Table 2.
Current and Emerging Pharmacotherapies for Cancer-Related Bone Loss and Bone Metastasis
| Drug Class | Specific Agents | Mode of Action | Adverse Effects |
|---|---|---|---|
| Bisphosphonate |
Nitrogenous: Alendronate* Ibandronate* Neridronate Olapadronate Pamidronate*† Risedronate Zoledronic acid*‡ Non-nitrogenous: Clodronate Etidronate* Tiludronate* |
FPPS blockade to induce apoptosis of the osteoclast and thereby slow bone resorption Metabolites toxic to osteoclasts |
Osteonecrosis of the jaw Upper gastrointestinal adverse events (related to oral drug delivery) |
| SERM | Raloxifene*§ | Mix of agonism/antagonism at estrogen receptors to modulate estrogen levels and thereby suppress bone resorption | Venous thromboembolism Stroke Hot flashes Leg cramps |
| Polypeptide hormone | Calcitonin* | Induces quiescence and retraction of osteoclasts to slow bone resorption | Potential for allergic reactions Nasal symptoms (related to nasal drug delivery) |
| Mineral salt | Strontium ranelate | Osteoblast/collagen stimulation (bone formation); osteoclast inhibition (inhibition of bone resorption) | Gastrointestinal adverse events Dermatitis/eczema |
| Monoclonal antibody | Denosumab | Binds to RANKL to suppress osteoclast formation | Arthralgia Gastrointestinal adverse events |
| Parathyroid hormone | Teriparatide* | Mimics osteoblast-stimulating effect of endogenous parathyroid hormone to increase bone formation | Osteosarcoma (animal models) Transient hypercalcemia Muscle spasm |
Abbreviations: FPPS, farnesylpyrophosphate synthase; RANKL, receptor activator of nuclear factor kappa B ligand; SERM, selective estrogen receptor modulator.
*
Approved by the US Food & Drug Administration.
†
Specifically approved for the management of hypercalcemia of malignancy and osteolytic bone metastasis.
‡
Specifically approved for the management of hypercalcemia of malignancy, multiple myeloma, and bone metastasis of solid tumors.