Postoperative joint pain is associated with long-term all-cause mortality after total joint arthroplasty

Ming Liu; Andrew Furey; Proton Rahman; Guangju Zhai

doi:10.1371/journal.pone.0327757

. 2025 Jul 3;20(7):e0327757. doi: 10.1371/journal.pone.0327757

Postoperative joint pain is associated with long-term all-cause mortality after total joint arthroplasty

Ming Liu ¹, Andrew Furey ², Proton Rahman ³, Guangju Zhai ^1,^*

Editor: Yuanyuan Wang⁴

PMCID: PMC12225861 PMID: 40608839

Abstract

The aims of this study were to assess (1) if postoperative joint pain can predict long-term all-cause mortality after total joint arthroplasty (TJA), and (2) if postoperative joint pain was associated with causes of death (COD) in TJA patients. Patients who underwent total knee or hip arthroplasty were assessed once for their postoperative joint pain at least one-year after TJA using the Western Ontario and McMaster Universities Osteoarthritis Index Likert 3.0 pain subscale. Three pain definitions were utilized: “sustained pain” – pain on all five questions, “pain while active” – pain while walking and taking stairs, and “pain at rest” – pain while sitting/lying and at night while in bed. Patients reporting no pain were classified as controls. Associations between postoperative joint pain and mortality were assessed using Kaplan-Meier survival analysis and multivariable Cox proportional hazards regression to adjust for age at TJA, sex, body mass index (BMI), cardiovascular diseases (CVD), and cancer. The distribution of COD between pain groups and controls were compared using Fisher’s exact test. A total of 727 patients were included in the study, of which 129 (18%) were deceased. The prevalence of postoperative sustained pain, pain while active, and pain at rest at 4-year after TJA was 10, 17, and 12%, respectively. The all-cause mortality rate at 11-year after TJA was 20, 26, 19, and 15% in these pain groups and controls, respectively, significantly higher in pain while active group (p = 0.006). Pain while active was positively associated with mortality when knee and hip patients were analyzed together and separately (p ≤ 0.03, hazard ratio (HR)≥1.80), and the significances became stronger after adjusting for age at surgery, sex, BMI, CVD, and cancer (p < 0.001, HR ≥ 2.57). No association was observed between postoperative joint pain and COD. Our results demonstrated that postoperative joint pain could be an important predictor for long-term all-cause mortality in TJA patients.

Introduction

Total joint arthroplasty (TJA) is an effective treatment for end-stage joint diseases to relieve joint pain, restore joint function, and improve patients’ quality of life. Over 1.3 million TJAs are performed annually in the United States alone [1], and this number continues to grow as the population ages. The estimated increase of annual arthroplasty volume is projected to be 469–659% by 2060 [2].

Mortality is an often-overlooked outcome measure of elective procedures such as TJA, but risk of death is paramount to patients and their families as they weigh pros and cons of proceeding with TJA. It is important to identify indicators for mortality to better inform patients, enhance patient care algorithms, and monitor surgical care systems. Studies on mortality of TJA patients mainly focus on the utilization of patients’ demographic and surgical factors, comorbidities, and revision status in predicting short-term mortality [3–5]. Patients’ post-surgery responses are important measures to assess the effectiveness of treatment and quality of recovery. Patient-reported outcome provides valuable information on aspects of patients’ health status that are relevant to their quality of life, yet very few studies investigated the associations between these factors and long-term post-surgery mortality in TJA patients.

Despite being a procedure with relatively high success rate, 10–34% of patients still suffer from persistent joint pain after TJA [6]. Postoperative pain is routinely assessed after TJA surgeries to evaluate the effectiveness of the procedure and patient satisfaction towards the surgery [7], however, this information has yet to be utilized in areas beyond monitoring patient recovery. Pain perception is highly subjective. Biological, psychological, and social factors all contribute to the individual variations in pain sensitivity, threshold, and tolerance [8,9]. Meanwhile, these factors could also affect the severity of pain-related conditions, some of which have high prevalence and fatality rates in older patients. It is meaningful to study the associations between pain intensity from the patient’s perspective and mortality in TJA patients.

Therefore, we undertook this study to investigate (1) if patient-reported postoperative joint pain can predict long-term all-cause mortality after TJA, and (2) if patient-reported postoperative joint pain was associated with causes of death (COD) in TJA patients.

Methods

Study participants

The study participants were derived from the Newfoundland Osteoarthritis Study (NFOAS) which recruited 1086 patients aged at least 20 years old who underwent total knee or hip arthroplasty largely due to osteoarthritis (OA) with a small number of patients due to other joint diseases between 30/11/2011 and 05/02/2017 in St. Clare’s Mercy Hospital and Health Science Centre General Hospital in St. John’s, Newfoundland and Labrador (NL), Canada [10]. Patients were recruited consecutively. The NFOAS was approved by the Health Research Ethics Authority of Newfoundland and Labrador (HREB # 2011.311) and informed written consent was obtained from all participants.

Postoperative joint pain assessment

Patients’ postoperative pain in the replaced joint was assessed once at least one year after TJA using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Likert 3.0 pain subscale. This pain subscale consists of five questions evaluating patients’ self-reported pain intensity while walking on a flat surface, going up and down stairs, in bed at night, sitting/lying, and standing upright, respectively. Each question is scored on a Likert scale of 0–4, with 0 representing no pain and 4 representing severe pain. For patients who answered at least one but not all five questions, the missing scores were imputed using the mean scores of the given questions. Three pain definitions were utilized in the analyses: “sustained pain” – pain scores ≥ 1 for all five questions; “pain while active” – pain scores ≥ 1 while walking on a flat surface and going up and down stairs; and “pain at rest” – pain scores ≥ 1 while sitting/lying and in bed at night. Patients reporting no pain for all five questions were classified as controls. These case definitions were used previously [11]. For patients who had both knee and hip replaced and had WOMAC pain data for both joints, both records were included in the analysis.

Demographic and mortality data collection

Sex, date of birth, and comorbidity data were collected using a general health questionnaire prior to the TJA and age at surgery and age at postoperative pain assessment were then calculated. Weight and height data were retrieved from the Eastern Health Meditech Health Care Information System, body mass index (BMI) was then calculated as weight in kg divided by squared height in meters. Data on three mortality variables, patients’ mortality, date of death, and COD, were retrieved from the Newfoundland and Labrador Centre for Health Information Mortality System.

