Characteristics of Interventions to Improve Bone Health in Children With Cerebral Palsy: A Systematic Review : Pediatric Physical Therapy

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Characteristics of Interventions to Improve Bone Health in Children With Cerebral Palsy: A Systematic Review

Liquori, Brianna M. MS; Gannotti, Mary E. PT, PhD; Thorpe, Deborah E. PT, PhD; Fuchs, Robyn K. PhD, FACSM

Author Information
Pediatric Physical Therapy 34(2):p 163-170, April 2022. | DOI: 10.1097/PEP.0000000000000878
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A systematic review evaluated exercise parameters and ages that produced the most improvement in bone among individuals with cerebral palsy (CP) ages 3 to 21 years.


PubMed, Scopus, Ebscohost, and Web of Science identified potential articles. Covidence was used to identify eligible citations and assess bias. The osteogenic index (OI) was used to evaluate intervention parameters.


The database search identified 312 citations. Twelve full-text articles were included. A 1-hour calisthenic exercise program performed 2 to 3 times a week for 8 months targeting each body region had the highest effect size and a substantial OI. Most of the interventions reviewed had low OIs. Activities of longer duration and greater intensity had greater OIs and prepubertal age-enhanced treatment effects.


Bone interventions for individuals with CP have low OIs, and principles of mechanostat theory should be applied to exercise dosing.


Eight systematic reviews synthesize research about exercise or other interventions for bone health among individuals with cerebral palsy (CP).1–8 However, it is not clear what type of physical activity or how much is needed to promote bone health among individuals with CP. The American Academy of Cerebral Palsy and Developmental Medicine (AACPDM) CarePathway for the management of osteoporosis among individuals with CP3 and others8 indicates that evidence to support the efficacy of weight-bearing activities to promote bone mineral density is unclear. However, it is clear that regardless if individuals with CP walk4,9 or not,10,11 there is a risk for poor bone health. The AACPDM CarePathway3 provides recommendations for surveillance, nutrition, and pharmacologic agents to manage bone health, but it does not provide guidance or education about the optimal dose of exercise for individuals with CP.

Physical therapists have not aggressively addressed interventions for bone health for individuals with CP.12 Consumers and clinicians need to be aware of the critical importance of skeletal health and the high risk for poor bone health among individuals with CP, of all ages, walking or not walking. Bone health should be a priority, and innovations are needed to address poor outcomes in this area.9,13–16

Poor skeletal health among adults with CP17 has consequences for pain, deformity, and function during the lifespan. Findings from public and private administrative claims data demonstrate adults with CP in all age groups have a higher prevalence of osteoporosis than age-matched peers.18

Using mechanostat theory and principles19 when assessing exercise to influence the skeleton among children with CP can provide new insights into effective programs. Mechanostat theory postulates that bone adaptation occurs in response to stresses or strains above a certain threshold.19 Additionally, bone responds to dynamic loading, not static loading, the loading periods can be short, and the bone needs approximately 4 hours of rest between loading bouts.19 Bone formation is a process that takes more than 6 months to measure reliably,20 and greater bone accrual is achieved during prepuberty or times with high growth hormones.19 Principles of mechanostat theory may be used to guide the design of exercise programs, specifically the osteogenic index (OI).19 The estimation of bone formation can be calculated using the OI, which is dependent on exercise intensity, number of repetitions, and frequency. Turner and Robling21 have identified an equation that predicts bone adaptation to loading (intensity × ln [frequency + 1] × times per week).

Among children developing typically around ages 9 years, Fuchs and Snow22 used 100 box jumps, 8 times greater than body weight, 3 times a week, for 7 months. Follow-up studies indicated sustainability of treatment effect.23 This study demonstrated the greatest treatment effect among bone interventions, and the gains were maintained over time.21,23 Improvement is result of the high-intensity, high-frequency, long-duration exercise and a result of the high level of growth hormones present among the participants in the study. The intervention yielded an estimated OI of 3101.36,21 and the participants had a mean age of 9 years. Loading during a time of high growth hormones enhances bone accrual.19 Previous systematic reviews for children with CP have reported on clinical dosing recommendations and synthesized them based on outcomes, not intervention characteristics.1,2 Bone is most likely underdosed among individuals with CP,12 and a critical examination of the osteogenic principles of the interventions employed can provide insight.

