Author(s): Sophia Antimisiaris, DO, MPH, Siam Ayon, DO, MS, Sammy Wu, MD
Originally published: September 20, 2013 Last updated: October 16, 2025
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Disease/Disorder

Definition

Bone metastases are defined as oncologic lesions within bones that occur distant from the primary site of cancer. Bone metastases occur at advanced stages of cancer and are one of the most common sites of tumor spread away from the primary location.

Epidemiology 

Bone metastases are extremely common in cancer. An estimated 300,000-600,000 new cases of bone metastasis are diagnosed in the United States annually.1 Approximately 350,000 people die each year from bone metastases.2 Bone is the third most common site of distant metastases, after lung and liver.3 Primary malignant tumors most likely to metastasize to bone include breast, prostate, lung, kidney, thyroid, and colon cancers. 4-7

Risk factors 

Risk factors for developing bone metastases include the presence of an osteophillic tumor that is not adequately controlled or treated. Bone metastases can occur in any location but are seen typically in the spine, pelvis, rib cage, and long bones such as the femur.7-10 A multivariable logistic regression analysis of patients with breast cancer showed that older age (≥65), white race, high-grade cancer, advanced T and N stages, synchronous lung, liver, and brain metastasis were risk factors for developing bony metastasis.10 On the other hand, married status, higher income, systemic therapy, and chemotherapy were identified as protective factors against bony metastases in patients with breast cancer.11 In a study of breast cancer patients, identifying a combination of risk factors, such as axillary lymph node metastases, elevated CA15-3, elevated alkaline phosphatase and lower hemoglobin, was found to be the most accurate in predicting bone metastases in breast cancer.12 Regarding prostate cancer, it was determined that high prostate-specific antigen (PSA) levels, high Gleason score, high monocyte percentage  (M%), advanced T and N stages were independent risk factors for bone metastasis.13

Etiology and pathophysiology

Bone metastases result from cancer cell seeding and subsequent growth at a site distant from the primary tumor.5 Growth at sites distant from the primary tumor site is dependent on several biochemical factors.5 The fertile microenvironment within bone encourages tumors to spread to this location and grow successfully.5,15

Metastases usually occur in the axial skeleton, which has a higher percentage of red marrow.4 Osteoclasts and osteoblasts are activated in the setting of bone metastases and increase several biochemical factors to enhance tumor cell growth.5,15 Metastases can be classified as osteolytic, osteoblastic, or mixed.15

Disease presentation

Bone metastases can present in a variety of ways. They may be asymptomatic and detected only on routine surveillance studies.3 Pain is the most common presentation of bone metastases.3,15 This may be a result of direct cortical bone involvement, resulting in localized inflammation and biologic pain.4

Skeletal related events (SREs) occur as a complication of bone metastases.3-6,15 Common SREs include pain, pathologic fracture, spinal cord compromise, and hypercalcemia resulting in an increased need for radiation therapy or surgery.3-6,9,15 These complications can cause increased morbidity and mortality.5 The prognosis of the individual patient with bone metastases varies depending on the type of primary tumor.4

Essentials of Assessment

History

Individuals with bone metastases may be asymptomatic or may present with biologic pain or neurologic symptoms.3-6,9,15 Patients may also present with fracture related pain as the initial symptom of metastases. Sudden severe pain in the absence of trauma is highly suggestive of pathological fracture.4 Spinal metastases often present with back pain prior to the onset of neurologic impairments.4 Biologic tumor pain is usually local to the site of involvement and occurs as a result of inflammation from tumor growth within bone.3-4 Biologic tumor pain is often worse at night and with lying supine.3-4 Mechanical pain is worsened by increased axial loading of the affected bone with activities such as walking or Valsalva maneuvers.4  Metastases can also cause mechanical instability within the bony spine with flexion and extension. Pain can be intermittent or constant and can be sharp and severe in quality.3 Patients may also present with pain in nearby structures due to altered biomechanics.16-17 In addition, due to hypercalcemia caused by the metastasis, the patient can develop fatigue and muscle weakness.4

In cases of changes in neurologic function as a result of bone metastases, patients can experience symptoms such as bowel or bladder impairment, weakness, or sensory alterations.4 Metastases can also result in neurologic symptoms and signs such as cranial nerve palsies and headache if they occur at the base of the skull.4

Physical examination

Physical examination can demonstrate erythema, swelling, or localized tenderness in addition to reduced range of motion. Caution is advised when performing manual muscle testing in patients with known or suspected long bone metastases or pathologic fractures.7 Discomfort with axial loading suggests mechanical instability or fracture.4 An abnormal neurologic exam may suggest radiculopathy or myelopathy with changes such as weakness, altered pin prick or light touch sensation, reduced proprioception, hyper or hyporeflexia, clonus, or a positive Babinski sign.4

Functional assessment

Patients should be individually evaluated for independence with activities of daily living, transfers, mobility, and balance in the setting of bone metastases. The home and social supportive environment should be assessed to maximize patient mobility, with an emphasis on patient and caregiver education.  

