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Open Access

Peer-reviewed

Research Article

Determinant of zinc deficiency in orthopaedic inpatients

  • Daisuke Iida,

    Roles Data curation, Validation

    Affiliation Department of Orthopaedic Surgery, Teikyo University Chiba Medical Center, Ichihara, Chiba, Japan

    ⨯
  • Tomonori Shigemura ,

    Roles Conceptualization, Formal analysis, Investigation, Methodology, Resources, Software, Validation, Writing – original draft, Writing – review & editing

    tshigepon@yahoo.co.jp

    Affiliation Department of Orthopaedic Surgery, Teikyo University Chiba Medical Center, Ichihara, Chiba, Japan

    ⨯
  • Yohei Yamamoto,

    Roles Validation, Visualization

    Affiliation Department of Orthopaedic Surgery, Teikyo University Chiba Medical Center, Ichihara, Chiba, Japan

    ⨯
  • Miki Morimoto,

    Roles Validation

    Affiliation Department of Orthopaedic Surgery, Teikyo University Chiba Medical Center, Ichihara, Chiba, Japan

    ⨯
  • Yasuaki Murata

    Roles Project administration, Supervision

    Affiliation Department of Orthopaedic Surgery, Teikyo University Chiba Medical Center, Ichihara, Chiba, Japan

    ⨯

Abstract

Zinc is vital for over 300 enzymes in major metabolic pathways, and deficiency can lead to serious conditions, especially post-surgery. This study aimed to investigate predictive factors of zinc deficiency in orthopaedic inpatients. A retrospective case-control study was conducted on patients admitted to Teikyo University Chiba Medical Center from 15 February to 31 August 2022. Patients were divided into zinc deficiency (< 60 µg/dL) and non-deficiency groups. Data included demographics, comorbidities, hospitalisation reasons, fracture details, medication use, and laboratory values. Fisher’s exact test and two-sample t-tests were used for analysis. Of 156 patients, 47 (30.1%) had zinc deficiency. The case group had higher fracture rates (68.1% vs. 33.9%; p < 0.001), and lower rates of spinal disease (2.1% vs. 31.2%; p < 0.001) and osteoarthritis (8.5% vs. 22.9%; p = 0.04). Fragility and hip fractures were more common in the case group. Anaemia, hip fracture, and hypoalbuminaemia were independent predictive factors of zinc deficiency.

Citation: Iida D, Shigemura T, Yamamoto Y, Morimoto M, Murata Y (2025) Determinant of zinc deficiency in orthopaedic inpatients. PLoS One 20(5): e0322142. https://doi.org/10.1371/journal.pone.0322142

Editor: Xinyan Bi, Agency for Science, Technology and Research (A*Star), SINGAPORE

Received: December 17, 2024; Accepted: March 17, 2025; Published: May 9, 2025

Copyright: © 2025 Iida et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper and Supporting Information files.

Funding: The author(s) received no specific funding for this work.

Competing interests: The authors have declared that no competing interests exist.

Introduction

Zinc is a nutritionally essential trace mineral required for the activity of more than 300 enzymes involved in major metabolic pathways [1]. It is distributed throughout the body, with 85% located in muscles and bones, 11% in the skin and liver, and the remainder in other tissues [1]. A zinc deficiency is known to cause a variety of symptoms, including skin disorders [2], taste disorders [3], gonadal dysfunction in men [4], loss of appetite [5], diarrhoea [6,7], delayed wound healing [8,9], and increased susceptibility to infection [10].

These symptoms can lead to serious complications, particularly postoperatively. For instance, a prospective 15-month study of 80 consecutive patients undergoing total hip arthroplasty (THA) demonstrated an association between zinc deficiency and delayed wound healing in THA patients [8]. Another prospective study of 97 patients undergoing hip hemiarthroplasty for hip fractures concluded that serum zinc levels predicted delayed wound healing [9]. Delayed wound healing after joint replacement surgery increases the risk of prosthetic joint infection (PJI) [11,12]. PJI is one of the most serious complications after arthroplasties, not only reducing patients’ quality of life [13], but also leading to longer hospital stays [14] and increased healthcare costs [15]. A study using data from the Nationwide Inpatient Sample in the United States demonstrated that length of stay was significantly longer for infected hip (9.7 days) and knee (7.6 days) arthroplasties compared to uninfected procedures (hip, 4.3 days; knee, 3.9 days) (p < 0.0001). The study also showed that hospitalisation charges were significantly greater for infected arthroplasties than for uninfected arthroplasties (hips, 1.76 times; knees, 1.52 times) (p < 0.0001) [16].

