The efficacy and safety of exercise in patients with bone metastasis: a systematic review and meta-analysis of randomized controlled trials

Abstract

Background

Exercise has proved to be beneficial for patients with advanced cancer, yet the presence of bone metastasis is commonly perceived as one of the contraindications in exercise prescription. Our objective is to determine the efficacy and safety in prescribing physical training for palliative patients with bone metastasis.

Methods

Pubmed, Embase, and Cochrane databases were searched up to 1st April 2022. Articles were screened and selected independently by two authors, based on the defined inclusion and exclusion criteria. The assessment for risk of bias of the included randomized controlled trials (RCTs) was examined by the Cochrane risk-of-bias tool for randomized trials (RoB 2). RevMan 5.4.1 was utilized for meta-analysis.

Results

Eight RCTs were eligible for this meta-analysis, with a sum of 234 subjects equally assigned to intervention and control groups. No statistical difference in the number of adverse events was identified between intervention and control groups (standardized mean difference (SMD): −0.05; 95% confidence interval (CI): −0.73 to 0.64; p = 0.89) with an inapplicable heterogeneity. No significant increase in bone pain was shown between groups at baseline; at the completion of radiotherapy and 6 months post-radiotherapy. Yet, significantly less pain was found in intervention groups after 3 months (SMD: −0.85, 95%CI: −1.55, −0.14, p = 0.02, 3 trials), (Chi² = 6.89, I² = 71%, p = 0.03). Exercise did not result in significant change in quality of life and physical function.

Conclusions

Guided training appeared safe in early-stage palliative cancer cases with bone metastasis. No significant change in physical function and quality of life was found in this review. In future, large-controlled investigations and structured exercise programs should be developed to look into the safety and efficacy of supervised exercise.

Keywords

Safety efficacy exercise bone metastasis

Introduction

Exercise is a key element in cancer rehabilitation. According to the American College of Sports Medicine, in spite of having the potential to improve physical function and quality of life (QOL), the majority of people with advanced cancer remain physically inactive.¹ Presence of bone metastases further complicates rehabilitation planning and patients’ compliance.^1,2 Currently, there are no clear exercise prescription guidelines for patients with bone metastases. Therapists reported uncertainties and frustrations towards the safety and efficacy of exercise prescription for this group of patients. Their concern centered on the heightened risk of skeletal-related events (SREs), including pathological fractures and spinal cord compression.^1,3

Some systematic reviews reported the positive impact of rehabilitation for participants with advanced cancer, but with the exclusion of individuals with bone metastasis. Several international conferences addressed the importance of physical training for patients with bone metastases, potential benefits included improvement in ambulation, aerobic fitness, and QOL.^4–14 Nonetheless, a paucity of randomized controlled trials were performed to evaluate the role of exercise for this target group. A systematic review with meta-analysis purely targeting bone metastases has not been investigated till now.

Improving physical function and QOL could bring clinically meaningful benefits to patients with bone metastases. Ensuring the safety of exercise could allay both the therapists’ and patients’ concern upon SREs, to further encourage these patients to stay active in daily life. To address the aforementioned concerns, this systematic review with meta-analysis was established to evaluate the safety and efficacy of exercise for individuals with bone metastases, as a reference for rehabilitation professionals in further research and clinical practice.

Methods

Literature search

Population, intervention, control, and outcomes (PICO) criteria were utilized in framing the research question. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were followed in reporting this systematic review with meta-analysis. This study was designed in July 2021.

Eligibility criteria

Studies that met the following criteria were included: (1) Randomized controlled trial (RCT) only; (2) Patients diagnosed with any type of primary tumor with bone metastasis, with medical clearance obtained from doctors; (3) Participated in at least one session of exercise supervised by therapists; (4) Outcome, including safety and/ or efficacy. The exclusion criteria were (1) Pediatric cancer patients (below the age of 18) and (2) Contraindications to exercise training, including health problems related to cardiopulmonary, neurologic and musculoskeletal function, especially those with significant bone pain.

