Bull Hosp Jt Dis (2013). 2022 Sep;80(3):260-264.
Chronic use of selective serotonin reuptake inhibitors (SSRIs) for the treatment of depression has been linked to an imbalance in bone metabolism leading to osteoporosis. More recently, the use of SSRIs in murine models has been shown to delay bone healing both in vivo and in vitro by decreasing the osteoblastic differentiation and mineralization. The purpose of this study was to evaluate whether or not chronic use of SSRI's in nonunion patients increases their time to union after surgical intervention.
We retrospectively analyzed 343 patients in a nonunion database to determine which patients were on SSRI medication. Of these patients, 139 could be contacted and of those 102 were not taking SSRIs and 37 were taking SSRIs. Patient's time to union from nonunion surgical intervention between each cohort at our institution was recorded as the primary outcome. Patient's medical comorbidities that could affect union rates such as diabetes and smoking status were also noted. Baseline Short Musculoskeletal Function Assessment (SMFA) index for bother and function were recorded from the time of nonunion surgery as well as last follow-up.
Compared to recent census data, we found significantly more patients in the nonunion cohort using SSRIs (26.6%) than patients in the general population using any type of antidepressant (11%). There was no significant difference in the patients' baseline characteristics other than patients on SSRI treatment had a higher body mass index (BMI) and age (p = 0.048 and p = 0.043, respectively). There was no significant difference noted in the fracture types (p = 0.2063). Patients on SSRIs had a higher SMFA bother index and function index on follow-up (p = 0.0103, p = 0.0147). Patients in the SSRI group had a mean time to union from nonunion surgery of 6.1 months compared to 6.0 in patients without SSRI usage (p = 0.74). These did not reach statistical significance when subcohort analysis for long bone fractures was performed for the femur, tibia, and humerus.
To our knowledge, this is the first clinical study to investigate the effects of SSRIs on fracture healing. While in vivo and in vitro murine models have shown that SSRIs can have a deleterious effect on osteoblastic activity, our retrospective analysis did not show a significant difference in time to union between patients with chronic SSRI use and patients who have not been on SSRIs. However, this investigation did show a higher incidence of SSRI use in the nonunion cohort when compared to the general population. In the context of the recent animal model study, this may point to a negative effect of SSRI use on the acute fracture healing process.
慢性使用选择性 5-羟色胺再摄取抑制剂（SSRIs）治疗抑郁症与骨代谢失衡有关，导致骨质疏松症。最近，在体内和体外研究中，使用 SSRIs 已被证明会通过减少成骨细胞分化和矿化来延迟骨愈合。本研究旨在评估非愈合患者慢性使用 SSRI 是否会增加其手术后的愈合时间。
我们回顾性分析了非愈合数据库中的 343 例患者，以确定哪些患者正在服用 SSRI 药物。其中，139 例患者可以联系到，其中 102 例患者未服用 SSRIs，37 例患者服用 SSRIs。我们记录了每个队列在我们机构从非愈合手术到愈合的时间作为主要结果。还记录了可能影响愈合率的患者的医疗合并症，如糖尿病和吸烟状况。还记录了从非愈合手术到最后随访时的基线短肌肉骨骼功能评估（SMFA）指数的困扰和功能。
与最近的人口普查数据相比，我们发现非愈合组中使用 SSRIs 的患者（26.6%）明显多于一般人群中使用任何类型抗抑郁药的患者（11%）。除了服用 SSRI 治疗的患者体重指数（BMI）和年龄较高（p = 0.048 和 p = 0.043）外，两组患者的基线特征没有显著差异。两组骨折类型无显著差异（p = 0.2063）。服用 SSRIs 的患者在随访时的 SMFA 困扰指数和功能指数较高（p = 0.0103，p = 0.0147）。SSRIs 组患者从非愈合手术到愈合的平均时间为 6.1 个月，而未使用 SSRIs 的患者为 6.0 个月（p = 0.74）。当对股骨、胫骨和肱骨的长骨骨折进行亚组分析时，这些结果没有达到统计学意义。
据我们所知，这是第一项研究 SSRIs 对骨折愈合影响的临床研究。尽管体内和体外的小鼠模型研究表明 SSRIs 可能对成骨细胞活性有有害影响，但我们的回顾性分析并未显示慢性使用 SSRIs 的患者与未使用 SSRIs 的患者之间愈合时间有显著差异。然而，这项研究确实表明，与一般人群相比，非愈合队列中 SSRIs 的使用发生率更高。在最近的动物模型研究的背景下，这可能表明 SSRIs 对急性骨折愈合过程有负面影响。
