Shi Leiyu, Lin Cheng-Li, Su Ching-Huang, Lin Keng-Chian, Leong Kam-Hang, Wang Yu-Ting Tina, Kuo Chien-Feng, Tsai Shin-Yi
Department of Health Policy and Management, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA.
College of Medicine, China Medical University, Taichung City 404, Taiwan.
J Clin Med. 2021 Jul 29;10(15):3364. doi: 10.3390/jcm10153364.
Hemolytic anemia (HA) renders erythropoietic stress on the bone marrow and has been linked to osteoporosis. In this nationwide retrospective cohort study, we examined this correlation by utilizing the Taiwan National Health Insurance Research Database (NHIRD). We identified two cohorts, matching population with and without HA in a 1:4 ratio. A total of 2242 HA patients and 8968 non-HA patients were enrolled. Patients with HA had a significantly higher cumulative incidence (log-rank test = 0.0073), higher incidence density (5.11 vs. 3.76 per 1000 persons-years), and a 1.31-fold risk of developing osteoporosis than non-HA patients (aHR = 1.31, 95% C.I. 1.04-1.63, = 0.01). After adjusting for age, sex, and comorbidities, patients with factors including female (aHR = 2.57, 95% C.I. 2.05-3.22, < 0.001), age > 65 (aHR = 9.25, 95% C.I. 7.46-11.50, < 0.001), diagnosis of cholelithiasis (aHR = 1.76, 95% C.I. 1.20-2.58, = 0.003) and peptic ulcer disease (aHR = 1.87, 95% C.I. 1.52-2.29, < 0.001) had significantly higher risk of osteoporosis. We propose that this correlation may be related to increased hematopoietic stress, increased consumption of nitric oxide (NO) by hemolysis, and the inhibitory effects of iron supplements on osteogenesis through the receptor activator of nuclear factor κB ligand (RANKL)/Osteoprotegerin pathway and the Runt-related transcription factor 2 (RUNX2) factor. Our findings suggest that patients with hemolytic anemia are at a higher risk of developing osteoporosis, and it would be in the patient's best interest for physicians to be aware of this potential complication and offer preventative measures.
溶血性贫血（HA）会给骨髓带来红细胞生成应激，并且与骨质疏松症有关。在这项全国性回顾性队列研究中，我们利用台湾国民健康保险研究数据库（NHIRD）来研究这种相关性。我们确定了两个队列，按照1:4的比例匹配有HA和无HA的人群。总共纳入了2242例HA患者和8968例非HA患者。HA患者的累积发病率显著更高（对数秩检验 = 0.0073），发病密度更高（每1000人年分别为5.11和3.76），并且发生骨质疏松症的风险是非HA患者的1.31倍（调整后风险比[aHR]=1.31，95%置信区间[C.I.]为1.04 - 1.63，P = 0.01）。在调整年龄、性别和合并症后，具有女性（aHR = 2.57，95% C.I.为2.05 - 3.22，P < 0.001）、年龄>65岁（aHR = 9.25，95% C.I.为7.46 - 11.50，P < 0.001）、胆结石诊断（aHR = 1.76，95% C.I.为1.20 - 2.58，P = 0.003）和消化性溃疡疾病（aHR = 1.87，95% C.I.为1.52 - 2.29，P < 0.001）等因素的患者发生骨质疏松症的风险显著更高。我们提出这种相关性可能与造血应激增加、溶血导致一氧化氮（NO）消耗增加以及铁补充剂通过核因子κB受体活化剂配体（RANKL）/骨保护素途径和 runt 相关转录因子 2（RUNX2）因子对骨生成的抑制作用有关。我们的研究结果表明，溶血性贫血患者发生骨质疏松症的风险更高，医生了解这种潜在并发症并提供预防措施将符合患者的最大利益。
