Development of a Model for Predicting the 4-year Risk of Symptomatic Knee Osteoarthritis in China

A Longitudinal Cohort Study

Limin Wang; Han Lu; Hongbo Chen; Shida Jin; Mengqi Wang; Shaomei Shang

Arthritis Res Ther. 2021;23(65)

Conclusion

In the present study, we developed the first model for predicting the 4-year risk of developing symptomatic KOA in China, using longitudinal cohort. Our simple score model may aid in the early identification of individuals at the greatest risk of developing KOA within 4 years in clinical practice or community setting. Such early identification may allow for improved patient education and modification of certain risk factors, which may in turn decrease rates of KOA incident.

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Abbreviations
ADLs: Activities of daily living; AIC: Akaike information criterion; AUC: Area under the receiver operating characteristic curve; BMI: Body mass index; CESD: Center for Epidemiologic Studies Depression Scale; CHARLS: China Health and Retirement Longitudinal Study; CI: Confidence intervals; IADLs: Instrumental activities of daily living; KOA: Knee osteoarthritis; LPA: Light physical activity; MPA: Moderate physical activity; MS: Metabolic syndrome; OR: Odds ratio; PA: Physical activity; PRO: Patient-reported outcome; SD: Standard deviation; TRIPOD: Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis; VPA: Vigorous physical activity

Acknowledgements
We thank the China Health and Retirement Longitudinal Study (CHARLS) team for providing nationally representative data.

Funding
This work was supported by the National Natural Science Foundation of China (no. 81972158).

Availability of data and materials
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Ethics approval and consent to participate
The Medical Ethics Board Committee of Peking University granted the study an exemption from review.

Consent for publication
Not applicable.

Arthritis Res Ther. 2021;23(65) © 2021 BioMed Central, Ltd.
Copyright to this article is held by the author(s), licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original citation.

Table 1. Baseline characteristics and outcomes of the study cohort summarized by their count and fraction ( N (%)) for categorical or the mean and standard deviation for continuous variables, respectively
Characteristics	Number of imputed data points	Total (N = 8193)	No symptomatic KOA (N = 7378)	Symptomatic KOA (N = 815)	P
Age, mean (SD) years	0	58.82 (9.01)	58.73 (9.06)	59.60 (8.45)	< 0.01
Sex	0				< 0.01
Male		3942 (48.11)	3664 (49.66)	278 (34.11)
Female		4251 (51.89)	3714 (50.34)	537 (65.89)
BMI, mean (SD) kg/m²	0	23.46 (3.49)	23.44 (3.47)	23.47 (3.48)	0.805
Waist circumference, mean (SD) cm	0	85.31 (9.58)	85.34 (9.54)	85.12 (9.56)	0.521
Residence area	0				< 0.01
Rural, %		5406 (65.98)	4816 (65.28)	590 (72.39)
Urban, %		2787 (34.02)	2562 (34.72)	225 (27.61)
Smoke behavior	40				< 0.01
No smoking, %		4945 (60.36)	4374 (59.28)	571 (70.06)
Ex-smoking, %		687 (8.39)	624 (8.46)	63 (7.73)
Current smoking, %		2561 (31.26)	2380 (32.26)	181 (22.21)
ADL/IADL difficulty	16				< 0.01
No, %		6283 (76.69)	5787 (78.44)	496 (60.86)
Yes, %		1910 (23.31)	1591 (21.56)	319 (39.14)
MS	1312				0.708
No, %		6794 (82.92)	6122 (82.98)	672 (82.45)
Yes, %		1399 (17.08)	1256 (17.02)	143 (17.55)
Hip fracture	72				< 0.01
No, %		7941 (96.92)	7167 (97.14)	774 (94.97)
Yes, %		252 (3.08)	211 (2.86)	41 (5.03)
Depression	1427				< 0.01
No, %		6132 (74.84)	5702 (77.28)	430 (52.76)
Mild, %		1896 (23.14)	1561 (21.16)	335 (41.1)
Moderate-to-severe, %		165 (2.01)	115 (1.56)	50 (6.13)
Comorbidities	0				< 0.01
None, %		3778 (46.11)	3498 (47.41)	280 (34.36)
1~2, %		3659 (44.66)	3253 (44.09)	406 (49.82)
≥ 3, %		756 (9.23)	627 (8.5)	129 (15.83)
Health status	3				< 0.01
Very good, %		289 (3.53)	278 (3.77)	8 (0.98)
Good, %		1075 (13.12)	1037 (14.06)	38 (4.66)
Fair, %		2752 (33.59)	2538 (34.4)	214 (26.26)
Poor, %		2957 (36.09)	2607 (35.33)	350 (42.94)
Very poor, %		1120 (13.67)	915 (12.4)	205 (25.15)
Physical Activity Score
VPA score	4743				0.507
No PA, %		4942 (60.32)	4462 (60.48)	480 (58.9)
Low level, %		590 (7.20)	524 (7.1)	66 (8.1)
Middle-to-high level, %		2661 (32.48)	2392 (32.42)	269 (33.01)
MPA score	4750				< 0.01
No PA, %		3192 (38.96)	2914 (39.5)	278 (34.11)
Low level, %		891 (10.88)	798 (10.82)	93 (11.41)
Middle-to-high level, %		4110 (50.16)	3666 (49.69)	444 (54.48)
LPA score	4751				0.842
No PA, %		1586 (19.36)	1431 (19.4)	155 (19.02)
Low level, %		1389 (16.95)	1245 (16.87)	144 (17.67)
Middle-to-high level, %		5218 (63.69)	4702 (63.73)	516 (63.31)

