Bisphosphonates are commonly used to treat bone metastases from cancers like breast, lung and prostate cancer. They work by inhibiting osteoclast activity and bone resorption, thereby reducing complications from bone metastases like fractures, bone pain and hypercalcemia. The document recommends bisphosphonates like zoledronate and pamidronate for reducing skeletal complications in patients with osteolytic bone tumors, multiple myeloma, hypercalcemia or those receiving aromatase inhibitor therapy. It provides guidance on screening patients, choosing agents, administration, monitoring side effects and treatment cycles.

1. Bisphosphonates in
metastasis
Dr Sitanshu

2. Introduction
• Common site of Mets – breast, lung,
prostrate, thyroid, kidney, MM
• Skeletal complications + morbidity
• Medications
• Skeletal related event
• Can affect survival – precluding future
disease directed therapy

3. Pathophysiology
• RANKL loop
• Osteoclast
differentiation
• Positive feedback
mechanism

4. Bisphosphonates mechanism of
action
• Structural analogs of pyrophosphate
• Absorb calcium phosphate
• Suppress normal functioning and
maturation of osteoclast
• Non nitrogeneous – eti, clo – apoptosis
• Nitrogeneous – pami, zole – block HMG
CoA pathway – genesis, survival, integrity

6. Summary of evidence
• Cochrane meta analysis
• Pain relief, reduction in analgesic
consumption, increased quality of life
• Do not support as primary analgesic,
adjuvant to opioid / NSAID
• Clinical effectiveness – 80% to 50%

7. Current recommendation
1. Osteolytic bone tumors (breast, solid)
2. Multiple myeloma
3. Hypercalcemia of malignancy
4. Aromatase inhibitor therapy

8. Screening in
1.Men aged >70 on androgen deprivation
therapy
2.In breast cancer with a) family history of
fractures b) weight < 70kg c) prior non
traumatic # in all post menopausal women
on aromatase inhibitors d) therapy induced
ovarian failure in premenopausal women

9. Choosing an agent
• Zoledronate, pamidronate – FDA approved
• Zoledronate potency 100 times more
• Peripheral / central access
• Pami – 60-90mg over 90 min
• Zole – 4mg over 15 min
• Renal failure – slower infusion + dose
adjustment according to CrCl
• Monthly creatinine, calcium monitoring
• Oral calcium, Vit D supplementation

10. Side effects
Osteonecrosis of jaw (1%)
1.Dental evaluation before Rx
2.Delay dental extraction
3.Assessment of oral, dental hygiene
4.Avoid dentures
Hypocalcemia
Routine calcium, albumin monitoring before
administration

11. Renal dysfunction
Routine CrCl monitoring before administration
Dose adjustment
Slowing of infusion
Fever
Antipyretic
Nausea
Antiemetic

12. Cycle
• 4 week cycle
• Upto 2 years is a must
• Multiple myeloma – indefinitely
• If skeletal related event occurs –
indefinitely, only Zoledronate
• Adjunct in pain control
• If for pain – for 1 year a must