Bone metastases are defined as oncologic lesions within bone 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.
Bone metastases are extremely common in cancer. An estimated 400,000 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.1,4-7
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.7-9 In breast cancer, tumor subtype in addition to size, stage, grade and nodal spread are risk factors for the development of bone metastases, while other variables such as age and body mass index are suggestive of risk but controversial.9-10 Prostate-specific antigen levels and rates of change have also been investigated as potential risk factors for the development of bone metastases in prostate cancer.11
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 a number of biochemical factors.5 The fertile microenvironment within bone encourages tumors to spread to this location and grow successfully.5,12
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 a number of biochemical factors to enhance tumor cell growth.5,12 Metastases can be classified as osteolytic, osteoblastic, or mixed.12
Bone metastases can present in a variety of ways. Bone metastases may be asymptomatic and detected only on routine surveillance studies.3 Pain is the most common presentation of bone metastases.3,12 Pain associated with bone metastases can occur from direct cortical bone involvement resulting in localized inflammation and biologic pain.4
Skeletal related events (SREs) occur as a complication of bone metastases.3-6,12 Common SREs include pain, pathologic fracture, spinal cord compromise and hypercalcemia resulting in an increased need for radiation therapy or surgery.3-6,9,12 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
Individuals with bone metastases may be asymptomatic or may present with biologic pain or neurologic symptoms.3-6,9,12 Patients may also present with fracture related pain as the initial symptom of metastases. 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 Valsava 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.13-14
In cases of changes in neurologic function as the 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 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.15 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
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 as well to maximize patient mobility.
In general, studies investigating different levels of bone markers to detect and monitor bone metastases are not recommended.16
Plain radiographs are poor screening tests for metastatic bone lesions as a result of very low sensitivity.13-14 Bone scans are sensitive for bone metastases but are nonspecific because they detect active bone remodeling and turnover which can occur in a number of conditions.3,13-14 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.13-14 Computer tomography (CT) and magnetic resonance imaging (MRI) both detect bone marrow changes which can signify bone metastases.3,13-14 Positron emission tomography-computed tomography (PET-CT) and MRI are reported to have the highest sensitivity and specificity for detecting bone metastases27. Bone metastases are areas within bone of low intensity on T1-weighted MRIs while on T2-weighted images bone metastases demonstrate high intensity.13-14
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 with regards to pain and psychosocial well-being is essential, and there are a number of instruments available for this task.17 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) and the Eastern Cooperative Oncology Group (ECOG) Scale of Performance Status.18-19
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.12 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.20 The Spinal Instability Neoplastic Score reliably evaluates tumor-related spinal instability.21
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.
Physiatrists hold a unique role within the medical team of the oncology patient with bone metastases. Forming realistic functional goals in regard to 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 a number of 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.3,5,7,23 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.3,5,22,28 In addition, orthosis treatment may help to stabilize bone structures in metastatic bone disease.27 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.27
Lesions of the hip and pelvis can be managed with prophylactic surgical fixation or reconstructive repair after a fracture.15,23 Post-operative patients are often placed on standard hip precautions with early mobilization and weight-bearing as tolerated.15 Upper extremity metastases can be treated conservatively with a sling or surgery with early active range of motion on a case by case basis.15 For spinal metastases, systematic treatment is often implemented unless there is spinal instability or spinal cord compromise with a focus on improving functional independence; bracing may also be considered.15
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 does not alter functional ability; rather, pain and neurologic impairment from bone metastases reduce mobility.8
Historically, patients were advised to maintain bedrest, but reducing activity does not necessarily prevent fracture.15,24 Exercise is often regarded as a contraindication and rehabilitation services are underutilized by physicians who are caring for patients with bone metastases. Passive or active-assisted range of motion is not advised.15 Only pain-limited active range of motion should be performed, and caution should be advised with manual muscle testing.15 Patients with stable spinal metastases did not experience any adverse effects but did experience reduced pain after undergoing an isometric resistance training program of the paravertebral muscles during ongoing radiation therapy.25 In one study, patients who performed eccentric and concentric resistive exercises in areas without bone metastases did not experience any adverse events.26 The same study demonstrated that resistive exercises in non-metastatically involved areas improved strength, aerobic capacity and ambulation.26
In cases where regular physical activity and exercise are contraindicated, neuromuscular electrostimulation with the goal to improve muscle strength/endurance ratio can be very helpful.27
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 are used 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 upon medical and surgical treatment.
