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Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. ROLE OF THE STUDY SPONSOR
  9. ADDITIONAL DISCLOSURES
  10. Acknowledgments
  11. REFERENCES

Objective

To compare cross-sectional and longitudinal side differences in thigh muscle anatomic cross-sectional areas (ACSAs), strength, and specific strength (strength/ACSA) between knees with early versus advanced painful radiographic osteoarthritis in the same person.

Methods

Forty-four of 2,678 Osteoarthritis Initiative participants (31 women and 13 men) met the inclusion criteria of bilateral frequent knee pain, medial joint space narrowing (JSN) in 1 knee, and no medial (or lateral) JSN in the contralateral knee. Thigh muscle ACSAs of the quadriceps, hamstrings, adductors, and individual quadriceps heads at consistent locations were determined using magnetic resonance imaging. Isometric muscle strength was determined in extension/flexion (Good Strength Chair). Baseline quadriceps ACSAs and strength were considered primary end points, and longitudinal changes of these factors were considered secondary end points (by paired t-tests).

Results

No significant side differences in quadriceps (or other thigh muscle) ACSAs, strength, or specific strength were observed between medial JSN knees versus knees without JSN, or between specific medial JSN knee strata and contralateral knees without JSN, either in men or women. Two-year longitudinal changes in thigh muscle ACSAs and strength were small (≤5.2%) and did not differ significantly between medial JSN knees and knees without JSN.

Conclusion

In the context of previous findings that side differences in pain are associated with side differences in quadriceps ACSAs, the current results suggest that quadriceps (and other thigh muscle) properties are not independently associated with radiographic disease status (JSN) once knees have reached frequent pain status. Further, our longitudinal findings indicate that a more advanced radiographic stage of knee osteoarthritis is not necessarily associated with a longitudinal decline in muscle function.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. ROLE OF THE STUDY SPONSOR
  9. ADDITIONAL DISCLOSURES
  10. Acknowledgments
  11. REFERENCES

Knee osteoarthritis (KOA) is the leading cause of knee pain in people ages >55 years ([1]). Radiographic signs of advanced KOA, specifically joint space narrowing (JSN), have been shown to be associated with pain when comparing knees with discordant radiographic KOA (RKOA) status in the same person ([2]). Several studies reported that quadriceps strength ([3-5]) is reduced in patients with KOA, although a recent report did not find a relationship between muscle anatomic cross-sectional areas (ACSAs) or strength with either obesity or KOA status ([6]). However, the above studies ([3-5]) did not disentangle whether differences in strength resulted from knees being at an advanced structural (radiographic) disease stage, or from being frequently painful. Berger et al ([7]) explored whether the “type” of disease severity (i.e., RKOA versus symptom status) had an impact on the magnitude of knee extensor force deficits in Osteoarthritis Initiative (OAI) participants. The authors reported significant differences in isometric strength between knees stratified by symptoms, but only small (nonsignificant) differences between knees stratified by the (radiographic) Kellgren/Lawrence (K/L) grade ([7]). Using computed tomography (CT), Conroy et al ([8]) determined ACSAs and muscle quality (muscle strength/ACSA) in knees with and without RKOA, and with and without pain. They concluded that muscle quality was significantly reduced in RKOA, regardless of pain status. Therefore, it remains controversial whether RKOA status is associated with deficits in muscle strength and quality independent of pain (frequency). Further, thigh muscles other than the quadriceps have been much less investigated.

In a between-knee, within-person comparison, we previously reported frequently painful knees to display significantly lower quadriceps ACSAs and strength, but not quality (strength/ACSA), compared with contralateral painless knees that had the same RKOA disease stage (K/L grade) ([9]). Taking this work further, here we aimed to explore differences in muscle ACSAs, strength, and specific strength between knees with OA discordant for radiographic (JSN) grade, but with bilateral frequent knee pain (i.e., without pain discordance). This (between-knee, within-person) study design eliminates confounding from between-person factors such as sex, physical activity levels, body mass index (BMI), psychological factors, and others that often are present ([8, 10]) and difficult to control for in between-person comparisons of knees with different JSN grades.

Further, the current investigation aimed to study longitudinal changes in muscle ACSAs, strength, and specific strength to explore whether thigh muscles in legs with JSN show measurable decline in comparison with the contralateral (without JSN) leg. This comparison was performed in view of recent findings that knees with JSN display substantially greater rates of structural deterioration (i.e., cartilage loss) than contralateral knees without JSN ([11]), and therefore are likely in a progressive disease stage. It also has been shown that knees with JSN have greater functional limitations ([12, 13]), and leg disuse may secondarily cause muscle atrophy and reduction in muscle quality, i.e., fiber degeneration ([14]). A previous study used CT ([8]) to explore a measure of muscle quality by determining the strength to ACSA ratio and therefore indirectly the amount of noncontractile tissue (i.e., fat).

