact FGF23 in elderly men: The Swedish MrOS study

Background: Fibroblast growth factor (FGF23) is a protein that is produced by osteoblasts and osteocytes. Increased serum levels of FGF23 have been associated with increased risks of osteoporotic fractures and cardiovascular disease, particularly in participants with poor renal function. Serum iron (Fe) has been suggested as a regulator of FGF23 homeostasis. Objective: To determine whether Fe and iron status are determinants of the levels of intact FGF23 (iFGF23) in elderly men. Methods: The MrOS study is a population-based study of elderly men (N = 1010; mean age, 75.3 years; range, 69–81 years). The levels of Fe, transferrin saturation (TS), and ferritin were evaluated in relation to the serum concentrations of iFGF23 before and after adjustments for confounders. Results: TS 60 mL/min, the levels of iFGF23 correlated (age-adjusted) negatively with the levels of Fe (r = − 0.15, p < 0.001) and TS (r = − 0.17, p < 0.001). The level of iFGF23 correlated positively (un-adjusted) with lumbar spine bone mineral density (BMD) (r = 0.14, p < 0.001), total body BMD (r = 0.11, p = 0.001), and total hip BMD (r = 0.09, p = 0.004). The corresponding correlations, when adjusted for age, weight, and height were: r = 0.08, p = 0.018; r = 0.05, p = 0.120; and r = 0.02, p = 0.624, respectively. No associations were found between BMD and the levels of Fe or TS. Multiple step-wise linear regression analyses [adjusting for age, body mass index (BMI), comorbidity index, cystatin C, C-reactive protein (hs-CRP), serum vitamin D 25-OH (25OHD), phosphate, calcium, parathyroid hormone (PTH), erythropoietin, hemoglobin, lumbar spine BMD, apolipoprotein B/A1 ratio] were performed in three separate models with Fe, TS or ferritin as potential explanatory variables. Fe and TS, but not ferritin, were independent predictors of iFGF23 level (standardized β-values: − 0.10, p < 0.001; − 0.10, p < 0.001; and − 0.05, p = 0.062, respectively). Conclusion: Low levels of Fe in elderly men are associated with high levels of iFGF23, independently of markers of inflammation and renal function, suggesting an iron-related pathway for FGF23 regulation

Trends in the prevalence, incidence and survival of non‐Hodgkin lymphoma subtypes during the 21st century – a Swedish lymphoma register study

Non-Hodgkin lymphoma (NHL) prognosis has improved in recent years, yet the number of patients living with the diagnosis, i.e. the prevalence, has seldom been reported. The prevalence provides a measure of the burden of disease, useful for healthcare planning and to optimise resource allocation. We provide a systematic presentation of temporal trends in absolute numbers of prevalent patients by NHL subtypes, linking them to trends in incidence, survival and mortality. Patients diagnosed 2000–2016 were identified in the national Swedish lymphoma register. Incidence and mortality rates, relative survival and prevalence were estimated for NHL overall and for major clinical and morphological subtypes. Poisson regression was used to test for temporal trends. Increasing incidence and improved survival have led to a 47% increase in the five-year prevalence of NHL overall in 2016 compared to 2004. An increasing prevalence was observed for all investigated subtypes during the study period, but most notably for diffuse large B cell lymphomas among aggressive subtypes (66%), and marginal zone lymphomas among indolent subtypes (135%). This dramatic increase in NHL prevalence underscores the need to develop and evaluate alternative follow-up schemes to use resources efficiently and still ensure optimal care of lymphoma survivors

Trends in the prevalence, incidence and survival of non-Hodgkin lymphoma subtypes during the 21st century – a Swedish lymphoma register study

