Joint pain is the most common complaint in children with JHS  and pain severity was therefore chosen as the primary outcome measure in this trial. Large effect sizes and statistically significant differences were found following the exercise period. Child reported mean knee pain decreased by 36%, maximum knee pain decreased by 32%, and parent-reported bodily pain improved by 37%. A 30% improvement in pain scores is considered clinically significant in other rheumatological conditions  and these improvements are similar to those found previously when assessing the efficacy of exercise for children with JHS . As the treatment was provided to children and adolescents of both genders across ages 7-16 years, the results suggest that this programme may provide similar pain reductions in pain intensity for other children and adolescents with JHS and knee pain seen within the Australian healthcare setting. To provide a more comprehensive understanding of the impact of physiotherapy based interventions on the child’s overall pain experience, future research should also assess pain frequency and duration.
As knee hyperextension may result in infrapatellar fat pad, or anterior capsule impingement eliciting pain, it is possible that the children exercising to full hyperextension may have had greater difficulties performing the exercise programme pain-free. Consequently, those patients who actively limited exercises to neutral knee extension only may have gained greater physical benefits from the exercise programme over the 8-week period. It may be appropriate when managing these patients to exercise first to neutral knee extension until symptoms settle, before challenging their motion control in the hyperextension range. Given the physical benefits of an exercise to neutral paradigm and the psychosocial benefits of an exercise into hypermobile exercise paradigm, we propose that clinicians begin with the neutral, and progress to the hypermobile range, to achieve a more holistic outcome. This graded approach to exercise in JHS has been previously proposed by a group of expert therapists . Rate of exercise progression and use of analgesia was not measured within this study, but would be worthwhile to consider in future research.
Considering the overall improvement when results of the two training groups were combined, moderate effect sizes were demonstrated in all other statistically significant findings. The effect sizes observed here suggests that studies with larger sample sizes would be worthwhile.
Parent ratings of a child’s behaviour, self-esteem and mental health are important indicators of their perception of their child’s psychosocial wellbeing. These measures were specifically influenced by an exercise program that took the child’s limbs into hypermobile range, over and above the general effects of exercise shared by both groups. The improvements seen in these domains were not only significantly different between groups, but also demonstrated that exercising into the hypermobile range significantly improved self-esteem and mental health levels to equal that of Australian normative values . The reason for this finding may be due to a shift in parental perception of their child’s condition contingent on them exercising into hypermobile range. Children and parents were only aware that two different exercise programmes were being studied and were blinded to the range differences. Having the physiotherapist encourage movement within the hypermobile range may have “normalised” the parent’s perception of their child’s everyday movements that they previously considered unusual and undesirable. The consequent impact on perception of their hypermobility may explain improvements in these psychosocial measures. In light of the known incidence of anxiety disorders with the adult JHS population , further research on the mechanism behind this finding is warranted, with the inference that measurement of the child’s own perception of their self-esteem and mental health would be worthwhile.
In contrast to the improvements in psychosocial measures, overall parent-rated physical function improvements favoured those children exercising to only neutral knee extension. Despite strict randomisation, the neutral training group were significantly younger, contrasting to the known effect of strength trainability increasing linearly with age . However, this result may have been due to a ceiling effect, as despite strict randomisation, the group exercising to neutral knee extension had significantly lower physical summary scores at baseline, while final summary scores for each group were similar. Future research with larger study samples would provide definitive results as to whether limiting exercises only to the neutral range does result in measurable differences in physical function outcome.
The CHAQ showed minimal effect from the training intervention and this may be due to the global nature of the questionnaire. Questions included those related to fine motor function and daily activities such as eating and dressing which would not be expected to change when undertaking an exercise programme aimed only at knee joint function. This provides important methodological considerations for future studies in this patient population as the use of a functional measure for children more specific to the knee joint might have been more sensitive to change. Recently, the Knee Injury and Osteoarthritis Outcome score has been modified for children (KOOS-Child)  and the Modified International Knee Documentation Committee Subjective Knee Form has demonstrated acceptable psychometric properties for use in children with a variety of knee disorders (Pedi-IKDC) . The use of one of these new measures is likely to be more appropriate in this population.
Similarly, no significant changes were seen in the child’s ability to climb flights of stairs in 2 minutes, most likely as a result of a ceiling effect. Each flight consisted of 12 stairs and even when running, no greater than 25 flights was ever achieved in the 2 minutes allowed. This provided minimal opportunity for improvement in many of the participants.
Significant moderate sized improvements in muscle strength resulted from training regardless of group allocation. As expected, as both training groups were exercising to the same intensity and duration, no differences were evident between groups.
Knee joint proprioception has previously been shown to be reduced in children with JHS  and exercise programmes in adults with JHS have demonstrated improvements in proprioception as a result of exercise training . The inclusion of knee joint proprioception as an outcome measure for this study may have provided further insight into the mechanisms by which pain intensity and function gained improvements.
No significant differences were found during the baseline period with the exception of parent-reported role limitations in emotion and behaviour and hence the psychosocial summary score. We hypothesise that the improvement in the child’s behaviour may have occurred as a result of enrolment into the trial. The first assessment occurred at this point and children met with a specialist in the area who acknowledged their symptoms and hypermobility as the cause of it, and provided reassurance that physiotherapy would help to improve their pain. Within this cohort, 83% of the children were previously unknown to the multidisciplinary hypermobility service at our centre. Despite all children having GJH and significant knee pain (mean 39.4/100 on the VAS over the previous week), these children had not previously been recognised as having JHS. Delayed diagnosis of this condition has previously been reported in the literature  and this delay may contribute to provision of less than optimal management .
A multi-system disorder, JHS has significant adverse impacts on the affected child and their family’s daily functioning. Adib et al  reported 41% of children with JHS miss important periods of schooling and 67% experience limitations in their physical activities as a result of their symptoms. Children with JHS and knee pain also experience significantly reduced quality of life compared to their healthy peers . There is therefore a critical need for empirically-based evidence to guide the management of this condition.
The present study is the first RCT comparing the effectiveness of performing individualised and progressive exercises either to neutral or into the full hypermobile range of motion for individuals with symptomatic hypermobility, and the second RCT on the effectiveness of physiotherapy management for children with JHS. It provides further evidence to support the use of physiotherapy management, however because no long term follow-up was undertaken within this study, it remains unknown if the effect of the intervention washes out. The impact of this intervention on medication use and participation in daily activities such as school attendance and physical activities also warrants further investigation.