Simultaneous Use of Multiple Anti-Osteoporotic Treatments
Combination therapy using multiple anti-osteoporotic treatments simultaneously is not recommended due to lack of evidence for improved fracture outcomes, increased costs, and potential for greater side effects.
Evidence Against Combination Therapy
The 2022 American College of Rheumatology (ACR) guidelines for glucocorticoid-induced osteoporosis (GIOP) conditionally recommend against using multiple osteoporosis therapies simultaneously in adults ≥40 years with high and very high fracture risk 1
Very low-level evidence does not support using combination therapy (e.g., PTH/PTHrP and denosumab, PTH/PTHrP and bisphosphonates) in glucocorticoid-induced osteoporosis 1
The American College of Physicians (ACOG) explicitly states that "combination therapy is not recommended" for osteoporosis treatment 1
Despite some studies showing synergistic increases in bone mineral density (BMD) with combinations like PTH with IV bisphosphonates, PTH with raloxifene, and PTH with denosumab, combination therapy is not currently recommended due to added cost, possibility of greater side effects, and lack of fracture evidence 1
Sequential Therapy vs. Combination Therapy
Sequential therapy (using one medication after another) is different from combination therapy (using multiple medications simultaneously) and is often necessary in osteoporosis management 2
Certain medications require sequential therapy with an anti-resorptive agent to prevent bone loss after discontinuation:
- Denosumab must be followed by a bisphosphonate beginning 6-7 months after the last dose to prevent rapidly progressive vertebral fractures 1
- Romosozumab requires 12 months of treatment followed by an anti-resorptive agent 1
- PTH/PTHrP (teriparatide) is typically used for 24 months and should be followed by an anti-resorptive agent 2
Concurrent therapy with anabolic agents (like teriparatide) and antiresorptive agents (like bisphosphonates) should be avoided, but sequential therapy with these agents might consolidate beneficial effects on the skeleton 3
Potential Risks of Combination Therapy
Combination treatment will increase cost and likely increase side effects 4
Therapy adherence may be reduced with combination treatments 4
None of the existing studies are large enough to determine whether combination treatment reduces fracture risk more than single-agent therapy 4
Recommended Approach to Osteoporosis Treatment
First-line therapy should be a single agent, typically an oral bisphosphonate, based on its efficacy across multiple skeletal sites 5
For patients who cannot tolerate or have contraindications to first-line therapy, alternative single agents should be considered rather than combinations 1
Treatment selection should be based on:
Regular monitoring is necessary to assess whether drug treatment should be interrupted, continued, or extended 2
Special Considerations
For very high-risk patients, anabolic agents (PTH and PTHrP) are conditionally recommended over antiresorptive agents (bisphosphonates or denosumab), but still as monotherapy rather than in combination 1
In patients with cancer-induced bone loss, bisphosphonates or denosumab are recommended as single agents rather than in combination 1
For patients who sustain fractures while undergoing osteoporosis therapy, specialist referral should be considered rather than adding a second concurrent medication 6