Can Prolia (denosumab) and Forteo (teriparatide) be used simultaneously?

Simultaneous Use of Prolia (Denosumab) and Forteo (Teriparatide)

Combination therapy with Prolia (denosumab) and Forteo (teriparatide) can be used simultaneously and may provide greater increases in bone mineral density than either medication alone, though this approach is not currently included in standard treatment guidelines.

Evidence for Combination Therapy

• Combination therapy with denosumab and teriparatide increases bone mineral density (BMD) more than either drug alone, with studies showing significantly greater increases at the lumbar spine, femoral neck, and total hip 1, 2
• After 12 months of treatment, combined therapy showed 9.1% increase in lumbar spine BMD compared to 6.2% with teriparatide alone and 5.5% with denosumab alone 2
• The DATA Extension Study demonstrated that after 24 months, lumbar spine BMD increased by 12.9% with combination therapy compared to 9.5% with teriparatide alone and 8.3% with denosumab alone 1
• Combination therapy also showed superior improvements in bone microarchitecture and estimated bone strength compared to monotherapy, particularly in cortical bone 3

Mechanism of Synergistic Effect

• Teriparatide is a recombinant human parathyroid hormone that works as an anabolic agent to increase bone formation 4
• Denosumab is a RANK ligand inhibitor that reduces bone resorption 5
• When used together, denosumab inhibits teriparatide-induced bone resorption while allowing continued teriparatide-induced bone formation, creating a synergistic effect 6

Important Considerations and Limitations

• Standard treatment guidelines do not specifically recommend combination therapy as a routine approach 5
• Teriparatide is typically reserved for patients with severe osteoporosis with documented fractures or those at very high fracture risk who have failed first-line therapies 7
• Teriparatide carries a black box warning for potential risk of osteosarcoma, which should be considered in the risk-benefit assessment 4
• Both medications have specific contraindications that must be considered:
  • Teriparatide: hypersensitivity to teriparatide or any of its components 5
  • Denosumab: hypocalcemia 5

Sequential Therapy Considerations

• If considering transitioning between these medications, evidence suggests that switching from teriparatide to denosumab results in continued BMD increases, while switching from denosumab to teriparatide may result in transient bone loss 8
• The combination to denosumab sequence showed the greatest increases in total hip BMD (8.6%) compared to teriparatide to denosumab (6.6%) or denosumab to teriparatide (2.8%) 8

Dosing in Combination Therapy

• Standard dosing when used in combination remains:
  • Teriparatide: 20 μg subcutaneous daily 5
  • Denosumab: 60 mg subcutaneous every 6 months 5
• Higher doses of teriparatide (40 μg daily) combined with denosumab have been studied and show even greater increases in BMD, but this is not an FDA-approved dosing regimen 6

Monitoring Recommendations

• Regular monitoring of bone mineral density via DEXA scan is recommended 7
• Ensure adequate calcium (1200mg daily) and vitamin D (800 IU daily) supplementation 4
• Monitor serum calcium levels, particularly when initiating therapy, due to the potential effects of both medications on calcium metabolism 5, 4

While combination therapy shows promising results for BMD improvement, treatment decisions should be based on individual fracture risk, previous treatment response, and cost considerations, as combination therapy is more expensive than monotherapy.