Understanding predictive factors of zinc deficiency before surgery is valuable for preventing symptoms arising from it. Furthermore, zinc deficiency has been linked to conditions such as cirrhosis [17,18], diabetes [19], chronic inflammatory bowel disease [20], and chronic kidney disease [21]. However, its association with orthopaedic disorders remains unclear. Additionally, predictive factors of zinc deficiency in orthopaedic inpatients before surgery are not well known.

To address these concerns, we conducted a retrospective case-control study, including patients with zinc deficiency in the case group and those without zinc deficiency in the control group, to examine predictive factors of zinc deficiency in hospitalised patients.

Materials and methods

Patient selection

The study included patients admitted to the Department of Orthopaedic Surgery of Teikyo University Chiba Medical Center between 15 February 2022 and 31 August 2022. The exclusion criteria were as follows: (1) patients whose zinc level was not measured during routine tests on admission, (2) patients who had previously been diagnosed with zinc deficiency, and (3) patients who were receiving zinc supplementation.

Study design

The study used a case-control design, with patients with zinc deficiency included in the case group and those without zinc deficiency included in the control group. In this study, serum zinc concentration served as the primary marker for assessing zinc deficiency, given its widespread use and availability as an indicator of zinc deficiency [22–25]. Zinc deficiency was characterized by a serum zinc concentration of less than 60 µg/dL, in accordance with the treatment guidelines for zinc deficiency as published by the Japanese Society of Clinical Nutrition [26]. Serum samples were obtained at the time of admission. This study was approved by the Institutional Review Board of Teikyo University, IRB No.23-155). Because this was a retrospective study, the requirement for informed consent was waived.

Data collection

The data used in this study were retrieved from the computerised database of Teikyo University Chiba Medical Center. The following data were retrieved from the patient records: demographics (gender, age, height, weight, body mass index [BMI]), comorbidity (diabetes mellitus, hypothyroidism, gastroesophageal reflux disease, depression, haemodialysis), the reason for hospitalisation, details of fractures, medication use (zinc, iron, magnesium, Vitamin D, and calcium supplements, proton pump inhibitors, H2 receptor antagonists, diuretics, antihypertensive, opioid, and antibiotics), and laboratory data (zinc, calcium, albumin, creatinine, estimated glomerular filtration rate, haemoglobin, haemoglobin A1c, C-reactive protein [CRP], and alkaline phosphatase). Height and weight were measured using height scales (Okada medical supply Co., Ltd.) and weight scales (TANITA Corporation), respectively.

Statistics

Means with standard deviations (SD) and percentages were used to report continuous and categorical variables, respectively. Statistical analyses were performed using Fisher’s exact test for categorical variables and a two-sample t-test for continuous variables. To identify factors associated with zinc deficiency, multivariate logistic regression analysis (backward stepwise regression model) was performed for items that were significantly different from the univariate analysis. All p values were two-sided, and p values less than 0.05 were considered statistically significant. All statistical analyses were performed using EZR version 1.52 [27], which is a graphical user interface for R version 4.02 (The R Foundation for Statistical Computing, Vienna, Austria). Specifically, it is a modified version of the R commander designed to add statistical functions frequently used in biostatistics.

