3.Iron accumulation and its impact on osteoporotic fractures in postmenopausal women.
Hui CAI ; Huimei ZHANG ; Weiting HE ; Heng ZHANG
Journal of Zhejiang University. Science. B 2023;24(4):301-311
Postmenopausal osteoporosis is a kind of degenerative disease, also described as "invisible killer." Estrogen is generally considered as the key hormone for women to maintain bone mineral content during their lives. Iron accumulation refers to a state of human serum ferritin that is higher than the normal value but less than 1000 μg/L. It has been found that iron accumulation and osteoporosis could occur simultaneously with the decrease in estrogen level after menopause. In recent years, many studies indicated that iron accumulation plays a vital role in postmenopausal osteoporosis, and a significant correlation has been found between iron accumulation and fragility fractures. In this review, we summarize and analyze the relevant literature including randomized controlled trials, systematic reviews, and meta-analyses between January 1996 and July 2022. We investigate the mechanism of the effect of iron accumulation on bone metabolism and discuss the relationship of iron accumulation, osteoporosis, and postmenopausal fragility fractures, as well as the main clinical treatment strategies. We conclude that it is necessary to pay attention to the phenomenon of iron accumulation in postmenopausal women with osteoporosis and explore the in-depth mechanism of abnormal bone metabolism caused by iron accumulation, in order to facilitate the discovery of effective therapeutic targets for postmenopausal osteoporosis.
Humans
;
Female
;
Osteoporotic Fractures
;
Osteoporosis, Postmenopausal/drug therapy*
;
Postmenopause
;
Osteoporosis
;
Bone Density
;
Estrogens
;
Iron/therapeutic use*
4.The efficacy and safety of intravenous sucrose iron therapy for recurrent iron deficiency anemia.
Jing Qian LIU ; Xia Wan YANG ; Xu LIU ; Jing HU ; Xiang Rong HU ; Xiao Xia LI ; Yu Fei ZHAO ; Yi Meng SHI ; Bao Hang ZHANG ; Wen Rui YANG ; Guang Xin PENG ; Xin ZHAO ; Feng Kui ZHANG
Chinese Journal of Hematology 2023;44(5):408-412
Objective: To evaluate the efficacy and safety of intravenous iron supplementation in patients with recurrent iron deficiency anemia (IDA) . Methods: This retrospective analysis of 90 patients with recurrent IDA from May 2012 to December 2021 was conducted, comparing the efficacy and safety of the intravenous iron therapy group and the oral iron therapy group. Results: Among the 90 patients with recurrent IDA, 20 were males and 70 were females, with a median age of 40 (range: 14-85) years. A total of 60 patients received intravenous iron supplementation and 30 received oral iron supplementation. The hematologic response rates in the intravenous iron group were significantly higher than those in the oral iron group at 4 and 8 weeks after treatment [80.0% (48/60) vs 3.3% (1/30) and 96.7% (58/60) vs 46.7% (14/30), all P<0.001, respectively]. The median increase in hemoglobin levels was also significantly higher in the intravenous iron group than in the oral iron group [38 (4, 66) g/L vs 7 (1, 22) g/L at week 4 and 44.5 (18, 80) g/L vs 19 (3, 53) g/L at week 8, all P<0.001]. The intravenous iron group had a significantly higher proportion of patients who achieved normal hemoglobin levels than the oral iron group (55.0% vs 0 and 90% vs 43.3%, all P<0.001, respectively). Iron metabolism indicators were tested before and after 8 weeks of treatment in 26 and 7 patients in the intravenous and oral iron groups, respectively. The median increase in serum ferritin (SF) levels in the intravenous iron group 8 weeks after treatment was 113.7 (49.7, 413.5) μg/L, and 54% (14/26) of these patients had SF levels of ≥100 μg/L, which was significantly higher than the median increase in SF levels in the oral iron group [14.0 (5.8, 84.2) μg/L, t=4.760, P<0.001] and the proportion of patients with SF levels of ≥100 μg/L (P=0.013). The incidence of adverse reactions was 3.3% (2/60) in the intravenous iron group, which was significantly lower than that in the oral iron group [20.0% (6/30), P=0.015]. Conclusion: Intravenous iron supplementation is more effective for hematologic response, faster hemoglobin increase, and higher iron storage replenishment rates compared with oral iron supplementation in patients with recurrent IDA, and it is well tolerated by patients.
