Exercise and Nutritional Approaches to Combat Cancer-Related Bone and Muscle Loss

Kiss, Nicole; Baguley, Brenton J.; Via, Jack Dalla; Bolam, Kate A.; Daly, Robin M.

doi:10.1007/s11914-020-00589-0

Cited by 16 publications

(13 citation statements)

References 83 publications

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“…[3][4][5][6] Further, given the severe metabolic dysregulation and hypercatabolism that persists with cachexia, it is no surprise that clinical and experimental investigations have identified perturbations in several tissues besides skeletal muscle, including fat, bone, and heart. 3,[7][8][9][10] Unfortunately, viable treatment options to counteract cachexia, especially in the most advanced stages of cancer, remain elusive.…”

Section: Introductionmentioning

confidence: 99%

“…Cachexia is a progressive cancer‐associated disease, which presents with ongoing loss of skeletal muscle mass and strength, impeding daily function of patients, reducing treatment tolerance, and ultimately elevating mortality 3–6 . Further, given the severe metabolic dysregulation and hypercatabolism that persists with cachexia, it is no surprise that clinical and experimental investigations have identified perturbations in several tissues besides skeletal muscle, including fat, bone, and heart 3,7–10 . Unfortunately, viable treatment options to counteract cachexia, especially in the most advanced stages of cancer, remain elusive.…”

Section: Introductionmentioning

confidence: 99%

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ACVR2B antagonism as a countermeasure to multi‐organ perturbations in metastatic colorectal cancer cachexia

Huot

Narasimhan

et al. 2020

J cachexia sarcopenia muscle

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Background Advanced colorectal cancer (CRC) is often accompanied by the development of liver metastases, as well as cachexia, a multi-organ co-morbidity primarily affecting skeletal (SKM) and cardiac muscles. Activin receptor type 2B (ACVR2B) signalling is known to cause SKM wasting, and its inhibition restores SKM mass and prolongs survival in cancer. Using a recently generated mouse model, here we tested whether ACVR2B blockade could preserve multiple organs, including skeletal and cardiac muscle, in the presence of metastatic CRC. Methods NSG male mice (8 weeks old) were injected intrasplenically with HCT116 human CRC cells (mHCT116), while sham-operated animals received saline (n = 5-10 per group). Sham and tumour-bearing mice received weekly injections of ACVR2B/Fc, a synthetic peptide inhibitor of ACVR2B. Results mHCT116 hosts displayed losses in fat mass (À 79%, P < 0.0001), bone mass (À 39%, P < 0.05), and SKM mass (quadriceps: À 22%, P < 0.001), in line with reduced muscle cross-sectional area (À 24%, P < 0.01) and plantarflexion force (À 28%, P < 0.05). Further, despite only moderately affected heart size, cardiac function was significantly impaired (ejection fraction %: À 16%, P < 0.0001; fractional shortening %: À 25%, P < 0.0001) in the mHCT116 hosts. Conversely, ACVR2B/Fc preserved fat mass (+ 238%, P < 0.001), bone mass (+ 124%, P < 0.0001), SKM mass (quadriceps: + 31%, P < 0.0001), size (cross-sectional area: + 43%, P < 0.0001) and plantarflexion force (+ 28%, P < 0.05) in tumour hosts. Cardiac function was also completely preserved in tumour hosts receiving ACVR2B/Fc (ejection fraction %: + 19%, P < 0.0001), despite no effect on heart size. RNA sequencing analysis of heart muscle revealed rescue of genes related to cardiac development and contraction in tumour hosts treated with ACVR2B/Fc. Conclusions Our metastatic CRC model recapitulates the multi-systemic derangements of cachexia by displaying loss of fat, bone, and SKM along with decreased muscle strength in mHCT116 hosts. Additionally, with evidence of severe cardiac dysfunction, our data support the development of cardiac cachexia in the occurrence of metastatic CRC. Notably, ACVR2B antagonism preserved adipose tissue, bone, and SKM, whereas muscle and cardiac functions were completely maintained upon treatment. Altogether, our observations implicate ACVR2B signalling in the development of multi-organ perturbations in metastatic CRC and further dictate that ACVR2B represents a promising therapeutic target to preserve body composition and functionality in cancer cachexia.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