Search strategies and data extraction

PubMed, Embase, and Cochrane Library were searched till 1st April 2022. The search keywords were set with reference to Medical Subject Headings (MeSh) and related review.¹⁵ The keywords were “bone metastasis”, “osseous metastasis” or “metastatic bone disease”. Exercise-related terms included “exercise”, “physical activity”, “muscle training”, “rehabilitation”, “sports” or “training therapy”. The following limitations were applied: (1) Year of publication: 2011–2021; (2) Language: English articles only.

This systematic review was set based on the PICO criteria. Participants were adults diagnosed with bone metastasis. They were allocated to either intervention group or control group. In the intervention group, exercise was categorized into aerobic, resistance, flexibility, or sports-related training; at least one session of physical training was guided by professionals. Control groups were those with usual care, progressive muscle relaxation, respiratory exercises, or hot roll treatments.

Safety, as the primary study outcome, was justified by the number of adverse events or SREs, including pathological fracture and spinal cord compression. Another parameter was the change in bone pain before and after the intervention, which was assessed by the visual analogue scale (VAS).¹⁶ Regarded as the secondary outcome, efficacy was measured by the change in physical function and QOL. Physical function refers to the difference in body composition (whole-body lean mass and fat mass), leg extension, Usual/ Fast 6-m walk, 400-m walk, Timed up and go and Balance-Sensory organization test. Quality of life comprises the influence of illness on function and the level of fatigue. It was evaluated by The European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire-Bone Metastases Module (EORTC-QLQ-BM22) and The European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire-Cancer related Fatigue (EORTC-QLQ-FA 13).

Based on the above selection criteria and limitations, all trials before the date of the search were screened, including but not limited to study protocols, conference abstracts, and articles in progress. In addition, all reference lists of eligible articles were looked through as supplementary. For identifying eligible articles, titles and abstracts are independently screened by two authors; disagreements related to study eligibility were discussed and compromised. Full texts of included studies were read thoroughly. Data were extracted for further meta-analysis by two reviewers independently. These data were collected from the full texts only, no further information was gathered from the corresponding authors.

Risk of bias assessment

With the use of the Cochrane risk-of-bias tool for randomized trials (RoB 2), the methodological quality of the included randomized controlled trials was assessed by two reviewers independently. According to the guideline from The Cochrane Handbook for Systematic Reviews of Interventions, this assessment tool covered six domains. They were selection bias (random sequence generation & allocation concealment), performance bias (blinding of participants and personnel), detection bias (self-reported outcomes & objective measures), attrition bias (incomplete outcome data), reporting bias (selective reporting), and other bias. Judgements could be interpreted as “low”, “some concerns”, or “high” risk of bias.

Statistical analysis

RevMan 5.4.1 was utilized for meta-analysis. Standardized Mean differences (SMDs) and 95% confidence intervals (CIs) with forest plots demonstrated the effect size of different variables. A p value < 0.05 referred to the statistical significance of the overall effect of the variables. Heterogeneity among the included studies was evaluated by the Chi² test and I² test, with p value < 0.1 in the Chi² test and I²> 50% representing significant heterogeneity. A random-effects model was applied for the identification of significant heterogeneity.

Results

Overview

592 publications, 412 publications and 156 publications were identified from PubMed, Embase, and Cochrane Library respectively. Additionally, 33 relevant articles were retrieved at the supplementary search in references of included studies. After removing 59 duplications, titles and abstracts of 1134 articles were screened. 46 full-text trials were assessed for their eligibility. 38 articles were excluded due to study protocols (n = 25); conference abstracts (n = 11); missing primary outcomes (n = 2). A total of 8 studies were included for meta-analysis.^16–23 The PRISMA flow diagram was illustrated in Figure 1.

Figure 1.

Flow diagram of the inclusion and exclusion process.

