Results discussion
The current finding of most substantial hip external rotation weakness, is fairly concurrent with three other case-control studies [
43‐
45]. Our ad hoc meta-analysis of these (studies) showed a large between-group difference (30% in mean; ES 0.9, 95% CI 0.4 to 1.37) based on 163 cases and 97 controls. Further, their gender distributions agreed with that seen in our study. Because there are now three studies with similar point estimated and variable discriminative findings, adding more studies with the same small-to-moderate severely affected KOA population might not change this evidence. As for clinical trial evidence, a recent systematic review [
11] of randomized control trials (RCTs) demonstrated large effects on pain and function of hip strengthening exercises and quadriceps exercises as compared to quadriceps exercises alone. Unfortunately, the methodological quality of these trials was low (i.e., a median PEDro score < 6). Interestingly though, none of these trials reported to have strengthened the hip external rotators, only the hip abductors. However, note that the hip abductor exercises in these trials probably indirectly exercised four out of 13 muscles known to externally rotate the hip [
46]. Thus, in sum, evidence indicate substantial discriminative value of assessing external rotation strength with a promising but insecure and indirect link to strength exercise therapy improving pain and function for patients with KOA.
Hip internal rotation weakness was reported in two previous case-control studies [
43,
44], a between-group difference documented in a meta-analysis [
12] to be large (29% in mean; ES 0.8, 95% CI 0.3 to 1.2). That result [
12] is in fair agreement with the current study through various differences: The proportion of females [88% [
44], ours 62%], not reported BMI [
43] and higher BMI [
44], various positions of measuring, and measurement modes [isometric [
43], isokinetic 30°/s [
44], ours isokinetic 60°/s]. As for clinical effects, however, through two recent systematic reviews [
11,
47] we found no trials that had specifically targeted the hip internal rotators. However, on pain and function, these reviews showed important indirect effects of exercising the hip internal rotators by using programs that applied hip abductor exercises which probably indirectly loaded three out of seven hip internal rotators [
46]. Thus, evidence indicate important test discrimination and indirect exercise effect of hip internal rotation strengthening on pain and function in KOA.
Ankle strength is the least examined construct as compared to studies on knee and hip strength. On the one hand, we did not find other case-control data on
ankle eversion strength. Such strength is also unreported for healthy individuals according to a recent systematic review [
48]. On the other hand, the
ankle inversion muscle weakness in the current study is slightly less pronounced than the finding of Park et al. (2016) [
45], whom reported a large effect size (0.84, 95% CI 0.25 to 1.43) of isometric testing presented as N/kg (vs ours Nm/kg). Strength, however, is most validly presented as Nm/kg [
49]. A more important risk of bias in that study [
45] appears to be the lack of reporting the exact method of measuring inversion strength. Thus, the above wide confidence interval, low number of studies, and the methodological uncertainty, makes this evidence very likely to change with future studies. As for clinical trial effects, we found no prior strength exercise studies having explicitly reported targeting these mainly frontal plane ankle muscles. Thus, in sum, evidence indicates uncertain but substantial discrimination on ankle strength mainly in the frontal plane with an unexplored therapeutic link in KOA.
The knee extension weakness in patients with KOA is large on average. According to a recent meta-analysis of 27 cross-sectional case-control studies [
13] whereto we added five more [
45,
50‐
53], the between-group difference amounted 23% and a large effect size (0.8, 95% CI 0.2 to 1.5). The present study’s moderate muscle weakness thus falls into the middle to lower range of this confidence interval. Possibly the muscle weakness in the current study could have been more pronounced if our data had been extracted in a more flexed knee position than 30°. Indeed, among the 11 highest ranked studies in our ad hoc meta-analysis, we found large knee extension weakness among all five isokinetic studies [
54‐
58] that recorded peak strength at 54° of knee flexion on average (our calculation). The large muscle weakness variability in the total meta-analyzed result and the small lower limit of its confidence interval, indicate that the true knee extension weakness does indeed vary largely in this population, a fact that is unlikely to change with future research. On pain and function, the clinical importance of knee extension strength exercises in KOA is indisputable [
8,
59].