Specifically, we tested the following hypotheses: 1) thigh muscle (particularly quadriceps) ACSAs, strength, and specific strength are lower in frequently painful knees with advanced RKOA (knees with JSN) than in frequently painful knees with early OA (knees without JSN), and 2) longitudinally, thigh muscle (particularly quadriceps) ACSAs, strength, and specific strength decrease, and this decrease is greater in frequently painful knees with advanced RKOA than in frequently painful knees with early OA. Further, we explored whether results differ for knees with more severe JSN (grade 2/3) versus knees without JSN compared with knees with less severe JSN (grade 1) versus knees without JSN, and potential sex differences in the above relationships.

Box 1. Significance & Innovations

  • This is the first study to compare thigh muscle anatomic cross-sectional areas, strength, and specific strength, cross-sectionally and longitudinally, in knees with painful early versus advanced radiographic osteoarthritis (medial joint space narrowing [JSN]).
  • A between-knee, within-person study design was used to eliminate between-person confounding by differences in sex, physical activity levels, body mass index, psychological factors, and others between knees with and without JSN.
  • The findings suggest that quadriceps (and other thigh muscle) properties are not associated with radiographic disease status (i.e., JSN) once knees have reached a status of frequent pain.
  • The longitudinal findings indicate that a more advanced radiographic stage of knee osteoarthritis (with JSN) is not necessarily associated with a progressive decline in muscle function.

PATIENTS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. ROLE OF THE STUDY SPONSOR
  9. ADDITIONAL DISCLOSURES
  10. Acknowledgments
  11. REFERENCES

Participants

Participants for this study were drawn from the first half (2,678 cases) of the OAI cohort (clinical data set 0.2.1), consisting of female and male participants ages 45–79 years (online at http://oai.epi-ucsf.org/). Participants for the current study were specifically selected to be discordant in their radiographic JSN, but not in their pain frequency status, to permit a between-knee, within-person comparison of painful knees with advanced radiographic knee OA (i.e., with JSN) versus painful knees with early OA (i.e., without JSN) ([11, 15, 16]). At baseline, the participants had a BMI >25 kg/m2, frequent pain in both knees (pain, aching, or stiffness in or around the knee for at least 1 month during the past 12 months), medial JSN (grade 1–3) ([17]) in 1 knee (with either no lateral JSN or less lateral JSN than medial JSN), and neither medial JSN nor lateral JSN in the contralateral knee. The selection was based on the radiographic baseline readings performed at the OAI clinical sites and was complemented by either central OAI readings or by consensus evaluation of 2 experienced readers (AG and DJH) ([11, 15, 16]). Compared with our previous study of 73 participants ([15]), 3 participants with infrequent pain in the knee without JSN were excluded.

This study has received the approval of the OAI Publications Committee based on a review of its scientific content and data interpretation.

Evaluation of thigh muscle ACSAs from magnetic resonance imaging (MRI).

Of the 70 participants, 44 had baseline axial MRI acquisitions of the thighs (imaging data set 0.C.2), and 37 also had 2-year followup MRIs (imaging data sets 3.C.2). Images were acquired using a 3T Magnetom Trio (Siemens Healthcare), with the distal femoral epiphysis being delineated by axial and coronal localizers (Figure 1A). The muscle acquisition of 15 axial non–fat-suppressed T1-weighted spin-echo images (repetition time 500 msec, echo time 10 msec) started 10 cm proximal to the epiphysis (Figure 1A) and extended 7.5 cm proximally (slice thickness 0.5 cm, in-plane resolution 0.977 mm, field of view 500 mm, matrix 512 × 512 pixels). Details regarding the MRI techniques and protocols are available online (http://oai.ucsf.edu/datarelease/operationsmanuals.asp).

image

Figure 1. A, Coronal localizer image. The acquisition of the 15 axial non–fat-suppressed T1-weighted spin-echo magnetic resonance images (MRIs; 0.5 cm) started 10 cm proximal to the distal femoral epiphyseal line and extended 7.5 cm proximally. Body height was used to determine 2 slices located at 30% and 33% of the femoral length from distal to proximal in each participant to perform muscle segmentations at a consistent anatomic location. B, Axial T1-weighted MRIs of the thigh with segmented muscles. The top image shows the segmented quadriceps (pink), hamstrings (dark blue), and adductors (turquoise) at 33% of the femoral length (from distal to proximal); the bottom image shows the segmented quadriceps heads: the vastus medialis (brown), lateralis (yellow), and intermedius (turquoise) and the rectus femoris (purple) at 30% of the femoral length (from distal to proximal). OAI = Osteoarthritis Initiative.