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, pathologic fracture or neurologic symptoms should be evaluated for an acute bony process, including metastatic bone disease. Unique 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 90 min a week (at least three times per week, for 30 min) for 8–12 weeks and resistance exercise at least two times a week.28 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 in order to adapt exercises to patients’ ability and to manage unique patient presentations.29 The use of different exercise regimens is currently being performed as discussed previously in regard to resistance exercises with respect to 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.29 Prescription of exercise must consider 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.29 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.
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.30 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 at 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.
A RCT in Australia published in 2013 evaluated the efficacy and safety of a 12-week resistance training program compared to usual-care in 20 men with established bone metastases secondary to prostate cancer. The participants had extensive disease burden with 65% presenting with 2 or more regions affected by bone metastases.31 The resistance training program involved twice-weekly hour-long sessions targeting the major muscle groups of the upper and lower body. Primary findings of the study found that there was improved physical function, physical activity levels, and lean mass in the resistance exercise group compared to the usual-care group.31 Specifically, maximal muscular strength as measured by 1 rep max on leg extension exercise, submaximal exercise capacity, and ambulation speed were greater in the intervention arm compared to the usual care group. Changes in appendicular and whole body lean mass also demonstrated favorable changes for the exercise group compared with the usual care group.
Future RCTs involving larger sample sizes are required in order to expand on these preliminary findings.
In addition, the importance of bone markers regarding the predictive power of metastatic bone disease has yet to be fully 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 adaptions to exercise in patients with metastatic bone disease.
Integration of physiatrists into cancer care and increase in the awareness regarding cancer rehabilitation remains a critical initiative.32
- Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin 2017; 67(1): 7–30.
- Mundy GR. Metastases to bone: Causes, consequences and therapeutic opportunities. Nat Rev Cancer. 2002. 2(8): 584-593.
- Hsiang-Hsuan MY, Ya-Yu T, Hoffe SE. Overview of the diagnosis and management of metastatic disease to bone. Cancer Control. 2012. 19(2):84-91.
- Coleman RE. Clinical Features of Metastatic Bone Disease and Risk of Skeletal Morbidity. Clin Cancer Res. 2006. 12(20 Suppl):6243s-6249s.
- Coleman R, Body JJ, Aapro M, et al. Bone health in cancer patients: ESMO Clinical Practice Guidelines. 2014. Annals of Oncology. 25(Supplement 3): iii124-iii137.
- Ashford RU and Randall RL. Bone Metastases: Epidemiology and Societal Effect. Metastatic Bone Disease. 2016. Springer Science+Business Media New York. DOI 10.1007/978-1-4614-5662-9_1
- Errani C, Mavrogenis AF, Cevolani L, et al. Treatment for long bone metastases based on a systematic literature review. Eur J Orthop Surg Traumatol. 2017. 27:205-211.
- Cheville AL, Murthy NS, Basford JR, et al. Imaging and Clinical Characteristics Predict Near-Term Disablement From Bone Metastases: Implications for Rehabilitation. Archives of Physical Medicine and Rehabilitation. 2016. 97: 53-60.
- Yamashiro H, Taka M, Nakatani E, et al. Prevalence and risk factors of bone metastasis and skeletal related events in patients with primary breast cancer in Japan. Int J Clin Oncol. 2014. 19:852-862.
- Pulido C, Vendrell I, Ferreira AR, et al. Bone metastasis risk factors in breast cancer. Ecancermedicalscience. 2017. 11:715.
- Petrylak DP. Risk Factors for the Development of Bone Metastases in Prostate Cancer. European urology supplements. 2007. 6(11). 677-682.
- Gralow JR, Biermann S, Farooki Z, et al. NCCN Task Force Report: Bone Health in Cancer Care. JNCCN. 2009. 7(Suppl 3): 1-32.
- Rosenthal DI. Radiologic diagnosis of bone metastases. Cancer. 1997. 80(8 suppl): 1595-1607.
- Rybak LD and DI Rosenthal. Radiological imaging for the diagnosis of bone metastases. QJ Nucl Med. 2001. 45: 53-64.
