Preventing Skeletal-Related Events in Patients

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BOSTON—Bone loss and related complications are common in patients with cancer. And the problem is growing, with more patients with cancer aged 65 years and older and increased use of newer treatments that compromise bone mineral density (BMD). “As nurses, we have a very significant role to play in both prevention and management of [bone loss] problems,” said Carrie Tompkins Stricker, PhD, RN, oncology nurse practitioner, Abramson Cancer Center, Philadelphia, Pennsylvania.

 

Osteoporosis is a systemic skeletal disease characterized by low BMD and deterioration of bone microarchitecture on dual-emission x-ray absorptiometry (DXA) scanning and/or bone fragility and susceptibility to fracture. Approximately 80% of people with osteoporosis are women, but men are also at risk. At the time cancer is diagnosed, many patients already have osteopenia, a precursor to osteoporosis.

 

Certain cancer treatments and their physiologic effects exacerbate bone loss. Primary breast cancer therapy, for example, often induces premature menopause and resulting loss of BMD. Androgen deprivation therapy, aromatase inhibitors (AIs), certain chemotherapeutics, and radiotherapy to the pelvis also cause bone deterioration. Stricker said seeing these in the treatment history should raise flags.

 

Oncology organizations offer guidance on when to screen patients with cancer for bone loss. DXA scans measure BMD at the hip, femoral neck, and lumbar spine and are recommended for at-risk patients. “The best predictor of fracture is the value of at the hip…it is most preferential for decision making,” said Stricker. The spine shows the first evidence of BMD loss, and T scores help track bone loss over time.

 

Studies show breast and prostate cancer patients are not getting recommended DXA screening for osteoporosis. “We need to be doing a better job,” Stricker said, especially for patients with bone metastases. She recommended the World Health Organization Fracture Risk Assessment tool (better known as FRAX) to guide treatment decisions for bone loss.

 

Treatment depends on BMD and history of fracture. Nutritional and behavioral strategies are often started before osteopenia. Beth Faiman, RN, MSN, APRN-BC, AOCN, oncology nurse practitioner with the Cleveland Clinic, Ohio, and editor-in-chief of The Oncology Nurse-APN/PA, recommended supplementation with calcium and vitamin D3 and weight-bearing exercise. Supplements should be taken in 2 daily doses. “You get better absorption.” Faiman cautioned that proton-pump inhibitors, protein, and coffee interfere with calcium absorption.

 

Pharmacologic options for antiresorptive therapy in cancer patients include bisphosphonates, selective estrogen receptor modulators (eg, raloxifene), serum calcitonin, and the RANK-ligand (RANK-L) inhibitor denosumab. Stricker said raloxifene can lead to cross-resistance with tamoxifen and should not be used in breast cancer patients.

 

Bisphosphonates have long been the standard of care, with pamidronate and zoledronic acid (ZA) the most common. The Z-FAST study showed initiating ZA at the start of AI therapy improved BMD, whereas waiting until osteopenia developed led to greater BMD loss. Both approaches were equally effective at preventing fractures.

 

Denosumab, a human monoclonal antibody that binds RANK-L, essentially deactivates osteoclasts and is approved to prevent bone loss in patients with solid tumors but is not recommended for multiple myeloma patients. It is administered subcutaneously every 6 months. Victoria Sinibaldi, MS, CRNP, AOCN, nurse practitioner and program coordinator for genitourinary research, Johns Hopkins Medical Institutions in Baltimore, Maryland, said whereas both drugs greatly increase time to first and subsequent skeletal-related events (SRE) compared with placebo, a head-to-head comparison of ZA and denosumab found that denosumab significantly delayed time to first and subsequent on-study SREs. Neither drug appears to improve survival.

 

Bisphosphonates cause significant gastrointestinal disturbance, hypocalcemia, increased parathyroid hormone, skin rash, and bone pain. Intravenous formulations are associated with fatigue, nausea, vomiting, myalgia, and osteonecrosis of the jaws (ONJ). ZA requires renal monitoring and management of acute-phase reactions. Faiman suggested premedicating patients with acetaminophen or a nonsteroidal antiinflammatory agent and having them drink ample fluids.

 

Denosumab causes fatigue, asthenia, hypophosphatemia, nausea, dyspnea, hypocalcemia, and ONJ. Hypocalcemia is sometimes severe. Sinibaldi said, “We need to make sure baseline calcium levels are within a normal range prior to initiating denosumab.”

 

Faiman said preventing bone loss and fracture helps maintain the patient’s quality of life. “Preventing SREs is integral to the patient’s well-being,” said Faiman, adding that nurses are central to effective patient management.

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