The primary objective of the systematic objective was to describe the treatment effectiveness along with the osteogenic characteristics of interventions in published studies. Osteogenic characteristics of interest include: (1) age; (2) type of exercise; (3) ground reaction force; (4) number of repetitions; (5) number of times of day or week; and (6) duration. This framework may advance our understanding of the varying effectiveness of activities based on osteogenic potential and age at time of intervention. The explicit question to be addressed is for individuals with CP ages 3 to 21 years, what are the exercise parameters (type, ground reaction force, number of repetitions, frequency, and duration) and what ages produced the most improvement in bone structure, mass or content, as compared with preintervention or a control group?


This systematic review followed Cochrane methodology, a protocol was prepared but not published, and the review is not registered. Treatment effectiveness was defined as changes in bone strength as measured peripheral quantitative computed tomography (pQCT), bone mass or size as measured dual-energy x-ray absorptiometry (DEXA) and reported as either areal bone mineral density in grams per centimeter2 (aBMD), bone mineral content in grams (BMC), volumetric bone mineral density in grams per centimeter3 (vBMD), and cortical area in grams per centimeter2 (CBA). Osteogenic characteristics included identifying the strain/load properties, with low indicating less than body weight (BW) to slightly over 1 time BW, moderate—1.5 times BW to 3 times BW, high—more than 3 times BW. The OI was calculated or estimated for each exercise. If a study reported the ground reaction forces created by the intervention, they were used to calculate the OI. If not, published values of activities were used.24–26 The OI value of 3101.6 generated by Fuchs et al27 was used as a benchmark for visual analysis of the selected studies for review.

Searches were performed using the PubMed, Scopus, Ebscohost, and Web of Science databases on January 15, 2020. Key words and phrases in the search included:

  1. Cerebral palsy and bone mineral density (BMD)
  2. Cerebral palsy and BMD
  3. Cerebral palsy and dual x-ray absorptiometry (DXA)
  4. Cerebral palsy and DXA
  5. Cerebral palsy and DEXA
  6. Cerebral palsy and peripheral quantitative computed tomography (pQCT)
  7. Cerebral palsy and pQCT
  8. Cerebral palsy and skeletal mineralization
  9. Cerebral palsy and bone health
  10. Cerebral palsy and bone

Several authors were contacted about additional investigations or intervention studies about young people with CP.

Selection Criteria

Studies were included if they met the following criteria:

  1. Study design was case study, case control, cohort, or randomized controlled trial (RCT).
  2. Included if the intervention group included only individuals with CP ages 3 to 21 years.
  3. Included an exercise intervention.
  4. Bone strength, mass, or size was an outcome measured using pQCT or DXA.

Studies were excluded if they:

  1. Were a narrative review
  2. Were a pharmacologic intervention
  3. Included no bone outcomes
  4. Were published more than 25 years ago
  5. Were written in a language other than English

Covidence (, an online Cochrane technology platform, was used to document the article selection process and generate a PRISMA flowchart. Each article was screened or reviewed by at least 2 authors. Duplicates were removed, and irrelevant articles were removed by examining title, and then, abstract. This was followed by full-text review and selection.

Articles selected were then reviewed independently for content and bias by at least 2 authors. Levels of evidence were assigned using categories from the Oxford Centre for Evidence-Based Medicine.28 Content extracted included child level of severity (Gross Motor Functional Classification System [GMFCS] level),29 distribution of impairment, type of activity, duration, frequency, loading of activity, and changes in bone pre- and postintervention. Consensus was obtained among authors on exercise parameters. Cochrane risk of bias30 was used to rate bias using a 3-point rating scale from low (0), unclear (1), to high (2) in the following areas: selection bias, performance bias, detection bias, attrition bias, reporting bias, and other bias. When conflicts arose, a third reviewer was used to resolve the conflict and achieve consensus. Summary bias scores 0 to 3 were considered low, 4 to 6 considered medium, and 7 or more considered high bias.

