De Nijs R N J
Center for Rheumatology, Máxima Medical Center, Eindhoven, The Netherlands.
Minerva Med. 2008 Feb;99(1):23-43.
Glucocorticoids, often regarded as ancient drugs, are still frequently used in modern medicine because of their strong anti-inflammatory and immunosuppressive properties. Nowadays, the side effects of glucocorticoids are well-known and physicians often anticipate on these side effects. Bone loss is one of the most important side effects of glucocorticoid use, even in low doses. The main effect of glucocorticoids on bone is inhibition of osteoblast function, leading to a decrease in bone formation. Also nongenomic effects (mediated by glucocorticoid interactions with biological membranes, either through binding to membrane receptors or by physicochemical interactions) may have a role in the pathogenesis of glucocorticoid-induced osteoporosis. Several studies and reports show a decrease in bone mineral density and an increased risk of fractures during glucocorticoid use. Prior and current exposure to glucocorticoids increases the risk of fractures beyond that explained by values of bone mineral density. This discrepancy could be explained by osteocyte apoptosis leading to rapid weakening of bone architecture and increase in fractures risk. Bone loss starts promptly after initiation of glucocorticoids and is mainly taking place in the first six months of treatment. Bone loss is predominantly found in bone with a high trabecular content, like vertebrae. The risk of glucocorticoid-induced osteoporosis can be reduced by general measurements like prescribing glucocorticoids in a low dose and for a short period of time. Furthermore, pharmacological intervention for prevention of glucocorticoid-induced osteoporosis is needed depending on glucocorticoid dose, expected duration of glucocorticoid treatment, age and gender of the patient and sometimes bone mineral density at start of the glucocorticoid treatment. Bisphosphonates seem to be the first choice of pharmacological intervention for prevention and treatment of glucocorticoid-induced osteoporosis and are cost-effective in subgroups of patients (depending on age, gender, glucocorticoid dose and fracture history). There is no evidence that one specific bisphosphonate is superior to another bisphosphonate due to lacking of head-to-head studies on glucocorticoid-induced osteoporosis. A recent study showed that alendronate is superior to alfacalcidol in prevention of glucocorticoid-induced osteoporosis in patients starting glucocorticoids of 7.5 mg or more on a daily basis. Calcium and plain vitamin D3 supplementation are considered as important support for prevention and treatment of glucocorticoid-induced osteoporosis. Despite the increased knowledge on bone loss and fracture risk during glucocorticoid use and the possibilities of pharmacological intervention of it, studies made clear that the care given by physicians in prevention and treatment of glucocorticoid-induced osteoporosis needs to be optimized in future years. Further training of health care workers in pathophysiology, general measurements and pharmacological intervention for prevention and treatment of glucocorticoid-induced osteoporosis, is needed.
糖皮质激素常被视为古老的药物，由于其强大的抗炎和免疫抑制特性，在现代医学中仍被频繁使用。如今，糖皮质激素的副作用已广为人知，医生也常常会预期这些副作用。骨质流失是使用糖皮质激素最重要的副作用之一，即使是低剂量使用也会出现。糖皮质激素对骨骼的主要作用是抑制成骨细胞功能，导致骨形成减少。此外，非基因组效应（由糖皮质激素与生物膜的相互作用介导，要么通过与膜受体结合，要么通过物理化学相互作用）可能在糖皮质激素诱导的骨质疏松症的发病机制中起作用。多项研究和报告表明，在使用糖皮质激素期间骨矿物质密度会降低，骨折风险会增加。既往和当前接触糖皮质激素会增加骨折风险，这种风险超出了骨矿物质密度值所能解释的范围。这种差异可以用骨细胞凋亡导致骨结构迅速变弱和骨折风险增加来解释。骨质流失在开始使用糖皮质激素后迅速发生，主要发生在治疗的前六个月。骨质流失主要发生在小梁含量高的骨骼中，如椎骨。通过一些常规措施，如低剂量、短疗程使用糖皮质激素，可以降低糖皮质激素诱导的骨质疏松症的风险。此外，根据糖皮质激素剂量、预期的糖皮质激素治疗持续时间、患者的年龄和性别，有时还需根据糖皮质激素治疗开始时的骨矿物质密度，采取药物干预措施来预防糖皮质激素诱导的骨质疏松症。双膦酸盐似乎是预防和治疗糖皮质激素诱导的骨质疏松症的首选药物干预措施，并且在某些患者亚组中具有成本效益（取决于年龄、性别、糖皮质激素剂量和骨折史）。由于缺乏关于糖皮质激素诱导的骨质疏松症的头对头研究，没有证据表明一种特定的双膦酸盐优于另一种双膦酸盐。最近一项研究表明，对于每天开始使用7.5毫克或更多糖皮质激素的患者，阿仑膦酸钠在预防糖皮质激素诱导的骨质疏松症方面优于阿法骨化醇。补充钙和普通维生素D3被认为是预防和治疗糖皮质激素诱导的骨质疏松症的重要支持措施。尽管人们对使用糖皮质激素期间的骨质流失和骨折风险以及对此进行药物干预的可能性有了更多了解，但研究表明，未来几年医生在预防和治疗糖皮质激素诱导的骨质疏松症方面所提供的护理仍需优化。需要对医护人员进行关于糖皮质激素诱导的骨质疏松症的病理生理学、常规措施和药物干预方面的进一步培训。