Data analyses

Normality of data distribution was tested with the Shapiro-Wilk test. Age at surgery, age at pain assessment, and BMI, which were not normally distributed, were compared using the Mann-Whitney U test. Sex distribution, prevalence of 37 comorbidities, and percentage of patients with multiple comorbidities (number of comorbidities > 2 to > 10) were tested with Chi-squared test or Fisher’s exact test. The associations between postoperative joint pain and mortality were assessed using Kaplan-Meier survival analysis, and multivariable Cox proportional hazards regression was utilized to adjust for age at surgery, sex, BMI, cardiovascular diseases (CVD), and cancer [12]. COD between pain groups and controls were compared using Fisher’s exact test. Analyses were performed for combined knee and hip joints as well as joint specifically. Significance level for prevalence of comorbidities/percentage of patients with multiple comorbidities was set at α = 0.001 to control for multiple testing of 46 comparisons using the Bonferroni method, and that for other variables was set at α = 0.05. All analyses were performed in R version 4.2.3 with survival [13] and survminer [14] packages. Visualizations of the results were performed with ggplot2 R package [15].

Results

Among the 1,086 consented patients, 95 patients had bipolar hemiarthroplasty, and TJA for three patients was cancelled, hence these patients were excluded from the analysis. Mortality data for 26 patients could not be linked because they lived outside of NL/Canada. Among the remaining 962 patients, 38 deceased prior to postoperative joint pain assessment, 30 were unable to participate due to health reasons, 27 withdrew consent or unwilling to answer questions, and 140 were unreachable (Fig 1). Out of the remaining 727 patients, four had both knee and hip replaced, therefore a total of 731 records were included in the final analyses (Fig 1). Compared to these patients, the excluded patients had higher age and lower BMI (p < 0.001, S1 Table).

Fig 1 — WOMAC: Western Ontario and McMaster Universities Osteoarthritis Index.

For combined knee and hip patients, 55% were women; mean age was 64.8 years and mean BMI was 33.6 kg/m². There were 493 patients who had knee arthroplasty, of which 57% were women; mean age was 65.0 years and mean BMI was 33.6 kg/m². There were 238 patients who had hip arthroplasty, of which 50% were women; mean age was 64.5 years and mean BMI was 31.3 kg/m². Hip patients had significantly lower BMI compared to knee patients (p < 0.001) but there was no difference in age or sex distribution (p = 0.99 and 0.06, respectively). More details are presented in Table 1.

Table 1. Characteristics of the study participants ^#.

Knee + Hip	All (n = 731)	Control (n = 546, 75%)	Sustained pain (n = 70, 10%)	P- value	Pain while active (n = 124, 17%)	P- value	Pain at rest (n = 89, 12%)	P- value
Female (%)	55	54	57	0.62	56	0.62	55	0.86
Age at surgery (yrs)	64.81 ± 8.77	65.69 ± 8.62	59.36 ± 9.02	<0.001**	61.76 ± 8.93	<0.001**	60.00 ± 8.87	<0.001**
Age at pain assessment (yrs)	68.80 ± 8.76	69.73 ± 8.59	63.16 ± 9.13	<0.001**	65.48 ± 8.98	<0.001**	63.79 ± 8.90	<0.001**
BMI (kg/m²)	33.57 ± 6.95	33.39 ± 7.06	33.10 ± 6.18	0.83	33.98 ± 6.59	0.21	33.13 ± 6.14	0.77
Knee	All (n = 493)	Control (n = 361, 73%)	Sustained pain (n = 44, 9%)	P- value	Pain while active (n = 89, 18%)	P- value	Pain at rest (n = 57, 12%)	P- value
Female (%)	57	56	61	0.52	60	0.57	56	0.99
Age at surgery (yrs)	64.97 ± 7.95	65.64 ± 8.02	60.05 ± 7.47	<0.001**	62.57 ± 8.02	0.003*	60.83 ± 7.49	<0.001**
Age at pain assessment (yrs)	68.97 ± 7.96	69.73 ± 8.02	63.80 ± 7.31	<0.001**	66.21 ± 7.98	<0.001**	64.59 ± 7.39	<0.001**
BMI (kg/m²)	33.64 ± 6.91	34.43 ± 7.04	34.71 ± 6.53	0.53	35.34 ± 6.63	0.14	34.67 ± 6.24	0.48
Hip	All (n = 238)	Control (n = 185, 78%)	Sustained pain (n = 26, 11%)	P- value	Pain while active (n = 35, 15%)	P- value	Pain at rest (n = 32, 13%)	P- value
Female (%)	50	50	50	0.98	49	0.90	53	0.72
Age at surgery (yrs)	64.49 ± 10.27	65.79 ± 9.70	58.21 ± 11.24	<0.001**	59.68 ± 10.76	<0.001**	58.52 ± 10.88	<0.001**
Age at pain assessment (yrs)	64.45 ± 10.23	69.73 ± 9.64	62.07 ± 11.66	<0.001**	63.64 ± 11.05	0.001*	62.35 ± 11.08	<0.001**
BMI (kg/m²)	31.34 ± 6.50	31.33 ± 6.63	30.38 ± 4.45	0.97	30.52 ± 5.09	0.77	30.38 ± 4.94	0.89

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: Values are the mean ± standard deviation unless indicated otherwise. P-values were obtained by the Mann-Whitney U test, Student’s t-test, or Chi-squared test wherever appropriate comparing each pain group with controls; *: P-value < 0.05; **: P-value < 0.001. BMI: body mass index.

Postoperative joint pain and mortality

The average follow-up time for postoperative pain in the operated joint was 4.0 years, and the last follow-up date was July 29, 2019. Out of the 731 WOMAC records, 725 had complete scores, and imputation was performed for the other six records that each had one or two missing scores. Mortality data was collected 11.0 years on average after the TJA. Data on mortality, date of death, and COD for patients who deceased prior to January 2022 were extracted on June 3, 2024, and COD data for patients who deceased in 2022 were extracted on January 15, 2025. The COD data for patients who deceased after 2022 were unavailable due to the timeline of data release to the Newfoundland and Labrador Centre for Health Information Mortality System.