As the measurement of bone mass, strength, or size can be dependent on equipment, positioning, software, individual deformities, and type of measurements, no comparisons were made among the studies on bone outcome measures directly. The formulas (d = Mean1-Mean2/Mean1-Mean2SDpooledSDpooled or d = ΔMeanΔSD)31 were used to calculate effect size based on study design. When the data were not available, the percent change, or raw change, was calculated. An effect size of 0.2 to 0.3 was considered small, 0.4 to 0.6 moderate, and over 0.6 was considered large.31,32

Articles were organized according to level of evidence, risk of bias, and then, treatment effect in the primary data extraction table. Order of articles was maintained in a second table, which identified age range and osteogenic characteristics of activities. The type of activity, strain/loading properties, site specificity, intensity, loading cycles, frequency, and duration were described and the estimated OI was calculated.21


The database search identified 312 citations. Duplicates and noneligible types of publications were removed and 246 studies were evaluated on title and abstract. Evaluated studies resulted in 224 studies being excluded and 22 full-text articles assessed for eligibility. After further evaluation by the authors, 10 studies were excluded and 12 full text-articles were included in the quantitative synthesis (Figure 1). Of these 12 studies, 5 randomized control trials, 2 pre-/posttests, and 5 case series and reports were included (Table 1). Two were categorized with low bias, 3 had medium bias, and 7 had high bias (Table 1). No adverse events were reported.

Fig. 1.:
PRIMSA flowchart.
TABLE 1 - Bias of Selected Studies
Cochrane Bias Tool
0 = Low
1 = Unclear
2 = High
Sequence Generation Allocation Concealment Blinding Participants and Personnel Blinding of Assessors Data Complete Outcome Reporting Other Sources Total Summary Score
Chad et al33 1 0 2 0 0 0 1 5 Medium
Wren et al38 0 0 1 0 0 0 1 3 Low
Chen et al34 0 0 2 2 2 1 1 8 High
Han et al36 0 2 2 1 0 0 1 6 Medium
Ruck et al37 0 0 1 1 0 0 1 3 Low
Gusso et al39 0 2 2 2 0 0 1 7 High
Stark et al40 1 1 2 1 0 0 1 6 Medium
Gannotti et al44 2 2 2 1 0 0 1 8 High
Damcott et al35 2 2 2 1 0 0 1 8 High
Golomb et al42 2 2 2 1 0 0 1 8 High
Golomb et al41 2 2 2 2 0 0 1 9 High
Gudjonsdottir and Stemmons Mercer43 0 2 2 2 1 0 1 8 High

A summary of the 5 RCTs,33–38 2 pre-/posttests,39,40 and 5 case report/case series designs35,41–44 of weight-bearing activities for individuals with CP is in Tables 1 and 2. The studies included 246 participants, 114 males, across all GMFCS levels with average ages of 9 years, and a range from 4.5 to 21 years. Study design, study bias, child age, means and standard deviations of the pre- and postintervention bone measures for the intervention group, and treatment effect are in Table 2. Table 3 lists the age range, type of activity, osteogenic characteristics, site specificity, intensity, loading cycles, frequency per week, duration, and estimated OI. Types of activities ranged from calisthenics, whole body vibration, weight lifting, cycling, multimodal programs, video games, to dynamic standing programs.