Male
;
Female
;
Humans
;
Adolescent
;
Young Adult
;
Adult
;
Middle Aged
;
Aged
;
Aged, 80 and over
;
Anemia, Iron-Deficiency/epidemiology*
;
Sucrose/therapeutic use*
;
Ferric Compounds/therapeutic use*
;
Retrospective Studies
;
Iron/therapeutic use*
;
Hemoglobins/therapeutic use*
6.Efficacy and Mechanism of Buxue Yimu Pills on Gynecological Anemia: A Combination of Clinical and Network Pharmacology Study.
Yan-Fang WANG ; Yan DENG ; Su-Ying ZHANG ; Dong LIU ; Bin LUO ; Xue WANG ; Miao DENG ; Rui-Lin MA ; Ai-Jun SUN
Chinese journal of integrative medicine 2022;28(12):1072-1080
OBJECTIVE:
To compare the clinical efficacy and safety of oral administration of Buxue Yimu Pills (BYP, ), ferrous sulfate (FS), and the combination of BYP and FS on gynecological anemia, and investigate the mechanisms using network pharmacology.
METHODS:
A randomized, controlled, multi-center clinical trial was conducted. Totally 150 patients with hemoglobin of 70-110 g/L due to gynecological conditions were recruited and randomized (using the block randomization method) into Buxue Yimu Pills group (24 g/d), oral iron group (FS Tablets, 0.9 g/d), and combined treatment group (BYP, 24 g/d plus FS Tablets, 0.9 g/d), 50 patients in each group. At the enrollment and 4-week treatment, complete blood count, serum iron indexes were evaluated. Adverse events, liver and renal functions, as well as blood coagulation were observed. Network pharmacology was conducted to identify the active ingredients and explore the potential mechanisms of BYP.
RESULTS:
Ten (20%) and 7 (14%) participants discontinued the therapy due to gastrointestinal symptoms in oral iron and combination treatment groups. All 3 groups showed elevated hemoglobin. The patients in the iron group exhibited typically elevated in serum iron and ferritin and decreased in total iron-binding capacity. No change in iron indexes was observed in BYP group. The patients in the combination treatment group neither showed significant changes in serum ferritin nor total iron-binding capacity. No significant adverse reactions were observed in the BYP group. The network pharmacology identified 27 bioactive compounds and 145 targets of BYP on gynecological anemia. Biological processes and pathways including regulation of inflammation, hormone, angiogenesis and hemostasis, response to decreased oxygen levels, effects on myeloma cell, and response to metal ions were identified.
CONCLUSION
BYP contributes to the practical improvement on gynecological anemia potentially through multi-target mechanisms and optimized iron re-distribution. (Trial registration: No. NCT03232554).
Humans
;
Anemia/drug therapy*
;
Anemia, Iron-Deficiency/drug therapy*
;
Ferritins/therapeutic use*
;
Hemoglobins
;
Iron/therapeutic use*
;
Network Pharmacology
;
Drugs, Chinese Herbal
7.Iron metabolism, ferroptosis, and lncRNA in cancer: knowns and unknowns.
Lei QU ; Xinyu HE ; Qian TANG ; Xiao FAN ; Jian LIU ; Aifu LIN
Journal of Zhejiang University. Science. B 2022;23(10):844-862
Cancer cells undergo substantial metabolic alterations to sustain increased energy supply and uncontrolled proliferation. As an essential trace element, iron is vital for many biological processes. Evidence has revealed that cancer cells deploy various mechanisms to elevate the cellular iron concentration to accelerate proliferation. Ferroptosis, a form of cell death caused by iron-catalyzed excessive peroxidation of polyunsaturated fatty acids (PUFAs), is a promising therapeutic target for therapy-resistant cancers. Previous studies have reported that long noncoding RNA (lncRNA) is a group of critical regulators involved in modulating cell metabolism, proliferation, apoptosis, and ferroptosis. In this review, we summarize the associations among iron metabolism, ferroptosis, and ferroptosis-related lncRNA in tumorigenesis. This information will help deepen understanding of the role of lncRNA in iron metabolism and raise the possibility of targeting lncRNA and ferroptosis in cancer combination therapy.
