P1: For P1, ankle plantar flexor, knee flexor, and hip flexor muscle length all decreased significantly during the intervention phase. The significant decreases were observed between weeks 16 and 36, which coincided with loss of functional ambulation. Muscle length remained low or decreased further during the withdrawal phase.
P2: For P2, who was status post surgical tendo achilles lengthening, plantar flexor muscle length remained stable across phases. Knee flexor muscle length improved significantly mid-intervention and returned to baseline during late intervention and withdrawal. Hip flexor muscle length showed a nonsignificant trend toward improvement with intervention that became significant during withdrawal.
P3: For P3, also status post surgical tendo achilles lengthening, plantar flexor muscle length remained stable across phases. Knee and hip flexor muscle length improved significantly during the intervention, and decreased to or toward baseline levels with withdrawal.
P4: For P4, who had 20° ankle plantar flexor muscle contractures at baseline, plantar flexor muscle length showed a nonsignificant trend toward decline during the intervention phase that became significant during withdrawal. Knee flexor muscle length declined significantly during the intervention phase, whereas hip flexor muscle length improved significantly.
Summary. Improved hip flexor muscle length was observed in 3 of the 4 boys (P2-P4) during or immediately after the standing intervention. Improved knee flexor muscle length was seen in 2 of the 4 boys (P2 and P3). Ankle plantar flexor muscle length was stable (P2-P4) or declined (P1) in all 4 boys.
Bone Mineral Density. BMD data were graphed using Hologic software-generated curves on the basis of sex and age at baseline (Figure 3).
P1: Total lumbar spine BMD of P1 was within 1 standard deviation of age-predicted mean at baseline (Z-score = −0.6), decreased significantly mid-intervention, and remained stable, yet significantly below baseline, through withdrawal. P1 was the only subject that was ambulatory at study start, and the significant loss of BMD corresponded to the period immediately after loss of functional ambulation.
P2 to P3: Baseline total lumbar spine BMDs of P2 to P3 (both non-ambulatory) were more than 2 standard deviations below age-predicted means at baseline (Z-scores = −2.9; −2.8). P2 showed a significant BMD decrease mid-intervention that recovered to baseline by intervention end and remained level through withdrawal. P3 showed stable lumbar BMD across baseline, intervention, and withdrawal phases.
P4: Baseline total lumbar spine BMDs of P4 (also nonambulatory) was nearly 2 standard deviations below age-predicted means at baseline (Z-score = −1.9), decreased significantly mid-intervention, recovered to baseline by late intervention, and remained at baseline level through withdrawal.
Summary. A significant decrease in lumbar BMD between baseline and early to mid-intervention was seen in 3 of the 4 boys. This decrease in BMD was transient in P2 and P4, and sustained in P1. Stable lumbar BMD across study phases was observed in P3. No boy showed increased BMD during or poststanding intervention.
The purpose of this study was to assess the safety and tolerability of a supported standing program in 4 boys with DMD and describe effects of standing on lower extremity muscle length and BMD before, during, and after an extended standing program. Although standing programs have been described and studied in several samples of children with impaired movement and mobility,12 this report is the first to provide empirical evidence related to supported standing programs in boys with DMD. Current evidence-based recommendations for PT intervention during the late ambulatory and nonambulatory phases include stretching, positioning, and orthoses (AFOs).9 Supported standing offers the possibility of an additional approach for targeting contracture management, with the potential for added positive effects on spinal and/or lower extremity BMD, and function and participation in home, school, and community settings.
Our findings support the safety of supported standing for boys with DMD. No injuries or serious adverse events related to the standing program were reported, and physical discomfort that occurred with supported standing did not last beyond daily standing times. The sample included boys aged 12 to 15 years at a typical height in the setting of long-term glucocorticoid therapy, but with elevated BMI for age compared with that of a recently described DMD cohort.28 Increased body weight may have provided better longitudinal axis bone loading in a standing position, but may also have had a negative effect on standing tolerance.
Maintenance of an upright standing position for 20 to 60 minutes at the maximum device angle (−15° from vertical) was achieved and tolerated by 75% of participants (P1, P2, and P3), despite mild to moderate hip, knee, and/or ankle range-of-motion restrictions. The maximum device angle position was tolerated across the intervention phase by 50% of participants (P1 and P3). P4 was the only participant who did not tolerate an upright position at the device maximum for more than 3 minutes at any point in the intervention phase. Comparative analysis of lower extremity muscle lengths across participants revealed that the only joint at which P4 showed more than 10° greater deficit than other participants at baseline was the ankle. P4's chief physical complaint when standing (and his reason for preferring a squat position) was increased anterior knee/shin pressure and forefoot/toe pressure, both clearly linked to redistribution of forces from plantar flexion contractures. This finding suggests supported standing programs may be less feasible in boys with plantar flexor contractures more than 15° to 20° and highlights the importance of vigilant preventive management of ankle plantar flexor muscle length to allow sustained supported standing as a viable intervention option. Other PT interventions targeting plantar flexor muscle length of boys with DMD have also noted 15° of plantar flexion as a cut-off point guiding clinical decision making,29 in this case related to the effectiveness of serial casting. P2's tolerance of the upright position across the intervention phase was most limited by low back pain that began mid-intervention and occurred as an intermittent complaint approximately 50% of intervention weeks. He adjusted his stand position to −25° to ameliorate physical discomfort or did not stand on days he was experiencing back pain more than 3/10.