For combined knee and hip patients, prevalence of postoperative sustained pain, pain while active, and pain at rest was 10, 17, and 12%, respectively, and 75% of patients were controls. Pain patients were significantly younger than controls at the time of surgery as well as pain assessment (p < 0.001, Table 1). Prevalence of clinical depression, Crohn’s disease, migraine, golfer’s elbow, and polycystic ovary syndrome and percentage of patients with more than 8 comorbidities were higher in pain groups, but the differences were not significant after controlling for multiple testing (p ≤ 0.04, S2 Table). The mortality rate was 18% for the entire cohort, and 20, 26, 19, and 15% for the three pain groups and controls, respectively, significantly higher in pain while active group compared to controls (p = 0.006, Table 2). Deceased patients were older at the time of TJA and included more men compared with those who were alive (p ≤ 0.003). The demographic factors of deceased and alive patients are presented in Table 3.

Table 2. All-cause mortality rate after joint arthroplasty in control and pain groups ^#.

	Control		Sustained pain			Pain while active			Pain at rest
Joint Group	N	Mortality rate (%)	N	Mortality rate (%)	P- value	N	Mortality rate (%)	P- value	N	Mortality rate (%)	P- value
Knee + Hip	546	15	70	20	0.32	124	26	0.006*	89	19	0.37
Knee	361	16	44	18	0.72	89	25	0.06	57	19	0.54
Hip	185	14	26	23	0.23	35	29	0.03*	32	19	0.49

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: P-values were obtained by the Chi-squared test comparing each pain group with controls; *: P-value < 0.05.

Table 3. Patient characteristics by death status in control and pain groups ^#.

Knee+Hip	Control (n = 546)			Sustained pain (n = 70)			Pain while active (n = 124)			Pain at rest (n = 89)
	Deceased (n = 84)	Alive (n = 462)	P- value	Deceased (n = 14)	Alive (n = 56)	P- value	Deceased (n = 32)	Alive (n = 92)	P- value	Deceased (n = 17)	Alive (n = 72)	P- value
Female (%)	39	57	0.003*	64	55	0.55	53	58	0.66	65	53	0.37
Age at surgery (yrs)	71.25 ± 8.57	64.68 ± 8.24	<0.001**	65.06 ± 6.76	57.94 ± 8.99	0.01*	66.77 ± 7.62	60.01 ± 8.73	<0.001**	63.88 ± 6.87	59.08 ± 9.08	0.09
BMI (kg/m²)	32.00 ± 6.49	33.63 ± 7.13	0.04*	32.43 ± 3.99	33.27 ± 6.64	0.95	33.69 ± 5.74	34.08 ± 6.88	0.97	33.06 ± 4.15	33.14 ± 6.54	0.63
Knee	Control (n = 361)			Sustained pain (n = 44)			Pain while active (n = 89)			Pain at rest (n = 57)
	Deceased (n = 58)	Alive (n = 303)	P- value	Deceased (n = 8)	Alive (n = 36)	P- value	Deceased (n = 22)	Alive (n = 67)	P- value	Deceased (n = 11)	Alive (n = 46)	P- value
Female (%)	40	59	0.005*	63	61	1.00	50	63	0.29	64	54	0.58
Age at surgery (yrs)	71.16 ± 8.37	64.58 ± 7.51	<0.001**	65.87 ± 3.55	58.75 ± 7.52	0.009*	67.69 ± 6.41	60.89 ± 7.82	<0.001**	63.82 ± 5.11	60.11 ± 7.83	0.22
BMI (kg/m²)	33.04 ± 6.51	34.70 ± 7.12	0. 12	31.98 ± 2.91	35.32 ± 6.98	0.25	33.98 ± 5.04	34.79 ± 7.05	0.31	33.09 ± 3.64	35.05 ± 6.69	0.45
Hip	Control (n = 185)			Sustained pain (n = 26)			Pain while active (n = 35)			Pain at rest (n = 32)
	Deceased (n = 26)	Alive (n = 159)	P- value	Deceased (n = 6)	Alive (n = 20)	P- value	Deceased (n = 10)	Alive (n = 25)	P- value	Deceased (n = 6)	Alive (n = 26)	P- value
Female (%)	38	52	0.22	67	45	0.64	60	44	0.47	67	50	0.66
Age at surgery (yrs)	71.44 ± 9.16	64.87 ± 9.50	0.005*	63.98 ± 9.94	56.47 ± 11.25	0.22	64.75 ± 9.87	57.66 ± 10.61	0.15	63.98 ± 9.94	57.25 ± 10.84	0.17
BMI (kg/m²)	29.47 ± 5.80	31.61 ± 6.72	0.07	33.03 ± 5.36	29.59 ± 3.95	0.04*	33.06 ± 7.33	29.51 ± 3.59	0.15	33.03 ± 5.36	29.77 ± 4.74	0.07

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: Values are the mean ± standard deviation unless indicated otherwise. P-values were obtained by the Mann-Whitney U test, Chi-squared test, or Fisher’s exact test wherever appropriate comparing deceased and alive patients in each group; *: P-value < 0.05; **: P-value < 0.001. BMI: body mass index.

For knee joint, prevalence of postoperative sustained pain, pain while active, and pain at rest was 9, 18, and 12%, respectively, and 73% of patients were controls (Table 1). The mortality rate was 18% for all knee patients, and 18, 25, 19, and 16% for the three pain groups and controls, respectively, not significantly different between pain groups and controls (p ≥ 0.06, Table 2).

For hip joint, prevalence of postoperative sustained pain, pain while active, and pain at rest was 11, 15, and 13%, respectively, and 78% of patients were controls (Table 1). The mortality rate was 17% for all hip patients, and 23, 29, 19, and 14% for the three pain groups and controls, respectively, significantly higher in pain while active group compared to controls (p = 0.03, Table 2).

Kaplan-Meier survival analysis showed that pain while active was positively associated with mortality with a hazard ratio (HR) of 1.92, 1.80, and 2.18 for knee and hip combined, knee, and hip, respectively (p ≤ 0.03, Table 4), and the HR became higher after adjusting for age at surgery, sex, BMI, CVD, and cancer (HR = 2.96, 2.57, and 4.31 for knee and hip combined, knee, and hip, respectively, p < 0.001, Fig 2). Sustained pain or pain at rest was not associated with mortality (p ≥ 0.25, Table 4).