Fatty Acids, Unsaturated
;
Ferroptosis
;
Humans
;
Iron/therapeutic use*
;
Neoplasms/metabolism*
;
RNA, Long Noncoding/genetics*
;
Trace Elements/therapeutic use*
8.Effects of pre-immunosupressive therapy iron overload on hematologic response of severe aplastic anemia.
Lei YE ; Liping JING ; Guangxin PENG ; Kang ZHOU ; Yang LI ; Yuan LI ; Jianping LI ; Huihui FAN ; Wenrui YANG ; Fengkui ZHANG ; Li ZHANG
Chinese Journal of Hematology 2016;37(4):324-328
OBJECTIVETo explore the effects of serum ferritin (SF) and iron overload (IO) pre-immunosupressive treatment (IST) on hematologic response of severe aplastic anemia (SAA/VSAA) patients treated with IST.
METHODS257 SAA/VSAA patients who underwent first-line IST from Feb, 2003 to Dec, 2011 in Anemia Therapeutic Centre, Institute of Hematology and Blood Diseases Hospital were retrospectively analyzed, the status of SF before IST and the IO-affected factors were studied. The effects of IO on hematologic response of SAA/VSAA patients were evaluated as well.
RESULTSThe median level of SF of 257 patients was 387 (6-2 004) μg/L. 36 patients (14%) had IO, including 20 SAA and 16 VSAA patients. According to univariate logistical regression analyses, IO was influenced by age>14 years (P=0.010) and blood transfusion (P<0.001). The multivariate logistic regression analysis showed that blood transfusion [P=0.001, OR=0.218 (95% CI 0.092-0.520)] was the only independent prognostic factor. SAA (but not for VSAA) patients with IO had much lower hematologic response rate in 6 month after IST (P=0.037). Absolute reticulocyte count and IO correlated with response at 6 month by univariate logistical regression analysis (P=0.014, 0.037). The multivariate logistic regression analysis showed that IO [P=0.021, OR=4.092 (95% CI 1.235-13.563)], ARC ≥20×10(9)/L [P=0.040, OR=2.743 (95% CI 1.049-7.175)] were independent prognostic factors.
CONCLUSION84.8% patients had high serum ferritin before IST, and 14.0% reached IO. Adult and more blood transfusion caused IO more likely. IO correlated with response at 6 month, and was independent prognostic factor.
Adult ; Anemia, Aplastic ; drug therapy ; physiopathology ; Blood Transfusion ; Ferritins ; blood ; Humans ; Immunosuppressive Agents ; therapeutic use ; Iron Overload ; physiopathology ; Logistic Models ; Reticulocyte Count ; Retrospective Studies
9.Efficacy and safety of deferasirox in aplastic anemia patients with iron overload: a single arm, multi-center,prospective study in China.
Jun SHI ; Hong CHANG ; Li ZHANG ; Yinqi SHAO ; Neng NIE ; Jing ZHANG ; Jinbo HUANG ; Li ZHANG ; Xudong TANG ; Richeng QUAN ; Chunmei ZHENG ; Haiyan XIAO ; Dengming HU ; Lingyan HU ; Feng LIU ; Yongming ZHOU ; Yizhou ZHENG ; Fengkui ZHANG
Chinese Journal of Hematology 2016;37(1):1-6
OBJECTIVETo explore the efficacy and safety of deferasirox in aplastic anemia (AA)patients with iron overload.
METHODSA single arm, multi- center, prospective, open- label study was conducted to evaluate absolute change in serum ferritin (SF)from baseline to 12 months of deferasirox administration, initially at a dose of 20 mg·kg(-1)·d(-1), and the safety in 64 AA patients with iron overload.