ADL, activities of daily living, BMI body mass index, IADL instrumental activities of daily living, LPA light physical activity, MPA moderate physical activity, MS metabolic syndrome, PA physical activity, SD standard deviation, VPA vigorous physical activity

Table 2. Results of logistic regression models for incident of KOA generated from 8193 participants in CHARLS 2011–2015
Predictors	Total N	KOA case n (%)	Univariable OR (95% CI)	Multivariable OR (95% CI)
Age (years)
45–49	1616	132 (8.17)	Reference	Reference
50–54	1241	112 (9.02)	1.12 (0.86–1.45)	1.06 (0.81–1.39)
55–59	1773	161 (9.08)	1.12 (0.88–1.43)	1.00 (0.78–1.29)
60–64	1477	183 (12.39)	1.59 (1.26–2.01)**	1.38 (1.08–1.77)**
65–69	989	121 (12.23)	1.57 (1.21–2.03)**	1.31 (1.00–1.72)**
≥ 70	1097	106 (9.66)	1.20 (0.92–1.57)	0.95 (0.71–1.26)
Sex
Male	3942	278 (7.05)	Reference	Reference
Female	4251	537 (12.63)	1.91 (1.64–2.22)**	1.51 (1.22–1.87)***
BMI level
Normal weight	318	35 (11.01)	Reference	–
Under weight	5198	503 (9.68)	1.15 (0.80–1.66)	–
Overweight	2201	225 (10.22)	1.06 (0.90–1.25)	–
Obese	476	52 (10.92)	1.14 (0.85–1.55)	–
Waist circumference, cm in male/female
< 85/80	3313	307 (9.27)	Reference	Reference
85~90/80~85	1414	144 (10.18)	1.11 (0.90–1.37)	1.07 (0.86–1.33)
90~95/85~90	1348	141 (10.46)	1.14 (0.93–1.41)	1.06 (0.85–1.33)
> 95/90	2118	223 (10.53)	1.15 (0.96–1.38)	1.06 (0.86–1.32)
Residence area
Urban	2787	225 (8.07)	Reference	Reference
Rural	5406	590 (10.91)	1.39 (1.19–1.64)**	1.24 (1.05–1.47)*
Smoke behavior
No smoking	4945	571 (11.55)	Reference	Reference
Ex-smoking	687	63 (9.17)	0.77 (0.59–1.02)	0.98 (0.71–1.35)
Current smoking	2561	181 (7.07)	0.58 (0.49–0.69)**	0.85 (0.68–1.08)
ADL/IADL difficulty
No	6283	496 (7.89)	Reference	Reference
Yes	1910	319 (16.7)	2.34 (2.01–2.72)**	1.49 (1.26–1.76)***
MS
No	6794	672 (9.89)	Reference	Reference
Yee	1399	143 (10.22)	1.13 (0.68–1.89)	1.03 (0.86–1.23)
Hip fracture
No	7941	774 (9.75)	Reference	Reference
Yes	252	41 (16.27)	1.80 (1.28–2.53)**	1.53 (1.07–2.20)*
Depression
No	6132	430 (7.01)	Reference	Reference
Mild	1896	335 (17.67)	2.85 (2.44–3.32)**	2.04 (1.73–2.41)***
Moderate-to-severe	165	50 (30.3)	5.77 (4.08–8.15)**	3.34 (2.32–4.82)***
Comorbidities
None	3778	280 (7.41)	Reference	Reference