TABLE 2 - Summary of Exercise Interventions to Improve Bone Health in Children With Cerebral Palsy
Author Study Design Bias Mean Age Bone Measure Preintervention Intervention Group Mean (SD) Postintervention Intervention Group Mean (SD) Treatment Effect Cohen's d % Change Raw Change
Chad et al33 RCT Low 9 y Femoral neck BMC, g
Femoral neck aBMD, g/cm3
Proximal femur BMC, g
1.57 (0.18)
0.36 (0.02)
8.55 (1.32)
1.72 (0.2)
0.38 (0.03)
9.53 (1.43)
d = 0.878
d = 0.83
d = 0.794
Wren et al38 RCT Low 9.4 y CBA for the tibia midshaft 163 (39) 182 (44) d = 0.508
Chen et al34 RCT Low 6-12 y aBMD femur, g/cm2
aBMD lumbar, g/cm2
0.720 (0.104)
0.578 (0.14)
0.744 (0.097)
0.583 (0.136)
d = 0.266
d = 0.04
Han et al36 RCT Low 34.43 mo BMD femur neck −4.98 (0.68) −4.8 (1.02) d = 0.22
Ruck et al37 RCT Low 6.2-12.3 y Lumbar spine aBMD, mg/cm2
Distal femur R1 aBMD, mg/cm2
Distal femur R2 aBMD (mg/cm2)
Distal femur R3 aBMD, mg/cm2
Not reported Not reported 0.013
Gusso et al39 Pretest, posttest Low 11.3-20.8 y DXA, BMD, lower limbs
DXA, BMC, lower limbs
DXA, BMD, lumbar spine
DXA, BMC, femur
DXA, BMC, lumbar spine
DXA, BMD, femur
pQCT, BMD, tibia 50%
pQCT, BMD, tibia 20%
1.048 (0.033)
642 (39)
1.095 (0.042)
25.43 (1.45)
51.85 (3.39)
0.954 (0.034)
754 (28)
687 (34)
1.071 (0.033)
655 (38)
1.109 (0.042)
25.68 (1.43)
54.51 (3.33)
0.969 (0.035)
755 (29)
686 (34)
d = 0.779
d = 0.377
d = 0.373
d = 0.194
d = 0.113
d = 0.094
d = 0.039
d = 0.033
Stark et al40 Pretest, posttest Unclear 9.76 y BMD
Not reported Not reported BMD = 2.3%
BMC = 5.74%
Gannotti et al44 Case report High 14-20 y BMD Lumbar Spine 0.445 0.805 0.360
Damcott et al35 Case Series High 4-9 y Dynamic standing BMC
Dynamic standing BMD
Passive standing BMC
Not reported Not reported Dynamic loading increased bone
Golomb et al42 Case Report High 15 y Lower total distal radius BMC
Lower ultradistal radius trabecular bone mineral content
Golomb et al41 Case series High 13-15 y (1 DXA) Plegic arm aBMD
(1 DXA) Plegic arm BMC
(1 DXA) Plegic arm B.Ar
(2 DXA) Plegic arm aBMD
(2 DXA) Plegic arm BMC
(2 DXA) Plegic arm B.Ar
(3 DXA) Plegic Arm aBMD
(3 DXA) Plegic arm BMC
(3 DXA) Plegic arm B.Ar
(1 pQCT) Plegic arm aBMD
(1 pQCT) Plegic Arm BMC
(1 pQCT) Plegic arm B.Ar
(2 pQCT) Plegic arm aBMD
(2 pQCT) Plegic Arm BMC
(2 pQCT) Plegic arm B.Ar
(3 pQCT) Plegic arm aBMD
(3 pQCT) Plegic Arm BMC
(3 pQCT) Plegic arm B.Ar
Gudjonsdottir and Stemmons Mercer43 Case series High 4.5-5.11 y 1 (static, lumbar spine)
1 (static, right distal femur)
1 (static, left distal femur)
2 (static, lumbar spine)
2 (static, right proximal femur)
2 (static, left proximal femur)
2 (static, right distal femur)
2 (static, left distal femur)
3 (dynamic, lumbar spine)
3 (dynamic, right proximal femur)
3 (dynamic, left proximal femur)
3 (dynamic, right distal femur)
3 (dynamic, left distal femur)
4 (dynamic, lumbar spine)
4 (dynamic, right distal femur)
4 (dynamic, left distal femur)
Abbreviations: aBMD, areal bone mineral density; B.Ar, bone area; BMC, bone mineral content; BMD, bone mineral density; CBA, cortical bone area; DXA, dual x-ray absorptiometry; pQCT, peripheral quantitative computed tomography; RCT, randomized controlled trial.

