Detecting Cancer-Induced Bone Disease Poses Challenges

Gary E. Friedlaender, MD

Cancer-induced bone disease (CIBD) is sometimes characterized by bone fragility; however, detection of CIBD can pose challenges for practitioners. Early detection is vitally important; bone destruction from tumor growth can lead to fractures, spinal cord compression, and the need for surgical intervention.¹CIBD may stem from a primary malignancy or metastases from a primary malignancy, or result from cancer pharmacotherapy.¹

“Virtually any cancer can spread to bone or to the musculoskeletal system, but some are far more common; prostate, breast, and lung are among the most common,” said Gary E. Friedlaender, MD, chair of the department of orthopedics at Yale School of Medicine in New Haven, Connecticut.²

Denise A. Yardley, MD, on the Treatment of Patients With Bone Health Issues

Yardley is a senior investigator at Sarah Cannon Research Institute.

Lung, thyroid, and kidney cancer bone metastases behave similarly to multiple myeloma (MM), causing osteolytic destruction. Prostate cancer metastases contribute to new, albeit disordered, bone growth, resulting in weakened bone; this type of metastatic growth is called an osteoblastic lesion. Breast cancer metastases typically have both osteoblastic and osteoclastic features.³

Pharmacologic Causes

Certain cancer treatments are known to increase bone fragility, causing osteoporosis and leading to a greater risk of fracture. Glucocorticoids, a common component of chemotherapy regimens, have a bone-weakening effect. Estrogen-deprivation therapy (EDT) and androgen-deprivation therapy (ADT), used in the treatment of breast cancer and prostate cancer, respectively, also contribute to bone loss. In one study, a 15% increase was found in the rate of fractures in women who had been treated for breast cancer versus those without breast cancer. Similarly, men treated with ADT have been shown to experience a decrease in bone mineral density (BMD) at rates up to 5.6% in just the first year of treatment.¹

Signs and Symptoms

The symptoms of CIBD are as varied as its causes and may be nonspecific, posing a diagnostic challenge. Pain is the most commonly reported symptom of CIBD, although it is important to note that lack of pain does not exclude its diagnosis. Approximately 80% of patients suffering from advanced-stage breast cancer will develop osteolytic bone metastases; however, two-thirds of these patients will not experience or report associated pain.⁴

Pain associated with CIBD is most often localized to the involved area with a gradual onset. The pain increases in severity at night and when the bone is being stressed by bearing weight.⁵

Spinal cord compression may occur because of involvement of the spinal vertebra. Pain associated with cord compression may be more evident when the patient is coughing or sneezing, although the pain often will be intense regardless of activity level. Cord compression may also result in weakness, sensory loss, abnormal reflexes, and dysautonomia.⁵

Hypercalcemia of malignancy (HCM) is another consequence of CIBD. The symptoms of HCM are nonspecific and include fatigue, loss of appetite, weight loss, and constipation.⁴The monoclonal antibody denosumab (Xgeva) received US Food and Drug Administration (FDA) approval on December 8, 2014, for the treatment of bisphosphonate-refractory HCM.⁶

Anemia from involvement of the bone marrow by tumor metastases is another nonspecific symptom that may occur in metastatic bone disease (MBD). Pathologic fracture, or bone fracture occurring in the absence of a traumatic injury, is perhaps the most indicative symptom of CIBD, although diagnosing CIBD before this point is optimal.

Assessment and Follow-Up

“The high incidence of bone marrow metastases warrants careful detection and follow-up,”⁷advised Hsiang-Hsuan Michael Yu, MD, department of radiation oncology, H. Lee Moffitt Cancer Center, Tampa, Florida, in an April 2012 editorial. Assessing which patients are at risk of developing CIBD can be a difficult task for clinicians, presupposing that a cancer diagnosis is already known. Patients who are already at risk for osteoporosis will be at greater risk for CIBD; therefore, determining a patient’s risk for osteoporosis is paramount. Patients should be asked about family history and their diet and exercise habits.¹

Clinical Pearls

• Breast, prostate, and lung cancers most commonly metastasize to bone.
• Metastatic bone lesions may be classified as osteolytic, osteoblastic, or mixed osteolytic-osteoblastic.
• Certain cancer therapies, especially androgen-deprivation and estrogen-deprivation therapies, can contribute to weakening of the bone.
• Symptomology of CIBD is varied, and a patient with CIBD does not have to be in pain.
• FRAX and BMD are helpful screening tools for at-risk patients.

Bone mineral density testing is important for assessing CIBD and fracture risk and is recommended for postmenopausal women with breast cancer who have been treated with aromatase inhibitors. Premenopausal women with secondary ovarian failure caused by cancer pharmacotherapy should also receive BMD testing, as should men with prostate cancer who have been treated with ADT.¹

The World Health Organization (WHO) fracture risk assessment tool (FRAX) can also be used in assessing risk for cancer patients, although the tool does not include any parameters specific to metastatic disease, and thus is limited to providing information about the patient’s baseline risk of osteoporosis.¹

Early detection and treatment of CIBD are the best ways to avoid serious complications such as fracture, cord compression, and paralysis. There are currently no established guidelines for follow-up care for patients with CIBD. The clinician must consider several factors to determine appropriate follow-up intervals for CIBD patients, including overall health status, current and past pharmacotherapy regimens, and osteoporosis and fracture risk assessments.¹

References

1. Rizzoli R, Body JJ, Brandi ML, et al. Cancer-associated bone disease.Osteoporos Int.2013;24(12:2929-2953.
2. Understanding cancer metastases. Available at: http://medicine.yale.edu/cancer/podcasts/471-89482.html. Accessed on December 3, 2014.
3. Metastatic Bone Disease. American Academy of Orthopaedic Surgeons. Available at: orthoinfo.aaos.org/topic.cfm?topic=a00093. Accessed December 2, 2014.
4. Coleman RE. Clinical features of metastatic bone disease and risk of skeletal morbidity.Clin Cancer Res.2006;12(20 pt 2):6243s-6249s.
5. Buga S, Sarria JE. The management of pain in metastatic bone disease.Cancer Control.2012;19(2):154-166.
6. FDA approves Amgen’s XGEVA (denosumab) for the treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy. Available at: http://www.prnewswire.com/news-releases/fda-approves-amgens-xgeva-denosumab-for-the-treatment-of-hypercalcemia-of-malignancy-refractory-to-bisphosphonate-therapy-300005931.html. Accessed December 8, 2014.
7. Yu H-HM, Hoffe SE. Multidisciplinary management of skeletal metastases: a work in progress.Cancer Control.2012;19(2):80-81.