Lems Willem F, Geusens Piet
aVU University Medical Center, Department of Rheumatology, Amsterdam bDepartment of Internal Medicine/Rheumatology, Maastricht University Medical Center and CAPHRI, Maastricht, The Netherlands cBiomedical Research Institute, University Hasselt, Belgium.
Curr Opin Rheumatol. 2014 May;26(3):245-51. doi: 10.1097/BOR.0000000000000057.
The aim of treatment in patients at high risk for fractures is to reduce the risk of a first or a subsequent fracture. New data are available on the antifracture effects and side-effects of antiresorptive and osteoanabolic drugs, and new emerging therapies with new modes of action are on the horizon.
Calcium and vitamin D intake should be sufficient, but not too high. Vertebral, nonvertebral (including hip fracture) prevention with antiresorptive drugs such as bisphosphonates (alendronate, risedronate and zoledronic acid) and denosumab exceeds the risk of rare side-effects such as atypical femur fracture and osteonecrosis of the jaw. Teriparatide is an osteoanabolic drug that improves quality of life in severe osteoporosis. Strontium ranelate decreases dynamic parameters of bone formation during the first year of treatment, and could increase the risk of cardiovascular events in high-risk patients. Initiation of and adherence to fracture prevention drugs are still low. New potential developments in antiresorptive drugs include odanacatib, a selective inhibitor of cathepsin K, and, in osteoanabolic drugs, monoclonal antibodies against sclerostin.
These recent data indicate that fracture prevention with antiresorptives and teriparatide is effective with a reasonable safety profile. Odanacatib and antisclerostin are promising new drugs with new mechanisms of action, as they are able to disconnect the normal coupling between bone resorption and bone formation.
骨折高危患者的治疗目标是降低首次或再次骨折的风险。关于抗吸收和骨合成代谢药物的抗骨折效果及副作用有了新数据,并且具有新作用模式的新兴疗法也即将出现。
钙和维生素D的摄入量应充足,但不宜过高。使用双膦酸盐(阿仑膦酸钠、利塞膦酸钠和唑来膦酸)和地诺单抗等抗吸收药物预防椎体、非椎体(包括髋部骨折)骨折的效果超过了非典型股骨骨折和颌骨坏死等罕见副作用的风险。特立帕肽是一种骨合成代谢药物,可改善严重骨质疏松症患者的生活质量。雷奈酸锶在治疗的第一年可降低骨形成的动态参数,并可能增加高危患者发生心血管事件的风险。预防骨折药物的起始使用和依从性仍然较低。抗吸收药物的新潜在进展包括组织蛋白酶K的选择性抑制剂奥达卡替,以及骨合成代谢药物中针对硬化蛋白的单克隆抗体。
这些最新数据表明,使用抗吸收药物和特立帕肽预防骨折有效且安全性合理。奥达卡替和抗硬化蛋白是有前景的具有新作用机制的新药,因为它们能够打破骨吸收与骨形成之间的正常耦合。