Sage Journals: Discover world-class research

Abstract

Purpose

It was aimed to reveal the relationship between CRP level after knee arthroplasty and gender difference and arthroplasty type.

Methods

Preoperative and postoperative (1st and 7th day, 1st and 3rd months) CRP values of the patients who underwent TKA or UKA were examined. The data were compared by categorizing them into primary male-female, secondary TKA-UKA groups.

Results

967 patients were included in the study (151 male, 685 female in the TKA group and 25 male, 106 female in the UKA group) In the TKA group, the mean age was 67.38 in males and 65.54 in females. In the UKA group, the mean age was 58.72 in males and 57,63 in females. CRP values were found to be statistically significantly lower in females compared to males in the preoperative period, postoperative 1st and 3rd months in patients who underwent TKA (p < .05). In the UKA group, it was found to be significantly lower in females in the preoperative period and at the postoperative 3rd month, p < .05). When the CRP values and their effect on the course of arthroplasty were evaluated according to the type of arthroplasty, there was no significant difference between the CRP values of the preoperative patients (p = .686). In addition, in the comparison made on the postoperative 1st day, 1st week, 1st month, and 3rd month, CRP values of the patient who underwent UKA were found to be significantly lower (p < .05). When analyzed separately by arthroplasty type, postoperative CRP values decreased to normal limits in 96.3% of patients who underwent TKA and 98.5% of patients who underwent UKA in the third month.

Conclusions

Our study showed that the uncomplicated course of CRP after TKA and UKA is gender-specific, and higher CRP values are observed in males than in females. The UKA group exhibited significantly lower postoperative CRP levels than the TKA group.

Keywords

osteoarthritis gender C-reactive protein (CRP)total knee arthroplasty (TKA)

Introduction

Despite surgical and technological advances, postoperative infections are one of the most devastating complications of knee arthroplasty and affect approximately 1%–3% of all total knee arthroplasty (TKA) cases.^1–4 Even if the infection is eradicated after the treatment of periprosthetic joint infections (PJI), it may result in decreased knee or hip joint function and a decrease in the patient's quality of life. If revision joint prosthesis cannot be applied in the treatment of PJE, arthrodesis, amputation, and permanent resection arthroplasty are other treatment options.⁵ PJE is a disease with high morbidity and may even result in mortality.⁵ The most important way to reduce morbidity and mortality is early diagnosis and treatment.⁶ There are many tests used both preoperatively and peroperatively for the diagnosis of PJE, but no diagnostic method has high sensitivity and high specificity.⁷ Serum C-reactive protein (CRP) is the most commonly used test in the diagnosis of PJE, as it is in all infections because it is simple and inexpensive.^8–12 In addition, CRP has been shown to be one of the most sensitive parameters in the evaluation of infection treatment outcomes.¹³

There is no clear consensus in the literature on the effect of patient-dependent and patient-independent factors on CRP values after knee arthroplasty. In particular, the potential effect of patient gender on CRP values after TKA is unclear.^14,15 In a study investigating the gender specificity of CRP values after unicondylar knee arthroplasty (UKA), no difference was demonstrated between males and females.¹⁶ Conversely, Windisch et al.¹⁷ showed for the first time that CRP values were gender-specific in the first 10 days after TKA. In addition, it may be difficult to distinguish between elevated CRP caused by postoperative infection and elevated CRP caused by surgery. The time-dependent course of CRP is important for the detection of early postoperative infection. For this reason, knowing when CRP values return to normal in the postoperative period may be important in differentiating PJE from surgery-related CRP elevation. This study was aimed primarily to investigate the effect of gender difference on CRP values and course and, secondarily, the effect of knee arthroplasty type (TKA and UKA) on CRP values and course.

