目的：骨质疏松症是一种以隐匿起病和骨骼脆弱性增加为特征的全身性骨骼疾病，易导致骨质疏松性骨折的发生。既往回顾性研究结果提示，血红蛋白水平可能作为骨质疏松症的潜在诊断标志物。然而，骨质疏松症与贫血之间的关联机制及其临床意义仍有待深入阐明。因此，本前瞻性研究旨在探究血红蛋白水平与骨质疏松症发生风险之间的关联性，并评估其潜在的临床应用价值。

方法：基于英国生物样本库（UK Biobank）的庞大数据集，纳入了一个包含452778名参与者的队列。为控制潜在的偏倚，本研究采用经过改良的Cox比例风险模型，充分考虑了社会人口统计学特征、生活方式因素以及健康相关因素等多重混杂因素，旨在更为准确地评估新发骨质疏松症与性别之间的关联。此外，我们还进一步分析了伴有或不伴有病理性骨折的骨质疏松症对研究结果的影响，以期更全面地理解骨质疏松症的疾病负担。

结果：经过中位5.85年的随访，共有4294名参与者被确诊为骨质疏松症。在充分校正了相关混杂因素后，研究结果显示，贫血患者发生骨质疏松症的风险显著高于非贫血患者，男性贫血患者的骨质疏松症风险是非贫血男性的2.15倍，女性贫血患者的骨质疏松症风险是非贫血女性的1.41倍。更进一步地分析表明，血红蛋白浓度每增加一个单位，男性骨质疏松症的风险降低0.83倍（风险比[HR] = 0.83），女性骨质疏松症的风险降低0.94倍（风险比[HR] = 0.94）。

结论：本研究结果揭示了血红蛋白水平与骨质疏松症之间存在显著的负相关关系，并且与女性相比，男性表现出更为明显的易感性。具体而言，无论男性还是女性，较高的血红蛋白浓度均与较低的骨质疏松症风险相关，尽管这种保护性效应在男性中更为显著。为验证本研究结果并深入探究观察到的关联背后的因果机制，我们建议未来扩大样本量，实施多中心、长期性的前瞻性研究。此外，亟需进行实验研究，以深入阐明贫血与骨质疏松症之间复杂的潜在病理生理机制，为骨质疏松症的防治提供了新的理论基石和潜在干预靶点。

Objective: Osteoporosis, a systemic skeletal disease characterized by insidious onset and increased bone fragility, predisposes individuals to osteoporotic fractures. Prior retrospective studies have suggested that hemoglobin levels may serve as a potential diagnostic marker for osteoporosis. However, the underlying mechanisms linking osteoporosis and anemia, along with their clinical significance, remain incompletely understood. Therefore, this prospective study aims to investigate the association between hemoglobin levels and the risk of developing osteoporosis, and to assess its potential clinical utility.

Methods: This study leveraged the extensive data resources of the UK Biobank, encompassing a cohort of 452,778 participants. To mitigate potential bias, a modified Cox proportional hazards model was employed, comprehensively accounting for multiple confounders including sociodemographic characteristics, lifestyle factors, and health-related variables. This approach aimed to more accurately estimate the association between incident osteoporosis and hemoglobin levels, stratified by sex. Furthermore, we analyzed the impact of osteoporosis, with and without pathological fractures, on study outcomes to more comprehensively understand the disease burden.

Results: Over a median follow-up period of 5.85 years, the study population comprised 4,294 individuals diagnosed with osteoporosis. After adjusting for relevant confounders, the results demonstrated that anemic individuals had a significantly higher risk of developing osteoporosis compared to non-anemic individuals. Specifically, anemic men had a 2.15-fold increased risk of osteoporosis compared to non-anemic men, while anemic women had a 1.41-fold increased risk compared to non-anemic women. Further analysis indicated that for each unit increase in hemoglobin concentration, the risk of osteoporosis decreased by 0.83-fold in men (hazard ratio [HR] = 0.83) and 0.94-fold in women (hazard ratio [HR] = 0.94).

Conclusion: This study revealed a significant inverse relationship between hemoglobin levels and osteoporosis, with men exhibiting a more pronounced susceptibility compared to women. Specifically, higher hemoglobin concentrations were associated with a lower risk of osteoporosis in both men and women, although this protective effect was more prominent in men. In order to corroborate these results and explore the etiological mechanisms responsible for the association, we recommend future large-scale, multi-center, and long-term longitudinal studies. Furthermore, experimental studies are warranted to elucidate the complex underlying pathophysiological mechanisms between anemia and osteoporosis, potentially providing new theoretical basis and therapeutic targets for osteoporosis prevention and treatment.