TABLE 3 - Osteogenic Characteristics of Interventions for Children With Cerebral Palsy Compared to Typical
Author Age Type Strain/Load Propertiesa Site Specificity Intensity Loading Cycles Time Frequency/wk Duration Estimated Osteogenic Index
Fuchs et al27 Typical children prepubescent Box jumps High LSFN 8x BW 100 LC 3x 7 mo 3101.36
Chad et al33 Prepubescent Calisthenics Low to moderate LS
∼2x BW ∼300 LC
60 min
2-3x 8 mo 986.19
Wren et al38 Prepubescent Vibrating platform Low to moderate Tibia 30 Hz at 0.3 g
∼1-1.2x BW
∼300 LC

10 min
7x 6 mo 958.79-1150.55
Chen et al34 Prepubescent Cycling Low Distal femur At 75% 1 RM
∼1-1.2x BW
∼300 LC
40 min
3x 3 mo 205.46-246.55
Han et al36 Toddler Supported standing Low LS ∼0.5-1x BW ∼100 LC
2 h
5x 6 mo 276.91-553.81
Ruck et al37 Prepubescent Whole body vibration therapy Low to moderate Tibia 12-18 Hz
2.6 g
∼1x BW
∼300 LC
9 min
5x 6 mo 684.85-821.82
Gusso et al39 Adolescent Whole body vibration training Low to moderate Tibia 20 Hz
1-mm amplitude
∼1-1.2x BW
∼300 LC
9 min
4x 5 mo 456.57-547.88
Stark et al40 Prepubescent Multimodal training Moderate Tibia
∼2x BW ∼300 LC
40 min
3-7x 6 mo ∼1369.71
Gannotti et al44 Adolescent Mixed martial arts and boxing; weightlifting Moderate Spine; upper extremities ∼2x BW ∼300 LC
90 min
2-3x 4 y ∼1643.65/y
∼6574.59 overall
Damcott et al35 Young child
Dynamic standing Low Femur ∼1.2 BW ∼300 LC
30 min
5x 3 mo 102.73
Golomb et al42 Adolescent Video games Low Distal radius Unclear 21 min 2-3x 14 mo Unclear
Golomb et al41 Adolescent Video games Low Distal radius Unclear 30 min 5x 3 mo Unclear
Gudjonsdottir and Stemmons Mercer43 Young child Standing program Low LS
∼1.2x BW 300 LC
30 min
5x 2 mo ∼273.94
Abbreviations: BW, body weight; FN, femoral neck; LC, loading cycles; LS, lumbar spine; RM, repetition maximum; x, times.
aOsteogenic index for each intervention was estimated using estimated ground reaction forces and loading cycles. It was calculated by the following formula: (intensity × ln [frequency + 1] × times per week) × number of week.

Table 2 identifies large treatment effects in 1 RCT,33 small treatment effects among 3 studies,34,36,38 and small to negative percent changes in 1 RCT.37 One cohort study had negligible effect sizes, while the other demonstrated 2.3% and 5.74% increases in BMD and BMC (Table 2). Among the case studies, there were positive changes.

Table 3 describes the OI of the interventions, and Figure 2 plots them in order of osteogenic characteristics. Interventions that include weight lifting, calisthenics, cycling, and high-intensity walking and exercise33,34,40,44 produced the largest OI (Figure 1). Among the RCTs, greatest treatment effect and OI was demonstrated by a 1-hour calisthenics program,33 2 to 3 times a week, for 8 months with 20 minutes allotted for each body region (Tables 1 and 2). Daily treatment with a vibrating platform for 6 months38 had the next highest treatment effect for the tibial midshaft, and had the next highest OI. In both studies, the activity was low to moderately osteogenic, but the frequency was high—3 times a week to daily, and the duration 6 months or more.

Fig. 2.:
Osteogenic index estimates for interventions.

Among pre-/posttest studies, a whole body vibration39 training program 4 times a week for 5 months had the largest effect size, specifically in the tibia. However, increased BMD40 in the femoral neck and lumbar spine was achieved with a multimodal program several times a week for 6 months with children classified as GMFCS levels II to IV and had the second estimated highest OI of studies reviewed. Case series included dynamic standing devices and mixed martial arts for individuals ranging from GMFCS levels III to V and video games for individuals with hemiplegia. The treatment effect was positive but small. Except for the mixed martial arts exercise, the estimated OIs of the activities were small (Table 3 and Figure 2),

