Parathyroid hormone therapy improves MRSA-infected fracture healing in a murine diabetic model.
Parathyroid hormone therapy improves MRSA-infected fracture healing in a murine diabetic model.
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DOI：
10.3389/fcimb.2023.1230568
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发表时间：
2023
影响因子：
5.7
通讯作者：
中科院分区：
文献类型：
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作者：
糖尿病（DM）损害骨折愈合，并与感染易感性相关，感染进一步抑制骨折愈合。虽然间歇性甲状旁腺激素（1-34）（iPTH）有效地改善骨折愈合，但目前尚不清楚感染相关的骨折愈合受损是否可以用PTH（特立帕肽）挽救。使用慢性饮食诱导的2型糖尿病小鼠模型来产生与瘦饲对照相比具有降低的葡萄糖耐量和增加的血糖水平的小鼠。将耐甲氧西林金黄色葡萄球菌（MRSA）接种到手术胫骨骨折模型中以模拟感染性骨折，之后用抗生素和预防性特立哌治疗的组合治疗小鼠。通过胫骨骨折放射学愈合评分（RUST）、显微计算机断层扫描（μCT）、生物力学测试和组织学评估骨折愈合。糖尿病小鼠的RUST评分明显低于非糖尿病小鼠。在2型糖尿病（T2 DM）小鼠中，骨痂结构的显微计算机断层扫描（μCT）参数（包括骨体积/总体积、骨小梁厚度和总矿物质密度）也随之降低。骨折股骨的生物力学测试表明，最大扭矩时扭转刚度、刚度和韧性降低。全身抗生素治疗辅助特立帕汀治疗改善了瘦型和T2 DM组的骨微结构骨体积的许多参数，增加了连接密度，并增加了骨小梁数量。尽管观察到MRSA感染进一步损害了T2 DM小鼠中不良的骨折愈合，但在感染的T2 DM骨折中，与单独抗生素治疗相比，辅助iPTH治疗显著改善了骨折愈合。 我们的研究结果表明，特立帕替尼可能构成一个可行的辅助治疗剂，以改善骨愈合和骨微结构，以防止在糖尿病条件下脓毒性骨不连的发展。
Diabetes mellitus (DM) impairs fracture healing and is associated with susceptibility to infection, which further inhibits fracture healing. While intermittent parathyroid hormone (1-34) (iPTH) effectively improves fracture healing, it is unknown whether infection-associated impaired fracture healing can be rescued with PTH (teriparatide). A chronic diet-induced type 2 diabetic mouse model was used to yield mice with decreased glucose tolerance and increased blood glucose levels compared to lean-fed controls. Methicillin-resistant Staphylococcus aureus (MRSA) was inoculated in a surgical tibia fracture model to simulate infected fracture, after which mice were treated with a combination of antibiotics and adjunctive teriparatide treatment. Fracture healing was assessed by Radiographic Union Scale in Tibial Fractures (RUST), micro-computed tomography (μCT), biomechanical testing, and histology. RUST score was significantly poorer in diabetic mice compared to their lean nondiabetic counterparts. There were concomitant reductions in micro-computed tomography (μCT) parameters of callus architecture including bone volume/total volume, trabecular thickness, and total mineral density in type 2 diabetes mellitus (T2DM) mice. Biomechanicaltesting of fractured femora demonstrated diminished torsional rigidity, stiffness, and toughness to max torque. Adjuvant teriparatide treatment with systemic antibiotic therapy improved numerous parameters of bone microarchitecture bone volume, increased connectivity density, and increased trabecular number in both the lean and T2DM group. Despite the observation that poor fracture healing in T2DM mice was further impaired by MRSA infection, adjuvant iPTH treatment significantly improved fracture healing compared to antibiotic treatment alone in infected T2DM fractures. Our results suggest that teriparatide may constitute a viable adjuvant therapeutic agent to improve bony union and bone microarchitecture to prevent the development of septic nonunion under diabetic conditions.
影响因子：
3.7
作者：
Aspenberg P;Johansson T
通讯作者：
Johansson T