Bone wound healing is a highly dynamic and precisely controlled process through which damaged bone undergoes repair and complete regeneration. External factors can alter this process, leading to delayed or failed bone wound healing. The findings of recent studies suggest that the use of selective serotonin reuptake inhibitors (SSRIs) can reduce bone mass, precipitate osteoporotic fractures and increase the rate of dental implant failure. With 10% of Americans prescribed antidepressants, the potential of SSRIs to impair bone healing may adversely affect millions of patients’ ability to heal after sustaining trauma. Here, we investigate the effect of the SSRI sertraline on bone healing through pre-treatment with (10 mg·kg^-1 sertraline in drinking water, n = 26) or without (control, n = 30) SSRI followed by the creation of a 5-mm calvarial defect. Animals were randomized into three surgical groups: (a) empty/sham, (b) implanted with a DermaMatrix scaffold soak-loaded with sterile PBS or (c) DermaMatrix soak-loaded with 542.5 ng BMP2. SSRI exposure continued until sacrifice in the exposed groups at 4 weeks after surgery. Sertraline exposure resulted in decreased bone healing with significant decreases in trabecular thickness, trabecular number and osteoclast dysfunction while significantly increasing mature collagen fiber formation. These findings indicate that sertraline exposure can impair bone wound healing through disruption of bone repair and regeneration while promoting or defaulting to scar formation within the defect site.

骨伤口愈合是一个高度动态且精确控制的过程，受损的骨骼通过该过程进行修复和完全再生。外部因素可能会改变这一过程，导致骨伤口愈合延迟或失败。最近的研究结果表明，使用选择性血清素再摄取抑制剂（SSRIs）会减少骨量，加速骨质疏松性骨折并增加种植牙失败率。 10% 的美国人服用抗抑郁药物，SSRIs 损害骨骼愈合的潜力可能会对数百万患者在遭受持续创伤后的愈合能力产生不利影响。在这里，我们通过使用（饮用水中 10 mg·kg ^-1舍曲林， n = 26）或不使用（对照， n = 30）SSRI 进行预处理，然后创建一个模型来研究 SSRI 舍曲林对骨愈合的影响。 5毫米颅骨缺损。将动物随机分为三个手术组：(a) 空/假手术组，(b) 植入浸泡负载无菌 PBS 的 DermaMatrix 支架，或 (c) 浸泡负载 542.5 ng BMP2 的 DermaMatrix 支架。 SSRI 暴露持续到暴露组在手术后 4 周处死。舍曲林暴露导致骨愈合下降，小梁厚度、小梁数量和破骨细胞功能显着减少，同时成熟胶原纤维形成显着增加。这些发现表明，舍曲林暴露可通过破坏骨修复和再生来损害骨伤口愈合，同时促进或默认缺损部位内的疤痕形成。