Results

Patient characteristics

Between 15 February 2022 and 31 August 2022, 201 patients were admitted to our hospital. Among these patients, 13 were excluded due to duplicate cases admitted during the study period, and 32 were excluded owing to incomplete data on serum zinc or other factors. None were excluded for having a prior diagnosis of zinc deficiency or for taking zinc supplements. The study ultimately included 156 patients, with a mean age of 68.1 years (SD: 16.8). This cohort comprised 67 men and 89 women. While there were no significant differences in age or BMI between the genders, notable differences were observed in height and weight. The men were significantly taller (1.66 m [0.07] vs. 1.51 m [0.07]; p < 0.001) and heavier (66.5 kg [16.3] vs. 52.2 kg [12.3]; p < 0.001) than the women. Regarding hospital admission reasons, the incidence of fractures showed no significant difference (p = 0.87). However, spinal diseases were more prevalent in men than in women (31.3% vs. 15.7%; p = 0.03), and osteoarthritis (OA) was less frequent in men (9.0% vs. 25.8%; p < 0.01). The fracture details between the two groups revealed no significant differences (Table 1).

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Table 1. Baseline characteristics of study patients.

https://doi.org/10.1371/journal.pone.0322142.t001

We found that 47 (30.1%) patients had a zinc deficiency. The case and control groups were similar in terms of sex, height, and comorbidities, although there were significant differences in age, weight, and BMI. In particular, the mean (SD) age of the case group was significantly higher than that of the control group (75.5 years [13.8] vs. 65.0 years [17.1]; p < 0.001). The mean (SD) weight of the case group was significantly lower than that of the control group (53.8 kg [14.4] vs. 60.3 kg [16.1], p = 0.02). The mean (SD) BMI of the case group was significantly lower than that of the control group (21.7 kg/m2 [4.5] vs. 24.0 kg/m2 [5.2]; p < 0.01).

Regarding the reasons for hospitalisation, significant differences were observed between the case and control groups. The fracture rate was significantly higher in the case group than in the control group (68.1% vs. 33.9%; p < 0.001); spinal disease was significantly less common in the case group than in the control group (2.1% vs. 31.2%; p < 0.001); and OA was significantly less common in the case group than in the control group (8.5% vs. 22.9%; p = 0.04). The rates of fragility and hip and pelvic fractures were significantly higher in the case group than in the control group (p < 0.001, p < 0.001, p < 0.01, respectively). Among the medications, patients were significantly more likely to take iron supplements than controls (10.6% vs. 1.8%; p = 0.03) (Table 2).

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Table 2. Characteristics of zinc deficiency and controls.

https://doi.org/10.1371/journal.pone.0322142.t002

Laboratory findings

The case group exhibited a significantly lower mean (SD) serum zinc concentration of 46.2 µg/dL (9.7), compared to the control group’s mean (SD) of 76.3 µg/dL (16.5) (p < 0.001). Additionally, patients with zinc deficiency had significantly lower mean (SD) blood concentrations of albumin (3.3 g/dL [0.7] vs. 4.0 g/dL [0.5]; p < 0.001) and haemoglobin (10.8 g/dL [2.0] vs. 13.1 g/dL [1.9]; p < 0.001) than the control group. Moreover, patients with zinc deficiency had significantly higher mean (SD) blood concentrations of CRP (2.9 mg/dL [4.2] vs. 1.2 mg/dL [2.6]; p < 0.01) than the control group.

The incidence of hypoalbuminaemia was significantly higher in the case group than in the control group (74.5% vs. 23.9%, p < 0.001). Finally, the incidence of anaemia was significantly higher in the case group than in the control group (70.2% vs. 16.5%; p < 0.001) (Table 3).

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Table 3. Laboratory Findings of patients with zinc deficiency and controls.

https://doi.org/10.1371/journal.pone.0322142.t003

Predictive factors of zinc deficiency

According to univariate analysis, statistically significant indicators (p < 0.05) were included in multivariate logistic regression analysis, including age ≥ 60 (p < 0.01), age ≥ 70 (p < 0.01), age ≥ 80 (p < 0.01), weight (p = 0.02), high BMI (p = 0.01), fracture (p < 0.001), spinal disease (p < 0.001), OA (p = 0.04), fragility fracture (p < 0.001), hip fracture (p < 0.001), pelvic fracture (p < 0.01), iron supplements (p = 0.03), hypoalbuminaemia (p < 0.001), anaemia (p < 0.001), and CRP (p < 0.01). The following indicators, which were not significant but had p < 0.15, were also included in multivariate logistic regression analysis, including age ≥ 50 (p = 0.10), age ≥ 90 (p = 0.07), low BMI (p = 0.11), H2 receptor antagonists (p = 0.11), and antihypertensive (p = 0.11). The multiple logistic regression analysis identified that anaemia (OR, 9.36; 95% CI, 3.35–26.10; p < 0.001), hip fracture (OR, 6.24; 95% CI, 1.96–19.90; p < 0.01), and hypoalbuminaemia (OR, 3.63; 95% CI, 1.33–9.89; p < 0.05) were independent predictive factors of zinc deficiency. The results also indicated that spinal disease was associated with a low predictive value of zinc deficiency (OR, 0.056; 95% CI, 0.006–0.49; p < 0.01) (Table 4).

