Ramchand Sabashini K, Seeman Ego
Department of Medicine, The University of Melbourne, Melbourne, VIC, Australia.
Department of Endocrinology, Austin Health, The University of Melbourne, Melbourne, VIC, Australia.
Front Endocrinol (Lausanne). 2018 Sep 6;9:505. doi: 10.3389/fendo.2018.00505. eCollection 2018.
The prevalence of fragility fractures increases as longevity increases the proportion of the elderly in the community. Until recently, the majority of studies have targeted women with osteoporosis defined as a bone mineral density (BMD) T score of < -2.5 SD, despite evidence that the population burden of fractures arises from women with osteopenia. Antiresorptive agents reduce vertebral and hip fracture risk by ~50 percent during 3 years but efficacy against non-vertebral fractures, 80% of all fractures in the community, is reported in few studies, and of those, the risk reduction is only 20-30%. Recent advances in the use of antiresorptives and anabolic agents has addressed some of these unmet needs. Zoledronic acid is now reported to reduce vertebral and non-vertebral fractures rates in women with osteopenia. Studies using teriparatide demonstrate better vertebral and clinical (symptomatic vertebral and non-vertebral) antifracture efficacy than risedronate. Abaloparatide, a peptide sharing amino acid sequences with teriparatide, reduces vertebral and non-vertebral fractures. Romosozumab, a monoclonal antibody suppressing sclerostin, reduces vertebral and non-vertebral fractures within a year of starting treatment, and does so more greatly than alendronate. Some recent studies signal undesirable effects of therapy but provide essential cautionary insights into long term management. Cessation of denosumab is associated with a rapid increase in bone remodeling and the uncommon but clinically important observation of increased multiple vertebral fractures suggesting the need to start alternative anti-resorptive therapy around the time of stopping denosumab. Antiresorptives like bisphosphonates and denosumab suppress remodeling but not completely. Antifracture efficacy may be limited, in part, as a consequence of continued unsuppressed remodeling, particularly in cortical bone. Bisphosphonates may not distribute in deeper cortical bone, so unbalanced intracortical remodeling continues to cause microstructural deterioration. In addition, suppressed remodeling may compromise the material composition by increasing matrix mineral density and glycosylation of collagen. As antiresorptive agents do not restore microstructural deterioration existing at the time of starting treatment, under some circumstances, anabolic therapy may be more appropriate first line treatment. Combining antiresorptive and anabolic therapy is an alternative but whether anti-fracture efficacy is greater than that achieved by either treatment alone is not known.
随着预期寿命的增加以及社区中老年人比例的上升，脆性骨折的患病率也在增加。直到最近，大多数研究都以骨质疏松症女性为目标，骨质疏松症定义为骨矿物质密度（BMD）T评分＜-2.5标准差，尽管有证据表明骨折的人群负担来自骨质减少的女性。抗吸收剂在3年内可将椎体和髋部骨折风险降低约50%，但针对非椎体骨折（社区中所有骨折的80%）的疗效，在少数研究中有报道，其中风险降低仅为20%-30%。抗吸收剂和促合成代谢药物使用方面的最新进展已经满足了其中一些未满足的需求。现在有报道称唑来膦酸可降低骨质减少女性的椎体和非椎体骨折发生率。使用特立帕肽的研究表明，其在椎体和临床（有症状的椎体和非椎体）抗骨折疗效方面优于利塞膦酸。阿巴洛帕肽是一种与特立帕肽共享氨基酸序列的肽，可降低椎体和非椎体骨折发生率。罗莫佐单抗是一种抑制硬化蛋白的单克隆抗体，在开始治疗的一年内可降低椎体和非椎体骨折发生率，且效果比利塞膦酸更显著。最近的一些研究表明了治疗存在不良影响，但为长期管理提供了重要的警示性见解。停用狄诺塞麦与骨重塑迅速增加以及罕见但临床上重要的多发性椎体骨折增加的观察结果相关，这表明在停用狄诺塞麦时需要开始替代抗吸收治疗。双膦酸盐和狄诺塞麦等抗吸收剂可抑制重塑，但并不完全。抗骨折疗效可能部分受到持续未被抑制的重塑的限制，尤其是在皮质骨中。双膦酸盐可能无法分布到更深层的皮质骨中，因此皮质内重塑失衡会继续导致微观结构恶化。此外，受抑制的重塑可能会通过增加基质矿物质密度和胶原蛋白糖基化来损害材料成分。由于抗吸收剂无法恢复开始治疗时就已存在的微观结构恶化，在某些情况下，促合成代谢疗法可能是更合适的一线治疗方法。联合使用抗吸收和促合成代谢疗法是一种选择，但抗骨折疗效是否大于单独使用任何一种治疗方法尚不清楚。
