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Abstract Number: 2250

The Relationship Between Sex and Incident Knee Osteoarthritis Is Mediated By Shape

Barton L. Wise1, Jingbo Niu2, Yuqing Zhang3, Felix Liu4, Joyce H. Pang5, John A. Lynch6 and Nancy E. Lane7, 1Department of Internal Medicine, UC Davis School of Medicine, Sacramento, CA, 2Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, MA, 3BUSM, Boston, MA, 4University of California at San Francisco, San Francisco, CA, 5University of Nevada School of Medicine, Reno, NV, 6University of California San Francisco, San Francisco, CA, 7Center for Musculoskeletal Health, Univ of California at Davis, Sacramento, CA

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: Mediation, osteoarthritis and radiography

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Session Information

Date: Tuesday, November 10, 2015

Title: Epidemiology and Public Health Poster III (ACR): Gout and Non-Inflammatory Musculoskeletal Conditions

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: Incidence of knee osteoarthritis (OA) is
higher in women than in men. We have previously shown that knee bone shape
differs between men and women. The purpose of the present study was to
determine whether knee bone shape is associated with risk of knee OA, and to
what extent the difference in the incidence of knee radiographic OA (ROA) between
men and women is mediated by bone shape.

Methods:   We used data collected from the NIH-funded
Osteoarthritis Initiative (OAI), a cohort of persons aged 45-79 at baseline who
either had symptomatic knee OA or were at high risk of it. We randomly sampled
304 knees with incident ROA (i.e., development of Kellgren/Lawrence grade
≥2 in central readings by month 48) and 304 knees without incident ROA. We
characterized distal femur and proximal tibia shape on baseline radiographs
using Active Shape Modeling. Thirteen modes were derived for proximal tibial
shape and for distal femoral shape, accounting for 95.5% of the total variance. 
We examined the relation of sex and each bone shape to the risk of incident ROA
using logistic regression.  If a specific bone shape was associated with the
risk of incident ROA, we then performed a marginal structural model to assess
the mediation effect of that bone shape on the relation of sex and risk of
incident knee ROA adjusting for baseline covariates.      

Results:  The mean age was 60.2 years (±8.5 SD) for both
cases and controls; the proportion of women was 65.1% in cases and 59.5% in
controls. Women had 49% increased odds of incident knee ROA compared with men.  Six
shape modes were associated with risk of incident knee ROA (tibia: mode 2, 9,
10, and 12; femur: mode 4 and 10).  Women had a lower value of tibial mode
2 (mean = -0.23 vs. 0.20) but a higher value of tibial mode 10 (mean = 0.25 vs.
-0.21) than men among controls; and higher value of femur mode 4 (mean = 0.30
vs. -0.21) and mode 10 (mean = 0.21 vs. -0.09).  The indirect effect of sex on
incident OA via tibial mode 2 was negative (OR = 0.96) and the direct effect (not
through this mode) was positive (OR = 1.56), suggesting there was inconsistent
mediation effect of mode 2. Similar findings were also observed when assessing the
mediation effect of tibia mode 10 and femur mode 4 (see Table).  See Figure for
images of all modes that were found to be significant mediators.

Conclusion:   The shapes of the distal femur and proximal
tibia that form the knee joint partially and inconsistently mediate the
relationship between sex and incident knee OA. Although women had higher risk
of incident ROA, their bone shape modestly protects them from even higher risk.

 

Table. Bone shape mode and sex, incident knee ROA

Mode

Association of mode and incident knee ROA

Mode among knees without incident TFROA, by gender

 

OR (95% CI)*

p-value

Men

mean (SD)

Women

mean (SD)

tibia, mode 2

1.18(1.03,1.37)

0.021

0.20 (1.00)

-0.23 (0.94)**

tibia, mode 9

1.15(1.00,1.32)

0.042

-0.06 (1.11)

-0.09 (1.00)

tibia, mode 10

0.79(0.67,0.93)

0.006

-0.21 (0.98)

0.25 (0.98)**

tibia, mode 12

0.86(0.75,0.99)

0.031

0.00 (1.08)

0.06 (1.04)

femur, mode 4

0.85(0.73,0.98)

0.025

-0.21 (1.00)

0.30 (0.89)**

femur, mode 10

0.81(0.70,0.94)

0.005

-0.09 (0.98)

0.21 (0.95)

 

 

 

 

 

Mediator effect of mode on sex and incident knee ROA

Indirect effect

Direct effect

 

OR (95% CI)*

p-value

OR (95% CI)*

p-value

tibia, mode 2

0.96(0.91,1.00)

0.043

1.56(1.08,2.27)

0.019

tibia, mode 10

0.96(0.92,1.00)

0.034

1.53(1.05,2.21)

0.025

femur, mode 4

0.97(0.94,1.00)

0.045

1.50(1.03,2.17)

0.034

Total effect of sex (women vs. men): OR (95% CI)* = 1.49 (1.04, 2.12)

*Adjusting for age, BMI, race, clinic site, knee injury and surgery

** p-value <0.05


Disclosure: B. L. Wise, None; J. Niu, None; Y. Zhang, None; F. Liu, None; J. H. Pang, None; J. A. Lynch, None; N. E. Lane, Genzyme-Sanofi, 5,Regeneron, 5.

To cite this abstract in AMA style:

Wise BL, Niu J, Zhang Y, Liu F, Pang JH, Lynch JA, Lane NE. The Relationship Between Sex and Incident Knee Osteoarthritis Is Mediated By Shape [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/the-relationship-between-sex-and-incident-knee-osteoarthritis-is-mediated-by-shape/. Accessed .
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