ACVR2B antagonism as a countermeasure to multi‐organ perturbations in metastatic colorectal cancer cachexia

Huot

Narasimhan

et al. 2020

J cachexia sarcopenia muscle

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“…Our results indicate that osteopenia may be a poor prognostic factor that precedes sarcopenia; however, further studies are warranted to investigate in detail the relationship between osteopenia and sarcopenia on the prognostic values in patients with digestive tract cancers. Methods to improve osteopenic conditions include exercise and oral nutritional support [40]. Exercise, especially progressive resistance training, weight-bearing impact activities or multimodal programs, is an important approach to manage cancer-related bone loss [41,42].…”

Section: Discussionmentioning

confidence: 99%

“…Methods to improve osteopenic conditions include exercise and oral nutritional support [ 40 ]. Exercise, especially progressive resistance training, weight-bearing impact activities or multimodal programs, is an important approach to manage cancer-related bone loss [ 41 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of preoperative low bone mineral density in patients with digestive cancers: a systematic review and meta-analysis

et al. 2022

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Purpose Osteopenia typically presents low bone mineral density (BMD) and has recently been reported as a prognostic factor in various cancers. However, the prognostic value of osteopenia in digestive tract cancers remains to be defined. We aimed to review the prognostic value of preoperative osteopenia in patients with digestive cancers. Methods Cohort studies evaluating the prognostic value of preoperative osteopenia in digestive cancers (colorectal, esophageal, hepatic, bile duct, and pancreatic cancer) were searched using electronic databases and trial registries. The exposure was defined as low BMD estimated by computed tomography at 11th thoracic vertebra, while comparator was normal BMD. The primary outcomes were overall survival and recurrence-free survival for osteopenia. Random effect meta-analyses were performed. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to assess the certainty of evidence. Results A total of 11 studies (2230 patients) were included. Osteopenia was an independent risk factor for overall survival (hazard ratio [HR] = 2.02, 95% CI = 1.47 to 2.78; I2 = 74%), along with sarcopenia. Osteopenia also predicted poor recurrence-free survival (HR = 1.96, 95% CI = 1.36 to 2.81; I2 = 85%). In subgroup analyses, osteopenia predicted prognosis in colorectal, esophageal, hepatic, and bile duct cancers, but not in pancreatic cancer. The certainty of the evidence was low due to inconsistency and publication bias. Conclusion Osteopenia may be independently associated with poor prognosis in patients with digestive tract cancer. Further studies are needed to establish the relevance of osteopenia in the operative prognosis of these patients.

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“…Health-related quality of life among people living with, or after, cancer can be improved through nutrition and exercise interventions, and these interventions may also improve survival (Albino de Queiroz et al 2021;Mishra et al 2012). There is emerging evidence that these interventions may also help to counter cancer related bone and muscle loss (Kiss et al 2020). Delivering these interventions in traditional face-to-face methods may not be feasible when meeting the increasing incidence of cancer patients globally (Duan et al 2021).…”

Section: Introductionmentioning

confidence: 99%

Self-guided technology to improve health-related behaviour and quality of life in people with cancer

McCracken

Harrison

Hill

2021

Br J Community Nurs

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Exercise and Nutritional Approaches to Combat Cancer-Related Bone and Muscle Loss

Cited by 16 publications

References 83 publications

ACVR2B antagonism as a countermeasure to multi‐organ perturbations in metastatic colorectal cancer cachexia

ACVR2B antagonism as a countermeasure to multi‐organ perturbations in metastatic colorectal cancer cachexia

Prognostic value of preoperative low bone mineral density in patients with digestive cancers: a systematic review and meta-analysis

Self-guided technology to improve health-related behaviour and quality of life in people with cancer

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