Prepubescent children with a mean age of 9 years demonstrated the largest treatment effects.33 Of the RCTs, 1 study lasted 8 months,33 3 studies lasted a duration of 6 months,33,36,38 and 1 lasted a duration of 3 months.34 The 2 pre-/posttest39,40 designs lasted a duration of 5 and 6 months and the case report/case series35,41–44 ranged in duration from 2 months to 4 years. Larger effect sizes were seen in interventions that were daily or at least 3 times per week, with a duration of more than 6 months.33,38

Activities provided site-specific results. Whole body vibration produced changes in the tibia.38 Whole body strengthening activities produced changes in the femoral neck.33 Cycling produced small changes in the distal femur.34 A multimodal program produced changes in the spine and femoral neck.40 Calisthenics yielded an estimated OI of 986.19.33 Mixed martial arts, boxing, and weightlifting yielded an estimated OI of 6574.59 over the duration of the study that lasted 4 years (or 1643.65 per year).44 Studies with activities that ranked high in osteogenic characteristics and had a higher estimated OI (Table 2 and Figure 2) yielded greater treatment effects. These interventions were multimodal and used multiple muscle groups in the exercise prescription.


For individuals with CP ages 3 to 21 years, there are a variety of exercise interventions that have a positive effect on bone mass strength, size, and mass. Exercises with a high ground reaction force or pull/strain on the skeleton, occurred over a long period of time, and occurred prepuberty tended to have a greater treatment effect. Despite differences in physiological development of the bones of individuals with CP and their peers, evidence supports positive response of bone to interventions as described by mechanostat theory.19 Osteogenic characteristics of bone interventions may have an effect on the treatment effectiveness, and should be considered when designing inter- ventions.

The AACPDM CarePathway for the management of osteoporosis indicates that there is a lack of evidence to support the efficacy of weight-bearing activities to promote bone mineral density. However, based on the studies that were reviewed, there is evidence that weight-bearing activities do promote bone mineral density in individuals with CP.

Interventions with a higher estimated OI were those that included multimodal, compound movements.33,40,44 Current interventions to improve bone mineral density may be underdosed.

Interventions reviewed did not load the skeleton greater than body weight, and did not use the intensity, frequency, or duration required for osteogenesis. The small sample sizes and varying durations indicate the need for multicenter trials and individuals with similar characteristics that investigate the effect of weight-bearing exercise over a longer period. Standardized interventions, specifically regarding the exercise prescription, assessment, and follow-up measures, are important in the understanding of how to promote bone mineral density.

Participants varied in physical abilities from the ability to walk with no limitations and had hemiplegia to individuals who had difficulty holding their heads up. Participants with more severe gross motor impairment were involved in standing programs, interventions with the lowest OI. More creative and innovative movement programs should be designed for individuals classified GMFCS level V to promote skeletal health and prevent secondary conditions. Individuals classified GMFCS level IV did participate in intense, high-frequency programs.40,44

There is risk of bias across studies, as many of the studies did not control for other factors highly related to bone health such as genetics, nutrition, and growth hormone levels. There was 1 crossover design to test the bone changes with and without the intervention in a group of children, but this did not control for some factors. There are a myriad of issues around measuring bone using either pQCT or DXA, including differences in software, hardware, technician, and interpretation.20 The OI was estimated for studies with no published ground reaction forces or unclear for the upper extremities. The sample sizes are small, and the characteristics of the participants heterogenous. This limits the ability to pool the findings and generalize.

Recommendations for clinicians and researchers include designing and using interventions that incorporate principles of mechanostat theory and use OI for activities. Individuals with CP regardless of their ability to walk have a propensity for poor bone health. Small bouts of more than usual loading with novel multidirectional forces are warranted for all individuals with CP across the lifespan, but particularly in prepuberty. Continued creativity and innovation are needed for those who cannot move voluntarily, for both the design of activities and the measurement of outcomes.


Bone interventions for individuals with CP have low OI, and principles of mechanostat theory should be applied to exercise dosing. Exercise with higher OI demonstrated increased treatment effect on bone health among individuals with CP 3 years to 21 years of age. Principles of mechanostat theory19 should be applied to interventions to improve bone health among individuals with CP. Use of these concepts may aid in improvement of treatment effectiveness among bone health interventions.


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bone health; cerebral palsy; exercise; mechanostat principles

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