Determination of Iron Metabolism-related Reference Values in a Healthy Adult Population

Bosch, Glenn Van den; Bossche, Jan Van den; Wagner, Carola; Schouwer, Pieter De; Vyvere, M. Van De; Neels, Hugo

doi:10.1093/clinchem/47.8.1465

Cited by 18 publications

(14 citation statements)

References 12 publications

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“…Similarly as in previous analyses, ferritin was explored as a continuous variable with a natural logarithm transformation and dichotomous variable (with the third quintile ferritin selected as the cutoff: ≤47.2 or >47.2 ng/ml). We found that male patients and the older group (>74 years old) had significantly higher ferritin levels ( P = 0.0001, 0.047 in Table 4 ), which was consistent with findings in the general population [ 36 ]. Interestingly, when defining radiographic severity based on medial JSW at baseline as a dichotomized variable by <4 mm (the top tertile), the severity group with smaller medial JSW had higher ferritin levels ( P = 0.032 by t-test).…”

Section: Resultssupporting

confidence: 89%

Age-dependent ferritin elevations and HFE C282Y mutation as risk factors for symptomatic knee osteoarthritis in males: a longitudinal cohort study

Kennish

Attur

et al. 2014

BMC Musculoskelet Disord

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BackgroundAge, gender and genetic predisposition are major intrinsic risk factors for osteoarthritis (OA). Iron increases are associated with age and gene mutation. In the present study, we examined whether serum ferritin, an indicator of total body iron stores, correlates with clinical features in patients with OA, and whether the hemochromatosis Fe (HFE) gene mutation plays a role.MethodsIn a 2-year longitudinal observational study, 127 patients with knee OA and 20 healthy individuals (controls) were enrolled. All patients underwent standardized weight-bearing fixed-flexion posteroanterior knee radiographs. Peripheral blood samples were analyzed for serum ferritin, and genotyped for HFE using allelic discrimination methods.ResultsHigher levels of serum ferritin were found in patients older than 56 years (P =0.0186) and males (P =0.0006), with a trend toward higher ferritin in patients with OA. HFE gene mutation carriers were more prevalent among patients with OA than among healthy controls. When stratified further by gender, we found that male patients with OA had higher levels of serum ferritin than male control subjects [odds ratio = 4.18 (limits of 95% confidence interval: 0.86–27.69, P = 0.048)]. Analyses of radiographic data indicated that higher ferritin was associated with narrower joint space width at baseline (P = 0.032) in male patients. Additionally, among men, risk prediction of radiographic severity [Kellgren-Lawrence (KL) grade >2)] in the higher ferritin group was almost five times that of the lower ferritin group (odds ratio = 4.74, P = 0.023).ConclusionOur data suggest that increased ferritin levels are associated with symptomatic knee OA in males. This finding needs to be validated in a larger cohort of patients.

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Section: Resultssupporting

confidence: 89%

Age-dependent ferritin elevations and HFE C282Y mutation as risk factors for symptomatic knee osteoarthritis in males: a longitudinal cohort study

Kennish

Attur

et al. 2014

BMC Musculoskelet Disord

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“…35 Furthermore, ferritin levels are expected to be similar in males and postmenopausal females, but may be reduced in premenopausal females. 36 The effect of tissue iron content on T2 is well known and has been described in the context of iron quantification in multiple organs, including bone marrow. [14][15][16]37 However, previous studies investigating T2 relaxation values with respect to bone marrow iron concentration did not consider general differences in blood parameters, including the hematocrit.…”

Section: Discussionmentioning

confidence: 99%

“…The observed difference between female and male subjects can potentially be explained by differences in the hematopoietic processes 12 and resulting differences in the composition of the hematopoietic components, especially with respect to iron‐containing components; for example, on average, male blood samples exhibit higher serum iron levels 34 and a higher hematocrit 35 . Furthermore, ferritin levels are expected to be similar in males and postmenopausal females, but may be reduced in premenopausal females 36 …”