RESULTSAll patients started their deferasirox treatment with a daily dose of 20 mg · kg(-1) ·d(-1). The mean actual dose was (18.6±3.60) mg · kg(-1)·d(-1). The median SF decreased from 4 924 (2 718- 6 765)μg/L at baseline (n=64) to 3 036 (1 474- 5 551)μg/L at 12 months (n=23) with the percentage change from baseline as 38%. A median SF decrease of 651 (126-2 125)μg/L was observed at the end of study in 23 patients who completed 12 months' treatment, the median SF level decreased by 1 167(580-4 806)μg/L [5 271(3 420-8 278)μg/L at baseline; 3 036(1 474-5 551)μg/L after 12 months' treatment; the percentage change from baseline as 42% ] after 12 months of deferasirox treatment. The most common adverse events (AEs) were increased serum creatinine levels (40.98%), gastrointestinal discomfort (40.98%), elevated liver transaminase (ALT: 21.31%; AST: 13.11%)and proteinuria (24.59%). The increased serum creatinine levels were reversible and non-progressive. Of 38 patients with concomitant cyclosporine use, 12(31.8%)patients had two consecutive values >ULN, 10(26.3%)patients had two consecutive values >1.33 baseline values, but only 1(2.6%)patient's serum creatinine increased more than 1.33 baseline values and exceeded ULN. For both AST and ALT, no patients experienced two post- baseline values >5 ×ULN or >10 × ULN during the whole study. In AA patients with low baseline PLT count (less than 50 × 10(9)/L), there was no decrease for median PLT level during 12 months' treatment period.
CONCLUSIONSAA patients with iron overload could achieve satisfactory efficacy of iron chelation by deferasirox treatment. The drug was well tolerated with a clinically manageable safety profile and no major adverse events.
Anemia, Aplastic ; drug therapy ; Benzoates ; therapeutic use ; Blood Transfusion ; China ; Ferritins ; blood ; Humans ; Iron ; blood ; Iron Chelating Agents ; therapeutic use ; Iron Overload ; drug therapy ; Liver ; Prospective Studies ; Triazoles ; therapeutic use
10.Overlooked Management and Risk Factors for Anemia in Patients with Intestinal Behcet's Disease in Actual Clinical Practice.
Bun KIM ; Soo Jung PARK ; Sung Pil HONG ; Jae Hee CHEON ; Tae Il KIM ; Won Ho KIM
Gut and Liver 2015;9(6):750-755
BACKGROUND/AIMS: Anemia in patients with inflammatory bowel disease significantly affects the quality of life. The aim of this study was to investigate the frequency of and risk factors for anemia and to describe the management of anemia in patients with intestinal Behcet's disease (BD) in actual clinical practice. METHODS: We included 64 patients with intestinal BD who visited the outpatient clinic of a tertiary referral center in June 2011 and had available laboratory data for the subsequent 6 months. RESULTS: Anemia was detected in 26 patients (40.6%). After 6 months, anemia was still present in 14 of these patients (53.8%). The cause of anemia was investigated in eight patients (30.8%), and oral iron supplementation was prescribed to four patients (15.4%). Of these four patients, two (50%) recovered completely within 6 months. Anemia was associated with a high Disease Activity Index for Intestinal Behcet's Disease (DAIBD, p=0.024), erythrocyte sedimentation rate (p=0.003), and C-reactive protein (p=0.049) in univariate analysis. In multivariate analysis, the factor predictive for anemia in patients with intestinal BD was a higher DAIBD (> or =40; odds ratio, 4.08; 95% confidence interval, 1.21 to 13.71; p=0.023). CONCLUSIONS: Although anemia is common in intestinal BD patients, its clinical importance is overlooked in daily practice. Moderate to severe disease activity is predictive of anemia.
Adult
;
Anemia/drug therapy/epidemiology/*etiology
;
Behcet Syndrome/blood/*complications/pathology
;
Blood Sedimentation
;
C-Reactive Protein/analysis
;
Dietary Supplements
;
Disease Management
;
Female
;
Humans
;
Intestinal Diseases/blood/*complications/pathology
;
Iron/therapeutic use
;
Male
;
Middle Aged
;
Multivariate Analysis
;
Odds Ratio
;
Predictive Value of Tests
;
Risk Factors
;
Severity of Illness Index
;
Trace Elements/therapeutic use

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