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Given the fixed distance between the epiphysis and the most proximal slice, the muscle region of interest had an inconsistent location relative to the femur (and the thigh muscles), dependent on individual femoral length. To adjust for this, we estimated the femoral length from body height, as described previously ([9, 18]). A 33% location (distal to proximal) was selected to analyze the quadriceps, hamstrings, and adductors. This was the most proximal slice that could be consistently selected across the study participants (given their range of body heights), with proximal slices being more representative of total thigh muscle volumes than distal slices ([19]). ACSAs of single quadriceps heads (vastus medialis, lateralis, and intermedius and rectus femoris) were assessed in the most distal slice that could be consistently measured in all participants (30% femoral length from distal), since these can be better separated distally than proximally. In some cases, image acquisition was not performed 10 cm from the epiphysis (Figure 1A), but from the knee joint space (n = 4). In these cases, the 33% and 30% locations were selected by adjusting for deviation from the protocol. In cases in which the localizer images were lacking (n = 10), the appropriate images were visually selected in agreement with other cases.

Custom software was used to manually segment the quadriceps, hamstrings, and adductors (33% slice), excluding intermuscular adipose tissue ([9]) (Figure 1B). The same software was used to segment the 4 quadriceps heads and to determine the ACSAs of the segmented muscles. All segmentations were performed by a single trained reader (AR), blinded to RKOA status and time point of acquisition (baseline and followup). Test–retest images were not available from OAI participants, but the reproducibility for similar measurements was 1.7% (coefficient of variation) in the quadriceps, 3.4% in the hamstrings, and 9.9% in the adductors ([20]).

Evaluation of thigh muscle strength

Measurements of maximum isometric extensor and flexor strength were available from the OAI database (clinical data set 0.2.2) for 42 of the above 44 participants; in 2 of the 42, the strength data were considered outliers (<10 N) and were not used. Of the 37 participants with longitudinal image data, 29 had strength measurements at baseline and 2-year followup (clinical data set 3.2.1). Muscle strength was measured using the Good Strength Chair (Metitur Oy) ([9, 21, 22]). Specific strength (N/cm2) was calculated by dividing maximal isometric strength by ACSA ([8, 9]).

Statistical analysis

Given its important documented role in knee biomechanics and the focus on the quadriceps in previous studies ([5]), the comparison between baseline differences in quadriceps ACSAs in medial JSN knees versus contralateral knees without JSN was considered the primary analysis, and the comparison of extensor strength and specific strength was considered the co–primary analysis. Longitudinal (2-year) change between quadriceps ACSAs in medial JSN knees versus contralateral knees without JSN was considered the secondary analysis, and the comparison of longitudinal change in extensor strength and specific strength was considered the co– secondary analysis. All other measures were considered exploratory. Data were carefully checked for possible outliers. Paired t-tests were used to evaluate baseline differences in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores ([23]) and measured variables. The correlation of quadriceps ACSAs with extensor strength and that of hamstring ACSAs with flexor strength was determined in knees without JSN and in medial JSN knees using Pearson's correlation coefficients and their 95% confidence intervals (95% CIs). Exploratory analyses were also performed for each sex and JSN stratum.

Paired t-tests were used to descriptively evaluate whether longitudinal changes over time were significantly different from zero, and whether longitudinal percentage changes were different between medial JSN knees and knees without JSN. Rates of change were further compared between medial JSN grade 1 knees versus medial JSN grade 2/3 knees, between knees without JSN of men versus women, and between medial JSN knees of men versus women (unpaired t-test). All tests were 2-sided and a P value less than 5% was considered as statistically significant. No adjustment for multiple comparisons was made to not inadequately dilute the power of this exploratory study. To account for potential interaction between knees, i.e., bilateral activation deficits in unilateral JSN knees ([24, 25]), the crude tests were confirmed using a generalized estimating equation (GEE) model. All analyses were performed using IBM SPSS, version 20, and Statistica, version 10 (StatSoft).