Laboratory studies

Laboratory studies to assess organ function and complications of skeletal involvement in patients with bone metastases include complete metabolic profile, complete blood count, alkaline phosphatase and urine analysis.18 Markers of bone metabolism may reflect the extent and progression of bone lesions, thereby providing important prognostic insight for patients with bone metastases.18 Some studies in patients with bone metastases from solid tumors suggest that alterations in the levels of bone resorption markers such as NTX (N-telopeptide of type 1 collagen) and ICTP (cross-linked carboxyterminal telopeptide of type I collagen) can predict progression of bone metastases with greater specificity than tumor markers.19 This can also provide insight into who may benefit from bisphosphate therapy.19  

Imaging

Plain radiographs are poor screening tests for metastatic bone lesions due to their very low sensitivity.16-17 Bone scans are sensitive for bone metastases but are nonspecific because they detect active bone remodeling and turnover, which can occur in several conditions.3,16-17 However, bone scans may not be positive in the presence of aggressive metastases, while diffuse uptake may be seen in diffuse skeletal disease and present as a false negative study.16-17Computer tomography (CT) and magnetic resonance imaging (MRI) both detect bone marrow changes, which can signify bone metastases.3,16-17 Positron emission tomography-computed tomography (PET-CT) and MRI are reported to have the highest sensitivity and specificity for detecting bone metastases.20 Bone metastases appear as low signal intensity on T1-weighted MRIs, while on T2-weighted images, bone metastases demonstrate high signal intensity.16-17

Supplemental assessment tools

There are a plethora of pain and function assessment scales that can be used for someone with bone metastases. Assessment of quality of life regarding pain and psychosocial well-being is essential, and there are several instruments available for this task.20 Commonly used scales in this population include the Brief Pain Inventory, the functional assessment of cancer therapy-general (FACT-G), the Karnofsky Performance Scale (KPS), the Eastern Cooperative Oncology Group (ECOG) Scale of Performance Status, and The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients with Bone Metastases 22 (EORTC QLQ‐BM22).20-22 

Early predictions of outcomes

The presence of bone metastases themselves can increase mortality, and lesions that occupy more than 50% of the cortical bone are particularly worrisome.5 Fractures and spinal cord compromise from bone metastases can reduce quality of life and mobility.15 Osteolytic tumors are more likely to fracture than osteoblastic lesions.6 The Mirels’ scoring system can be used to predict the risk of pathologic fracture of long bones based on pain, size, location and nature of the lesion; and is used to guide recommendations for prophylactic surgical fixation.23The Spinal Instability Neoplastic Score (SINS) assesses the mechanical stability of vertebrae affected by spinal metastases.24 In recent years, a refined version of the SINS (rSINS) has been developed, which relies primarily on radiographic evaluation and removes the pain variable of the original SINS, previously felt to be too subjective a component.25 The Bilsky classification is also utilized in clinical practice to assess for epidural spinal cord compression due to metastatic lesions.26

Environmental

In the evaluation of a cancer patient with bone metastases, reducing the potential for falls is of the utmost importance to avoid a pathologic fracture or spinal cord compromise. Patients should be evaluated for individualized needs of durable medical equipment, bracing, assistive devices, and home modifications to improve independence and reduce the potential for falls.

Social role and social support system

The individual family and social support structures influence the functional goals of patients with bone metastases. Understanding the individual patient’s overall prognosis assists with appropriate and realistic goal formation in the setting of impairments and disability.

Professional issues

Physiatrists hold a unique role within the medical team of the oncology patient with bone metastases. Forming realistic functional goals regarding specific impairments from bone metastases allows patients and families to plan and make modifications where necessary.

Rehabilitation Management and Treatments

Impairment and treatment overview

Bone metastases often lead to a decrement in physical activity and functional independence, resulting in a reduction in the cancer patients’ quality of life. The main goal of treatment for bone metastases in patients is to reduce the incidence of SREs, improve mobility, and improve quality of life.

