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Chapter 47: Indications for Bone-Modifying Agents in Hematology-Oncology

Reem Abozena Shalabi; James N. Frame

Updated chapter to come.

INTRODUCTION

Primary Indications in Patients with Cancer

  1. To protect bone from new metastatic lesions

  2. To treat hypercalcemia of malignancy

  3. To prevent treatment-related bone demineralization, osteolysis, and pathologic fractures

  4. To treat osteolytic lesions, decrease the incidence of pathologic fractures, prevent skeletal deformities, and prevent and decrease the severity of pain

Intravenous Versus Oral Bisphosphonates

Intravenous

  1. Much more effective than oral agents at reversing hypercalcemia and relieving bone pain, particularly in patients with breast cancer and multiple myeloma

  2. Can overcome disadvantages associated with oral agents, including poor absorption from the GI tract (<3% oral bioavailability); have a lower incidence of adverse GI events

  3. Require clinic/hospital administration

 

Oral

  1. Convenient

  2. Absorption can be impaired by food and beverages other than water

  3. Associated with greater incidence of upper GI toxicity than with intravenous administration, including dysphagia; esophagitis; and esophageal, gastric, or duodenal erosion; ulceration; and perforation

 

Body JJ et al. J Clin Oncol 1998;16:3890–3899

Riccardi A et al. Tumori 2003;89:223–236

Hypocalcemic Effects

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Hypocalcemic Effects
Bisphosphonate Median Time to Normocalcemia Duration of Normocalcemia % Achieving Normocalcemia
Zoledronic acid1 4 days 32 days 87
Pamidronate2,3 4 days 28 days 70-100
Clodronate3 3 days 14 days 80
Alendronate4 4 days 15 days 74
Ibandronate5 4 days 14 days 76.5
Etidronate6 4 days 29 days 63

References

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1. +
Major  P  et al. J Clin Oncol 2001;19:558–567  [PubMed: 11208851]
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2. +
Body  JJ, Dumon  JC Ann Oncol 1994;5:359–363  [PubMed: 8075034]
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3. +
Purohit  OP  et al. Br J Cancer 1995;72:1289–1293
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4. +
Nussbaum  SR  et al. J Clin Oncol 1993;11:1618–1623  [PubMed: 8336198]
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5. +
Pecherstorfer  M  et al. Support Care Cancer 2003;11:539–547  [PubMed: 12783289]
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6. +
Singer  FR  et al. Arch Int Med 1991;151:471–476

Notes

Osteonecrosis of the Jaw

  1. The American Society of Bone and Mineral Research Task Force has defined osteonecrosis of the jaw (ONJ) as the presence of exposed bone in the maxillofacial region that does not heal within 8 weeks after identification by a healthcare professional1

  2. Potential risk factors for developing ONJ in patients with cancer2:

    1. Poor oral hygiene and periodontal disease3

    2. History of dental procedures for extractions or denture use (that may cause soft tissue injury)

    3. Prolonged exposure to high doses of intravenous bisphosphonates

    4. Intravenous bisphosphonate use poses greater risk than oral bisphosphonates

    5. Zoledronic acid seems to cause more ONJ compared to pamidronate4

    6. ONJ developed in 7% to 10% of patients with myeloma and 4% of patients with breast cancer

    7. Among patients on oral bisphosphonates (eg, alendronate), there is a very low risk (estimated at 0.7 cases of per 100,000 person-years exposure) of developing bone osteonecrosis...

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