Materials and methods

The study was designed as a retrospective cohort study after local ethics committee approval (No:KAEK-2022-12/19). The data recording file system of 2076 patients diagnosed with knee osteoarthritis and underwent either total knee arthroplasty (TKA) or unicompartmental knee arthroplasty (UKA) between January 2010 and December 2021 was examined. Out of these patients, 1823 underwent TKA, while 253 underwent UKA. Preoperative and postoperative (1st and 7th day, 1st and 3rd months) CRP values of the patients examined. Patients with inflammatory arthritis or inflammatory disease, a history of cancer, no CRP values, and patients with complications were excluded from the study. Preoperative and postoperative (1st and 7th day, 1st and 3rd months) CRP values of the patients examined. Patients with inflammatory arthritis or inflammatory disease, underwent revision arthroplasty, a history of cancer, no CRP values, and patients with complications were excluded from the study. Major surgical complications can be listed as recorded late and early joint infections, surgical site infections, revision surgery, perioperative fractures, urinary or intestinal infections, and pulmonary embolism. A standard surgical technique was applied to the patients by a single surgeon. Spinal block and spinal anesthesia were used as routine anesthesia methods, but when these methods were ineffective, general anesthesia was added. A standard parapatellar approach with a tourniquet was applied to each case. Femoral, tibial, and patellar components were fixed using polymethylmethacrylate cement containing gentamicin. A negative pressure hemovac drain was used and removed on the first day after surgery. All patients were mobilized on the first postoperative day.

CRP was measured using the latex particle-enhanced nephelometric immunoassay on the BN ProSpec analyzer (Dade Behring, Germany) and expressed in milligrams/deciliter (mg/dl). The CRP normal reference range of the device used in our center is 0–25. Primarily, the effect of gender difference on CRP values and course, and secondarily, the effect of knee arthroplasty type (Total or Unicondylar knee arthroplasty) on CRP values and course were examined.

Statistical analysis

Statistical analysis was performed using SPSS version 22 (SPSS Inc., IBM, NY, USA). Categorical variables were given as frequency and percentage, while numerical variables were given as mean values. After the normalization tests, the Mann-Whitney U test was used to compare the means of numerical data between the two groups. p values less than .05 were considered statistically significant.

Results

In the study cohort consisting of 2076 patients, after the exclusion criteria, 967 patients, including 176 (18.2%) male and 791 (81.8%) female, constituted the study sample. There were 685 females and 151 males in the TKA group and 106 females and 25 males in the UKA group. The mean age was 57.84 in UKA patients and 65.87 in TKA patients. There was a statistically significant difference (p < .05) (Table 1). In the TKA group, the mean age of males was 67.38, and the mean age of females was 65.54, which was statistically significant. In the UKA group, the mean age of males was 58.72, and the mean age of females was 57.63, which was not statistically significant (Table 2).

Table 1.

Comparison of the mean age of the patients according to the type of arthroplasty applied.

		N	Age mean	Std. Deviation	p value
Type of arthroplasty	UKA	131	57.84	5.87	0,00
Type of arthroplasty	TKA	836	65.87	7.49	0,00

Man Whitney U test.

TKA:Total Knee Arthroplasty, UKA:Unicompartmental Knee Arthroplasty.

Table 2.

Comparison of age values of groups by gender.

	Gender	N	Age mean	Std. Deviation	p value
UKA	Male	25	58.72	6.148	0.55
UKA	Female	106	57.63	5.820	0.55
TKA	Male	151	67.38	8.091	0.001
TKA	Female	685	65.54	7.326	0.001

Man Whitney U test.

TKA:Total Knee Arthroplasty, UKA:Unicompartmental Knee Arthroplasty.

When the effect of gender difference on CRP values and course was evaluated, it was found that there was a statistically significant decrease in females who underwent TKA in the preoperative period, in the 1st and 3rd months of the postoperative period (p < .05) (Table 3). When the CRP values of the patients who underwent UKA were compared according to gender, it was found that females were significantly lower in the preoperative period and in the postoperative 3rd-month p < .05) (Table 4).

Table 3.

Comparison of CRP values of patients who underwent TKA by gender.

