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Iron Supplementation for Anemia After Hip Fracture SurgeryA Randomized Trial of 300 Patients
Martyn J. Parker, MD, FRCS(Edinb)1
1 Peterborough District Hospital, Thorpe Road, Peterborough PE3 6DA, United Kingdom. E-mail address: Martyn.Parker@pbh-tr.nhs.uk
View Disclosures and Other Information
Disclosure: In support of his research for or preparation of this work, the author received, in any one year, a grant of less than $10,000 from the Peterborough Hospital Hip Fracture Fund. Neither he nor a member of his immediate family received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity.

A commentary by Henry D. Clarke, MD, is available at www.jbjs.org/commentary and as supplemental material to the online version of this article.
Investigation performed at the Peterborough District Hospital, Peterborough, United Kingdom

Copyright ©2010 American Society for Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2010 Feb 01;92(2):265-269. doi: 10.2106/JBJS.I.00883
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Abstract

Background: 

Anemia as a consequence of surgery is often treated with iron therapy. The evidence base for this practice is limited. To determine if oral iron therapy is beneficial for the treatment of anemia after surgery for the treatment of a hip fracture, we undertook a prospective, randomized controlled trial.

Methods: 

Three hundred patients with a hemoglobin level of <110 g/L after treatment for a hip fracture were randomized to receive either a twenty-eight-day course of ferrous sulfate therapy or no iron therapy. Hemoglobin levels were measured at six weeks after surgery. The length of the hospital stay and the mortality rate at one year were compared between groups.

Results: 

The mean rise in hemoglobin levels six weeks after discharge from the hospital was 21 g/L in the iron group, compared with 18 g/L in the no-iron group (p = 0.07). There was no significant difference between the two groups with regard to the length of hospital stay or the mortality rate. Seventeen percent of the patients who were allocated to iron therapy reported adverse effects of the medication.

Conclusions: 

The present study demonstrated that iron therapy had no clinically relevant benefit when used to treat anemia associated with a hip fracture.

Level of Evidence: 

Therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence.

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    References

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    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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    Martyn J. Parker, MD, FRCS(Edinb)
    Posted on September 02, 2010
    Mr. Parker responds to Mr. Maple and Mr. Tavakkolizadeh
    Peterborough and Stamford Hospital NHS Foundation Trust, Peterborough, United Kingdom

    I thank Doctors Maple and Tavakkolizadeh for their interest in my study. Clearly hip fractures patients have multiple co-morbidities and to analyze the study results in relationship to the patients age, sex, past medical history, hematological, gastrointestinal and genitourinary conditions etc. is too complex for such a limited study and would not add anything to the results.

    It is possible that measuring the patients iron, iron binding capacity or ferritin levels at admission may identify a subgroup of patients who benefit from iron therapy. Ideally this should have been part of this study but was precluded due to financial restrictions.

    The trial was specifically not designed to study the subgroup of patients who are anemic on admission. Clearly these patients merit further investigation as there may be iron deficiency anemia and it would be inappropriate to include such patients in a study of iron therapy versus none.

    The trial was designed to advise clinicians on the appropriate management for the majority of hip fracture patients who are not anemic on admission, but then are as a direct consequence of the fracture and surgery. Of course there are limitations in the interpretation of the data to specific patient subgroups for which a much larger study would be required. Given the negative conclusions of this study and the large bureaucratic limitations now imposed on clinical trials it is unlikely such a study will ever be undertaken and we have to use the best (albeit limited) evidence we have.

    Najma H. Maple
    Posted on August 01, 2010
    Response to 'Iron Supplementation for Anemia after Hip Fracture Surgery'
    NULL

    To the Editor:

    We read the article by Parker entitled, "Iron Supplementation for Anemia after Hip Fracture Surgery: A Randomised Trial of 300 Patients" with great interest (2010;92:265-9). We congratulate the author on trying to enhance our knowledge on this important topic.

    However, there are several queries that need addressing: firstly, the paper excluded those under the age of 60. We can assume that this was in order to focus attention on the elderly population in which anemia following surgery for hip fracture is often an issue. In light of this, an appreciation of the participants’ past medical histories, especially hematological, gastrointestinal and genitourinary conditions, is of great clinical relevance.

    Secondly, there was no distinction made between male and female patients. Given the difference in normal reference ranges, we think it would have been more appropriate to consider different inclusion criteria for men and women.

    Thirdly, patients with hemoglobin of less than 110g/L on admission were automatically excluded from the trial. By excluding those who may be anemic either acutely as a direct consequence of hip fracture or due to chronic iron deficiency or chronic disease, we think the author may have excluded a group of patients who may have been able to provide valuable information on the utilization of iron in the setting of an acute hip fracture.