Table 4. Kaplan-Meier survival estimates ^#.

	Sustained pain		Pain while active		Pain at rest
Joint Group	HR (95% CI)	P-value	HR (95% CI)	P-value	HR (95% CI)	P-value
Knee + Hip	1.38 (0.78, 2.43)	0.26	1.92 (1.28, 2.88)	0.001*	1.36 (0.81, 2.28)	0.25
Knee	1.22 (0.58, 2.56)	0.60	1.80 (1.10, 2.94)	0.02*	1.34 (0.70, 2.55)	0.37
Hip	1.67 (0.69, 4.06)	0.25	2.18 (1.05, 4.52)	0.03*	1.38 (0.57, 3.35)	0.48

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#: P-values, hazard ratios, and confidence intervals were obtained by the Kaplan-Meier survival analysis; *: P-value < 0.05. HR: hazard ratio; CI: confidence interval.

Fig 2 — **(A), knee patients (B) and hip patients** **(C)**. P-values, hazard ratios, and confidence intervals were obtained by the multivariable Cox proportional hazards regression analysis adjusting for age, sex, body mass index, cardiovascular diseases, and cancer. HR: hazard ratio.

Postoperative joint pain and COD

COD data were available for 78 patients and classified into eight categories: neurological conditions, cardiac/circulatory conditions, pulmonary conditions, digestive system conditions, genito/urinary/reproductive conditions, infections, neoplasms, and unspecified conditions. The two leading CODs were cardiac/circulatory conditions and neoplasms, causing 35 and 27% of deaths, respectively (Table 5). Cardiac/circulatory conditions were the leading COD in the three pain groups and controls, responsible for 83, 40, 56, and 34% of deaths, respectively. Neoplasms were the second leading COD in all four groups, responsible for 17, 30, 22, and 24% of deaths, respectively (Table 5). There was no difference in COD between pain groups and controls (p ≥ 0.47, Table 5).

Table 5. Cause of death in study groups.

	All with COD (n = 78)	Controls with COD (n = 50)	Sustained pain with COD (n = 8)		Pain while active with COD (n = 22)		Pain at rest with COD (n = 9)
COD	N (%)	N (%)	N (%)	P- Value *	N (%)	P- Value *	N (%)	P- Value *
				0.65		0.90		0.47
Cardiac/circulatory conditions	27 (35)	17 (34)	5 (83)		8 (40)		5 (56)
Neoplasms	21 (27)	12 (24)	1 (17)		6 (30)		2 (22)
Pulmonary conditions	13 (17)	10 (20)	–		2 (10)		–
Neurological conditions	6 (8)	3 (6)	–		2 (10)		1 (11)
Infections	5 (6)	3 (6)	–		1 (5)		–
Digestive system conditions	2 (3)	1 (2)	–		1 (5)		1 (11)
Genito/urinary/reproductive conditions	2 (3)	2 (4)	–		–		–
Unspecified	2 (3)	2 (4)	–		–		–

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* P-values were obtained by the Fisher’s exact test comparing each pain group with controls. COD: cause of death.

Discussion

Assessing long-term mortality following TJA is important to help elucidate the potential benefits of TJA to overall patient health. Meta-analysis on studies published between 2011 and 2021 showed that the average 10-year mortality rate was 16.43% after total hip arthroplasty [16] and 10.18% after total knee arthroplasty [17]. Our cohort had a comparable mortality rate in hip patients (17%) but higher rate in knee patients (18%). This could be due to the differences in study populations and study duration. Our NL population has a unique genetic structure [18] which could affect its susceptibility to diseases, and our evaluation for mortality covered the entire coronavirus disease 2019 (COVID-19) pandemic period [19] during which higher mortality rate was observed in TJA patients [20].

Older age and male sex have been reported to be risk factors for long-term mortality after TJA [21,22]. We also observed deceased patients were most likely to be men and older at the time of surgery than the patients who were alive. Older age has long been recognized as a risk factor for post-surgery mortality which has been connected to the increased vulnerability to stressors resulting in decreased physiological reserves and deregulation of multiple systems [23]. The higher percentage of men in the deceased group could be due to the lower life expectancy of men, which has been attributed to the differences in biological characteristics such as sex hormones and genetic factors, stress level, as well as behavioral and epidemiological factors between men and women [24,25].

Postoperative joint pain and mortality

WOMAC is a widely used self-administered questionnaire to evaluate patient-reported joint pain [26], and it has been demonstrated that the WOMAC pain subscale has a high test-retest reliability [27]. Using WOMAC pain subscale and the three pain definitions, we observed that 9–18% patients experienced chronic joint pain after TJA, consistent with previous reports [6]. Our results showed that pain while active was positively associated with mortality at 11 years after TJA, and this association was not specific to patients who had knee or hip arthroplasty, suggesting that this type of pain might affect patients on a broader scope. To date, the only other study that investigated the predictive value of postoperative WOMAC pain scores in long-term mortality of TJA patients was a study conducted by Klimek et al. which reported no association between joint-specific WOMAC assessment and long-term mortality [28]. The conflicting findings could be due to the differences in pain evaluation period, pain classification method, as well as study population as mentioned above. Klimek et al. evaluated joint pain at 12-month after TJA in a German cohort, while our pain evaluation was conducted at four years on average after TJA in the NL population, when the pain had become more chronic. The pain intensity in their study was classified into four groups based on the total pain scores, 0–8, 9–11, 12–14, and 15–20, while our study used three pain definitions based on the characteristics of pain reflected by the five questions, which were more relevant to the impairment of different aspects of patients’ daily activities [11]. Our findings are supported by previous reports which showed that joint pain was associated with 21–65% increased risks of death [29], and chronic pain nearly doubled mortality rate [30].

We did not observe any association between sustained pain or pain at rest and mortality after TJA, which could be due to the smaller sample sizes in these pain groups. Future studies are needed to further investigate the predictive values of these two types of pain in mortality in TJA patients.