TKA
	Gender	N	CRP Mean	Std. Deviation	p value
Preop	M	151	10.80	5.19	0.008
Preop	F	685	9.61	4.95	0.008
Postop 1. day	M	151	66.90	25.38	0.322
Postop 1. day	F	685	64.17	21.81	0.322
Postop 1. week	M	151	42.58	17.08	0.679
Postop 1. week	F	685	42.48	17.45	0.679
Postop 1. month	M	151	25.89	14.6	0.037
Postop 1. month	F	685	23.14	12.92	0.037
Postop 3. month	M	151	13.96	7.5	0.012
Postop 3. month	F	685	12.38	6.71	0.012

Man Whitney U test.

TKA:Total Knee Arthroplasty, M:male, F:female.

Normal CRP value:0-25.

Table 4.

Comparison of CRP values of patients who underwent UKA by gender.

UKA
	Gender	N	CRP Mean	Std. Deviation	p value
Preop	M	25	11.07	5.76	0.017
Preop	F	106	8.28	5.3	0.017
Postop 1. day	M	25	46.92	19.52	0.808
Postop 1. day	F	106	45.48	18.13	0.808
Postop 1. week	M	25	30.62	13.78	0.367
Postop 1. week	F	106	28.6	15.61	0.367
Postop 1. month	M	25	21.93	11.28	0.233
Postop 1. month	F	106	19.32	11.3	0.233
Postop 3. month	M	25	12.3	6.06	0.017
Postop 3. month	F	106	9.16	5.17	0.017

Man Whitney U test.

UKA:Unicompartmental Knee Arthroplasty, M:male, F:female.

Normal CRP value: 0-25.

When the CRP values and their effect on the course of arthroplasty were evaluated according to the type of arthroplasty, there was no significant difference between the CRP values of the preoperative patients (p = .686). In addition, in the comparison made on the postoperative 1st day, 1st week, 1st month, and 3rd month, CRP values of the patient who underwent UKA were found to be significantly lower (p < .05) (Table 5). In the TKA group, CRP values were within normal limits at a rate of 2% on the postoperative first day, while this rate was 96.3% on the postoperative 3rd month. In the UKA group, CRP values were within the normal range at a rate of 8.4% on the postoperative 1st day, while this rate was 98.5% on the postoperative 3rd month. When a general evaluation is made, according to the type of arthroplasty, postoperative CRP values decreased to normal limits in 96.3% of the patients who underwent TKA and 98.5% of the patients who underwent UKA in the third month. In Tables 6 and 7, CRP values obtained in the postoperative period are given in detail for TKA and UKA separately.

Table 5.

Comparison of CRP values according to arthroplasty type.

	Type of arthroplasty	N	CRP Mean	Std. Deviation	p value
Preop	TKA	836	10.58	5.16	0.75
Preop	UKA	131	10.53	5.76	0.75
Postop 1. day	TKA	836	66.41	24.78	0.000
Postop 1. day	UKA	131	46.64	19.20	0.000
Postop 1. week	TKA	836	42.56	17.13	0.000
Postop 1. week	UKA	131	30.24	14.10	0.000
Postop 1. month	TKA	836	25.39	14.34	0.008
Postop 1. month	UKA	131	21.44	11.28	0.008
Postop 3. month	TKA	836	13.67	7.39	0.008
Postop 3. month	UKA	131	11.70	6.01	0.008

Man Whitney U test.

TKA:Total Knee Arthroplasty, UKA:Unicompartmental Knee Arthroplasty, M:male, F:female.

Normal CRP value: 0-25.

Table 6.

CRP values of patients who underwent TKA in the postoperative period.

CRP value	Postop 1. Day		Postop 1. Week		Postop 1. Month		Postop 3. Month
CRP value	Frequency(N)	Percent (%)	Frequency(N)	Percent (%)	Frequency (N)	Percent (%)	Frequency (N)	Percent (%)
0–25 (Normal)	17	2.0	110	13.2	479	57.3	805	96.3
26–50	224	26.8	494	59.1	303	36.2	29	3.5
51–75	340	40.7	199	23.8	46	5.5	1	0.1
Over 75	255	30.5	33	3.9	8	1	1	0.1

TKA:Total Knee Arthroplasty.