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. ROLE OF THE STUDY SPONSOR
  9. ADDITIONAL DISCLOSURES
  10. Acknowledgments
  11. REFERENCES

Demographics

Forty-four participants (31 women and 13 men, ages 47–78 years) fulfilled the specific inclusion criteria of the cross-sectional component of this between-knee, within-person comparison (mean ± SD height 164 ± 10 cm, mean ± SD weight 83.1 ± 14.0 kg, mean ± SD BMI 30.8 ± 4.3 kg/m2). Of 27 medial JSN grade 1 knees, 17 and 10 were from women and men, respectively, and of 17 medial JSN grade 2/3 knees, 14 and 3 were from women and men, respectively. Forty-one participants provided information on their “dominant” leg (response to the OAI question: “Which leg do you use to kick a ball?”): in 38, the dominant leg was the right leg and in 3, the dominant leg was the left leg; in 18, the dominant leg had JSN and in 23, the dominant leg did not have JSN. The mean ± SD WOMAC knee pain score (range 0–20, where 20 = the worst) was 5.9 ± 4.5 versus 4.5 ± 4.2 in the medial JSN knees versus the knees without JSN (P = 0.002), 4.1 ± 3.5 versus 3.6 ± 3.4 in the medial JSN grade 1 knees versus the knees without JSN (P = 0.23), and 8.8 ± 4.6 versus 6.1 ± 4.9 in the medial JSN grade 2/3 knees versus the knees without JSN (P = 0.0009).

Cross-sectional comparisons

There were no significant differences between quadriceps ACSAs in medial JSN knees versus knees without JSN (P = 0.60) (Table 1). Further, no significant differences were observed in absolute extensor strength and specific strength (P = 0.91 and 0.33, respectively) (Table 1). The correlation between quadriceps ACSAs and extensor strength was 0.43 in knees without JSN (95% CI 0.14–0.65) and 0.54 in medial JSN knees (95% CI 0.27–0.73). The correlation between hamstring ACSAs and flexor strength was 0.38 in knees without JSN (95% CI 0.08–0.61) and 0.60 in medial JSN knees (95% CI 0.35–0.77). These correlations were significantly different from zero (P < 0.05), but not significantly different between the knees without JSN and the medial JSN knees. Further, no significant differences were found in other exploratory end points of quadriceps heads ACSAs, hamstring and adductor ACSAs, and flexor (specific) strength (P ≥ 0.12) (Table 1).

Table 1. Baseline absolute and percent differences (mean ± SD) in thigh muscle ACSAs and (specific) strength between painful osteoarthritic knees with and without medial radiographic JSN*
 Knees without JSN (n = 44)JSN knees (n = 44)JSN vs. no JSN, absolute differenceJSN vs. no JSN, % differenceP, JSN vs. no JSN
  1. ACSAs = anatomic cross-sectional areas; JSN = joint space narrowing; VM = vastus medialis; VL = vastus lateralis; VIM = vastus intermedius; RF = rectus femoris.

  2. a

    Muscle (specific) strength data were available for 40 (of 44) participants.

ACSAs     
Quadriceps, cm247.0 ± 12.046.5 ± 12.8−0.47 ± 5.69−0.7 ± 140.60
Hamstrings, cm232.1 ± 8.1432.2 ± 7.84+0.12 ± 2.51+0.9 ± 80.75
Adductors, cm29.43 ± 4.5510.0 ± 5.21+0.53 ± 2.25+7.8 ± 260.12
VM, cm217.7 ± 4.3317.1 ± 4.64−0.59 ± 2.71−2.8 ± 180.16
VL, cm212.0 ± 3.8412.1 ± 4.23+0.11 ± 2.52+2.6 ± 220.78
VIM, cm213.2 ± 3.9913.2 ± 4.01−0.07 ± 1.81+0.2 ± 150.79
RF, cm21.84 ± 1.501.74 ± 1.56−0.10 ± 0.58+2.2 ± 340.26
Muscle strengtha     
Extensors, N292 ± 112291 ± 107−0.98 ± 53.9+2.2 ± 230.91
Flexors, N123 ± 47.9126 ± 52.2−1.05 ± 32.3+1.2 ± 240.84
Specific strengtha     
Extensors, N/cm26.36 ± 1.996.63 ± 2.14+0.20 ± 1.24+5.1 ± 240.33
Flexors, N/cm23.91 ± 1.194.01 ± 1.20−0.04 ± 1.03+0.5 ± 250.79

Results were similar when stratifying the analysis for medial JSN grade 1 knees versus knees without JSN and for medial JSN grade 2/3 knees versus knees without JSN (Table 2); only the adductors in medial JSN grade 2/3 knees displayed significantly greater (but not smaller) ACSAs than contralateral knees without JSN (P = 0.0018).

Table 2. Baseline absolute and percent differences (mean ± SD) in thigh muscle ACSAs and (specific) strength between painful osteoarthritic knees with radiographic JSN grades 1 and 2/3*
 JSN grade 1 (n = 27)JSN grade 2/3 (n = 17)% difference, JSN grade 1 vs. no JSN% difference, JSN grade 2/3 vs. no JSN
  1. ACSAs = anatomic cross-sectional areas; JSN = joint space narrowing; VM = vastus medialis; VL = vastus lateralis; VIM = vastus intermedius; RF = rectus femoris.