Postoperative joint pain and COD

We also examined the relationships between postoperative joint pain and COD in TJA patients but did not find any significant association. The conditions that caused most of the deaths in pain patients and controls were cardiac/circulatory conditions followed by neoplasms. These two conditions were previously reported as leading CODs in TJA patients [17]. This indicated that postoperative joint pain might accelerate the courses of these diseases and eventually lead to higher mortality.

Pain while active is negatively associated with total volume of physical activity mediated by physical activity enjoyment [31]. Physical activity has been shown to have inverse relationships with all-cause mortality and deaths from cardiovascular diseases, coronary heart diseases, and cancers [32,33], all of which were leading CODs in patients with postoperative pain in our study. It is plausible that the positive association between pain while active and mortality observed in the current study might be driven by deaths from these conditions in which lower levels of physical activity played a role. In addition, conditions causing joint pain are associated with an increased prevalence of long-term opioid use [34]. Opioids have been widely used for postoperative pain management and 24–29% of senior patients reported being on opioids at 12-month after TJA [35,36]. Chronic opioid use is associated with increased risk for myocardial infarction/coronary revascularization and can cause a myriad of cardiovascular complications [37]. Unfortunately, we did not have data on opioid use in our cohort. The role of opioid use in the relationship between postoperative pain and mortality requires further investigation. Another common observation in chronic pain patients is the high prevalence of depression. In our cohort, 11% of patients with pain while active reported having clinical depression while the prevalence in control group was only 4% (S2 Table). Evidence has suggested that chronic pain and depression may be based on common neuroplasticity mechanism changes and their coexistence tends to further aggravate the severity of both disorders [38]. Depression is positively associated with cancer recurrence and mortality [39], and can also lead to an increased risk of cardiovascular disease by driving the development or exacerbation of traditional cardiac risk factors [40]. Interestingly, cardiac rehabilitation and exercise training has been shown to reduce psychological distress, especially depression [40], while pain is limiting patients in performing these exercises. The intertwined relationships between chronic pain, depression, and cardiovascular diseases as well as cancers could be important players behind the observed high mortality in patients with postoperative joint pain.

Alleviating joint pain or helping patients to achieve a pain-free state is the primary goal of TJA and the focus in postoperative care. However, the observation of the current study raised an interesting question: are all joint pains equal? Or, in other words, is treating pain itself enough in patients with joint pain during activities after TJA? Given the previous evidence on the associations between pain, physical activity, depression, and cardiovascular diseases and cancers, it might be time to open new topics for discussion: whether treating other conditions closely related to pain and helping these patients resume regular daily activities should also be important parts in the therapeutic regime for TJA patients, a question not only involving the health care system but also social support.

There were some limitations in this study. The percentage of study participants lost to follow-up was high as often seen in long-term follow-up studies, and age and BMI differed between the included and excluded participants, and this could potentially bias the results. Data on COD was not available for all patients, which further reduced our sample size and statistical power. Post-operative joint pain scores were imputed for a small number of patients, although it was unlikely that this would have affected the results given that > 99% of the WOMAC records were complete. As the main aim of this study was to investigate whether postoperative joint pain as the outcome of TJA could be associated with long-term mortality, our analysis did not account for preoperative level of pain. Studies on the relationship between surgery response such as the changes between preoperative and postoperative joint pain and mortality are also needed to broaden our understanding of the impact of TJA on mortality. In addition, no data on medication use was available, so we were unable to determine whether patients in the control group were indeed pain free or taking pain medication for other comorbidities. Furthermore, the unique structure of the NL population could limit the generalizability of our findings to other populations. More studies are needed to further evaluate the predictive value of postoperative joint pain in long-term mortality and investigate the deeper connections between such pain and mortality in TJA patients.

Conclusions

Patient-reported postoperative joint pain, particularly pain while active, could be a valuable predictor of long-term all-cause mortality in TJA patients. The findings could help inform patients in postoperative care and develop more targeted patient care algorithms in TJA patients.

Supporting information

S1 Table. Patient characteristics of included and excluded TJA patients.

Values are the mean ± standard deviation unless indicated otherwise. P-values were obtained by the Mann-Whitney U test or Chi-squared test wherever. *: P-value < 0.001. BMI: body mass index; TJA: total joint arthroplasty.

(DOCX)

pone.0327757.s001.docx^{(15.2KB, docx)}

S2 Table. Comparison of prevalence of comorbidities and percentage of patients with multiple comorbidities between pain groups and controls.

Values are p values obtained with Chi-squared test or Fisher’s exact test comparing each pain group with controls. Values smaller than 0.05 are marked in bold.

(DOCX)

pone.0327757.s002.docx^{(44.7KB, docx)}

Acknowledgments

We thank all study participants who made this study possible.

Abbreviations

BMI: body mass index
COD: causes of death
CVD: cardiovascular diseases
HR: hazard ratio
NFOAS: Newfoundland Osteoarthritis Study
NL: Newfoundland and Labrador
OA: osteoarthritis
TJA: total joint arthroplasty
WOMAC: Western Ontario and McMaster Universities Osteoarthritis Index

Data Availability

Data cannot be shared publicly because of the study's ethics application approved by the Health Research Ethics Authority (HREA) of Newfoundland and Labrador (Email: info@hrea.ca). Data are available from the HREA of Newfoundland and Labrador (contact via info@hrea.ca) or corresponding author Dr. Guangju Zhai (contact via gzhai@mun.ca) for researchers who meet the criteria for access to confidential data.

Funding Statement

Author GZ received the following funding: the Canadian Institutes of Health Research (https://cihr-irsc.gc.ca/e/193.html, FRN#175015; 153298; 143058; 132178; 191966), the Arthritis Society (https://arthritis.ca/, ID# 22-121), the Research and Development Corporation of Newfoundland and Labrador (https://www.gov.nl.ca/iet/royalties/innovation-business-dev-fund/, 5404.1423.102), and Memorial University of Newfoundland Medical Research Fund (https://www.mun.ca/medicine/research/medical-research-foundation/). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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PLoS One. doi: 10.1371/journal.pone.0327757.r001

Decision Letter 0

Yuanyuan Wang

PONE-D-25-06222Postoperative joint pain is associated with long-term all-cause mortality after total joint arthroplastyPLOS ONE

Dear Dr. Zhai,

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Reviewer #1: The manuscript “Postoperative joint pain is associated with long-term all-cause mortality after total joint Arthroplasty” examined the effect of post-operative pain on mortality among patients undergoing TJR. Specific comments and clarifications are below:

1. Abstract (lines 14-16): “… their postoperative joint pain at least one-year after TJA…” Was WOMAC collected at several time points after surgery? Please clarify.