The current study found moderate weakness in ankle plantar flexion. Previous case-control results were meta-analyzed [
45,
50,
52,
60‐
63] and showed large difference (24% in mean; ES 0.82, 95% CI 0.3 to 1.3) between 301 cases and 272 controls. Again, this muscle weakness is more substantial than our moderate finding and those studies represent a lower proportion of females (38% females vs. our 64%). Further, the mean difference in percentage from the meta-analyzed material ranged from 50 to 1% (vs ours 19%) and confidence intervals ranged from small to large. Thus, this evidence is likely to change with future studies, although it might as well indicate a truly large sample variation. Of promising therapeutic importance, the plantar and invertor muscles have indicated a substantial external knee abduction moment via their impact on the ground reaction force during gait [
64]. This seems important, due to its possible mitigating effect on a highly prevalent medial radiographic KOA shown to be positively associated with (although unproven to be caused by) an increase in the external knee adduction moment [
65]. However, on pain and function, the only evidence of therapeutic effects of ankle plantar flexion exercise appears to be indirect; that is, through trial programs strengthening the kinetic chain through the one-legged press only [
66,
67]. Thus, evidence indicate substantial point discrimination and variability of assessment and indirect exercise effects on pain and function of ankle plantar flexors strength in KOA.
The biomechanical mechanisms of KOA appear to be knee instability and muscle weakness in the frontal [
51,
68], transverse [
64,
69], and sagittal plane [
13]. That is, the mechanisms behind the long-term symptomatic KOA might be selective weakness of the soleus and gastrochnemius [
64], the fibularii, the tibialis anterior, the hip internal-external rotators, and the quadriceps muscle [actuating sagittal and frontal plane control [
70]]. Here we present recent arguments, starting off in the frontal plane.
A particularly strong cross-sectional case-control study [
51] indicate joint instability in the frontal plane and thereto cartilage wear as a plausible injury mechanism. Having applied highly accurate dynamic stereo X-rays and instrumented gait-way analyses in patients with medial KOA, Farrokhi et al. (2016) [
51] found significant (i) elevated tibiofemoral contact point excursions and (ii) elevated frontal plane motion, both during the loading response phase of downhill gait. Further, a case-control simulation study based on in vivo biomechanical analysis of horizontal gait in patients with varus misaligned KOA [
64], indicated that the soleus and gastrocnemius muscles offered a significant deficit in external knee abduction moment (effected actively via the ground reaction force) in patients with KOA. That is, a deficit capable of explaining the patients’ increased external knee adduction moment at its second peak during late stance phase. This second peak was three times higher than that in the control individuals as compared to the first peak (that was mainly caused by gravity). In the same study [
64], gluteus medius was the primary contributor to the external knee adduction moment (via the ground reaction force) in both cases and controls (i.e., a normal finding). However, a major limitation of their [
64] muscle modelling was not having included the large gluteal muscles as knee-spanning muscles (i.e., the tensor fascia lata, gluteus medius, and gluteus maximus via their common long tendon - the fascia lata/iliotibial band) [
71,
72]. The knee-spanning gluteals probably contribute substantially to the
internal (i.e., possibly protective) knee abductor moment due to its large cross-sectional area, long tendon, and large moment arm (as compared to that of the quadriceps in the frontal plane [
70]). Comparingly, when preparing for the present study, we found no reliable test for knee abduction strength. Further, the tests found reliable for hip abductor strength in patients with KOA didn’t apply resistance inferior to the knee joint, and therefore did not include any knee-spanning moment of the gluteal knee abductor muscles.
Further in the frontal plane, a prospective cohort study [
68] biomechanically assessed patients with varus mal-aligned KOA during gait. Here, Hodges et al. (2016) [
68] documented positive correlation between annual loss of medial tibial cartilage volume and (i) greater duration of medial knee muscle (vastus, semimembranosus) co-activation, and (ii) greater duration of medial relative to lateral knee muscle (vastus lateralis, biceps femoris) co-activation.
Higher lateral thigh-muscle co-contraction correlated significantly with
decreased cartilage loss. A possible explanation for these patients’ apparent mal-adaptive increase in muscular compression across the medial tibiofemoral joint, is that these medial knee-spanning muscles are capable of increasing the external knee abduction moment via their (joint-coupled) influence on the ground reaction force [
64].
