Cancer-Treatment-Induced Bone Loss, Part 2

Laura Boehnke Michaud; Susan Goodin


Am J Health Syst Pharm. 2006;63(6):534-546. 

In This Article

Implications for Pharmacists

CTIBL will likely become more common among cancer patients and survivors because of the increased use of cancer therapies that induce bone loss, such as ADT for early-stage prostate cancer and the use of aromatase inhibitors in the treatment of postmenopausal women with breast cancer. Pharmacists can play an active role in the prevention, diagnosis, treatment, and education of patients with or at risk of CTIBL.

Identification of Patients With or at Risk of CTIBL

All cancer patients at risk of CTIBL should have a thorough clinical assessment of possible bone-loss risk factors, past or current cancer therapies, menstrual history, and other drugs known to cause bone loss.[4] For example, postmenopausal women should be asked about their past and current use of HRT. A recent study found that postmenopausal women with breast cancer receiving tamoxifen who had discontinued HRT at the time of diagnosis experienced bone loss rather than the expected BMD increases during the first few years of tamoxifen therapy.[54] In addition, height should be measured regularly during follow-up visits. If height loss has occurred, further assessment should be performed to determine if vertebral fractures or bone loss has occurred.[10] If bone-loss risk factors are present, BMD should be measured and therapy initiated if bone loss has occurred.

Treatment Selection

Clinical Issues. Selection of the appropriate pharmacologic therapy for the prevention or treatment of CTIBL depends on many factors, including clinical trial results, tolerability of therapy, contraindications, availability, compliance, cost, and reimbursement.[8] A patient's quality of life and life expectancy should also be considered when determining whether therapy is indicated. The American Society of Clinical Oncology (ASCO) developed evidence-based guidelines to assist clinicians with the treatment of CTIBL in patients with breast cancer (Figure 2).[5] These guidelines recommend BMD testing for patients with a high risk of CTIBL. This group includes premenopausal women with cancer-treatment-induced menopause, postmenopausal women receiving aromatase inhibitors, women older than 65 years, and women 60-64 years old with risk factors for bone loss or fracture. Treatment and BMD-monitoring decisions are based on the results of the BMD assessment. Recommended therapies for CTIBL in patients with breast cancer and osteoporosis include alendronate, risedronate, and zoledronic acid; raloxifene may also be an option but not for women receiving concurrent aromatase inhibitors or who have received previous tamoxifen therapy. The ASCO guidelines do not recommend that therapy be administered to all breast cancer patients who have osteopenia but that therapy be individualized; high-risk patients with normal BMD should not receive bone-loss therapies. However, all breast cancer patients should be monitored annually for BMD changes (high-risk patients) or risk-factor status and history (low-risk patients).

Guidelines do not exist for prostate cancer patients with CTIBL, but oncologists specializing in prostate cancer treatment and representatives of various oncology groups recently convened to review published data on the diagnosis and treatment of CTIBL in this population.[123] Using data from the symposium, an algorithm was designed to identify and manage high-risk prostate cancer patients undergoing ADT (Figure 3). All patients receiving ADT should undergo BMD testing. Like breast cancer patients, prostate cancer patients with osteoporosis should receive bone-loss therapies; recommended therapies include alendronate, pamidronate, risedronate, and zoledronic acid. Prostate cancer patients with osteopenia or normal BMD should undergo BMD testing periodically. A few oncologists participating in the development of this algorithm have published recommendations for managing CTIBL patients.[7,38] These recommendations are similar to those of the consensus group but provide additional suggestions, such as monitoring criteria and risk-group definitions.

Figure 3.

Expert panel clinical algorithm for identifying and managing cancer-treatment-induced bone loss in prostate cancer patients beginning androgen deprivation therapy (ADT). BMD = bone mineral density, DEXA = dual energy x-ray absorptiometry, QCT = quantitative computed tomography. Zoledronic acid and pamidronate do not have approved labeling for the treatment of osteoporosis.