Patient characteristics

A total of 234 subjects were equally assigned to the intervention group and control group, with the average age of 65.9 and 66 years old respectively. All participants had the diagnosis of “bone metastasis”. 5 out of 8 included trials (62.5%) set Karnofsky performance status [KPS] > 70 as part of the inclusion criteria. 69 out of 117 participants (59%) in each group were diagnosed with metastatic prostate cancer. Other primary tumor sites were lung (17.9%), breast (10.2%), renal (1.28%), melanoma (0.85%), and others (10.7%). The majority of bone lesion sites were “Thoracic/ribs,” “Pelvis,” and “Lumbar”, involving 146, 84, and 82 individuals correspondingly. Locations of long bone metastases include “Femur” and “Humerus,” involving 34 and 15 individuals, respectively. Details of patient characteristics were displayed in Supplemental Table 1.

Intervention characteristics

Details of exercise prescription among the included trials were listed in Supplemental Table 2, based on the frequency, intensity, time, and type (FITT) principle. Five trials (62.5%) provided resistance training; one trial mixed resistance exercise with home-based aerobic exercise; one trial combined resistance, aerobic and flexibility exercises; and one trial prescribed football training. All individuals participated in at least one session of exercise supervised by professionals. The training duration ranged from 45 min to 180 min per week and lasted from 3 to 6 months. In the control group, usual care (n = 3), respiratory exercises (n = 4), and progressive muscle relaxation (n = 1) were prescribed.

Risk of bias

The risk of bias assessment was illustrated in Figures 2 and 3. In general, the methodological quality was fair. All articles resulted in low risk of bias in random sequence generation, blinding of participants and personnel, as well as blinding of outcome assessment in self-reported outcome and objective measures. One trial with unclear risk of bias was found in allocation concealment; it had no information about the concealment of the allocation sequence⁸; one trial had attrition bias, as one participant dropped out due to operation error.¹⁶ Four trials had a high risk of multiple publication bias, resulting in the overestimation of intervention effects.^19,21–23 Among these four trials, one selectively reported the decrease in oral morphine equivalent dose (non-opioid analgesics) in the intervention group over the course of six months, but omitted the increased use in concomitant medication.²² Additionally, the result of concomitant medication lasted till 12-week follow-up only. The supplementary effect of OMED and other medications might be underestimated.

Figure 2.

Risk of bias of including studies.

Figure 3.

Overview of risk of bias.

Safety

No adverse events occurred in seven out of eight studies (87.5%). One study from Rief (2014) reported 23.3% of the individuals in intervention group and 30.0% of the individuals in control group had pathological fractures at baseline, while 3 participants (20%) in intervention group and 5 participants (27.8%) in control group had pathological fractures in 6 months.²¹ No significant statistical difference between groups in the primary outcome was found at baseline measurement, 3 and 6 months (p = 0.559, p = 0.592, and p = 0.604). Of importance, overall, no heightened risk of SREs or adverse events had occurred among patients with bone metastasis participating in resistance, aerobic, flexibility, and soccer training (SMD: −0.05, 95%CI: −0.73, 0.64, p = 0.89) (Figure 4(A)) with non-applicable heterogeneity.

Figure 4.

Forest plot of safety of exercise in patient with bone metastasis (a) Number of skeletal-related events or adverse events (b) Visual analogue scale (VAS) at baseline (c) Visual analogue scale (VAS) after completed radiotherapy (d) Visual analogue scale (VAS) after 3 months (e) Visual analogue scale (VAS) after 6 months.

