Combination therapy for osteoporosis: a reappraisal

Area of Science:

• Orthopedics and Endocrinology
• Pharmacology and Bone Metabolism

Background:

• Osteoporosis management often involves anabolic and antiresorptive agents.
• Combinations aim for superior bone density and strength compared to monotherapy.
• Numerous trials have explored combinations of parathyroid hormone (PTH) with various antiresorptives.

Purpose of the Study:

• To review clinical trial data on combined anabolic and antiresorptive osteoporosis therapies.
• To evaluate the efficacy of combination treatments on bone mineral density (BMD) and bone strength.
• To identify optimal combination strategies based on drug type, timing, and skeletal site.

Main Methods:

• Systematic review of clinical trials evaluating PTH (1-34 or 1-84) combined with hormone therapy, raloxifene, bisphosphonates (alendronate, risedronate, ibandronate, zoledronic acid), or denosumab.
• Analysis of dual-X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) derived BMD outcomes.
• Assessment of finite element modeling for bone strength where available.

Main Results:

• Combination therapy consistently showed superior hip BMD compared to PTH monotherapy, particularly with bisphosphonates or denosumab.
• Spine BMD benefits were less consistent, with exceptions noted for PTH/denosumab and sequential PTH/alendronate.
• No trials were powered to compare fracture incidence between combination and monotherapy.

Conclusions:

• Combining antiresorptives with PTH can enhance hip BMD and strength, especially in patients with low hip BMD or hip fractures.
• Consideration of teriparatide with continued or switched antiresorptives (zoledronic acid, denosumab) is recommended for maximizing hip outcomes.
• For severe osteoporosis, combination therapy with PTH and denosumab, or sequential PTH with potent bisphosphonates/denosumab, may optimize early BMD gains.