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Table 4. Predictive factors associated with zinc deficiency.

https://doi.org/10.1371/journal.pone.0322142.t004

Discussion

This study demonstrated that anaemia, hip fracture, and hypoalbuminaemia were independent predictive factors of zinc deficiency in orthopaedic inpatients. Additionally, our study identified a correlation between spinal disease and a decreased likelihood of zinc deficiency.

Hip fracture was identified as one of the independent predictive factors of zinc deficiency in orthopaedic inpatients by our hospital-based study (OR, 6.24; 95% CI, 1.96–19.90; p < 0.01). Gau et al. conducted a retrospective prevalence study involving 157 community residents aged 50 years or older, regularly followed up at a geriatric clinic in southeast Ohio [28]. They concluded that a previous hip fracture was a significant predictive factor for zinc deficiency (OR, 9.65; 95% CI, 1.69–55.15; p = 0.011), consistent with the finding of our study. We speculate that hip fractures serve as a predictive factor of zinc deficiency because of the involvement of background factors such as osteoporosis, a well-established contributor to zinc deficiency [29]. A study involving 122 osteoporotic patients aged 65 years and over with zinc deficiency demonstrated a significant increase in bone mineral density from baseline after 6 and 12 months of zinc treatment [30]. Consequently, in cases where osteoporosis is present in patients with hip fractures, monitoring zinc levels is advisable, and zinc supplementation should be considered if a deficiency is detected.

Anaemia was also shown to be one of the predictive factors for zinc deficiency in orthopaedic inpatients in our multivariate logistic regression analysis (OR, 9.36; 95% CI, 3.35–26.10; p < 0.001). This result is consistent with that of Gau et al. (OR, 1.73; 95% CI, 0.60–4.95; p = 0.308) [28]. The association between zinc and anaemia has been extensively documented in women of reproductive age [31–34], preschool-aged children [35–37], and adults [38,39]. It is hypothesized that the mechanism underlying anaemia related to zinc deficiency involves impaired functionality of the zinc finger protein GATA-1, crucial for the differentiation and proliferation of erythroblasts [40]. Jeng and Chen conducted a literature review and concluded that zinc status should be carefully monitored and that zinc supplementation could prevent and treat anaemia [41]. If anaemia remains refractory to treatment, the possibility of zinc deficiency should be considered.

Hypoalbuminaemia was identified as one of the predictive factors for zinc deficiency in orthopaedic inpatients by this retrospective case-control study (OR, 3.63; 95% CI, 1.33–9.89; p < 0.05). This result is consistent with the following previous studies [25,28]. Gau et al. reported that hypoalbuminaemia (serum albumin < 3.5 g/dL) was risk factors associated with zinc deficiency (OR, 5.17; 95% CI, 1.80–14.90; p = 0.002) by the retrospective prevalence study took place from 2014 to 2017 [28]. Hennigar et al. also showed that study participants with hypoalbuminaemia (serum albumin ≤ 3.5 g/dL) were more likely to have low serum zinc concentrations (OR, 11.2; 99% CI, 3.4–37.3; p < 0.0001) [25]. Serum zinc concentrations may be influenced by the status of zinc-binding proteins, such as albumin, which binds approximately 80–85% of serum zinc [42]. Conversely, zinc deficiency may affect albumin synthesis. A prior study demonstrated that serum albumin concentrations improved following zinc supplementation in individuals with severe zinc deficiency [43]. Therefore, if either zinc deficiency or hypoalbuminaemia is identified, investigating the other is advisable.