Because CTIBL therapies have not been compared in clinical trials and guidelines do not support the use of one particular therapy, the most appropriate therapy should be based on compliance, tolerability, and cost. For example, oral bisphosphonates require frequent (daily or weekly regimen) and proper administration to avoid adverse gastrointestinal effects. These factors may reduce compliance, which has been reported as less than 50% in patients with osteoporosis treated with long-term oral bisphosphonate therapy, and ultimately a reduction in efficacy.[166,183] Because of the risk of adverse gastrointestinal effects, oral bisphosphonates are not recommended for patients who have had previous upper-gastrointestinal-tract disorders or who are expected to develop these disorders during cancer therapy (e.g., HSCT patients).[10] Although i.v. bisphosphonates are administered less frequently than oral bisphosphonates (every three to six months) and without regard to food intake, administration of these drugs requires a visit to a health care professional and monitoring of serum creatinine, magnesium, calcium, and phosphate levels and hematologic values.[173,174] Some patients may find this option more convenient than daily or weekly administration, especially with the use of zoledronic acid, which can be administered over 15 minutes.[8] However, the cost of i.v. bisphosphonates is generally higher than oral bisphosphonates and, because neither pamidronate nor zoledronic acid is approved for the prevention or treatment of osteoporosis, providers may not be reimbursed for these therapies.[173,174,184]

Clinical trials are warranted to determine the optimal CTIBL therapy, dose, schedule, and therapy duration. Ongoing clinical trials are evaluating (1) risedronate in premenopausal women with breast cancer receiving adjuvant or neoadjuvant chemotherapy, postmenopausal women receiving aromatase inhibitors, and prostate cancer patients receiving ADT, (2) zoledronic acid for the prevention of CTIBL in patients with breast cancer undergoing adjuvant chemotherapy and postmenopausal breast cancer patients receiving aromatase inhibitors, as well as CTIBL prevention in prostate cancer patients receiving ADT, and (3) tamoxifen for the prevention of CTIBL in premenopausal breast cancer patients undergoing adjuvant chemotherapy.[5,185]

Reimbursement. None of the drugs discussed have approved labeling for the prevention or treatment of CTIBL. Payers may make case-by-case decisions to cover CTIBL as an unlabeled indication, based on the results of peer-reviewed clinical literature that supports the use of a particular therapy. Generally, payers cover unlabeled indications that are listed in authoritative compendia, supported by peer-reviewed literature, or deemed medically necessary for the patient's diagnosis; however, insurance coverage and reimbursement for CTIBL therapies vary widely among insurers and are most often determined on a case-by-case basis.

If private insurers or state Medicaid agencies choose to reimburse for CTIBL therapies, oral therapies are usually reimbursed through pharmacy benefits and i.v. formulations through medical benefits. Prior authorization is necessary in most cases. Because many of the oral CTIBL therapies have FDA-approved labeling for similar indications (e.g., osteoporosis), many private insurers and Medicaid programs have created formularies or preferred-drug lists, which have different coverage criteria and copayments. Currently, however, Medicare does not cover most oral or self-administered CTIBL therapies, but i.v. products that require physician administration, such as pamidronate and zoledronic acid, may be covered. For example, the Medicare Part B carrier for Illinois, Michigan, Minnesota, and Wisconsin covers pamidronate and zoledronic acid for the treatment of CTIBL because peer-reviewed literature is available to support the unlabeled indication.[186] All claims for this indication, however, must be accompanied by appropriate documentation supporting the medical necessity, and appropriate diagnosis and service codes must be used in the billing process. Because each Medicare contractor has different standards for submitting claims for non-FDA-approved indications and because a specific diagnosis code for CTIBL does not exist, verification of the requirements is recommended before claim submission.

Patient Education

Successful prevention and treatment of CTIBL depend, in part, on the patient's understanding of the disease and management of bone loss. Pharmacists can play a valuable role in educating patients with or at risk of CTIBL. Pharmacists can discuss the rationale, selection, proper administration, and adverse effects of pharmacologic therapies, as well as the appropriate intake and administration of calcium and vitamin D, lifestyle modifications that can reduce the likelihood of bone loss and fractures, and an appropriate exercise program.[10] Patients receiving a bisphosphonate should be instructed on proper oral hygiene and the necessity for regular dental examinations and consultation with their oncologist before having invasive dental procedures performed.[173] In addition, patients should be instructed to continue with regular follow-up visits with an endocrinologist or a general practitioner after cancer therapy has been completed for continued evaluation and management of CTIBL.


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