Bone metastases can be treated in several ways. Asymptomatic metastases may be treated conservatively and watched over time. Other metastases may be treated in an interdisciplinary and multimodal setting by using radiation therapy, chemotherapy, antihormonal therapy, immunotherapy, bone-modifying agents (bisphosphonates/denosumab), and surgical interventions such as prophylactic or reconstructive repair.3,5,7,27 Effective analgesia is essential to maximizing a patient’s participation in exercise and may include acetaminophen, nonsteroidal anti-inflammatory drugs, neuropathic pain medications (antiepileptics, antidepressants), muscle relaxants, and opioid medications.3,5,28 In addition, orthosis treatment may help to stabilize bone structures in metastatic bone disease in cases of nonsurgical or nonimmediate surgical management.26 Physical medical modalities (e.g., transcutaneous electrical nerve stimulation) may also be used; however, modalities increasing local blood flow, such as ultrasound therapy, thermotherapy, massage, and various electrotherapy options, are not performed over tumor sites.29

Lesions of the hip and pelvis can be managed with prophylactic surgical fixation or reconstructive repair after a fracture.27 In proximal femur fractures, which are one of the most common fracture sites related to bony metastases, peri-prosthetic surgery has been shown to have better outcomes and lower risk of revision as compared to total hip replacement. However, it has higher postoperative risk and requires longer rehabilitation, which narrows the population of appropriate patients to undergo this option.27 Upper extremity metastases are frequently treated conservatively with a sling. If a complete pathological fracture occurs, it will typically be treated surgically to allow for patient mobilization and pain control management. Complete pathological fractures of the axial skeleton, including the ribs, innominate bone, sternum, and scapula are very infrequently managed surgically.27 For spinal metastases, systematic treatment targeted at improving functional independence, taking into account neurological impairment, oncological prognosis, and overall patient condition is often implemented unless there is spinal instability or spinal cord compromise, which calls for immediate and emergent surgical intervention.27

Restoring function with return to full weight bearing is extremely important in this population.3 Generally, the rehabilitation program of an individual with bone metastases must be unique based on the location and level of involvement of other lesions. The location and total amount of bone metastases do not alter functional ability; instead pain and neurologic impairment from bone metastases reduce mobility.8

Historically, patients were advised to maintain bedrest; however, recent systematic reviews show exercise to be overall safe and beneficial in this population.30 Exercise improves overall function, fatigue, and psychosocial morbidity in early-stage cancers. Greater caution is warranted in advanced cancer cases where bone metastases, and their associated complications pose increased risks, making the promotion of exercise and physical activity more complex and potentially hazardous. Reviews have noted resistance amongst healthcare professionals when it comes to prescribing physical activity, due to fear of complications.30 Overall, recommendations have shifted towards encouraging increased physical activity due to overarching benefits, both in patients with stable oncologic conditions and those who are preparing to undergo future treatment.30 In one study, patients who performed eccentric and concentric resistive exercises in areas without bone metastases did not experience any adverse events.32 The same study demonstrated that resistive exercises in non-metastatically involved areas improved strength, aerobic capacity, and ambulation.32 A multidisciplinary approach to exercise programming should be utilized to assess the safety of each component of a program with regard to each specific patient. The International Exercise Guidelines for Cancer Survivors, developed by The American College of Sports Medicine outlines recommendations for reducing the risk of complications associated with exercise. For example, the guide recommends avoiding rapid or loaded end-range movements involving areas of lesions to prevent increasing the risk of pathological fracture.30

In cases where regular physical activity and exercise are contraindicated, neuromuscular electrostimulation with the goal of improving muscle strength/endurance ratio may be beneficial.33

Coordination of care

A comprehensive multidisciplinary and interdisciplinary team consisting of medical, surgical, and radiation oncologists, in addition to physiatrists, diagnostic and interventional radiologists, pain specialists, hospice and palliative specialists, and physical and occupational therapists should be utilized to manage patients with bony metastases in order to define weight-bearing capacity and to optimize mobility and function of the patient. Individualized rehabilitation programs can be designed based on medical and surgical treatment, taking into account prognosis and patient goals.

Patient & family education

Patients and families should be educated about the individualized medical and surgical treatment plan, in addition to the rehabilitation plan. Precautions and exercises should be explained in detail by the treating physiatrist and therapists to maximize safety. Open communication regarding goals and expectations of the treating team, patient, and family should be emphasized during clinical visits and therapy sessions.

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

Any individual with a history of cancer or significant risk factors for cancer who presents with new pain, acute fracture, or neurologic symptoms should be evaluated for an acute bony process, including metastatic bone disease. Unique and comprehensive rehabilitation prescriptions should provide sufficient detail to the treating therapists in order to simultaneously maximize function and safety.

Cutting Edge/Emerging and Unique Concepts and Practice

According to the American College of Sports Medicine (ACSM), all cancer survivors are recommended to be as physically active as their conditions and abilities allow and, if possible, to perform moderate-intensity aerobic exercise for at least 90 min a week (at least three times per week, for 30 min) and resistance exercise at least two times a week.35 This combination of aerobic and resistance exercise aims to reduce anxiety, fatigue, depressive symptoms, and improve quality of life and perceived physical function in cancer patients.