Based on a national micronutrient survey, Gebremedhin reported that CRP concentration demonstrated statistically significant negative correlations with serum zinc in both children and women of reproductive age. The correlation coefficients between CRP and serum zinc were -0.159 in children (p < 0.001) and -0.019 in women (p = 0.010) [44]. Interestingly, our study yielded similar results, indicating that patients with zinc deficiency had significantly higher mean (SD) blood concentrations of CRP (2.9 mg/dL [4.2] vs. 1.2 mg/dL [2.6]; p < 0.01) than the control group. However, multivariate logistic regression analysis revealed that CRP concentration was not a predictive factor for zinc deficiency.

The strength of this study is that it investigated zinc deficiency in orthopaedic inpatients, which had not previously been investigated, and it identified predictors of zinc deficiency. On the other hand, this study has several limitations. First, it was a retrospective study with a relatively small sample size, and the data were confined to a single centre. Second, the study exclusively included Japanese individuals, and race or ethnicity was not considered as a variable in the logistic regression analysis. Third, background factors like osteoporosis were not assessed in multiple logistic regression analyses. Fourth, this study assessed zinc deficiency using solely serum zinc concentration as an indicator, excluding consideration of zinc intake and symptoms of zinc deficiency. This decision aligns with common practices in the field, where serum zinc levels are widely employed as a key marker for assessing zinc deficiency [22–25]. To overcome these limitations, it is imperative to conduct large-scale, multinational clinical trials. This study is anticipated to act as a stimulus for such initiatives.

Conclusions

The study concluded that anaemia, hip fracture and hypoalbuminaemia were independent predictors of zinc deficiency in orthopaedic inpatients.