  2. a

    P = 0.002 without adjustment for multiple comparisons.

  3. b

    Muscle (specific) strength measures were available for 23 (of 27) JSN grade 1 knees and 16 (of 17) JSN grade 2/3 knees.

ACSAs    
Quadriceps, cm247.9 ± 13.044.3 ± 12.6+0.9 ± 12−3.4 ± 16
Hamstrings, cm231.4 ± 7.2233.5 ± 8.80+0.5 ± 8+1.7 ± 9
Adductors, cm29.81 ± 5.3610.2 ± 5.09−0.6 ± 25+21 ± 22a
VM, cm217.5 ± 3.9216.5 ± 5.67−0.7 ± 18−6.2 ± 18
VL, cm212.4 ± 4.6811.6 ± 3.48+4.0 ± 21+0.3 ± 25
VIM, cm213.6 ± 4.1912.4 ± 3.72+1.0 ± 11−0.9 ± 19
RF, cm21.62 ± 1.141.92 ± 2.08−0.5 ± 32+6.5 ± 37
Muscle strengthb    
Extensors, N302 ± 119275 ± 88.6+3.8 ± 220.1 ± 25
Flexors, N131 ± 59.1119 ± 41.1+2.9 ± 26−1.2 ± 22
Specific strengthb    
Extensors, N/cm26.62 ± 1.856.63 ± 2.54+5.3 ± 23+4.8 ± 26
Flexors, N/cm24.22 ± 1.193.71 ± 1.18+2.1 ± 25−1.7 ± 26

Although medial JSN knees tended to have greater quadriceps ACSAs than knees without JSN in men (mean ± SD +3.0% ± 14%), and lower in women (mean ± SD −2.3% ± 14%) (Table 3), the opposite trend was observed for quadriceps strength (mean ± SD −0.6% ± 18% and +3.2% ± 24%, respectively). However, none of the differences reached statistical significance (Table 3). Further, no significant differences were observed in the medial JSN grade 1 and medial JSN grade 2/3 knee strata versus contralateral knees without JSN in either men or women (Table 3); only adductor ACSAs in medial JSN grade 2/3 knees in women were significantly greater than those in contralateral knees without JSN (P = 0.01). GEEs confirmed the above results, including greater adductor ACSAs in medial JSN knees than in the contralateral knees without JSN (P = 0.005).

Table 3. Baseline absolute and percent differences (mean ± SD) in thigh muscle ACSAs and (specific) strength between painful osteoarthritic knees with radiographic JSN in men and women*
 MenWomen
JSN vs. no JSN (n = 13)JSN grade 1 vs. no JSN (n = 10)JSN vs. no JSN (n = 31)JSN grade 1 vs. no JSN (n = 17)JSN grade 2/3 vs. no JSN (n = 14)
  1. Because of the small sample size (n = 3), there is no JSN grade 2/3 stratum for men. ACSAs = anatomic cross-sectional areas; JSN = joint space narrowing; VM = vastus medialis; VL = vastus lateralis; VIM = vastus intermedius; RF = rectus femoris.

  2. a

    P = 0.01 (JSN grade 2/3 vs. no JSN).

  3. b

    Muscle (specific) strength data were available for 10 (of 13) JSN grade 1 knees in men and 30 (of 31) JSN grade 1 knees in women.

ACSAs     
Quadriceps, cm2+3.0 ± 14+3.1 ± 14−2.3 ± 14−0.4 ± 11−4.6 ± 17
Hamstrings, cm2+0.5 ± 7−0.2 ± 8+1.1 ± 9+0.9 ± 8+1.4 ± 10
Adductors, cm2+5.6 ± 25−2.3 ± 21+8.7 ± 27+0.4 ± 28+18.7 ± 23a
VM, cm2+3.1 ± 22+2.5 ± 24−5.3 ± 16−2.6 ± 13−8.7 ± 19
VL, cm2+4.6 ± 17+6.9 ± 17+1.7 ± 25+2.3 ± 23+1.0 ± 27
VIM, cm2+1.3 ± 13+0.01 ± 12−0.2 ± 15+1.5 ± 11−2.3 ± 20
RF, cm2−5.2 ± 28−10.7 ± 27+5.3 ± 36+5.5 ± 34+5.0 ± 39
Muscle strengthb     
Extensors, N−0.6 ± 18+0.2 ± 16+3.2 ± 24+5.4 ± 24+0.6 ± 25
Flexors, N−5.2 ± 22−2.2 ± 23+3.5 ± 25+5.1 ± 28+1.4 ± 22
Specific strengthb     
Extensors, N/cm2−0.1 ± 20+2.5 ± 22+6.8 ± 25+6.6 ± 24+7.1 ± 28
Flexors, N/cm2−5.6 ± 21−1.7 ± 21−0.8 ± 32+3.7 ± 27−5.9 ± 37