2. Methods, Page 5: Please include the exact duration of the follow-up period (e.g., last date, average # of years of follow-up) and the number of post-operative measurements.

3. Page 5, lines 79-80: Please clarify what post-operative time point was used for the analysis.

4. Page 6: I think that the label ‘sustained pain’ is misleading as it is based on a one-time pain reporting based on a question asking for pain in the past 48 hours.

Furthermore, I think that post-operative pain status is not the best variable to accomplish the study objectives, as it does not account for the level of pre-operative pain. I think a variable looking at changes in pain pre- and post- operatively is more appropriate for the study question. Please comment on the choice of the pain variables used.

5. Page 7: Given that comorbidity data was available, I wonder why the models did not control for comorbidities. Please, clarify

6. Results, Page 7: Given the significant attrition (33%), please expand on the sources of loss to follow-up. For example, how many did not have mortality data and why (e.g., unable to link?), how many did not complete WOMAC? Additionally, how the sample of patients include and excluded differ in terms of basic demographic variables collected. Please include this information in the discussion of the study limitations.

7. Table 1 (knee): the data for age and sex appears to be scrambled.

8. Table 4: Are these estimates from Kaplan-Meier or Cox models?

9. Supplementary Table 1: I suggest including the prevalence of comorbidities. I don’t think that p-values without the prevalence are useful.

Reviewer #2: Authors present retrospective, secondary analysis of data derived from the Newfoundland Osteoarthritis Study regarding correlation between WOMAC pain scores (classified as ‘sustained pain,’ ‘pain while active,’ and ‘pain at rest) and long-term (11-year) mortality with the idea that post-arthroplasty pain is understudied outside of directly assessing surgical outcomes and that this is an important area of study as chronic pain may have important consequences on health outcomes and mortality. Authors set the stage by reviewing the rising use of arthroplasty surgery as well as previously published work discussing mortality and post-operative pain following hip and knee arthroplasty. After analysis (Kaplan-Meier survival analysis, multivariable Cox proportional hazards regression) the authors conclude that “patient-reported postoperative joint pain, particularly pain while active, could be a valuable predictor of long-term all-cause mortality in TJA patients” and further recommend that this pain be addressed in patients who experience it.

The authors (2 from the division of Genetics & Genomics, 1 from the department of internal medicine, 1 from the department of surgery) having educational training in epidemiology and clinical experience caring for this patient population appear to have the appropriate training to undertake this study.

While successful arthroplasty surgery and the prevention of post-operative pain/mortality are important topics, there are several considerations to be addressed in this manuscript before it will add clearly and positively to the literature.

1. Statistical analysis. Do the authors control for any of the comorbidities listed in the primary analysis? It does not appear that this was the case. It would be important to control for comorbidities (coronary artery disease, chronic obstructive pulmonary disease, peripheral arterial disease, diabetes) which are likely stronger predictors of mortality post-operative mortality in the post-operative setting than pain. It would also be important to control for these comorbidities as some of them may be associated with pain with activity (i.e., CAD, PAD). The authors mention 37 comorbidities being examined with Chi-squared or Fisher’s exact test – however many of these comorbidities are not relevant predictors of mortality. Olsen et al. offer a more concise and relevant list of comorbidities in the citation below.

Olsen F, Hård Af Segerstad M, Nellgård B, Houltz E, Ricksten SE. The role of bone cement for the development of intraoperative hypotension and hypoxia and its impact on mortality in hemiarthroplasty for femoral neck fractures. Acta Orthop. 2020 Jun;91(3):293-298. doi: 10.1080/17453674.2020.1745510. Epub 2020 Apr 2. PMID: 32237931; PMCID: PMC8023921.

2. Selection and interpretation of PROM (WOMAC). The authors bin patients into four groups (‘sustained pain’ versus ‘pain while active’ versus ‘pain at rest’ and controls). Is there any basis for using this approach previously in the literature? The authors citation for utilizing this approach references one of their previous studies which correlated metabolic biomarkers with ‘sustained’ pain. This previous work does not adequately prove that parsing apart the WOMAC measure in this way is valid. How specifically were patients binned? If a patient answered a 1 on both activity (walking, going up/down stairs) questions and a 1 on only a single rest (pain at night, pain while sitting) question were they still binned as a “pain while active” patient? What about the contralateral scenario?

3. Discussion/interpretation of results. The conclusion that ‘Efforts should be taken to address such pain in these patients, especially in those with preexisting cardiac/circulatory conditions and/or neoplasms to potentially reduce increased mortality’ highlights the disconnect between the studies methodology, conclusions, and the literature. This study’s findings are too preliminary to make a recommendation such as this. Further, the recommendation is disconnected form the clinical literature as arthroplasty surgeons are always trying to treat their patient’s pain – so they are already doing this. The introduction presents a more compelling interpretation of the goals for the data: ‘It is important to identify indicators for mortality to better inform patients, enhance patient care algorithms, and monitor surgical care systems.’ The discussion could also be made more concise.

Other Specifics:

-70: Is there a citation that can be included that can link to the study protocol or provide more detail on the index study. It is outside the scope of this specific article but readers should be able to easily access what the goal of the original study is, what the inclusion/exclusion criteria were, etc.

-79: Is there a citation that can be included which provides data on the validity of the WOMAC?

-117-118: Not ideal loss to follow-up.

-97-99 + page 16 ‘postoperative joint pain and COD’ section: cause of death data was only available for 10% of the original sample.

Reviewer #3: I thank the authors and the editorial team for the opportunity to review their work on the association of joint pain one year postoperatively and mortality. I think I do understand how this study came to be conceptually, but have difficulties to understand the conclusions drawn from the results. Foremost: What would your biological explanation be for the established association? Would mortality go down if we would give patients more pain killers? Why did your model not include comorbidity even though you had access to this important information? In summary, I am afraid that I do not consider that this study adds to the literature in a meaningful way.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes: Anders Brüggemann, MD, PhD

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Attachment

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PLoS One. 2025 Jul 3;20(7):e0327757. doi: 10.1371/journal.pone.0327757.r002

Author response to Decision Letter 1

28 May 2025

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We have reformatted the manuscript to meet the PLOS ONE's style requirements as instructed.