Non-Hodgkin lymphoma (NHL) prognosis has improved in recent years, yet the number of patients living with the diagnosis, i.e. the prevalence, has seldom been reported. The prevalence provides a measure of the burden of disease, useful for healthcare planning and to optimise resource allocation. We provide a systematic presentation of temporal trends in absolute numbers of prevalent patients by NHL subtypes, linking them to trends in incidence, survival and mortality. Patients diagnosed 2000–2016 were identified in the national Swedish lymphoma register. Incidence and mortality rates, relative survival and prevalence were estimated for NHL overall and for major clinical and morphological subtypes. Poisson regression was used to test for temporal trends. Increasing incidence and improved survival have led to a 47% increase in the five-year prevalence of NHL overall in 2016 compared to 2004. An increasing prevalence was observed for all investigated subtypes during the study period, but most notably for diffuse large B cell lymphomas among aggressive subtypes (66%), and marginal zone lymphomas among indolent subtypes (135%). This dramatic increase in NHL prevalence underscores the need to develop and evaluate alternative follow-up schemes to use resources efficiently and still ensure optimal care of lymphoma survivors

Nationwide Assessment of Patient Trajectories in Mantle Cell Lymphoma: The Swedish MCLcomplete Project

Mantle cell lymphoma (MCL) is a B-cell malignancy currently considered incurable. Although some patients obtain prolonged remission after first-line chemoimmunotherapy, many will need several treatment lines. Here, we present a nationwide assessment of treatment strategies, time to progression and survival in MCL. All patients diagnosed with MCL 2006–2018 were identified in the Swedish Lymphoma Register. Information on all lines of therapy was extracted from the medical records. Overall and progression-free survival (OS and PFS) were assessed through August 2021. In total, 1367 patients were included (median age, 71 years) and median follow-up was 6.8 years. Two hundred and one (15%) were managed initially with watch-and-wait, but 1235 (90%) eventually received treatment. The most frequently used first-line regimens were rituximab-bendamustine (BR) (n = 368; 30%) and Nordic MCL2 (n = 342; 28%). During follow-up, 630 patients (46%) experienced relapse/progression and 546 (40%) received second-line treatment. The most frequently used second-line regimen was BR (n = 185; 34%) but otherwise a wide variety of second-line treatments were used. Further, 382 and 228 patients experienced a second or third relapse/progression, respectively. Median PFS after first (PFS-1), second (PFS-2), third (PFS-3), and fourth (PFS-4) treatment lines was 29.4, 8.9, 4.3, and 2.7 months. Patients with early progression, defined as a PFS-1 <24 months, had an inferior median OS of 13 versus 37 months in patients with later relapse. For patients treated with frontline BR, however, time to relapse had no impact on later outcome. By use of nationwide population-based data, we provide important benchmarks for future studies of all treatment lines in MCL

Effects of homocysteine lowering with B vitamins on cognitive aging: meta-analysis of 11 trials with cognitive data on 22,000 individuals.

BACKGROUND: Elevated plasma homocysteine is a risk factor for Alzheimer disease, but the relevance of homocysteine lowering to slow the rate of cognitive aging is uncertain. OBJECTIVE: The aim was to assess the effects of treatment with B vitamins compared with placebo, when administered for several years, on composite domains of cognitive function, global cognitive function, and cognitive aging. DESIGN: A meta-analysis was conducted by using data combined from 11 large trials in 22,000 participants. Domain-based z scores (for memory, speed, and executive function and a domain-composite score for global cognitive function) were available before and after treatment (mean duration: 2.3 y) in the 4 cognitive-domain trials (1340 individuals); Mini-Mental State Examination (MMSE)-type tests were available at the end of treatment (mean duration: 5 y) in the 7 global cognition trials (20,431 individuals). RESULTS: The domain-composite and MMSE-type global cognitive function z scores both decreased with age (mean ± SE: -0.054 ± 0.004 and -0.036 ± 0.001/y, respectively). Allocation to B vitamins lowered homocysteine concentrations by 28% in the cognitive-domain trials but had no significant effects on the z score differences from baseline for individual domains or for global cognitive function (z score difference: 0.00; 95% CI: -0.05, 0.06). Likewise, allocation to B vitamins lowered homocysteine by 26% in the global cognition trials but also had no significant effect on end-treatment MMSE-type global cognitive function (z score difference: -0.01; 95% CI: -0.03, 0.02). Overall, the effect of a 25% reduction in homocysteine equated to 0.02 y (95% CI: -0.10, 0.13 y) of cognitive aging per year and excluded reductions of >1 mo per year of treatment. CONCLUSION: Homocysteine lowering by using B vitamins had no significant effect on individual cognitive domains or global cognitive function or on cognitive aging