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Parathyroid hormone therapy improves MRSA-infected fracture healing in a murine diabetic modelopen access

Authors
Kwon, Hyuk-KwonCahill, Sean V.Yu, Kristin E.Alder, Kareme D.Dussik, Christopher M.Jeong, JainBack, Jung HoLee, Francis Y.
Issue Date
Sep-2023
Publisher
FRONTIERS MEDIA SA
Keywords
diabetes; MRSA; fracture; nonunion; osteomyelitis; parathyroid hormone
Citation
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v.13
Indexed
SCIE
SCOPUS
Journal Title
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
Volume
13
URI
https://scholarworks.gnu.ac.kr/handle/sw.gnu/68766
DOI
10.3389/fcimb.2023.1230568
ISSN
2235-2988
Abstract
IntroductionDiabetes 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).MethodsA 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 (mu CT), biomechanical testing, and histology.ResultsRUST score was significantly poorer in diabetic mice compared to their lean nondiabetic counterparts. There were concomitant reductions in micro-computed tomography (mu CT) 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.DiscussionOur 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.
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