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ORCID iD for the corresponding author has been validated.

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We have clarified in the Methods section that “informed written consent was obtained from all participants.” (Revised Manuscript with Track Changes, Page 5, lines 81-82)

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Response:

The ethical application for this study that was approved by the Health Research Ethics Authority (HREA) of Newfoundland and Labrador specified that all electronic data for this study shall be stored on a secure Health Science Information and Media Service (HSIMS) server with restricted password-protected access as well as password-protected databases, and the data guardian is Dr. Guangju Zhai. The contact information for HREA of Newfoundland and Labrador is as follows: Email: info@hrea.ca, Phone: (709) 864-8871.

Data availability statement:

5. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please delete it from any other section.

Response:

The ethics statement now only appears in the Methods section, and the statement written in other sections has been deleted (Revised Manuscript with Track Changes, Page 25, Lines 330-335).

Response:

We have added captions for our Supporting Information files at the end of our manuscript (Revised Manuscript with Track Changes, Page 33, Lines 483-492), and updated in-text citations to match accordingly (Revised Manuscript with Track Changes, Page 8, line 132-133; Page 11, line 166, Page 23, line 289).

Additional Editor Comments:

The reviewers have made comments to improve the manuscript, in particular statistical analysis, interpretation of the results, and implication of study findings.

Response:

We thank the reviewers for their constructive comments and have revised the manuscript accordingly.

Query on May 22, 2025:

1. We dispatched the following message on May 20th, 2025. We note that you have resubmitted your manuscript/updated your statement, but have not replied directly to this query. Additionally, your statement and answer remain the same. Please respond to the following query at your earliest convenience.

Your Data Availability statement currently reads:

"Data cannot be shared publicly because of confidentiality reasons."

Additionally, you indicated that your data is not publicly available, and checked the “No - some restrictions will apply" box when submitting your manuscript.

You also provided some Data Availability information via your Response to Reviewers:

"We have stated in “Availability of data and materials” section that “The datasets used and/or analyzed during the current study are available from the corresponding author on upon reasonable request.” (Revised Manuscript with Track Changes, Page 25, Lines 338-339). The ethical application for this study that was approved by the Health Research Ethics Authority (HREA) of Newfoundland and Labrador specified that all electronic data for this study shall be stored on a secure Health Science Information and Media Service (HSIMS) server with restricted password-protected access as well as password-protected databases, and the data guardian is Dr. Guangju Zhai. The contact information for HREA of Newfoundland and Labrador is as follows: Email: info@hrea.ca <mailto:info@hrea.ca>, Phone: (709) 864-8871."

Before we proceed, we’ll require some additional information to ensure your submission adheres to the PLOS ONE Data Availability policy (https://journals.plos.org/plosone/s/data-availability <https://journals.plos.org/plosone/s/data-availability>)

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-The reason for the restriction (i.e., confidentiality of patients, etc.) -The name of the restricting institution -A non-author, institutional point of contact (preferably email) for a data access committee, ethics committee, or other institutional body that other researchers would require to request access to your data. Note that it is not acceptable for an author to be the sole named individual responsible for ensuring data access.

We note that you have provided what appears to be a Data Availability statement associated with restricted data via your Response to Reviewers, but have not updated your statement in the submission system. A manuscript's Data Availability statement should only appear in the submission system, and is generally not included in the body of a manuscript. In your response to this message, please reply to the following queries:

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Response:

We have now removed the Data Availability Statement from our manuscript (changed tracked and clean versions).

In the submission system, we have provided a revised Data Availability Statement which includes the information conveyed via our Response to Reviewers, and it includes information on 1) The reason for the restriction (ethics application approved); 2) The name of the restricting institution (the Health Research Ethics Authority (HREA) of Newfoundland and Labrador); 3) A non-author, institutional point of contact (and email) for an ethics committee (the HREA of Newfoundland and Labrador, info@hrea.ca) that other researchers would require to request access to our data (in addition to the corresponding author). Researchers can contact the HREA of Newfoundland and Labrador to request access to data via the email address we provided (info@hrea.ca).

Please see our response to requirement #4 above.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #1: Partly

Reviewer #2: Partly

Reviewer #3: No

________________________________________

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: I Don't Know

________________________________________

3. Have the authors made all data underlying the findings in their manuscript fully available?

Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes

________________________________________

4. Is the manuscript presented in an intelligible fashion and written in standard English?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

________________________________________

5. Review Comments to the Author

Reviewer #1:

The manuscript “Postoperative joint pain is associated with long-term all-cause mortality after total joint Arthroplasty” examined the effect of post-operative pain on mortality among patients undergoing TJR. Specific comments and clarifications are below:

1. Abstract (lines 14-16): “… their postoperative joint pain at least one-year after TJA…” Was WOMAC collected at several time points after surgery? Please clarify.

Response:

The postoperative joint pain was accessed only once for each patient. We have now clarified this in the Abstract (Revised Manuscript with Track Changes, Page 2, Line 19) and Methods (Revised Manuscript with Track Changes, Page 6, Line 85) sections.

2. Methods, Page 5: Please include the exact duration of the follow-up period (e.g., last date, average # of years of follow-up) and the number of post-operative measurements.

Response:

The average follow-up time for postoperative joint pain assessment and the average time from TJA to mortality data extraction were already specified in the Results section (4.0 and 11.0 years after TJA for postoperative joint pain assessment and mortality data extraction, respectively, Manuscript with Track Changes, page 11, line 151, line 154), and we have now added the last follow-up date for postoperative joint pain assessment (July 29, 2019. Manuscript with Track Changes, page 11, lines 151-152) as well as the date of mortality data extraction (June 3, 2024 and January 15, 2025. Manuscript with Track Changes, page 11, lines 154-156). We have also specified in the Methods section that data on postoperative joint pain evaluated by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Likert 3.0 pain subscale (five questions, Manuscript with Track Changes, page 6, lines 85-89) and three mortality variables were collected (Manuscript with Track Changes, page 6, lines 104-105) after the TJA.