Cancer-induced bone pain was common among patients with bone metastasis and undoubtedly impaired their role functioning and even lifespan.²⁴ No statistically significant increase in VAS was shown between groups at baseline (SMD: −0.14, 95%CI: −0.42, 0.14, p = 0.33, 4 trials), (Chi² = 0.22, I² = 0%, p = 0.97) (Figure 4(B)); at the completion of radiotherapy (SMD: −0.23, 95%CI: −0.51, 0.06, p = 0.12, 4 trials), (Chi² = 2.39, I² = 0%, p = 0.50) (Figure 4(C)) and 6 months post-radiotherapy (SMD: −0.90, 95%CI: −2.54, 0.75, p = 0.28, 2 trials), (Chi² = 6.88, I² = 85%, p = 0.009) (Figure 4(E)). Significantly less pain in intervention groups was found after 3 months (SMD: −0.85, 95%CI: −1.55, −0.14, p = 0.02, 3 trials), (Chi² = 6.89, I² = 71%, p = 0.03) (Figure 4(D)).

To minimize the potential harm to the participants, strict selection criteria and safety precautions were implemented. All participants with bone metastasis had medical clearance obtained from doctors. Five trials underwent computerized tomography (CT) scan and/or magnetic resonance imaging (MRI) for staging,^19–23 whilst three trials conducted bone scanning.^16–18 All studies excluded the individuals with contraindications in exercise training, including health problems related to cardiopulmonary, musculoskeletal function, and/ or neurologic issues. Despite that, one trial highlighted unstable spinal metastasis as their targeted group, exercise modifications were applied.²³

All individuals participated in at least one session of exercise training supervised by professionals. Three trials emphasized their exercise prescriptions were based on the location or extent of bone metastases, to avoid specific loading over those affected regions.^16,18,23 Three trials stressed on the importance of progression in physical training, i.e. warm-up and/or cool-down periods before and after the training.^16–18 Aside from standardized exercise training programs, one included trial written by Cormie (2013) also addressed patients’ feedback upon perceived exercise intensity and perceived tolerance of the exercise sessions.¹⁸

Efficacy – physical function

There were no significant changes between intervention and control group in body composition. The standardized mean difference of whole-body lean mass was 0.25 (95%CI: −0.23, 0.73, p = 0.30, 2 trials); (Chi²=0.96, I²=0%, p = 0.33) (Figure 5(A)) and that of whole-body fat mass was 0.01 (95%Cl: −0.46, 0.49, p = 0.96, 2 trials); (Chi²=0.01, I²=0%, p = 0.93) (Figure 5(B)).

Figure 5.

Forest plot of efficacy (in physical function) of exercise in patients with metastasis (a) Physical function—body composition (whole-body lean mass) (b) Physical function—body composition (whole-body fat mass) (c) Physical function—Leg extension (d) Physical function—Usual 6-m walk (e) Physical function—Fast 6-m walk (f) Physical function—400-m walk (g) Physical function—Timed up and go (h) Physical function—Balance—sensory organization test.

No significant differences between intervention and control group were demonstrated in leg extension (SMD: 0.56, 95%CI: −0.07, 1.19, p = 0.08, 2 trials), (Chi²=0.00, I²=0%, p = 0.95) (Figure 5(C)); Usual 6-m walk (SMD: −0.53, 95%CI: −2.01, 0.95, p = 0.48, 2 trials), (Chi²=6.76, I²=85%, p = 0.009) (Figure 5(D)); Fast 6-m walk (SMD: 0.04, 95%CI: −0.59, 0.68, p = 0.90, 2 trials), (Chi²=1.54, I²=35%, p = 0.21) (Figure 5(E)); 400-m walk (SMD: −0.45, 95%CI: −1.21, 0.32, p = 0.25, 2 trials), (Chi²=1.65, I²=39%, p = 0.20) (Figure 5(F)); Timed up and go (SMD: 0.11, 95%CI: −0.50, 0.72, p = 0.73, 2 trials), (Chi²=1.46, I²=32%, p = 0.23) (Figure 5(G)) and Balance—sensory organization test (SMD: −0.00, 95%CI: −0.51, 0.50, p = 0.99, 2 trials), (Chi²=0.17, I²=0%, p = 0.68) (Figure 5(H)).

