Neck of femur (NOF) fracture is a prevalent fracture type amongst the ageing and osteoporotic populations, commonly requiring total hip replacement (THR) surgery. Increased fracture risk has also been associated with Alzheimer’s disease (AD) in the aged. Here, we sought to identify possible relationships between the pathologies of osteoporosis and dementia by analysing bone expression of neurotropic or dementia-related genes in patients undergoing THR surgery for NOF fracture. Femoral bone samples from 66 NOF patients were examined for expression of the neurotropic genes amyloid precursor protein (APP), APP-like protein-2 (APLP2), Beta-Secretase Cleaving Enzyme-1 (BACE1) and nerve growth factor (NGF). Relationships were examined between the expression of these and of bone regulatory genes, systemic factors and bone structural parameters ascertained from plain radiographs. We found strong relative levels of expression and positive correlations between APP, APLP2, BACE1 and NGF levels in NOF bone. Significant correlations were found between APP, APLP2, BACE1 mRNA levels and bone remodelling genes TRAP, RANKL, and the RANKL:OPG mRNA ratio, indicative of potential functional relationships at the time of fracture. Analysis of the whole cohort, as well as non-dementia (n = 53) and dementia (n = 13) subgroups, revealed structural relationships between APP and APLP2 mRNA expression and lateral femoral cortical thickness. These findings suggest that osteoporosis and AD may share common molecular pathways of disease progression, perhaps explaining the common risk factors associated with these diseases. The observation of a potential pathologic role for AD-related genes in bone may also provide alternative treatment strategies for osteoporosis and fracture prevention.

股骨颈 (NOF) 骨折是老龄化和骨质疏松人群中常见的骨折类型，通常需要进行全髋关节置换 (THR) 手术。骨折风险增加也与老年人的阿尔茨海默病（AD）有关。在这里，我们试图通过分析接受 THR 手术治疗 NOF 骨折的患者的嗜神经或痴呆相关基因的骨表达来确定骨质疏松症和痴呆之间可能存在的关系。检查了来自 66 名 NOF 患者的股骨样本的嗜神经基因淀粉样前体蛋白 ( APP )、APP 样蛋白-2 ( APLP2 )、β-分泌酶切割酶-1 ( BACE1 ) 的表达) 和神经生长因子 (NGF)。检查了这些和骨调节基因的表达、全身因素和从平片确定的骨结构参数之间的关系。我们发现 NOF 骨中APP、APLP2、BACE1和NGF水平之间存在较强的相对表达水平和正相关性。APP、APLP2、BACE1 mRNA 水平与骨重塑基因TRAP、RANKL和RANKL:OPG mRNA 比率之间存在显着相关性，表明骨折时存在潜在的功能关系。整个队列的分析，以及非痴呆（n  = 53）和痴呆（n= 13) 亚组，揭示了APP和APLP2 mRNA 表达与股骨外侧皮质厚度 之间的结构关系。这些发现表明，骨质疏松症和 AD 可能共享疾病进展的共同分子途径，或许可以解释与这些疾病相关的共同危险因素。观察骨中 AD 相关基因的潜在病理作用也可能为骨质疏松症和骨折预防提供替代治疗策略。