- Bunting RW and B Shea. Bone Metastases and Rehabilitation. 2001. Cancer. 92 (4 Suppl): 1020-1028.
- Coleman R, Costa L, Saad F, et al. Consensus on the utility of bone markers in the malignant bone disease setting. Critical Reviews in Oncology/Hematology. 2011. 80: 411-432.
- Tharmalingam S, Chow E, Harris K et al. Quality of life measurement in bone metastases: A literature review. J Pain Res. 2008. 1:49-58.
- Von Moos R, Body JJ, Egerdie B, et al. Pain and analgesic use associated with skeletal-related events in patients with advanced cancer and bone metastases. 2016. Supportive Care in Cancer. 24(3): 1327-1337.
- Peterson JR, Decilveo AP, O’Connor IT et al. What Are the Functional Results and Complications With Long Stem Hemiarthroplasty in Patients With Metastases to the Proximal Femur? Clinical Orthopaedics and Related Research. 2017. 475(3): 745-756.
- Jawad MU and SP Scully. Classifications in Brief: Mirels’ Classification: Metastatic Disease in Long Bones and Impending Pathologic Fracture. Clin Orthop Relat Res. 2010. 468: 2825-2827.
- Fourney DR, Frangou EM, Ryken TC et al. Spinal Instability Neoplastic Score: Analysis of Reliability and Validity From the Spine Oncology Study Group. Journal of Clinical Oncology. 2011. 29(22): 3072-3077.
- Mantyh P. Bone cancer pain: Causes, consequences, and therapeutic opportunities. Pain. 2013. 154: S54-S62.
- Wood TJ, Racano A, Yeung H, et al. Surgical Management of Bone Metastases: Quality of Evidence and Systematic Review. Ann Surg Oncol. 2014. 21: 4081-4089.
- Bunting R, Lamont-Havers W, Schweon D and A Kliman. Pathologic fracture risk in rehabilitation of patients with bony metastases. Clin Orthop Relat Res. 1985. 192: 222-227.
- Rief H, Welzel T, Omlor G, et al. Pain response of resistance training of the paravertebral musculature under radiotherapy in patients with spinal bone metastases – a randomized trial. BMC Cancer. 2014. 14: 485.
- Cormie P, Galvao DA, Spry N, et al. Functional benefits are sustained after a program of supervised resistance exercise in cancer patients with bone metastases: longitudinal results of a pilot study. Support Care Cancer. 2014. 22: 1537-1548.
- Keilani M, Kainberger F, Pataraia A, et al. Typical aspects in the rehabilitation of cancer patients suffering from metastatic bone disease or multiple myeloma. Wien Klin Wochenschr. 2019 Nov;131(21-22):567-575.
- Campbell KL, Winters-Stone KM, Wiskemann J, May AM, Schwartz AL, Courneya KS, Zucker DS, Matthews CE, Ligibel JA, Gerber LH, Morris GS, Patel AV, Hue TF, Perna FM, Schmitz KH. Exercise Guidelines for Cancer Survivors: Consensus Statement from International Multidisciplinary Roundtable. Med Sci Sports Exerc. 2019 Nov;51(11):2375-2390.
- Gráinne Sheill, Emer M. Guinan, Nicola Peat, et al. Considerations for Exercise Prescription in Patients With Bone Metastases: A Comprehensive Narrative Review, PM&R, Volume 10, Issue 8, 2018, Pages 843-864.
- Galvão DA, Taaffe DR, Spry N, et al. Exercise Preserves Physical Function in Prostate Cancer Patients with Bone Metastases. Med Sci Sports Exerc. 2018 Mar;50(3):393-399.
- Cormie, P., Newton, R., Spry, N. et al. Safety and efficacy of resistance exercise in prostate cancer patients with bone metastases. Prostate Cancer Prostatic Dis 16, 328–335 (2013).
- Bae, C.R., Gelvosa, M.N. & Jeon, J.Y. Rehabilitation in Advanced Cancer Patients with Bone Metastases and Neural Compromise: Current Status and Future Directions. Curr Oncol Rep 24, 1023–1033 (2022).
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.
Christian M Custodio, MD
Nothing to Disclose
Sammy Wu, MD
Nothing to Disclose