Efficacy—quality of life

The European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire-Bone Metastases Module (EORTC-QLQ-BM22) and Cancer related Fatigue (EORTC-QLQ-FA 13) were conducted to measure subjective changes in life quality among oncology patients, in terms of the influence of illness in function and the level of fatigue. Result from the meta-analysis suggested that no statistical difference was found in functional interference at the end of radiotherapy (RT), the standardized mean difference was 0.16 (95%CI: −0.20, 0.53, p = 0.38, 2 trials), (Chi² = 0.90, I² = 0%, p = 0.34) (Figure 6(A)); after 3 months (SMD: −0.02, 95%CI: −0.74, 0.70, p = 0.96, 2 trials), (Chi² = 2.53, I² = 61%, p = 0.11) (Figure 6(B)) and after 6 months (SMD: −0.52, 95%CI: −1.08, 0.04, p = 0.07, 2 trials), (Chi² = 0.85, I² = 0%, p = 0.36) (Figure 6(C)).

Figure 6.

Forest plot of quality-of-life (in functional interference) of exercise in patients with bone metastasis (a) Quality-of-life—functional interference at the end of radiotherapy (b) Quality-of-life—functional interference after 3 month (c) Quality-of-life—functional interference after 6 month.

Similar results were found in cancer-related fatigue level, with no statistical difference between the intervention and control groups in the level of symptomatology. This included (1) Physical fatigue level at the end of RT (SMD: 0.12, 95%CI: −0.25, 0.49, p = 0.52, 2 trials), (Chi² = 0.71, I² = 0%, p = 0.40) (Figure 7(A)); after 3 months (SMD: −0.22, 95%CI: −0.67, 0.22, p = 0.33, 2 trials), (Chi² = 0.05, I² = 0%, p = 0.82) (Figure 7(B)) and after 6 months (SMD: −0.58, 95%CI: −1.53, 0.36, p = 0.23, 2 trials), (Chi² = 2.48, I² = 60%, p = 0.11) (Figure 7(C)). (2) Emotional fatigue level at the end of RT (SMD: 0.19, 95%CI: −0.18, 0.56, p = 0.31, 2 trials), (Chi² = 0.48, I² = 0%, p = 0.49) (Figure 7(D)); after 3 months (SMD: −0.24, 95%CI: −0.69, 0.20, p = 0.29, 2 trials), (Chi² = 0.13, I² = 0%, p = 0.72) (Figure 7(E)) and after 6 months (SMD: −0.41, 95%CI: −0.96, 0.15, p = 0.15, 2 trials), (Chi² = 1.01, I² = 1%, p = 0.32) (Figure 7(F)).

Figure 7.

Forest plot of association between quality-of-life (in physical and emotional fatigue level) and exercise in patients with bone metastasis (a) Physical fatigue level at the end of RT (b) Physical fatigue level after 3 months (c) Physical fatigue level after 6 months (d) Emotional fatigue level at the end of RT (e) Emotional fatigue level after 3 months (f) Emotional fatigue level after 6 months.

Discussion

Summary of main findings

This systematic review with meta-analysis aimed to investigate the efficacy and safety of exercises in patients with bone metastasis. Guided training appeared safe in palliative cancer cases with bone metastasis. Resistance, aerobic, flexibility exercise, soccer training, or their combinations did not induce changes in pain level, except significant pain reduction in intervention groups after 3 months training. No improvement in life quality was shown in terms of functional interference and cancer-related fatigue level (i.e. physical and emotional fatigue). No change in physical function was demonstrated in this review, including body composition (whole-body lean mass and fat mass), muscle strength, functional mobility, and physical fitness. Taking note of the limitations, which encompass small sample size, limited generalizability, non-standardized inclusion, and heterogeneity of patient characteristics at baseline, results ought to be analyzed with caution.