Longitudinal comparisons

The longitudinal (percent) changes were generally small (≤1.9% for the quadriceps and <10% for other thigh muscle ACSAs; ≤5.2% for extensor and ≤6.1% for flexor strength); no significant changes were observed in quadriceps ACSAs, strength, or specific strength over 2 years (Table 4). Only the hamstring ACSAs of the knees without JSN (but none of the other measures) showed a significant reduction between baseline and followup (mean ± SD −2.2% ± 6%; P = 0.03) (Table 4). No significant differences in longitudinal rates of change were observed between medial JSN knees and contralateral knees without JSN (P ≥ 0.16) (Table 4). Although longitudinal loss in muscle ACSAs tended to be greater in medial JSN grade 2/3 knees than medial JSN grade 1 knees, the opposite trend was observed for strength; however, none of these trends reached statistical significance (P ≥ 0.20) (Table 4).

Table 4. Longitudinal percent changes over 2 years (mean ± SD) in thigh muscle ACSAs and (specific) strength in painful osteoarthritic knees with and without radiographic JSN and in knees with JSN grades 1 and 2/3*
 Δ% no JSN (n = 37)Δ% JSN (n = 37)P, Δ% no JSN vs. Δ% JSNΔ% JSN grade 1 (n = 17)Δ% JSN grade 2/3 (n = 14)P, Δ% JSN grade 1 vs. Δ% JSN grade 2/3
  1. ACSAs = anatomic cross-sectional areas; JSN = joint space narrowing; Δ% = percent rate of change; VM = vastus medialis; VL = vastus lateralis; VIM = vastus intermedius; RF = rectus femoris.

  2. a

    P = 0.03 (rate of change for followup vs. baseline).

  3. b

    Muscle (specific) strength measures were available for 29 (of 37) participants.

ACSAs      
Quadriceps, cm2−1.1 ± 8−1.1 ± 80.98−0.7 ± 6−1.9 ± 110.68
Hamstrings, cm2−2.2 ± 6a−0.9 ± 80.16−0.5 ± 7−1.8 ± 110.65
Adductors, cm2+3.8 ± 29+4.5 ± 340.77+9.5 ± 38−5.9 ± 220.20
VM, cm2−1.3 ± 8−1.7 ± 90.79−1.6 ± 9−1.8 ± 90.30
VL, cm2−0.2 ± 17−2.7 ± 160.22−0.3 ± 14−7.9 ± 200.55
VIM, cm2+0.9 ± 8+0.8 ± 90.93+2.0 ± 8−1.6 ± 120.53
RF, cm2−1.5 ± 38+0.4 ± 380.66+1.4 ± 42−1.9 ± 310.89
Muscle strengthb      
Extensors, N+4.6 ± 22+1.3 ± 290.52+0.7 ± 31+3.3 ± 230.84
Flexors, N+1.3 ± 39−2.4 ± 300.71−5.0 ± 30+5.5 ± 310.43
Specific strengthb      
Extensors, N/cm2+5.2 ± 22+1.5 ± 290.40+1.7 ± 32+0.8 ± 200.94
Flexors, N/cm2+4.6 ± 43−2.0 ± 301.00−4.7 ± 30+6.1 ± 320.43

A trend toward greater loss of quadriceps ACSAs and extensor strength was observed in women than in men (both in knees without JSN and in medial JSN knees), but none of the differences (between baseline and followup) were statistically significant, except for adductors ACSAs in medial JSN knees versus knees without JSN in men (P = 0.04) (Table 5). Rates of change did not differ significantly between both sexes (P ≥ 0.14) (Table 5). As for the cross-sectional results, GEEs on the longitudinal data confirmed the crude tests.

Table 5. Longitudinal percent changes over 2 years (mean ± SD) in thigh muscle ACSAs and (specific) strength in painful osteoarthritic knees with and without radiographic JSN in men and in women*
 MenWomenP, no JSNaP, JSNa
No JSN (n = 12)JSN (n = 12)No JSN (n = 25)JSN (n = 25)
  1. ACSAs = anatomic cross-sectional areas; JSN = joint space narrowing; VM = vastus medialis; VL = vastus lateralis; VIM = vastus intermedius; RF = rectus femoris.

  2. a

    Percent rate of change in men vs. percent rate of change in women.

  3. b

    P = 0.04 (change in JSN vs. no JSN).

  4. c

    Longitudinal muscle (specific) strength data were available for 20 (of 25) women and 8 (of 12) men; there are no JSN strata because of small sample sizes.