However, there are no current standard exercise prescription guidelines specific to patients with bone metastases.

Individualized exercise prescription is required when treating the heterogeneity of patients with bone metastases to tailor exercises to each patient’s ability and to manage unique patient presentations and provide safety measures in an effort to reduce adverse outcomes of exercise in this population.35 The use of different exercise regimens is currently being performed as discussed previously regarding resistance exercises concerning safety in patients with bone metastases. Exercise prescriptions must incorporate safety precautions to accommodate patients’ medical history, comorbidities, pathologic fracture risk, treatment-related side effects, peripheral neuropathy, lymphedema risk, immunosuppression, and/or cardiopulmonary issues.35 The prescription of exercise must consider the location of bone metastases to ensure affected regions are not targeted and mechanical force, including sheer/compressive load at areas of metastases is minimized.

Gaps in the Evidence-Based Knowledge

Multiple randomized controlled trials (RCTs) determining the optimal rehabilitation course for individuals with bone metastases of different primary cancers have been performed and have provided evidence that appropriately designed and supervised exercise prescriptions are well tolerated and do not significantly increase skeletal complications.35 Some of the RCTs have prescribed aerobic and resistance exercise as a multimodal intervention, while others have prescribed aerobic training only or resistance training only.

The multinational RCT PREFERABLE-EFFECT published in 2024 studied the outcomes of a 9 month supervised exercise in 357 patients with metastatic breast cancer (MBC) in five European countries and Australia.36 Components of the exercise program included balance training, aerobic training, and resistance exercise. Balance tasks, such as tandem standing on a balance pad, were progressed as appropriate for each subject to incorporate more challenging aspects of the exercise. Resistance exercises primarily included leg press, leg curl, leg extension, seated row, lat pulldown and chest press. Aerobic training gradually increased in intensity throughout the study. The program was structured such that the subjects would engage in two supervised sessions of 1 hour of exercise weekly for six months, followed by one supervised and one unsupervised session weekly for three additional months. The subjects were provided with recommendations to participate in physical activity 30 minutes daily on days they did not engage in these sessions. The study showed significantly positive outcomes in both fatigue ratings and quality of life ratings at 6 months, which were maintained for up to 9 months. Two serious adverse events were noted, which were fractures not related to bone metastases.36 

A RCT in Australia published in 2017 evaluated the efficacy and safety of a supervised multimodal exercise program (aerobic, resistance, and flexibility training three times per week), compared to usual care, in 57 patients with prostate cancer metastatic to bone.37 Exercise sessions lasted an hour, and the location and extent of the metastasis were taken into consideration to avoid direct loading to the metastatic lesions. The resistance training targeted the major trunk and upper and lower body muscle groups at a moderate intensity with a maximal weight that could be lifted 10-12 times for 3 sets per exercise. The aerobic exercise component consisted of 20-30 minutes of cardiovascular exercise, including walking on a treadmill, cycling, or rowing on a stationary ergometer at a target intensity of 60-85% of estimated maximal heart rate. The flexibility exercise component involved static stretching of 2-4 repetitions for 30-60 seconds per stretch for all major joints considered important for maintaining function. Spinal flexion/extension/rotation stretches were excluded in patients with axial or widespread metastases. At 3 months, compared to the control group, the supervised multimodal exercise program group had higher self-reported improvements in physical function (via the SF-36 questionnaire) and higher objectively measured lower body muscle strength (1 rep max on leg extension exercise). In addition, there were no skeletal fractures or increased bone pain in the exercise group compared to the control group.  

In addition, the importance of bone markers in predicting metastatic bone disease has yet to be thoroughly investigated.16 Future studies will need to investigate the effect of exercise on bone turnover markers and radiologic imaging results in order to understand skeletal adaptations to exercise in patients with metastatic bone disease.

Integration of physiatrists into cancer care and an increase in awareness regarding cancer rehabilitation remains a critical initiative.30

References

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Original Version of the Topic

Christian M. Custudio, MD, Jessica Au, MD, Jesuel Padro-Guzman M.D. Rehabilitation interventions for metastatic bone tumors. 9/20/2013.

Previous Revision(s) of the Topic

Jesuel Padro-Guzman, MD, Sasha Elizabeth Knowlton, MD. Rehabilitation interventions for metastatic bone tumors. 9/20/2017.

Author Disclosure

Sophia Antimisiaris, DO, MPH
Nothing to Disclose

Siam Ayon, DO, MS
Nothing to Disclose

Sammy Wu, MD
Nothing to Disclose