双膦酸盐防治骨质疏松性骨折的研究进展

骨质疏松症(osteoporosis,OP)是一种全身高发骨骼疾病,其特点主要为骨密度下降、骨矿物质削减,破坏骨组织微细结构布局,进而致使骨机械强度下降、脆性增高,容易导致病理性骨折。骨质疏松性骨折(osteiporotic fracture,OPF)又称脆性骨折,是OP最严重的并发症之一,多发于老年人,发生率较高,因OP的特征故而导致OPF多呈粉碎性,愈合慢。且因骨强度低和骨脆性高而容易引起内固定松动和再骨折发生,故而残疾率和死亡率相对较高。就目前的研究现状来说,双膦酸盐(bisphosphonates,BPs)类药物成为临床防治OPF最常用的一线药物,其治疗目标是防止进一步的骨质流失,以减少初始或后续骨折的风险,故该类药物的应用显著降低OPF的发生,脊柱骨折发生率降低了40%～70%,髋部骨折发生率降低了40%～50%。然而,考虑到BPs类药物的主要作用机制,基于抑制破骨细胞活性和随后抑制骨形成,人们担心它们是否会延迟或损害骨折愈合的能力,甚至引起新发骨折形成,即非典型性骨折,这是一种罕见的无创伤性或极小创伤性股骨骨折。所以这个问题不禁引起了人们的思考:长期使用BPs类药物预防继发性骨折的疗效是否掩盖了与使用BPs类药物相关的骨折愈合障碍风险,最终引发非典型性骨折的出现?本文就BPs类药物对OPF防治的研究进展作一综述,为后续BPs类药物研究和临床用药提供一定的依据。

Progress of bisphosphonates in the prevention and treatment of osteoporotic fractures

Osteoporosis (OP) is a systemic multiple bone disease. It is mainly characterized by decreased bone mineral density and bone mineral loss, thereby destroying the fine structure of bone tissue, resulting in decreased mechanical strength of the bone and increased fragility, thus increased risk of related pathological fracture. Osteoporotic fracture (OPF, also known as brittle fracture) is one of the most serious complications of OP. It occurs more frequently in older people and has a high incidence. Due to the characteristics of the OP, the OPF is mostly crushed and slowly healed. Because low bone strength and high bone fragility could easily lead to internal fixation loosening and re-fracture, the incidence of disability and mortality is relatively high. At the current status of research, bisphosphonates is the first-line drugs for the prevention and treatment of OPF. Its therapeutic goal is to prevent further bone loss to reduce the risk of initial or subsequent fractures. The use of these drugs can significantly reduce the occurrence of OPF: the incidence of spinal fractures decreased by 40%-70%, and the incidence of hip fractures decreased by 40%-50%. However, considering the main mechanism of action of BPs is the inhibition of osteoclast activity and subsequent inhibition of bone formation, there is concern about whether they would delay or impair the ability of fracture healing, and even cause new fractures, i.e. atypical fractures, which is a rare type of non-traumatic or minimally invasive femoral fracture. Therefore, this question has caused people to think: whether the long-term use of BPs to prevent secondary fractures masks the risk of fracture healing disorders associated with the use of BPs, and ultimately leads to the emergence of atypical fractures. This article reviews the progress of research on the prevention and treatment of OPF using bisphosphonates and provides a basis for the subsequent study of bisphosphonates and clinical application.