    Finally, we believe the paper would have benefited from collaboration with the hematologists with regard to the physiology of iron utilization in the trauma setting. No mention was made of the Mean Cell Volume or Mean Corpuscular Hemoglobin which are relevant in this elderly population. There was also no mention of iron, iron binding capacity or ferritin levels which are often requested by hematologists when investigating anemia. This is especially so if the group with a hemoglobin of less than 110g/L on admission had been included in the study. This is likely to have been the group which benefited most from iron supplementation.

    Therefore we feel the conclusions of this study are somewhat limited in relation to benefits of iron supplementation in acute hip fractures.

    The authors did not receive any outside funding or grants in support of their research for or preparation of this work. Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity.

    Martyn J. Parker, MD, FRCS(Edinb)
    Posted on March 16, 2010
    Mr. Parker responds to Mr. Wall
    Peterborough and Stamford Hospital NHS Foundation Trust, Peterborough, United Kingdom

    I thank Mr. Wall for his interest in my study. Regarding the reference used to support the routine use of iron therapy, I have to agree with his comment that the reference given is not ideal. Iron therapy after anemia caused by surgery was routine in my practice and by my colleagues prior to this study. A search of the literature failed to find any reasonable paper to support this practice, hence the reason for the study being undertaken.

    Of course there remain issues related to iron therapy for anemia after surgery. Should a longer course of iron be given, should a larger dose be used, or should parental iron be given? In addition, it is possible that the small rise in the hemoglobin (0.3g/l) demonstrated in this study from iron therapy does have a clinical benefit. This study lacked the financial support to measure other outcome measures such as tiredness or perform a more detailed activity level assessment.

    My interpretation of the studies to date is that, because there is at present a lack of evidence to say that iron therapy has any beneficial clinical effect and clear evidence that iron therapy does have side effects (as well as financial costs, inconvenience, and administrative costs), iron therapy should not be used in this situation. Of course there are those that take the view of prescribing iron on the basis that it may have some benefit which has not been demonstrated so far. I personally cannot support this practice as my belief in medicine is that the potential proven benefit should always outweigh the risk of harm. Of course further detailed studies on iron therapy are warranted, however, because of the lack of funding available for such studies and the large administrative costs now imposed on drug studies, it is currently unlikely that such studies will be undertaken in the near future.

    Peter D.H. Wall
    Posted on March 03, 2010
    Small Differences with Large Consequences?
    North West Wales NHS Trust, Gwynedd, Wales, United Kingdom

    To the Editor:

    I would like to make two points about this interesting study (1):

    1. The author proposes that the background to the study was that the routine practice amongst clinicians for postoperative anemia is a course of iron therapy (2). The reference made is to a paper by Helm et al., who developed a protocol for reducing blood transfusion requirements in elective orthopaedic surgery in 2003 (2). Helm et al. provided patients with a two-week course of ferrous sulphate 200mg three times per day compared to ferrous sulphate 200mg twice daily by the current author. This cannot be overlooked as a potential outcome changing measure. In fact, a paper by Zauber et al. quoted for the author's power study used ferrous sulphate doses of 325mg four times per day (3).

    2. The author has tackled the issue of iron supplements for post operative anemia in non-elective hip fracture surgery. Hip fracture patients are very different from elective orthopaedic patients. They often have multiple co-morbidities and many have serious underlying medical conditions that precipitate falls and fractures. Therefore, crossover assumptions with elective orthopaedics may not be valid. The author has set a cut off of a 5% difference in hemoglobin (with a baseline 136g/l) as being the minimum level that would have any clinical significance for patients. The author references Zauber et al. for a 5% difference in hemoglobin having no clinical significance (3). In fact, Zauber et al. do not make this claim in their paper. Indeed they actually excluded patients who developed post operative morbidity such as myocardial infarction and renal failure, the very factors that may be influenced by differences in hemoglobin level. It would be very difficult to prove that differences in hemoglobin levels of 5%in this population of patients have no effect. To coin a phrase a difference in hemoglobin of 6g/l (5% of 136) could be the straw that breaks the camels back! The author's power studies and therefore study group size, were not set up to deal with differences of this magnitude and as such they would go undetected.

    The author did not receive any outside funding or grants in support of his research for or preparation of this work. Neither he nor a member of his immediate family received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the author, or a member of his immediate family, is affiliated or associated.

    References

    1. Parker MJ. Iron supplementation for anemia after hip fracture surgery: a randomized trial of 300 patients. J Bone Joint Surg Am. 2010;92:265-9.

    2. Helm AT, Karski MT, Parsons SJ, Sampath JS, Bale RS. A strategy for reducing blood-transfusion requirements in elective orthopaedic surgery. Audit of an algorithm for arthroplasty of the lower limb. J Bone Joint Surg Br. 2003;85:484-9.

    3. Zauber NP, Zauber AG, Gordon FJ, Tillis AC, Leeds HC, Berman E, Kudryk AB. Iron supplementation after femoral head replacement for patients with normal iron stores. JAMA. 1992;267:525-7.

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