Combination treatment of osteoporosis: A clinical review

Objective: Because of the limited efficacy of available agents and to limit toxicity, there is considerable interest in combination pharmacotherapy for osteoporosis. Methods: A search was performed for randomized controlled trials in MEDLINE (1966-present) using the keywords osteoporosis treatment and combination. Results: Twenty-four randomized controlled trials evaluated osteoporosis medications in combination. Study duration ranged from 1 to 4 years. No serious adverse events were definitively attributable to study drugs. Fracture reduction outcome is not shown for any combination regimen. The literature was mixed regarding bone density augmentation. Combinations of nandrolone decanoate plus calcitonin, calcitonin plus growth hormone (GH), or pamidronate plus GH may be contradictory or detrimental to bone mineral density (BMD). For postmenopausal osteoporosis or osteopenia, four combinations appear to increase hip and lumbar BMD: 10 mg alendronate with 0.625 mg conjugated equine estrogens (CEE), cyclic etidronate with 0.625mg CEE, 10 mg alendronate with 2 mg estradiol (E-2), and tibolone with fluoride. For steroid-related osteoporosis, intermittent etidronate with fluoride increases lumbar BMD. Conclusions: The few trials including Food and Drug Administration (FDA)-approved medications suggest that 10 mg/day alendronate with estrogen (equivalent of 0.625 mg CEE daily) can increase BMD moreso than each medication given singly in postmenopausal osteoporotic women. Estrogen dose and type must be controlled in future trials. Long-term safety data are lacking. The utility of these combinations rests on whether bone density changes will translate into decreased fracture rates.