In the transverse plane, in downhill walking – the most problematic activity for patients with KOA [
51] – most of the deep external rotators of the hip are at short length and thus force–length weakened (due to the slightly flexed-to-extended positions of the hip) [
73,
74]. That is, the already weakened external rotators, as tested in lengthened positions in the present study, become even weaker by the downhill-walking hip movement pattern. Further, the external rotators of the hip are documented as the group most vulnerable to muscle weakness during gait [
75]. As for the role of muscle weakness of the hip internal rotators, however, we speculate that they have an important co-contracting and hip-stabilizing role in concert with the external rotators, much similarly to that of the hamstring muscles concerting the main knee muscle quadriceps during external knee flexion moment loading in the sagittal plane [
70].
Thus, in support of (i) the present study, (ii) strength trial meta-analyses [
12,
13], and (iii) in-vivo anchored simulations [
64], possible therapeutic solutions might be as follows: To increase the strength of the hip external and internal rotators and knee-spanning hip abductors, the lateral knee extensors and flexors (i.e., the knee-spanning knee abductors), and the ankle invertors and plantar flexors (i.e., the non-knee spanning knee abductors). On the core outcomes pain and function, evidence from two systematic reviews of randomized controlled trials [2018] [
11,
47] evaluating the effect of hip muscle strength exercises [
47], and hip muscle strength exercises in addition to knee extension strength exercises [
11], indirectly hints towards such a mechanism in patients with KOA.
Methods discussion
The current study has its methodological limitations and strengths. On the one hand, we did not manage to level the groups equally on age, and some readers might miss an alpha correction for the multiplicity of testing according to classical statistical texts [
76‐
80]. Further, the results of the peak knee extensor and flexor strength were confined to the 30° knee position, and the sample size was moderate [
76,
77]. Moreover, there is evidence of relation between reduced strength with increasing radiographic KL-grade of KOA [
81] unadjusted for in the present study. Yet further, one may claim that these strength differences are due to malalignment [
82]. Finally, one can ask: could not all the current muscle weaknesses be explained by pain [
83‐
86]? On the other hand, this is the only study so far to have comprehensively explored muscle strength in all main joints and directions bilaterally in a single case-control sample for patients with KOA. Further, we statistically adjusted for the difference in age. Supportingly therein, there was no substantive difference in the statistical inferences between the age-adjusted and the unadjusted analysis. The latter fact is understandable, due to the mean in groups being within the same middle-aged maturational category [45–64 years old] (MeSH, PubMed). Thus (therein), the groups were presenting themselves with the similar age-vs-strength decline risk profile. Concordantly, our findings (adjusted or unadjusted) were well aligned with those from appropriately age-matched confirmatory case-control studies. Indeed, in the present study we generally found
less pronounced between-group differences than what was found in prior studies summarized in meta-analyses thus contradicting an alleged age bias. Further, the explorative nature of this study justifies its main findings by highly significant differences, and corrections for multiple comparisons are judged by reputable statisticians not to be needed in exploratory studies [
14‐
16,
40‐
42]. Yet further, our peak knee extension strength position of 30° adds valuable data compared to the average peak strength position of 54° of prior isokinetic case-control studies [
13]. Moreover, there is way more evidence
against an association between radiographic grade of KOA and strength [
82,
87,
88] than the indirect association found
for it in a single cohort [
81]. Yet further, there is systematic review and meta-analysis evidence against the association between KOA and malalignment [
13]. Even further, although several studies show an association between increased pain and decreased strength (chiefly in the knee extensor muscles), there exists opposing evidence [
83,
89‐
91]. More importantly thereto, the current study was not designed to build a strong presumably causative or associative claim as to
why these patients were weaker in all these muscle-groups. Thus, we infer adequate internal validity of the current study.
The extensiveness of our testing of muscle groups in the lower limb is limited by excluding the toe flexor muscles [
92‐
94]. Additionally, the external validity of the study is limited to patients below 70 years of age and BMI obesity class I (excluding WHO’s obesity grade II-III). Furthermore, because the current sample size was moderate and the study exploratory designed [
14,
15], we acknowledge the need for larger exploratory and confirmatory studies to further substantiate the present findings. Still, we infer the current study to be appropriately externally valid.