References

  1. 1. Tapiero H, Tew KD. Trace elements in human physiology and pathology: zinc and metallothioneins. Biomed Pharmacother. 2003;57:399–411.
  2. 2. Zou P, Du Y, Yang C, Cao Y. Trace element zinc and skin disorders. Front Med (Lausanne). 2023;9:1093868. pmid:36733937
  3. 3. Pisano M, Hilas O. Zinc and Taste Disturbances in Older Adults: A Review of the Literature. Consult Pharm. 2016;31(5):267–70. pmid:27178656
  4. 4. Liu Y-L, Zhang M-N, Tong G-Y, Sun S-Y, Zhu Y-H, Cao Y, et al. The effectiveness of zinc supplementation in men with isolated hypogonadotropic hypogonadism. Asian J Androl. 2017;19(3):280–5. pmid:27768007
  5. 5. Suzuki H, Asakawa A, Li JB, Tsai M, Amitani H, Ohinata K, et al. Zinc as an appetite stimulator - the possible role of zinc in the progression of diseases such as cachexia and sarcopenia. Recent Pat Food Nutr Agric. 2011;3(3):226–31. pmid:21846317
  6. 6. Lazzerini M, Wanzira H. Oral zinc for treating diarrhoea in children. Cochrane Database Syst Rev. 2016;12(12):CD005436. pmid:27996088
  7. 7. Lazzerini M. Oral zinc provision in acute diarrhea. Curr Opin Clin Nutr Metab Care. 2016;19(3):239–43. pmid:26963581
  8. 8. Zorrilla P, Gómez LA, Salido JA, Silva A, López-Alonso A. Low serum zinc level as a predictive factor of delayed wound healing in total hip replacement. Wound Repair Regen. 2006;14:119–22.
  9. 9. Zorrilla P, Salido JA, López-Alonso A, Silva A. Serum zinc as a prognostic tool for wound healing in hip hemi-arthroplasty. Clin Orthop Relat Res. 2004;420;304–8.
  10. 10. Shankar AH, Prasad AS. Zinc and immune function: the biological basis of altered resistance to infection. Am J Clin Nutr. 1998;68(2 Suppl):447S–463S. pmid:9701160
  11. 11. Schmalzried T.P.; Amstutz H.C.; Au M.K.; Dorey F.J. Etiology of deep sepsis in total hip arthroplasty. The significance of hematogenous and recurrent infections. Clin Orthop Relat Res. 1992;280:200–7.
  12. 12. Saleh K, Olson M, Resig S, Bershadsky B, Kuskowski M, Gioe T, et al. Predictors of wound infection in hip and knee joint replacement: results from a 20 year surveillance program. J Orthop Res. 2002;20(3):506–15. pmid:12038624
  13. 13. Shichman I, Sobba W, Beaton G, Polisetty T, Nguyen HB, Dipane MV, et al. The Effect of Prosthetic Joint Infection on Work Status and Quality of Life: A Multicenter, International Study. J Arthroplasty. 2023;38(12):2685–2690.e1. pmid:37353111
  14. 14. Ehrlichman RJ, Seckel BR, Bryan DJ, Moschella CJ. Common complications of wound healing. Prevention and management. Surg Clin North Am. 1991;71(6):1323–51. pmid:1948577
  15. 15. Bernstein LH, Shaw-Stiffel TA, Schorow M, Brouillette R. Financial implications of malnutrition. Clin Lab Med. 1993;13(2):491–507. pmid:8319432
  16. 16. Kurtz SM, Lau E, Schmier J, Ong KL, Zhao K, Parvizi J. Infection burden for hip and knee arthroplasty in the United States. J Arthroplasty. 2008;23(7):984–91. pmid:18534466
  17. 17. Nishikawa H, Asai A, Fukunishi S. The Significance of Zinc in Patients with Chronic Liver Disease. Nutrients. 2022;14(22):4855. pmid:36432541
  18. 18. Ozeki I., Yamaguchi M., Suii H., Tatsumi R., Arakawa T., Nakajima T., Kuwata Y. The association between serum zinc levels and subjective symptoms in zinc deficiency patients with chronic liver disease. J Clin Biochem Nutr. 2020;66:253–261.
  19. 19. Walter RM Jr, Uriu-Hare JY, Olin KL, Oster MH, Anawalt BD, Critchfield JW, et al. Copper, zinc, manganese, and magnesium status and complications of diabetes mellitus. Diabetes Care. 1991;14(11):1050–6. pmid:1797486
  20. 20. McClain C, Soutor C, Zieve L. Zinc deficiency: a complication of Crohn’s disease. Gastroenterology. 1980;78(2):272–9. pmid:7350050
  21. 21. Fukasawa H, Furuya R, Kaneko M, Nakagami D, Ishino Y, Kitamoto S, et al. Clinical Significance of Trace Element Zinc in Patients with Chronic Kidney Disease. J Clin Med. 2023;12(4):1667. pmid:36836202
  22. 22. Hambidge M, Krebs N. Assessment of zinc status in man. Indian J Pediatr. 1995;62(2):169–80. pmid:10829865
  23. 23. Wood RJ. Assessment of marginal zinc status in humans. J Nutr. 2000;130(5S Suppl):1350S-4S. pmid:10801942
  24. 24. Hess SY, Peerson JM, King JC, Brown KH. Use of serum zinc concentration as an indicator of population zinc status. Food Nutr Bull. 2007;28(3 Suppl):S403-29. pmid:17988005