3. Page 5, lines 79-80: Please clarify what post-operative time point was used for the analysis.

Response:

Please see response to comment #2.

4. Page 6: I think that the label ‘sustained pain’ is misleading as it is based on a one-time pain reporting based on a question asking for pain in the past 48 hours.

Response:

We thank the reviewer for pointing this out. The term “sustained pain” was to describe the status of having j

Attachment

Submitted filename: Response letter v.2.docx

pone.0327757.s004.docx^{(46.1KB, docx)}

PLoS One. doi: 10.1371/journal.pone.0327757.r003

Decision Letter 1

Yuanyuan Wang

PONE-D-25-06222R1Postoperative joint pain is associated with long-term all-cause mortality after total joint arthroplastyPLOS ONE

Dear Dr. Zhai,

Please submit your revised manuscript by Aug 01 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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We look forward to receiving your revised manuscript.

Kind regards,

Yuanyuan Wang, PhD

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

The authors have addressed the reviewers' comments appropriately. One reviewer requested a minor revision by adding a limitation.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #1: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

Reviewer #1: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

Reviewer #1: Yes

**********

6. Review Comments to the Author

Reviewer #1: I thank the authors for addressing my comments thoroughly. My only remaining comment, though, is that I suggest adding a sentence to the limitations section pointing out that the analysis did not account for pre-operative level of pain.

**********

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Reviewer #1: No

**********

PLoS One. 2025 Jul 3;20(7):e0327757. doi: 10.1371/journal.pone.0327757.r004

Author response to Decision Letter 2

18 Jun 2025

Journal Requirements:

Response:

We have reviewed the reference list and corrected reference #27. In PubMed, the journal name for this article is listed as “Arthritis Rheum”, which was presented as the journal name for this reference when we added it using PMID number. However, the full text shows that this article was published in “Arthritis Care & Research”. The volume, issue, and page numbers were correct. We have corrected the journal name of this reference. We did not cite any papers that have been retracted. The reference list is now complete and correct.

Additional Editor Comments:

The authors have addressed the reviewers' comments appropriately. One reviewer requested a minor revision by adding a limitation.

Response:

We thank the editor and reviewers for approving the changes we have made according to the editor and reviewers’ constructive comments. We have added a limitation as suggested by reviewer #1.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #1: All comments have been addressed

________________________________________

2. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #1: Yes

________________________________________

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

________________________________________

4. Have the authors made all data underlying the findings in their manuscript fully available?

Reviewer #1: Yes

________________________________________

5. Is the manuscript presented in an intelligible fashion and written in standard English?

Reviewer #1: Yes

________________________________________

6. Review Comments to the Author

Response:

We thank the reviewer for the suggestion. We have added this limitation in the revised manuscript (Revised Manuscript with Track Changes, Page 24, Lines 311-315).

________________________________________

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Attachment

Submitted filename: Response letter.v.3.docx

pone.0327757.s005.docx^{(17.5KB, docx)}

PLoS One. doi: 10.1371/journal.pone.0327757.r005

Decision Letter 2

Yuanyuan Wang

Postoperative joint pain is associated with long-term all-cause mortality after total joint arthroplasty

PONE-D-25-06222R2

Dear Dr. Zhai,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Yuanyuan Wang, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

The authors have addressed all the reviewers' comments.

Reviewers' comments:

PLoS One. doi: 10.1371/journal.pone.0327757.r006

Acceptance letter

Yuanyuan Wang

PONE-D-25-06222R2

PLOS ONE

Dear Dr. Zhai,

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team.

At this stage, our production department will prepare your paper for publication. This includes ensuring the following:

* All references, tables, and figures are properly cited

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Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Yuanyuan Wang

Academic Editor

PLOS ONE

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

S1 Table. Patient characteristics of included and excluded TJA patients.

(DOCX)

pone.0327757.s001.docx^{(15.2KB, docx)}

S2 Table. Comparison of prevalence of comorbidities and percentage of patients with multiple comorbidities between pain groups and controls.

Values are p values obtained with Chi-squared test or Fisher’s exact test comparing each pain group with controls. Values smaller than 0.05 are marked in bold.

(DOCX)

pone.0327757.s002.docx^{(44.7KB, docx)}

Attachment

Submitted filename: PONE-D-25-06222_comments to authors.docx

pone.0327757.s003.docx^{(16.5KB, docx)}

Attachment

Submitted filename: Response letter v.2.docx

pone.0327757.s004.docx^{(46.1KB, docx)}

Attachment

Submitted filename: Response letter.v.3.docx

pone.0327757.s005.docx^{(17.5KB, docx)}

Data Availability Statement

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PERMALINK

Postoperative joint pain is associated with long-term all-cause mortality after total joint arthroplasty

Ming Liu

Andrew Furey

Proton Rahman

Guangju Zhai

Roles

Abstract

Introduction

Methods

Study participants

Postoperative joint pain assessment

Demographic and mortality data collection

Data analyses

Results

Fig 1. Flowchart of study participants.

Table 1. Characteristics of the study participants #.

Postoperative joint pain and mortality

Table 2. All-cause mortality rate after joint arthroplasty in control and pain groups #.

Table 3. Patient characteristics by death status in control and pain groups #.

Table 4. Kaplan-Meier survival estimates #.

Fig 2. Cox survival plot for pain while active in knee and hip patients combined.

Postoperative joint pain and COD

Table 5. Cause of death in study groups.

Discussion

Postoperative joint pain and mortality

Postoperative joint pain and COD

Conclusions

Supporting information

Acknowledgments

Abbreviations

Data Availability

Funding Statement

References

Decision Letter 0

Yuanyuan Wang

Roles

Author response to Decision Letter 1

Decision Letter 1

Yuanyuan Wang

Roles

Author response to Decision Letter 2

Decision Letter 2

Yuanyuan Wang

Roles

Acceptance letter

Yuanyuan Wang

Roles

Associated Data

Supplementary Materials

Data Availability Statement

ACTIONS

PERMALINK

RESOURCES

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Cited by other articles

Links to NCBI Databases

Table 1. Characteristics of the study participants ^#.

Table 2. All-cause mortality rate after joint arthroplasty in control and pain groups ^#.

Table 3. Patient characteristics by death status in control and pain groups ^#.

Table 4. Kaplan-Meier survival estimates ^#.