Table 7.

CRP values of patients who underwent UKA in the postoperative period.

UKA
CRP value	Postop 1. Day		Postop 1. Week		Postop 1. Month		Postop 3. Month
CRP value	Frequency (N)	Percent (%)	Frequency (N)	Percent (%)	Frequency (N)	Percent (%)	Frequency (N)	Percent (%)
0–25 (Normal)	11	8.4	58	44.3	96	73.3	129	98.5
26–50	76	58.0	59	45.0	32	24.4	2	1.5
51–75	28	21.4	13	9.9	3	2.3	0	0
Over 75	16	12.2	1	0.8	0	0	0	0

UKA:Unicompartmental Knee Arthroplasty.

Discussion

In summary, our study shows that CRP level after knee arthroplasty is associated with gender difference. In addition, postoperative CRP values of patients who underwent UKA were generally lower than those of patients who underwent TKA. In the 3rd postoperative month, CRP values decreased to normal limits in 96.3% of the patients who underwent TKA and 98.5% of the patients who underwent UKA.

Infection following joint arthroplasty is a primary concern for surgeons. Despite the availability of multiple modalities, the diagnosis of PJE remains a challenge.¹⁸ The CRP value is often used to detect PJE. In addition, it is widely used to investigate the course of postoperative inflammation after TKA.^9,14,19 Although there are many studies on CRP values after TKA, the potential effect of patient gender is not clear enough.¹⁷ An anthropometric study demonstrated a gender-specific course of CRP independent of specific operations.²⁰ Larsson et al.¹⁶ evaluated the postoperative course of CRP after UKA according to the gender of the patients and stated that CRP was independent of gender. In contrast, Windisch et al.¹⁷ emphasized for the first time that the course of CRP in the first 10 days after TKA is gender specific. A higher course of CRP in males after total hip arthroplasty and spine surgery has been confirmed in other studies.^21,22 Our study data support the literature. In addition, according to the literature review we conducted, we believe that our study data is the first study to examine the gender difference in the course of CRP up to the 3rd month after arthroplasty.

It is unclear how gender difference affects the CRP level after arthroplasty. Sex hormones may cause a variation in the inflammatory and hemostatic response. Angele et al.²³ stated that sex hormones have an effect on the post-traumatic immune response. It has also been reported in studies that the anti-inflammatory response elicited by higher testosterone levels in males is reduced.^24,25 Siennicka et al.²⁶ In their study investigating serum levels of inflammatory and hemostatic markers in patients after acute coronary syndrome, they observed a variation in the inflammatory and hemostatic response between males and females after acute coronary syndrome and observed a higher CRP and IL-6 level in male patients than in females. In a multicenter study evaluating clinical outcomes in severely injured adults with blunt hemorrhagic shock, serum levels of IL-6, which increases CRP release, were statistically higher in males than females.²⁷ In addition, Sperry and Minei²⁵ reported a higher IL-6 level in males after traumatic injury and hemorrhagic shock. Bohl et al.²⁸ pointed out that the male gender is a risk factor for postoperative sepsis after total joint arthroplasty and supports the thesis that the inflammatory response after surgery is gender-dependent.

In addition, the severity of surgical trauma may also affect the CRP level.²⁹ Larson et al.¹⁶ showed that the postoperative CRP increase depended on the type of tissue affected, such as fat, bone, and muscle. Watt et al.¹⁵ showed that a higher level of CRP would be associated with increased surgical trauma. In conclusion, greater tissue damage during the surgical procedure in males may explain the higher CRP level. This can theoretically be explained by the larger male bones, the more stimulating cells (macrophages and platelets), and the greater release of proinflammatory mediators.³⁰ In our study, CRP values were significantly lower in patients treated with UKA than in patients treated with TKA. Our data support that tissue damage has an effect on the CRP value after surgery. Because less bone and soft tissue are traumatized in UKA, it causes a lower CRP rise compared to traditional TKA. Shen et al.¹⁹ compared CRP levels after four different types of arthroplasty. He found that CRP levels after hip resurfacing and computer navigation-assisted TKA were lower than those after conventional primary total hip arthroplasty and TKA. It can be assumed that less or no trauma to the medullary space in UKA would explain the lower CRP level. Our study data shows the long-term course of CRP, including data at the 1st and 3rd months after surgery. We believe these results can guide the course of CRP after knee arthroplasty without complications in male and female patients. It can contribute to the interpretation of early and late postoperative CRP values.

