Table 5.
Notable toxicities of osteoclast-targeted therapies
| Toxicity | Approximate Incidence | Management/Notes |
|---|---|---|
| Hypocalcemia | Zoledronic acid: approximately 6% (1% grade 3-4) Denosumab: approximately 11-13% (2-5% grade 3-4), higher if impaired renal function |
Many cases asymptomatic Severe/symptomatic cases can lead to hospitalization for calcium repletion We recommend serum 25-OH vitamin D testing and repletion prior to initiation We recommend oral calcium (500-1000 mg daily) and vitamin D3 (600-1000 IU daily) |
| Acute phase reaction | Zoledronic acid: approximately 15-18% Denosumab: approximately 7-8% |
Characterized by flu-like symptoms such as malaise, myalgias, and fever Generally occurs within 24 hours of dosing and resolves without specific intervention |
| Osteonecrosis of the jaw (ONJ) | 1-2% with zoledronic acid or denosumab on phase III trials of metastatic solid tumors41, 54, 55 4-5% over 3-4 years with monthly denosumab for metastasis prevention48 |
Exposed non-healing bone of the jaw93, 94 Key risk factors include drug potency, duration of therapy, and invasive dental procedures95, 96 Published guidelines focus on maintenance of good oral hygiene, avoidance of invasive dental procedures during therapy97-101 |
| Nephrotoxicity | Zoledronic acid: nephrotoxicity was notably observed in the 039 phase III study with 8 mg dose and 5 minute infusion time7; nephrotoxicity is rare with current practice Denosumab: not observed |
Acute tubular necrosis102; severity ranges from mild/reversible to irreversible and requiring hemodialysis Zoledronic acid package insert recommends 15 minute infusion time, 4 mg maximum dose, and specific dose modifications for stable renal dysfunction with creatinine clearance >30 mL/min103 |
Note: Unless otherwise noted, incidence and grade are listed for monthly use of either zoledronic acid (4 mg) or denosumab (120 mg). Estimates are taken from phase III studies involving men with castration-resistant prostate cancer metastatic to bone41 and a mixed population of patients with solid tumors or multiple myeloma involving bone55.