Gutteridge D H, Price R I, Kent G N, Prince R L, Michell P A
Department of Endocrinology & Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia.
J Bone Miner Res. 1990 Mar;5 Suppl 1:S205-15. doi: 10.1002/jbmr.5650051332.
Spontaneous fractures were reported to be rare (less than 1%) in 1664 hospital admissions for hip fracture in the 1950s in Sweden. We report 11 fluoride-treated postmenopausal patients who developed spontaneous fractures of the femoral necks, all subcapital initially. In 7 patients who continued treatment there were later femoral neck or shaft fractures; in 6, these were bilateral (one followed a fall). In all there were 19 spontaneous fractures: 5 were asymptomatic, including 2 with deformity; 12 fractures required surgery. Five were incomplete (stress) fractures. All were treated with supplementary calcium 1 g daily; 10 had vitamin D supplementation. In all patients where the timing was known, the initial and subsequent fractures were preceded by, or associated with increased bone turnover as measured by plasma alkaline phosphatase (pAlP) (i.e., they were all "good responders"). Two had pretreatment hip fractures following falls. We compared these 11 (Group 1) and another identically treated group of 14 patients (Group 2), without spontaneous femoral fractures and not different in mean age, pretreatment vertebral fractures, years since menopause, fluoride dosage, and plasma creatinine. Group 1 had a lower (p less than 0.05) index of cortical bone in the femoral neck, as assessed by the ratio "calcar width/femoral neck minimum width." The 6 biopsied fluorotic patients from Group 1 had a higher (p less than 0.05) bone fluoride content than the 4 biopsied fluorotic patients from Group 2. Furthermore, histological cortical features of thinning, increased porosity, and advanced tunneling resorption characterized Group 1 posttreatment biopsies. There were no significant differences in peak pAlP responses in the two groups. Mild asymptomatic vitamin D excess may have been a contributing factor in three Group 1 patients. Two further treatment groups have been studied more recently by forearm single-photon absorptiometry (SPA) at two sites; a cyclic NaF group (Group 3) and a calcium +/- vitamin D group (Group 4). Neither showed significant changes in forearm cortical bone density on treatment for 2 and 1.5 years, respectively, but Group 3 showed a significant increase in density at an ultradistal (60% trabecular) site. The pAlP response in Group 3 was significantly less than in Group 1. Spontaneous femoral neck or shaft fractures did not occur in either Groups 3 or 4. Therefore, we recommend: (1) Avoidance of sodium fluoride (NaF) treatment if pretreatment femoral fracture or thin femoral neck cortices exist.(ABSTRACT TRUNCATED AT 400 WORDS)
据报道，20世纪50年代瑞典1664例因髋部骨折入院的患者中，自发性骨折很少见（不到1%）。我们报告了11例接受氟化物治疗的绝经后患者发生了股骨颈自发性骨折，最初均为股骨头下型。7例继续治疗的患者后来发生了股骨颈或股骨干骨折；6例为双侧骨折（其中1例是跌倒后发生的）。总共发生了19例自发性骨折：5例无症状，包括2例有畸形；12例骨折需要手术治疗。5例为不完全（应力）骨折。所有患者均每日补充1克钙；10例补充了维生素D。在所有已知时间的患者中，最初和随后的骨折之前或与血浆碱性磷酸酶（pAlP）测量的骨转换增加相关（即他们都是“良好反应者”）。2例患者在治疗前因跌倒发生髋部骨折。我们将这11例患者（第1组）与另一组14例接受相同治疗的患者（第2组）进行了比较，第2组没有自发性股骨骨折，平均年龄、治疗前椎体骨折情况、绝经后年限、氟化物剂量和血浆肌酐水平与第1组无差异。通过“距骨宽度/股骨颈最小宽度”比值评估，第1组股骨颈皮质骨指数较低（p<0.05）。第1组6例接受活检的氟中毒患者的骨氟含量高于第2组4例接受活检的氟中毒患者。此外，第1组治疗后活检的组织学皮质特征为变薄、孔隙率增加和进行性隧道状吸收。两组的pAlP峰值反应无显著差异。3例第1组患者可能存在轻度无症状维生素D过量。最近通过双部位前臂单光子吸收测定法（SPA）对另外两个治疗组进行了研究；一个是周期性氟化钠组（第3组）和一个钙加或不加维生素D组（第4组）。分别治疗2年和1.5年后，两组前臂皮质骨密度均无显著变化，但第3组在超远端（60%小梁骨）部位的密度显著增加。第3组的pAlP反应明显低于第1组。第3组和第4组均未发生自发性股骨颈或股骨干骨折。因此，我们建议：（1）如果存在治疗前股骨骨折或股骨颈皮质薄的情况，避免使用氟化钠（NaF）治疗。（摘要截短至400字）