Section: Discussionmentioning

confidence: 99%

Physiological variation of the vertebral bone marrow water T2 relaxation time

et al. 2020

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The aim of this study was to investigate physiological variations of the water T2 relaxation time in vertebral bone marrow with respect to age, body mass index (BMI), sex and proton density fat fraction (PDFF) based on single-voxel magnetic resonance spectroscopy (MRS) at 3 T. Multi-TE single-voxel STEAM MRS data of a single lumbar vertebra (L4 or L5) from 260 subjects (160/100 female/male, age: 0.7/37.1/77.7 years, BMI: 13.6/26.2/44.5 kg/m 2 [min./median/max.]) with no history of vertebral bone marrow pathologies were retrospectively included. All data were processed using a joint series T2-constrained time domain-based water-fat model. Water T2 and PDFF data were analyzed using (a) Pearson's correlation r and (b) multiple linear regression without interactions of the independent variables. Min./ median/max. water T2 and PDFF were 11.2/21.1/42.5 ms and 4.0%/36.8%/82.0%, respectively. Pearson's correlation coefficients were significant (P < .05) for water T2 versus age (r = −0.429/−0.210 female/male) and for water T2 versus PDFF (r = −0.580/−0.546 female/male) for females and males, respectively. Females showed significant higher water T2 values compared with males (P < .001). Multiple linear regression for water T2 without interactions revealed a R 2 = 0.407 with PDFF (P < .001) and sex (P < .001) as significant predictors. The current study suggests that under physiological conditions vertebral bone marrow water T2 is negatively correlated with age and PDFF and shows significant differences between females and males. The observed systematic trends are of relevance for the evaluation of T2 values and T2-weighted bone marrow parameters. Further research on the exact mechanisms and drivers of the observed water T2 behavior is required.

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“…Our main hypotheses were that (1) OSA shows inverse associations with ferritin levels; (2) low ferritin levels are associated with high PLMI; and (3) low ferritin levels are associated with high levels of subjective sleepiness (Figure 1). Because serum ferritin is well known to be lower in women than men, at least prior to menopause, 26 we explored sex-specific analyses and also considered premenopausal and postmenopausal women separately. Possible confounding variables that were taken into account included age, sex, BMI, likely RLS, and AHI when this was not the main explanatory variable.…”

Section: Discussionmentioning

confidence: 99%

Iron Stores, Periodic Leg Movements, and Sleepiness in Obstructive Sleep Apnea

O’Brien

Koo

Fan

et al. 2009

Journal of Clinical Sleep Medicine

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Scientific inveStigAtionSStudy Objectives: Most clinical sleep studies are performed for suspected obstructive sleep apnea (OSA), yet one-quarter to onehalf show periodic leg movements (PLMs), for reasons that remain unknown. Several other disparate sleep disorders also increase the risk for PLMs. We examined the novel hypotheses that OSA as a representative sleep disorder could promote lower body iron stores, as reflected by serum ferritin levels, and, through downstream effects on dopaminergic transmission, increase PLMs and daytime sleepiness. Methods: Subjects were recruited as they underwent laboratorybased polysomnography for suspected OSA. Serum ferritin levels were measured the next morning. Each subject completed an Epworth Sleepiness Scale and a brief questionnaire to assess for restless legs syndrome (RLS). Results: The frequency of apneic events showed no association with serum ferritin levels, before or after adjustment for age, sex, body mass index, and likely RLS (each p value > 0.3). Serum ferritin levels did not predict the frequency of PLMs (p = 0.7) or Epworth scores (p = 0.8). Iron deficiency as a dichotomous variable, determined by ferritin levels less than < 50µg/L or in combination with low transferrin saturation or mean corpuscular volume, showed similar results. In exploratory analyses, contrary to expectations, lower minimum oxygen saturation and increased sleep-stage shifts predicted increased rather than decreased ferritin levels (p = 0.03 and p = 0.02, respectively). Conclusions: Results of this study, powered to detect small to moderate effect sizes, strongly suggest that OSA does not cause lower serum ferritin levels, which, in turn, cannot explain PLMs or daytime sleepiness in these patients.

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Determination of Iron Metabolism-related Reference Values in a Healthy Adult Population

Cited by 18 publications

References 12 publications

Age-dependent ferritin elevations and HFE C282Y mutation as risk factors for symptomatic knee osteoarthritis in males: a longitudinal cohort study

Age-dependent ferritin elevations and HFE C282Y mutation as risk factors for symptomatic knee osteoarthritis in males: a longitudinal cohort study

Physiological variation of the vertebral bone marrow water T2 relaxation time

Iron Stores, Periodic Leg Movements, and Sleepiness in Obstructive Sleep Apnea

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