Association between exercise and safety

Four out of eight trials suggested “stable bone metastasis” as one of the eligibility criteria.^19–22 One trial recruited high-risk subjects with unstable spinal metastasis as their targeted group.²³ Yet, this did not alter the significance of primary outcome—supervised exercise appeared safe in individuals with bone metastasis.

This raised the importance of establishing safety guidelines as a reference in clinical practice and for running future randomized controlled trials with subgroup analysis. In addition to aforementioned safety precautions in Result 3.5, it is noteworthy to understand the characteristics of each palliative case before exercise prescription and standardize the inclusion data in “Patient characteristics”. Details should include (1) time since cancer diagnosis; (2) time since bone metastatic disease diagnosis; (3) type, location, and severity of bone lesion at baseline, objectively measured by commonly used classification systems, such as The spine instability neoplastic score (SINS) and The Mirel's classification; (4) comorbidities like osteoporosis; (5) previous & ongoing treatment, like androgen deprivation therapy (ADT), bisphosphonate supplement, and palliative radiotherapy; 6) difference in analgesics consumption among intervention and control group, before, and after exercise, and 7) others: usual exercise habit, smoking history, calcium, and vitamin D supplements.

Association between exercise and physical function

Our result showed no improvement in physical function after supervised training, in the aspect of body composition, muscle strength, functional mobility, and physical fitness. The US DHHS guideline for aerobic activity highlighted 150 min of moderate-intensity exercise or 75 min of vigorous-intensity exercise per week.²⁵ None of the studies strictly followed the guideline in achieving 150 min moderate-intensity training. Only the study from Cormie (2013) emphasized their effort in encouraging participants to have additional aerobic exercise training sessions at home, aiming to meet the target of the US DHHS guideline.¹⁸ Conservative physical training might hinder the effect of exercise in physical function. In addition, the level of rehabilitation engagement was not explored in this meta-analysis, the benefit of exercise might be underestimated, especially when home-based training was prescribed in six trials and it was only monitored by daily log.^18–23 Under close supervision by the professionals, an exercise program running in an exercise clinic, day hospital, or day care center is suggested. Therapists can ensure patients’ adherence to exercise; motivation can be boosted up through face-to-face interaction and in a group-based training. Alternatively, in order to minimize health-care cost and allow flexibility in health-care delivery, it is necessary to wisely utilize well-designed health-related technology. For instance, apps in mobile phones, smartwatches, or tablets with motion capture systems, to monitor the patients’ rehabilitation compliance at remote districts.²⁶

Association between exercise and quality of life

No signiﬁcant difference in QOL was found between groups, as it is a subjective complex multidimensional construct.²⁷ It can be reflected by a multitude of factors, like physical symptoms, discrepancy between premorbid and current functional capacity, role functioning and social well-being.²⁸ Conditions are rapidly fluctuating in palliative oncology patients, influencing factors include disease progression, dose titration and timing of analgesics intake, side effects of drugs and sleeping quality. It is difficult for them to provide meaningful answers in rating their QOL under this constantly changing condition,²⁴ especially when EORTC-QLQ requires patients to recall their subjective feelings upon their well-being “in the past week”. Recurrent change in symptom intensity and frequency may immediately influence their self-perception of life quality. It is crucial not only to evaluate the life quality in the short-term, but also for immediate and sustained effect after exercise training.

Strength and limitations

The major strengths of this systematic review and meta-analysis are the subject recruitment of purely individuals with bone metastasis, detailed stratification of patient characteristics and exercise prescription. This can specifically evaluate the significance of clinical outcome—the safety and efficacy of exercise in oncology patients with bone metastasis. For ongoing improvement of clinical practice, this can build up the foundation for running future randomized control trials.

A paucity of randomized controlled trials with limited number of participants would hinder the significance of clinical outcomes. Furthermore, a relatively high drop-out rate was observed, with four out of eight trials having discontinuation rate more than 40%.^19,21–23 The main reasons were disease deterioration, ongoing treatment and lost to follow-up.

