Should bisphosphonates be used for long-term treatment of glucocorticoid-induced osteoporosis?
Should bisphosphonates be used for long-term treatment of glucocorticoid-induced osteoporosis?
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是否应该使用双磷酸盐长期治疗糖皮质激素引起的骨质疏松症？
DOI：
10.1002/art.30135
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发表时间：
2011
影响因子：
--
通讯作者：
Saag,KennethG
中科院分区：
文献类型：
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作者：
Teitelbaum,StevenL;Seton,MargaretP;Saag,KennethG
骨质量反映了骨合成成骨细胞和再吸收破骨细胞的相对活性。当后者的活动取代前者的活动时，就会发生骨质流失，如果严重的话，最终会导致骨质疏松症（1）。虽然他们的临床表现可能相似，但骨质疏松症的原因很多，最常见的是更年期。雌激素缺乏通常会导致骨质疏松症的高转换形式，其中形成和吸收都加速，但破骨细胞的相对活性大于成骨细胞（2-3）。因此，使用激素替代抑制破骨细胞是几十年来的标准治疗。随着人们认识到雌激素会增加老年妇女患乳腺癌和心血管并发症的风险，双膦酸盐已成为绝经后骨质疏松症最常见的治疗方法。考虑到雌激素缺乏性骨质疏松症中破骨细胞活性的绝对增加，双膦酸盐的有效性并不令人惊讶。例如，阿仑膦酸钠可维持绝经后骨质疏松症妇女的骨量，降低骨折风险长达10年之久，绝大多数患者的并发症最少（4）。骨质疏松症最常见的继发性形式是糖皮质激素引起的，但其骨骼动力学明显不同于雌激素剥夺。绝经后骨形成增强，糖皮质激素对成骨细胞的抑制是进行性骨丢失的主要原因（5-8）。然而，在糖皮质激素的影响下，骨吸收的动力学更为复杂。治疗开始后，吸收加速。通过尿中游离脱氧吡啶啉的排泄测定，正常女性服用低剂量糖皮质激素后可立即抑制骨降解（9），这一事实表明，在治疗患病患者时，骨吸收的早期加速可能代表破骨细胞活化炎性细胞因子的作用持续存在（10-12）。在糖皮质激素诱导的骨质疏松症（GIO）的自然史中，正是在这一早期阶段，减少的形成和加速的吸收相结合产生了最严重的骨丢失（13-14）。糖皮质激素加速破骨细胞活性的误解，无论给药时间长短，形成了美国流变学学院（15），皇家医师学院（16）和基本上所有国际指南建议的理论基础，即双膦酸盐常规给药用于预防和治疗GIO。事实上，随着长期治疗性暴露于类固醇，
Skeletal mass is a reflection of the relative activities of bone synthesizing osteoblasts and resorbing osteoclasts. When the activity of the latter supersedes that of the former, bone loss occurs, which if profound, eventuates into osteoporosis (1). While their clinical manifestations may be similar, the causes of osteoporosis are many, the most common attending menopause. Estrogen-deficiency typically prompts a high turnover form of osteoporosis in which both formation and resorption are accelerated but the relative activity of the osteoclast is greater than that of the osteoblast (2–3). Thus, suppression of the osteoclast using hormone replacement was standard of care for decades. With the realization that estrogens increase risk of breast cancer and cardiovascular complications in older women, bisphosphonates have become the most common treatment for post-menopausal osteoporosis. Given the absolute increase in osteoclast activity in estrogen-deficient osteoporosis, the effectiveness of bisphosphonates is not surprising. Alendronate, for example, maintains bone mass and reduces fracture risk of post-menopausal, osteoporotic women for as long as a decade with minimal complications in the great majority of patients (4).The most common secondary form of osteoporosis is that induced by glucocorticoids, but its skeletal dynamics are distinctly different than those attending estrogen deprivation. Whereas bone formation is enhanced following the menopause, inhibition of the osteoblast by glucocorticoids is a major cause of progressive bone loss (5–8). The dynamics of bone resorption, under the influence of glucocorticoids are, however, more complex. Upon initiation of therapy, resorption is accelerated. The fact that low dose glucocorticoids given to normal women immediately suppresses bone degradation as determined by urinary excretion of free deoxypyridinoline (9), suggests the early acceleration of resorption attending treatment of afflicted patients may represent persistence of the effects of osteoclast-activating inflammatory cytokines (10–12). It is during this early stage that the combination of reduced formation and accelerated resorption yields the most profound bone loss in the natural history of glucocorticoid-induced osteoporosis (GIO)(13–14). The misconception that glucocorticoids accelerate osteoclast activity, regardless of duration of administration, forms the theoretical basis for the recommendations of the American College of Rheumatology (15), Royal College of Physicians (16) and essentially all international guidelines, that bisphosphonates be routinely administered for prevention and treatment of GIO. In fact, with chronic, therapeutic exposure to the steroids, resorption turns from