In conclusion, our study findings suggest that CRP increase in both sexes is similar due to the trauma caused by surgery in the early postoperative period. However, after the decrease in the effect of trauma in the late postoperative period, CRP again shows a similar course as in the preoperative period due to gender differences. This indicates that gender plays a significant role in the long-term course of CRP after arthroplasty.

Limitations

The retrospective design of the study was a natural limitation. The unequal sample size of the male and female groups was another limitation of our study. The CRP value taken from the patients' blood shows the systemic inflammatory response. This response may be caused not only by surgery but also by inflammation from other parts of the body. The most important disadvantage of this study is that local inflammation was not examined from the synovial fluid in the knee, and a systemic inflammatory test was used instead. Inflammation in another part of the patient during the test will increase the CRP value. Another limitation is that the tobacco use of the patients is not questioned. This may affect CRP values. Other inflammatory markers were not measured in our study besides CRP to confirm its course.

Conclusions

Footnotes

Authors contributions

Study conception and design: HA, OB, Data collection: HA,YSK,OB, Drafting of the article: HA, OB,YSK, Data analysis and interpretation: HA, OB,YSK, Critical revision of the article: HA, YSK.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Ethics approval

Ethical Principles of Research: Ethies committee approval with the registration number SÜKAEK-2022 12/19 was received from the Clinical Research Ethics Committee of Health Sciences University Samsun Training and Research Hospital.

Consent

Written informed consent from participants was not required because the study was retrospective and analyzed anonymized data with no risk to the patients.

Availability of data and materials

The datasets generated and analyzed during the current study are not publicly available due to privacy concern of participants but are available from the corresponding author on reasonable request.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs

Harun Altinayak

Yavuz Selim Karatekin

Orhan Balta

References

Huotari

Lyytikäinen

Hospital Infection Surveillance Team . Impact of postdischarge surveillance on the rate of surgical site infection after orthopedic surgery. Infect Control Hosp Epidemiol 2006; 27: 1324–1329.

Parvizi

Ghanem

Sharkey

, et al. Diagnosis of infected total knee: findings of a multicenter database. Clin Orthop Relat Res 2008; 466: 2628–2633.

Peersman

Laskin

Davis

, et al. Infection in total knee replacement: a retrospective review of 6489 total knee replacements. Clin Orthop Relat Res 2001; 392: 15–23.

Phillips

Crane

Noy

, et al. The incidence of deep prosthetic infections in a specialist orthopaedic hospital: a 15-year prospective survey. J Bone Joint Surg Br 2006; 88: 943–948.

Volin

Hinrichs

Garvin

. Two-stage reimplantation of total joint infections: a comparison of resistant and non-resistant organisms. Clin Orthop Relat Res 2004; 427: 94–100.

Parvizi

. Orthopedic infections: no one is denying anymore that we have a problem!. Berlin, Germany: Springer, 2019, pp. 1–2.

Berbari

Mabry

Tsaras

, et al. Inflammatory blood laboratory levels as markers of prosthetic joint infection: a systematic review and meta-analysis. J Bone Joint Surg Am 2010; 92: 2102–2109.

Kushner

Gewurz

Benson

. C-reactive protein and the acute-phase response. J Lab Clin Med 1981; 97: 739–749.

Moreschini

Greggi

Giordano

, et al. Postoperative physiopathological analysis of inflammatory parameters in patients undergoing hip or knee arthroplasty. Int J Tissue React 2001; 23: 151–154.

10.

Parvizi

Ghanem

Menashe

, et al.