Target standing times of 60 minutes per day were reached by 75% of participants (P1, P2, and P3), but target numbers of days (5) and hours (5) per week were not consistently achieved or were not sustained, making the overall dose of standing across the intervention period markedly less than prescribed. Program adherence was affected by both practical factors (device malfunction, family vacations, long school days limiting home time) and motivational factors (“I just didn't feel like standing”) for all boys, as well as by physical factors for P2 and P4. More frequent monitoring (>1 times/month), implementation of standing programs in school-based settings, and identification of incentives that motivate program commitment may help improve adherence in future standing studies.
The pattern of stability and change seen in lower extremity muscle length with supported standing was not uniform across the 4 participants, or across muscle groups. However, our findings support the idea that improvements in hip and knee flexor muscle length are possible for boys in the early nonambulatory phase, even with standing times less than 7.5 hours per week. Significant improvements ranged from 15° to 16° in hip flexors and 10° to 12° in knee flexors, both beyond the 5° to 10° of measurement error expected for joint range of motion.30 The clinical relevance of the improvements at the hip and knee is not clear, particularly given the nonambulatory status of the boys. At the ankle, clinical relevance for DMD has been based upon achieving and maintaining a neutral (plantigrade) position, which supports ambulation.29,31 Much needed are studies that more closely examine the association between hip and knee extension ROM and the ability to attain and sustain a supported standing position.
The natural history of contracture development in DMD predicts a progressive decline in muscle length, particularly once the ability to ambulate has been lost.14 Evidence supports improved ankle dorsiflexion ROM with serial casting in boys with DMD in the early ambulatory stage of the disease.31 However, nonsurgical interventions for contracture management in boys not ambulating (eg, orthotics and stretching) have mainly been effective at slowing contracture progression.32 Therefore, the possibility of improvement in muscle length with supported standing in boys who are not ambulating warrants further exploration, particularly if improved muscle length relates to improved tolerance of supported standing. Importantly, boys with DMD not participating in regular stretching programs (all participants in this study) show increased variability in range of motion,33 which may increase “noise” in baseline muscle length measurements in some subjects.
The significant loss of hip flexor, knee flexor, and ankle plantar flexor muscle length seen in P1, who was ambulatory at study start, is characteristic of the transition to the non-ambulatory phase,34 and suggests that supported standing programs of less than 3 to 4 hours per week may be insufficient to counteract the expected loss of lower extremity muscle length that comes with loss of the ability to walk. One unexpected finding was the continued improvement in P2's hip flexor muscle length in the withdrawal phase. A possible explanation is that P2 continued with sporadic supported standing beyond the end of the intervention phase, despite withdrawal phase instructions. His back pain tempered during the withdrawal phase and he reported occasional standing “helped his legs feel better.” Thus, he may have continued to benefit from the stretch provided by supported standing and gained a few more degrees of motion. Alternatively, because all hip flexor measurements after mid-intervention were relatively stable (within 5°), the significant change in withdrawal might merely reflect maintenance of the improvements from intervention.
Given low baseline bone density and high risk of fractures in boys with DMD,7,8 BMD was chosen as a secondary outcome measure. Dual-energy x-ray absorptiometry requires exposure to small amounts of ionizing radiation and only detects changes in BMD within 4 to 6 months in children older than 10 years,35 rendering the typical, repeated baseline testing of a single-subject design untenable. Compared with a single baseline BMD, only P1, who lost ambulation in the course of the intervention phase, showed a significant and sustained loss of BMD with supported standing. This finding suggests that a dose of 3 to 4 hours of supported standing per week may not be sufficient to counteract the loss of BMD associated with loss of ambulation in boys with DMD.22 Of perhaps greater interest is the finding of relative stability in BMD in 3 of 3 boys who were not ambulating, particularly in the setting of ongoing glucocorticoid therapy. Given increased risk of vertebral and lower limb fractures, particularly for boys receiving long-term glucocorticoids,36 a PT intervention that stabilizes or slows loss of BMD and, potentially, lowers risk of fracture is desirable. Although both cross-sectional and 2-time-point longitudinal data describing bone changes in DMD have been reported,7,37,38 a detailed, longitudinal natural history of BMD within and across disease stages in glucocorticoid-treated boys with DMD is not yet available, making more in-depth interpretation of stable BMD findings a challenge.