1~2	3659	406 (11.1)	1.56 (1.33–1.83)**	1.25 (1.05–1.48)*
≥ 3	756	129 (17.06)	2.57 (2.05–3.22)**	1.54 (1.19–1.98)**
Health status
Very good	286	8 (2.8)	Reference	Reference
Good	1075	38 (3.53)	1.27 (0.59–2.769)	1.13 (0.52–2.46)
Fair	2752	214 (7.78)	2.93 (1.43–6.00)**	2.21 (1.07–4.54)*
Poor	2957	350 (11.84)	4.67 (2.29–9.50)**	2.99 (1.46–6.13)**
Very poor	1120	205 (18.3)	7.77 (3.79–15.98)**	3.67 (1.76–7.63)***
Physical Activity Score
VPA score
No PA	4942	480 (9.71)	Reference	Reference
Low level	590	66 (11.19)	1.17 (0.89–1.54)	1.15 (0.86–1.53)
Middle-to-high level	2661	269 (10.11)	1.05 (0.89–1.22)	1.03 (0.87–1.22)
MPA score
No PA	3192	278 (8.71)	Reference	Reference
Low level	891	93 (10.44)	1.22 (0.95–1.56)	1.35 (1.02–1.73)*
Middle-to-high level	4110	444 (10.8)	1.27 (1.08–1.49)**	1.31 (1.10–1.56)**
LPA score
No PA	1586	155 (9.77)	Reference	–
Low level	1389	144 (10.37)	1.07 (0.84–1.36)	–
Middle-to-high level,	5218	516 (9.89)	1.01 (0.84–1.22)	–

*P ≤ 0.05, **P ≤ 0.01, ***P < 0.001; ADL activities of daily living, BMI body mass index, 95% CI 95% confidence interval, IADL instrumental activities of daily living, LPA light physical activity, MPA moderate physical activity, MS metabolic syndrome, OR odds ratio, PA physical activity, VPA vigorous physical activity

Table 3. Risk score model of KOA incident prediction
Predictors	Risk score	Predictors	Risk score
Age (years)		Depression
45–49	0	No	0
50–59	1	Mild	7
60–69	3	Moderate-to-severe	12
≥ 70	0	Comorbidities
Sex		None	0
Male	0	1 ~ 2	2
Female	5	≥3	4
Waist circumference, cm in male/female		Health Status
< 85/80	0	Very good	0
≥ 85/80	1	Good	1
Residence Area		Fair	8
Urban	0	Poor	11
Rural	2	Very poor	13
ADLs/IADLs difficulty		MPA score
No	0	No PA	0
Yes	4	Low level	3
Hip fracture		Middle-to-high level	3
No	0
Yes	4

Total score of 0 indicates lowest risk and score of 51 indicates greatest risk
A cut-off of 20.5 was identified, which meant patients with a 20.5 or more total risk scores were at the greatest risk to develop symptomatic KOA in 4 years
The incident probability of KOA within 4 years was calculated by the total risk score divided by 51 and multiplied by 100%
MPA moderate physical activity, AD activities of daily living, IADL instrumental activities of daily living