Periprosthetic infection: what are the diagnostic challenges?

JBJS 2006; 88: 138–147.

11.

Parvizi

McKenzie

Cashman

. Diagnosis of periprosthetic joint infection using synovial C-reactive protein. J Arthroplasty 2012; 27: 12–16.

12.

Pepys

. C-reactive protein fifty years on. Lancet 1981; 1: 653–657.

13.

Foglar

Lindsey

. C-reactive protein in orthopedics. Orthopedics 1998; 21: 687–691.

14.

Neumaier

Braun

Sandmann

, et al. C-reactive protein in orthopaedic surgery. Acta Chir Orthop Traumatol Cech 2015; 82: 327–331.

15.

Watt

Horgan

McMillan

. Routine clinical markers of the magnitude of the systemic inflammatory response after elective operation: a systematic review. Surgery 2015; 157: 362–380.

16.

Larsson

Thelander

Friberg

. C-reactive protein (CRP) levels after elective orthopedic surgery. Clin Orthop Relat Res 1992; 275: 237-242.

17.

Windisch

Brodt

Roehner

, et al. Erratum to: The C-reactive protein level after total knee arthroplasty is gender specific. Knee Surg Sports Traumatol Arthrosc 2017; 25: 3990–3990.

18.

Kurtz

Ong

Lau

, et al. Prosthetic joint infection risk after TKA in the Medicare population. Clin Orthop Relat Res 2010; 468: 52–56.

19.

Shen

Zhang

, et al. C-reactive protein levels after 4 types of arthroplasty. Acta Orthop 2009; 80: 330–333.

20.

Lear

Chen

Birmingham

, et al. The relationship between simple anthropometric indices and C-reactive protein: ethnic and gender differences. Metabolism 2003; 52: 1542–1546.

21.

Chung

Won

Kwon

, et al. Comparison of serum CRP and procalcitonin in patients after spine surgery. J Korean Neurosurg Soc 2011; 49: 43–48.

22.

Rohe

Röhner

Windisch

, et al. Sex differences in serum C-reactive protein course after total hip arthroplasty. Clin Orthop Surg 2022; 14: 48–55.

23.

Angele

Frantz

Chaudry

. Gender and sex hormones influence the response to trauma and sepsis: potential therapeutic approaches. Clinics 2006; 61: 479–488.

24.

Kahlke

Angele

Ayala

, et al. Immune dysfunction following trauma-haemorrhage: influence of gender and age. Cytokine 2000; 12: 69–77.

25.

Sperry

Minei

. Gender dimorphism following injury: making the connection from bench to bedside. J Leukoc Biol 2008; 83: 499–506.

26.

Siennicka

Jastrzebska

Smialkowska

, et al. Gender differences in hemostatic and inflammatory factors in patients with acute coronary syndromes: a pilot study. J Physiol Pharmacol 2018; 69: 91–98.

27.

Sperry

Friese

Frankel

, et al. Male gender is associated with excessive IL-6 expression following severe injury. J Trauma 2008; 64: 572–578.

28.

Bohl

Sershon

Fillingham

, et al. Incidence, risk factors, and sources of sepsis following total joint arthroplasty. J Arthroplasty 2016; 31: 2875–2879.

29.

Neumaier

Metak

Scherer

. C-reactive protein as a parameter of surgical trauma: CRP response after different types of surgery in 349 hip fractures. Acta Orthop 2006; 77: 788–790.

30.

Pichardo

Trindade

Brindle

, et al. Method for estimating skeletal spongiosa volume and active marrow mass in the adult male and adult female. J Nucl Med 2007; 48: 1880–1888.

The relationship of C-reaktif protein level after knee artroplasty with gender difference and type of artroplasty

Abstract

Purpose

Methods

Results

Conclusions

Keywords

Introduction

Materials and methods

Statistical analysis

Results

Discussion

Limitations

Conclusions

Footnotes

Authors contributions

Declaration of conflicting interests

Ethics approval

Consent

Availability of data and materials

Funding

ORCID iDs

References