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Cancer patients often experience muscle weakness, which can be caused by the cancer itself or its treatment. This condition is called cancer cachexia, which is a wasting syndrome that leads to dramatic weight loss and loss of skeletal muscle mass. Cachexia is estimated to occur in up to 80% of people with advanced cancer, and it can drastically impair quality of life and worsen survival outcomes. There is currently no approved treatment for cachexia, but researchers are studying its causes and testing new treatments. The mechanisms underlying cancer-associated muscle weakness are complex and involve inflammation, autophagy, disrupted protein synthesis, and mitochondrial dysfunction. Tumor metastasis to bone can also cause muscle weakness by disrupting normal bone remodeling and releasing growth factors that fuel tumor growth and bone destruction.
| Characteristics | Values |
|---|---|
| Cancer-associated muscle weakness | Cachexia, a wasting syndrome causing dramatic weight loss and loss of skeletal muscle |
| Cancer types | Colorectal cancer, breast cancer |
| Treatments | Chemotherapy, radiotherapy |
| Symptoms | Fatigue, shortness of breath, impaired exercise tolerance, reduced heart function, muscle atrophy |
| Causes | Tumor cells, chemotherapy, malnutrition, impaired intrinsic capacity, neuromuscular disconnection, loss of motor unit connectivity |
| Treatment for cancer-associated muscle weakness | No approved treatments, novel interventions and mechanistic insights are needed |
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Tumour metastasis in bones
Cancer-associated muscle weakness is a significant co-morbidity of bone metastases. Bone metastasis is cancer that starts in another part of the body and then spreads to the bones. Nearly all types of cancer can spread to the bones, but some types are more likely to, including breast cancer, kidney cancer, lung cancer, multiple myeloma, prostate cancer, and thyroid cancer. Bone metastasis can happen in any bone, but it is most common in the spine, pelvis, upper leg bone (femur), upper arm bone (humerus), ribs, and skull.
Bone metastasis can cause bone pain, which is often the first symptom of cancer that has spread to the bone. This pain may come and go at first, but it can become constant and worsen during activity. Bone metastasis can also lead to bone fractures, as the condition makes bones more fragile and likely to break, even during normal activities. High levels of calcium in the blood, called hypercalcemia, can also occur due to bone metastasis. Hypercalcemia can cause nausea, vomiting, constipation, and confusion, as well as muscle weakness, fatigue, and kidney and heart problems.
Spinal cord compression is another complication of bone metastases. When cancer spreads to the bones of the spine, it can press on the spinal cord, leading to nerve damage and potential paralysis if not treated promptly. Treating bone metastases early is crucial to prevent these serious complications. Treatment options include addressing the cancer itself, using local treatments like radiation therapy or surgery to shrink or treat the affected area, and managing pain with medications.
Muscle weakness associated with bone metastases can be caused by reduced muscle mass or function, or a combination of both. This muscle weakness can drastically impair the quality of life and worsen survival outcomes for cancer patients. While there are currently no approved treatments for cancer-associated muscle weakness, research is ongoing to develop novel interventions to address this debilitating issue.
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Vitamin D deficiency
Vitamin D is essential for maintaining bone and muscle health. It helps the body absorb calcium and phosphorus, which are crucial for strong and healthy bones. When an individual has a severe vitamin D deficiency, their body cannot absorb calcium effectively, leading to hypocalcemia or low calcium levels in the blood. This triggers secondary hyperparathyroidism, where the parathyroid glands work harder to maintain normal blood calcium levels. Both hypocalcemia and hyperparathyroidism can cause muscle weakness, cramps, fatigue, and even depression.
The recommended daily intake of vitamin D varies depending on age, and it can be obtained through sun exposure, diet, or supplements. Sunlight on the skin triggers the production of vitamin D. However, excessive sun exposure without sunscreen increases the risk of skin cancer, so many people opt for dietary sources or supplements. Fatty fish like salmon, tuna, mackerel, and sardines, beef liver, cod liver oil, and egg yolks are good natural sources of vitamin D. Vitamin D-fortified foods such as cow's milk, plant-based milk alternatives, breakfast cereals, and orange juice are also recommended.
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Malnutrition
Cancer-associated muscle weakness is a common co-morbidity of bone metastases, often linked to cancer cachexia. Cachexia is a syndrome characterised by severe wasting due to a loss of skeletal muscle mass and abnormal metabolism. While malnutrition is a distinct condition, it is a contributing factor to muscle weakness in cancer patients.