This study had a number of limitations. First, the single-subject A-B-A design used for muscle length, while experimental, is challenging to interpret when a return to baseline does not occur during withdrawal. In our study, we saw both patterns of stability and continued decline from intervention through withdrawal phases, making evaluation of the treatment effects difficult. A second intervention period (eg, an A-B-A-B design) with comparable study phase lengths might better characterize treatment effects. Second, our sample of 4 boys with DMD was heterogeneous with respect to functional level at baseline. Loss of ambulation in 1 participant, with the associated loss of muscle length and bone density, confounded interpretation of individual and group treatment effects. Third, lower extremity joint angles were not measured in a supported standing position, which limits the ability to evaluate the relationship between hip, knee, and ankle contracture and standing tolerance, a finding that would guide clinical decision making when initiating supported standing programs. In particular, measurement of standing knee flexor muscle length, rather than popliteal angle, may have more clinical relevance for predicting standing tolerance. Finally, daily standing times were based on self or parental report, which may have introduced bias and/or inaccuracy related to intervention dose.
The findings from this study can serve as a foundation for future studies of supported standing in boys with DMD. A randomized controlled trial or cohort study with a larger sample is warranted to more fully explore outcomes and potential benefits of supported standing. Strategies for increasing adherence and maintaining motivation to achieve longer standing duration are needed. Better adherence to a standing program could also allow a comparison of multiple dosing regimens. Katz et al25 demonstrated benefits of standing on BMD in children with cerebral palsy with 10 weekly hours, but not with less than 7.5 hours. Optimal dosing in boys with DMD may be different than in children with other developmental disabilities, but this study provides a starting point for exploring various standing durations. Finally, weight-bearing load in supported standing (eg, percent body weight) should be measured alongside the postural alignment/stand angle to more clearly quantify standing dose.
For evaluation of changes in BMD with supported standing, lateral distal femur should be included as an anatomical DXA site in future studies. Normative reference data are now available,23 and current consensus identifies lateral distal femur as a target scan in boys with DMD.19,22 Because glucocorticoid-treated boys with DMD have reduced stature, areal BMD should also be adequately corrected for bone size and skeletal maturity using 1 of several existing methods.24
As part of a 2010 systematic review, Glickman et al11 concluded that supported standing clinical investigations should seek to include functional, behavioral, and cognitive outcomes, alongside physiological measures. Therefore, future studies of supported standing in boys with DMD should include outcomes across all 3 components of the International Classification of Functioning, Disability and Health model, particularly those that reflect activity and participation components. Participants in this study reported a host of new functional abilities associated with supported standing, including accessing higher height shelves, cabinets, and counters. These abilities were reported to enhance both independence and social interaction. Social engagement was recently identified as a limitation in older boys with DMD.39 The ability to engage in a supported standing program after the loss of functional ambulation may well have implications beyond any potential effect on muscle length and bone density. Identifying measurement tools that can capture the effect of supported standing in the activity and participation levels of the ICF should be an important priority.40 Current work by the Cooperative International Neuromuscular Research Group includes a longitudinal study of the relationships among impairment, activity, participation, and quality of life in boys with DMD,41 and may inform our understanding of key outcomes to include in future studies of supported standing in boys living with what is, for now, a progressive neuromuscular disorder.
This is the first study exploring the safety and tolerability of supported standing for a subset of boys with DMD in the late ambulatory and non-ambulatory disease stages. Findings provide initial evidence that supported standing is safe and, in the absence of marked ankle equinovarus contractures, may be well tolerated and have positive effects on lower extremity hip and knee flexor muscle length in boys with DMD who are not ambulating.
Two standing devices were loaned by ATG Rehab (now NuMotion). We thank PT graduate students Nidhi Nandakumar, Spiros Papagianopoulos, Eileen Kirk, and Amy Shipley for their work with data collection and management. Gratitude is extended to Brian Tseng, MD, PhD, pediatric neurologist and former Director of the Pediatric Neuromuscular Clinic at MGH and to Madhu Misra, MD, MPH, pediatric endocrinologist and co-chair of the MGH Clinical Research Center for consultation on study design and methods.
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Keywords:Copyright © 2016 Academy of Pediatric Physical Therapy of the American Physical Therapy Association
adolescence; bone mineral density; Duchenne muscular dystrophy; exercise therapy; exercise tolerance; patient safety; physical therapy methods; range of motion; standing position; weight-bearing