[Combination of alendronate plus alfacalcidol in the treatment of osteoporosis. Rationale, preclinical data and clinical evidence].

BACKGROUND: The therapeutic strategy for the reduction of fracture risk in osteoporosis should not only aim to increase bone strength, but should also improve muscle function and reduce falls without increasing the risk of significant side effects. Since 2008 a combination therapy of the antiresorptive active bisphosphonatealendronate and the pleiotropic active D-hormone-prodrug alfacalcidol is licensed in Germanyfor treatment of postmenopausal osteoporosis (Tevabone).

METHODS: In the review the results of numerous preclinical and clinical studies are reported, showing the efficacy of the combination of alendronate plus alfacalcidol.

RESULTS: In preclinical trials with ovariectomized rats the combination has shown a significantly better effect on increased bone turnover in comparison with bisphosphonate monotherapy. Presumably the "oversuppression" of bone remodeling and the resulting risk of reduced microfracture healing, which is known to occur after long-term therapy with bisphosphonates, will be reduced by the combination. Clinical studies have shown better efficacy of the combination in the increase of bone density and reduction of fracture rate (vertebral and non-vertebral fractures). Less falls were reported compared to alendronate plus genuine vitamin D. The reduction of increased parathormone levels by the alendronate plus alfacalcidol combination compared to alendronate alone was proven to increase the responder rate of the alendronate therapy. The potential risks of alendronate-induced hypocalcemia as well as alfacalcidol-induced hypercalcemia or hypercalcuria are reduced due to the contrasting mode of action of both compounds.

CONCLUSION: Treatment with the alendronate plus alfacalcidol combination meets the demands of an optimized therapy for osteoporosis.With the especially developed, self-explanatory combination package better compliance and less dispensing mistakes can be expected.