The impact of malnutrition on muscle weakness is complex and multifaceted. Malnutrition can directly contribute to a loss of muscle mass, which is a key factor in muscle weakness. Additionally, malnutrition can impair intrinsic capacity, leading to contractile dysfunction and intramuscular impairments, further exacerbating muscle weakness.
The prevention and management of malnutrition in cancer patients are crucial. Early and regular dietary counselling, nutritional support, and multimodal rehabilitation interventions have been shown to be effective in treating and preventing malnutrition and its associated muscle weakness. Prehabilitation trials, including nutritional and exercise interventions, have emerged as promising approaches to offsetting weight and muscle loss, particularly in patients undergoing gastrointestinal and colorectal surgeries.
However, it is important to differentiate between 'simple' caloric restriction and cachexia. While both conditions result in the depletion of fat and protein stores, cachexia is characterised by the additional presence of systemic inflammation, which can strain multiple organ functions. Therefore, comprehensive assessments and interventions targeting nutritional risks are essential to effectively managing malnutrition and its impact on muscle weakness in cancer patients.
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Chemotherapy
Muscle weakness is a common and debilitating consequence of cancer and its treatments. Chemotherapy, a treatment for cancer, can cause muscle weakness and bone loss, a condition known as cachexia. Cachexia is characterised by weight loss, depletion of fat and muscle, increased fatigue, reduced quality of life, and high mortality. The exact molecular mechanisms underlying cachexia are not yet fully understood, but it is a significant problem that impairs the quality of life and worsens survival outcomes in cancer patients.
Several studies have investigated the effects of chemotherapy on muscle weakness using animal models, particularly mice. These studies have shown that chemotherapy can lead to skeletal muscle wasting and weakness, negatively impacting muscle function. For example, one study found that mice receiving chemotherapeutic agents like folfiri and cisplatin exhibited reduced muscle force and motor unit number estimation (MUNE) compared to control groups. Another study using a canine model observed muscle atrophy and weakness with doxorubicin treatment. These findings suggest that chemotherapy-induced muscle weakness may be associated with a loss of motor unit connectivity and altered innervation of the muscles.
Furthermore, oxidative stress has been implicated in chemotherapy-induced muscle weakness. Certain chemotherapeutic agents can decrease antioxidant levels, leading to elevated levels of oxidants in the body. These elevated oxidants can then cause muscle weakness and accelerate fatigue. Specifically, doxorubicin, a chemotherapeutic drug, has been shown to negatively affect skeletal muscle function through oxidative stress via a two-fold pathway. Doxorubicin can directly stimulate the production of reactive oxygen species (ROS) through redox cycling or indirectly via TNF-signaling, both of which can contribute to skeletal muscle weakness.
The muscle weakness caused by chemotherapy can persist for months or years after treatment, leading to problems such as fatigue and falls, which can result in fractures and increased mortality. Currently, there are no approved treatments specifically for cachexia. However, researchers are actively investigating the underlying mechanisms and developing new treatment approaches to improve musculoskeletal health and quality of life for cancer patients undergoing chemotherapy.
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Radiotherapy
The development of effective therapies to prevent and treat the negative consequences of radiotherapy is an ongoing area of research. While radiotherapy has improved in accuracy, reducing the amount of healthy tissue exposed to radiation, the long-term side effects can significantly impact the health and physical performance of cancer survivors.
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Frequently asked questions
Yes, cancer can cause muscle weakness, a condition known as cancer-associated muscle weakness or cancer-induced muscle wasting (CIMW).
Muscle weakness in cancer patients can be caused by a variety of factors, including the malignancy itself, the tumour environment, chemotherapy, radiotherapy, and malnutrition.
Muscle weakness in cancer patients can result in fatigue, shortness of breath, impaired exercise tolerance, and reduced quality of life. It can also lead to severe weight loss, weakness, and fatigue, as well as changes in appearance and mental health struggles.
Muscle weakness is a common co-morbidity of bone metastases and cancer cachexia, affecting up to 80% of people with advanced cancer.
Currently, there are no approved treatments for cancer-associated muscle weakness or cachexia. However, there are several pharmacological therapies in pre-clinical and clinical testing that appear promising, including resiniferitoxin and selective androgen receptor modulators.
