Clinical Trial Unit, Orthopedic Department, University of Wuerzburg, Brettreichstrasse 11, 97074, Wuerzburg, Germany.
Osteoporos Int. 2018 Aug;29(8):1815-1825. doi: 10.1007/s00198-018-4552-3. Epub 2018 May 17.
Risk for subtrochanteric and diaphyseal femoral fractures is considered increased in patients with hypophosphatasia (HPP). Evaluating a large cohort of HPP patients, we could for the first time quantify the prevalcence and identify both morphometric features as well as predisposing factors for this complication of severe HPP.
Subtrochanteric and diaphyseal femoral fractures have been associated with both, long-term antiresorptive treatment and metabolic bone disorders, specifically Hypophosphatasia (HPP). Building on a cross-sectional evaluation of real-world data, this study reports risk factors, prevalence, treatment outcome and morphometric particularities for such fractures in HPP as compared to Atypical Femoral Fractures (AFF) in long-term antiresorptive treatment.
For 15 out of 150 HPP patients identified with having experienced at least one such fracture, medical records were reviewed in detail, extracting medical history, genotype, lab assessments, bone mineral density (DXA), radiographic data on femoral geometry and clinical aspects of fracture etiology and healing.
Bilateral fractures were documented in 10 of these 15 patients, yielding a total of 25 fractures for evaluation. Disease-inherent risk factors included autosomal-recessive, childhood onset HPP, apparently low alkaline phosphatase (ALP) ≤ 20 U/l and substantially elevated pyridoxal 5'-phosphate (PLP) > 3 times upper limit of normal as well as high lumbar spine BMD. Fracture morphology met definition criteria for AFF in 88% of cases. Femoral geometry revealed additional risk factors previously described for AFF, including decreased femoral neck-shaft angle and increased femoral offset. Extrinsic risk factors include Hypovitaminosis D (80%) and pre-treatment with bisphosphonates (46,7%) and Proton-Pump Inhibitors (40%).
Increased risk for subtrochanteric and diaphyseal femoral fractures in HPP appears to result from both compromised bone metabolism as well as disease-associated bone deformities. In severe HPP, generous screening for such fractures seems advisable. Bisphosphonates and Hypovitaminosis D should be avoided. Healing is compromised and requires mindful consideration of both pharmacological and surgical options.
患有低磷酸血症（HPP）的患者发生转子下和骨干股骨骨折的风险被认为增加。通过评估大量 HPP 患者，我们首次能够量化这种严重 HPP 并发症的患病率，并确定其形态特征和诱发因素。
转子下和骨干股骨骨折与长期抗吸收治疗和代谢性骨疾病有关，特别是低磷酸血症（HPP）。基于对真实世界数据的横断面评估，本研究报告了与长期抗吸收治疗中的非典型股骨骨折（AFF）相比，在 HPP 中发生此类骨折的危险因素、患病率、治疗结果和形态学特点。
对于 150 名 HPP 患者中确定至少经历过一次此类骨折的 15 名患者，详细审查了病历，提取了病史、基因型、实验室评估、骨矿物质密度（DXA）、股骨几何形状的放射学数据以及骨折病因和愈合的临床方面。
10 名患者中有 10 名患者记录了双侧骨折，共评估了 25 处骨折。疾病固有危险因素包括常染色体隐性、儿童发病的 HPP、碱性磷酸酶（ALP）明显低≤20 U/l 和吡啶醛 5'-磷酸（PLP）显著升高>3 倍正常值以及腰椎骨密度高。88%的病例骨折形态符合 AFF 的定义标准。股骨几何形状显示了以前描述的 AFF 的其他危险因素，包括股骨颈干角减小和股骨偏移增加。外在危险因素包括维生素 D 缺乏症（80%）和治疗前使用双膦酸盐（46.7%）和质子泵抑制剂（40%）。
在 HPP 中，转子下和骨干股骨骨折的风险增加似乎是由受损的骨代谢以及与疾病相关的骨畸形共同导致的。在严重的 HPP 中，似乎需要对这种骨折进行广泛筛查。应避免使用双膦酸盐和维生素 D 缺乏症。愈合受损，需要认真考虑药物和手术治疗。
