Department of Orthopaedics and Traumatology and Bone Quality and Health Center, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
Chin Med J (Engl). 2013 Jan;126(1):27-33.
The association of long-term bisphosphonate treatment for osteoporosis and related safety problems such as atypical fractures were not clearly defined. This study was to evaluate the structural, densitometric and biomechanical properties of the prolonged bisphosphonate-loaded bones.
Bone mineral density (BMD) at hip and femoral midshaft, bone cross-sectional area, moment of inertia of both femurs, bone formation and resorption biochemical markers were compared between 28 elderly with at least 4 years of bisphosphonate treatment from 2002 through 2006 and age-matched group of 37 elderly.
The total hip BMD and t-score were found not different between two groups. However, bisphosphonate treated patients were found to have significantly lower bone mineral content in the femoral shaft (P < 0.05); morphological study showed lower cross-sectional area in subtrochanteric and mid-diaphyseal region and thus significantly lower moment of inertia (P < 0.01). High resolution-peripheral quantitative computed tomography showed significantly decreased trabecular density, bone volume ratio, trabecular number but increased trabecular spacing in tibia and distal radius. Finite element analysis further confirmed significantly lower stiffness and failure load in tibia. Biochemical studies also showed lower bone resorption and severely suppressed bone formation activity (P < 0.001).
The unchanged total hip BMD between two groups confirmed the beneficial effects of bisphosphonate on trabecular bone, thus preventing osteoporotic fractures at large in previous studies. However, the inferior structural, densitometric and biomechanical properties at cortical bones, especially femur midshaft, need a special attention to look into the association between long-term bisphosphonate intake and the occurrence of stress fractures. When patients taking bisphosphonate complain of proximal thigh pain or discomfort, plain X-ray film can be the first line screening. All patients prescribed with bisphosphonate should be informed of such a complication though we must stress its rarity.
长期使用双磷酸盐治疗骨质疏松症以及与非典型骨折等相关安全问题的关联尚不清楚。本研究旨在评估长期双磷酸盐负载骨骼的结构、骨密度和生物力学特性。
通过比较 2002 年至 2006 年间至少接受 4 年双磷酸盐治疗的 28 名老年患者和年龄匹配的 37 名老年患者的髋部和股骨中段骨密度（BMD）、骨横截面积、股骨的惯性矩、骨形成和吸收生化标志物，来评估双磷酸盐治疗组和对照组的各项数据。
两组患者的总髋部 BMD 和 t 评分无差异。然而，双磷酸盐治疗组的股骨干骺端骨矿物质含量明显较低（P < 0.05）；形态学研究显示，转子下区和骨干中段的横截面积较低，因此惯性矩明显较低（P < 0.01）。高分辨率外周定量计算机断层扫描显示，胫骨和桡骨远端的骨小梁密度、骨体积比、骨小梁数量明显降低，而骨小梁间距明显增加。有限元分析进一步证实，胫骨的刚度和破坏载荷明显降低。生化研究也显示，骨吸收减少，骨形成活性严重抑制（P < 0.001）。
两组患者的总髋部 BMD 无差异，证实了双磷酸盐对小梁骨的有益作用，从而防止了之前研究中大多数骨质疏松性骨折的发生。然而，皮质骨（尤其是股骨中段）的结构、骨密度和生物力学特性较差，需要特别注意长期双磷酸盐摄入与应力性骨折发生之间的关系。当服用双磷酸盐的患者出现大腿近端疼痛或不适时，可先进行 X 线平片筛查。所有开处双磷酸盐的患者均应被告知这种并发症的存在，尽管我们必须强调其罕见性。