All articles only provided brief reasons for participants dropping out of intervention and control groups. There is insufficient data mentioning their patient characteristics, such as primary tumor location, metastatic site, onset time, and oncology treatment performed. A standardized reporting of participants data at baseline and at the time of discontinuation can advocate further subgroup analysis, which may offer more insight on when exercise prescription is safe and beneficial.

Generalization was limited by the uneven distribution of participants with regard to primary cancer type. More than half of them (59%) were diagnosed with metastatic prostate cancer. Future trial designs should clearly stratify primary tumors, or purely focus on one primary tumor that is of particular interest.

World Health Organizations (WHO) stated cancer as a chronic disease with different stages.²⁹ In this systematic review, participants were largely in the early stage of illness. Five included articles recruited candidates with Karnofsky performance score ≥ 70, which indicated patients were at least capable of self-care tasks.^19–23,30 Among those five trials, four of them had a median score of 80, which represented their ability to perform normal activities with effort.^19–22,30 The result of this meta-analysis cannot be generalized to all oncology patients under different stages.

Medical staff also showed concern upon the occurrence of pathological fracture in rehabilitation and supportive care services for those fragile patients who found difficulty in performing self-care.³¹ Fractures might occur even during trivial events, including gentle mobilization initiated by therapists and usual bed care conducted by patient care assistants, like regular bed turning, diaper change, and towel bathing on bed.³² The safety and efficacy of different treatments for patients with various functional levels should be addressed, so that multiple disciplines can evaluate the need of early intervention, such as prophylactic fixation and early prescription of resting splint for bone protection before mobilization. This can echo the professionals’ and patients’ actual concern and build up evidence-based practice in clinical assessments and treatments.

Lastly, Bisphosphonate therapy might be a protective factor in advanced cancer cases with bone metastasis. Participants in five out of eight studies had already initiated bisphosphonate therapy at baseline.^19–23 Clemons (2012) stated bisphosphonates significantly reduced the risk of SREs in women with advanced breast cancer by 17%³³; Gralow (2007) stated its analgesic effect on individuals with cancer-related bone pain³⁴; Diel (2004) claimed the significant improvements in QOL through intravenous administration of ibandronate.³⁵ Acting as a prophylactic treatment of SREs, with its potential benefits in pain control and promotion of well-being. Bisphosphonate therapy became a confounding factor that may mask an actual association between exercise and its treatment response. This might overestimate the safety and efficacy of exercise for individuals with bone metastasis.

Conclusion

Physical training appears safe in early-stage oncology cases with bone metastasis, yet no change in physical function and QOL was found in this meta-analysis. Targeting on a specific cancer type with bone metastasis, with larger sample size, standardized reporting of participants data and structured exercise programs are necessary to confirm the above findings.

Supplemental Material

sj-pdf-1-otr-10.1177_22104917241286062 - Supplemental material for The efficacy and safety of exercise in patients with bone metastasis: a systematic review and meta-analysis of randomized controlled trials

Supplemental material, sj-pdf-1-otr-10.1177_22104917241286062 for The efficacy and safety of exercise in patients with bone metastasis: a systematic review and meta-analysis of randomized controlled trials by Long-Ching Keung, Wayne Yuk-Wai Lee, Tak-Ming Chan and Sheung-wai Law in Journal of Orthopaedics, Trauma and Rehabilitation

Supplemental Material

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Supplemental material, sj-png-2-otr-10.1177_22104917241286062 for The efficacy and safety of exercise in patients with bone metastasis: a systematic review and meta-analysis of randomized controlled trials by Long-Ching Keung, Wayne Yuk-Wai Lee, Tak-Ming Chan and Sheung-wai Law in Journal of Orthopaedics, Trauma and Rehabilitation

Footnotes

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Long-Ching Keung

Supplemental material

Supplemental material for this article is available online.

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