• For those patients in whom bisphosphonates were withdrawn after 2 years, the drug
should be resumed upon relapse with new-onset skeletal-related events.
• Denosumab should NOT be stopped abruptly given its reversible mechanism of action.
Monitoring
➤ The Expert Panel recommends that serum creatinine should be monitored
before each dose of pamidronate or zoledronic acid, in accordance with
FDA-approved labeling.
• Denosumab does not require monitoring of renal function.
➤ In patients who develop renal deterioration without apparent cause
during bisphosphonate therapy, zoledronic acid or pamidronate should be
withheld.
• Bisphosphonate therapy can be resumed, at the same dosage as that before treatment
interruption, when the serum creatinine returns to within 10% of the baseline level.
• Denosumab requires no dose modification.
➤ Serum calcium should be monitored regularly, and serum vitamin D levels
should be evaluated intermittently.
• Hypocalcemia is an adverse effect of all bone resorptive agents and is more pronounced
with denosumab.
• Patients should be calcium and vitamin D repleted.
➤ The Expert Panel also recommends intermittent evaluation (every 3–6
months) of all patients receiving pamidronate or zoledronic acid therapy
for the presence of albuminuria on a spot urine sample.
• In patients experiencing unexplained albuminuria, then a 24 hour urine should be
obtained to assess for >500 mg/24 hours of urinary albumin, and discontinuation of
the drug is advised until the renal problems are resolved.
• These patients should be reassessed every 3–4 weeks (with a 24 hour urine collection
for total protein and urine protein electrophoresis), and pamidronate should be
reinstituted over a longer infusion time (≥4 hours) and at doses not to exceed 90 mg
every 4 weeks when the renal function returns to baseline.
➤ The Expert Panel supports the use of screening urinalysis for proteinuria
but underscores that a 24 hour urine collection for determination of total
protein and electrophoresis is required if the test is positive.
• Although no similar guidelines are available for zoledronic acid, some Expert Panel
members recommend that zoledronic acid be reinstituted over a longer infusion time
(≥30 minutes).
Biochemical Markers
➤ The use of the biochemical markers of bone metabolism to monitor bone
modifying therapy use is NOT suggested for routine care.
Treatment