  25. 25. Hennigar SR, Lieberman HR, Fulgoni VL 3rd, McClung JP. Serum Zinc Concentrations in the US Population Are Related to Sex, Age, and Time of Blood Draw but Not Dietary or Supplemental Zinc. J Nutr. 2018;148(8):1341–51. pmid:29947812
  26. 26. The Japanese Society of Clinical Nutrition. The treatment guideline of zinc deficiency. 2018 [cited 20 March 2020]. Available from: http://jscn.gr.jp/pdf/aen2018.pdf (In Japanese).
  27. 27. Kanda Y. Investigation of the freely available easy-to-use software “EZR” for medical statistics. Bone Marrow Transplant. 2013;48(3):452–8. pmid:23208313
  28. 28. Gau JT, Ebersbacher C, Kao TC. Serum zinc concentrations of adults in an outpatient clinic and risk factors associated with zinc deficiency. J Am Osteopath Assoc. 2020;120:796–805.
  29. 29. Rondanelli M, Peroni G, Gasparri C, Infantino V, Naso M, Riva A, et al. An overview on the correlation between blood zinc, zinc intake, zinc supplementation and bone mineral density in humans. Acta Ortop Mex. 2021;35(2):142–52. pmid:34731914
  30. 30. Nakano M, Nakamura Y, Miyazaki A, Takahashi J. Zinc Pharmacotherapy for Elderly Osteoporotic Patients with Zinc Deficiency in a Clinical Setting. Nutrients. 2021;13(6):1814. pmid:34071733
  31. 31. Nishiyama S, Kiwaki K, Miyazaki Y, Hasuda T. Zinc and IGF-I concentrations in pregnant women with anemia before and after supplementation with iron and/or zinc. J Am Coll Nutr. 1999;18(3):261–7. pmid:10376783
  32. 32. Ma A-G, Chen X-C, Xu R-X, Zheng M-C, Wang Y, Li J-S. Comparison of serum levels of iron, zinc and copper in anaemic and non-anaemic pregnant women in China. Asia Pac J Clin Nutr. 2004;13(4):348–52. pmid:15563439
  33. 33. Gibson RS, Abebe Y, Stabler S, Allen RH, Westcott JE, Stoecker BJ, et al. Zinc, gravida, infection, and iron, but not vitamin B-12 or folate status, predict hemoglobin during pregnancy in Southern Ethiopia. J Nutr. 2008;138(3):581–6. pmid:18287370
  34. 34. Özhan O, Erdem N, Aydoğdu İ, Erkurt A, Kuku İ. Serum Zinc Levels in Iron Deficient Women: A Case-Control Study. Turk J Haematol. 2016;33(2):156–8. pmid:27211046
  35. 35. Angelova MG, Petkova-Marinova TV, Pogorielov MV, Loboda AN, Nedkova-Kolarova VN, Bozhinova AN. Trace element status (iron, zinc, copper, chromium, cobalt, and nickel) in iron-deficiency anaemia of children under 3 years. Anemia. 2014; 2014:718089.
  36. 36. Ece A, Uyanik BS, Işcan A, Ertan P, Yiğitoğlu MR. Increased serum copper and decreased serum zinc levels in children with iron deficiency anemia. Biol Trace Elem Res. 1997;59(1–3):31–9. pmid:9522044
  37. 37. Gürgöze MK, Olçücü A, Aygün AD, Taskin E, Kiliç M. Serum and hair levels of zinc, selenium, iron, and copper in children with iron-deficiency anemia. Biol Trace Elem Res. 2006;111(1–3):23–9. pmid:16943594
  38. 38. Kelkitli E. Ozturk N. Aslan N.A. Kilic-Baygutalp N. Bayraktutan Z. Kurt N. Bakan N. Bakan E. Serum zinc levels in patients with iron deficiency anemia and its association with symptoms of iron deficiency anemia. Ann Hematol. 2016;95:751–6.
  39. 39. Abdelhaleim AF, Abdo Soliman JS, Amer AY, Abdo Soliman JS. Association of zinc deficiency with iron deficiency anemia and its symptoms: results from a case-control study. Cureus. 2019;11:e3811.
  40. 40. Zheng J, Kitajima K, Sakai E, Kimura T, Minegishi N, Yamamoto M, et al. Differential effects of GATA-1 on proliferation and differentiation of erythroid lineage cells. Blood. 2006;107(2):520–7. pmid:16174764
  41. 41. Jeng S-S, Chen Y-H. Association of Zinc with Anemia. Nutrients. 2022;14(22):4918. pmid:36432604
  42. 42. Craig G.M.; Evans S.J.; Brayshaw B.J.; Raina S.K. A study of serum zinc, albumin, alpha-2-macroglobulin and transferrin levels in acute and long stay elderly hospital patients. Postgrad Med J. 1990;66:205–9.
  43. 43. Bates J, McClain CJ. The effect of severe zinc deficiency on serum levels of albumin, transferrin, and prealbumin in man. Am J Clin Nutr. 1981;34(9):1655–60. pmid:6792896
  44. 44. Gebremedhin S. Adjusting serum zinc concentration for inflammation based on the data of Malawian preschool children and women of reproductive age. Nutrition. 2020;79–80:110841. pmid:32574846