ACSAs      
Quadriceps, cm2+0.1 ± 8+0.01 ± 8−1.6 ± 8−1.6 ± 80.550.56
Hamstrings, cm2−3.4 ± 8−0.003 ± 8−1.7 ± 5−1.4 ± 80.450.64
Adductors, cm2−0.9 ± 21b−1.5 ± 25b+6.0 ± 33+7.4 ± 380.510.47
VM, cm2+1.2 ± 11+0.8 ± 5−3.0 ± 7−2.3 ± 90.170.31
VL, cm2−3.8 ± 18−2.6 ± 17−2.3 ± 16+1.0 ± 170.800.55
VIM, cm2−0.6 ± 10+2.2 ± 8+1.5 ± 9+0.3 ± 80.530.50
RF, cm2−10.7 ± 30−14.8 ± 30+5.7 ± 41+5.0 ± 410.230.14
Muscle strengthc      
Extensors, N+3.7 ± 21+1.9 ± 20+5.1 ± 23+1.1 ± 320.880.95
Flexors, N+6.8 ± 64−6.3 ± 40−1.1 ± 22−0.8 ± 260.620.67
Specific strengthc      
Extensors, N/cm2+3.4 ± 20+2.0 ± 22+6.0 ± 24+1.2 ± 320.780.95
Flexors, N/cm2−12.9 ± 70−7.0 ± 40+0.9 ± 24−0.01 ± 270.490.59

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. ROLE OF THE STUDY SPONSOR
  9. ADDITIONAL DISCLOSURES
  10. Acknowledgments
  11. REFERENCES

Previous studies provided evidence that muscle strength is reduced in painful knees in the absence ([10]) and presence ([9]) of RKOA. However, because RKOA is associated with knee pain ([2]), it is controversial whether deficits in muscle strength and specific strength are associated with RKOA status independently of pain status ([7, 8]). In an attempt to disentangle the relationship between muscle status, pain, and RKOA (JSN) status, we compared side differences in thigh muscle ACSAs, strength, and specific strength between knees with painful early versus painful advanced RKOA in the same person, i.e., knees that were discordant for JSN but not for pain frequency status. We only found small (nonsignificant) differences in (quadriceps) ACSAs, strength, and specific strength between medial JSN knees and contralateral knees without JSN. Further, we found only small longitudinal changes over time that did not differ significantly between medial JSN knees and contralateral knees without JSN.

Limitations of our study include the relatively small sample size, resulting from the very specific inclusion criteria. However, its strength is the between-knee, within-person approach ([2, 11, 15, 16]), studying participants discordant for JSN, but not discordant in pain frequency status. This design is particularly beneficial when investigating muscle ACSAs and strength that are confounded by between-person differences in body height and weight ([5]), age ([26]), occupation and physical activity levels ([27]), psychological factors such as depression ([10]), willingness/ability to perform maximal voluntary muscle activation ([28-34]), and others.

In contrast to other studies using OAI data ([26, 35]), the anatomic location of the muscle measurements was adjusted to variation in body height (and femoral length). Yet, another benefit of the between-knee design is that potential remaining variations due to nonlinear relationships between body height and femoral length could not affect the current comparison because the same (anatomic) level was compared between both thighs of the same person using the same MRI. Using a similar study design ([9]), we were recently able to identify highly significant differences in quadriceps ACSAs and strength between knees with frequent pain versus contralateral knees without pain in a similar number of OAI participants (n = 48). Given means, SDs, and correlations of quadriceps ACSAs between medial JSN knees and knees without JSN in the current study, a post hoc analysis revealed that a side difference of ≥5.9% could be detected with a power of at least 90% (noncentral Student's t-test distribution). On the other hand, we cannot rule out that the results of the current study might be influenced by the between-knee study design, since previous studies suggest that patients with unilateral or unilaterally more pronounced KOA may show bilateral voluntary quadriceps activation deficits ([24, 25]). Although our results were confirmed by GEE analyses that account for between-knee interaction, they should be confirmed in larger cohorts using alternative study designs. Further, we did not adjust for leg dominance, but leg dominance was almost equally split between the JSN side and the side without JSN. Further, a previous study did not detect a relationship between ACSAs and leg dominance in healthy subjects ([36]). Finally, a limitation of the study is the relatively large number of parameters tested. However, to account for this, we focused on the quadriceps as the primary (cross-sectional) and secondary (longitudinal) end points, but also explored other parameters and relationships in other thigh muscles.

Our findings are in principal agreement with those of Berger et al ([7]), who found a stronger relationship between muscle strength with pain than with K/L grade; we extend these findings to muscle ACSAs and specific strength and to the flexors and adductors, which also play an important role in the loading of the knee ([37]). Although we only included participants with bilateral frequent pain to study the independent relationship with RKOA status, WOMAC scores were still slightly greater in the medial JSN knees versus the knees without JSN. Although these differences may cause potential overestimation of differences between knees with discordant RKOA status, no differences were recorded. This is despite our previous study on discordant knee pain, showing that the design and methods are highly sensitive in small numbers of participants ([9]). Our results are in contrast to the between-knee comparison of Petterson et al ([38]), who found significantly lower muscle strength in patients with unilateral knee OA. However, the authors compared knees with end-stage radiographic status (K/L grade 4, prior to knee replacement) with contralateral knees with a pain score of <5 (of 10) on a verbal analog scale and were yet unaffected by disease, and their study therefore was unable to disentangle the relationship with pain versus RKOA status.

In the current study, the observed correlation coefficients between strength and ACSA tended to be greater in medial JSN knees than in knees without JSN, whereas in a previous study they tended to be lower in end-stage OA knees (r = 0.52) than in the contralateral knee without OA (r = 0.64). Yet, the correlation coefficients did not differ significantly between each other, and they were in a similar range as those reported in healthy subjects ([39, 40]) and in our previous study in OAI participants with discordant knee pain status ([9]).

We did not find significant differences in longitudinal rates of change in (quadriceps) muscle ACSAs, strength, and specific strength between medial JSN knees and knees without JSN, indicating that early or advanced RKOA status is not associated with a (measurable) decline in muscle mass or (specific) strength. Yet, the methodology used for measuring ACSAs previously has been shown to be sensitive to change over time in a short-term (12-week) exercise intervention ([27]). Our results are particularly noteworthy because medial JSN knees studied here were shown to display substantially greater longitudinal cartilage loss than those without JSN ([11]), suggesting that these knees are in a progressive disease stage. In our current study, muscle ACSA rates of change tended to be greater in women than in men, but the difference did not reach significance; confirmation of this observation is therefore required in a larger cohort. Our findings are in agreement with those of Beattie et al ([26]), who found similar rates of change in quadriceps muscle volume over 2 years in female OAI participants with RKOA compared to those without ([26]). Therefore, RKOA severity does not appear to be necessarily associated with a concomitant loss of muscle mass, strength, or specific strength.

Taken together with previous studies revealing a more evident relationship between muscle status and pain ([7, 9, 10]), the current results suggest that quadriceps (and other thigh muscle) properties are not independently associated with RKOA (JSN) status once knees have reached a status of frequent pain. Further, our longitudinal findings indicate that a more advanced RKOA status is not necessarily associated with a progressive decline in muscle function.

AUTHOR CONTRIBUTIONS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. ROLE OF THE STUDY SPONSOR
  9. ADDITIONAL DISCLOSURES
  10. Acknowledgments
  11. REFERENCES

All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Dr. Ruhdorfer had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study conception and design. Ruhdorfer, Wirth, Hitzl, Hunter, Benichou, Eckstein.

Acquisition of data. Ruhdorfer, Dannhauer, Kwoh.

Analysis and interpretation of data. Ruhdorfer, Wirth, Hitzl, Kwoh, Guermazi, Hunter, Benichou, Eckstein.

ROLE OF THE STUDY SPONSOR

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. ROLE OF THE STUDY SPONSOR
  9. ADDITIONAL DISCLOSURES
  10. Acknowledgments
  11. REFERENCES

The Osteoarthritis Initiative private funding partners (Merck Research Laboratories, Novartis Pharmaceuticals Corporation, GlaxoSmithKline, and Pfizer Inc.) had no role in the study design, data collection, data analysis, or writing of this manuscript. Publication of this article was not contingent on the approval of these sponsors. The manuscript has received the approval of the Osteoarthritis Initiative Publication Committee based on a review of its scientific content and data interpretation.

ADDITIONAL DISCLOSURES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. ROLE OF THE STUDY SPONSOR
  9. ADDITIONAL DISCLOSURES
  10. Acknowledgments
  11. REFERENCES

Authors Dannhauer, Wirth, and Eckstein are employees of Chondrometrics. Author Benichou is an employee of Eli Lilly.

Acknowledgments

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. ROLE OF THE STUDY SPONSOR
  9. ADDITIONAL DISCLOSURES
  10. Acknowledgments
  11. REFERENCES

The authors would like to thank the OAI participants, the OAI investigators, and the OAI Clinical Center staff for generating this publicly available image data set.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. ROLE OF THE STUDY SPONSOR
  9. ADDITIONAL DISCLOSURES
  10. Acknowledgments
  11. REFERENCES
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