Erythropoietin does not improve fracture healing in aged mice

Orth, Marcel; Baudach, J.; Scheuer, Cláudia; Osche, David; Veith, Nils T.; Braun, Benedikt J.; Rollmann, Mika F.; Herath, Steven C.; Pohlemann, Tim; Menger, Michael D.; Histing, Tina

doi:10.1016/j.exger.2019.04.005

Cited by 10 publications

(6 citation statements)

References 22 publications

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“…According to Balaian et al (2018), EPO's bone remodelling effect could be age-dependent, resulting in greater mineralization only in young, healthy patient's cells [65]. Additionally, in contrast to young mice, EPO may not be used to improve bone healing in the elderly [66].…”

Section: Discussionmentioning

confidence: 99%

Effects of Erythropoietin-Promoted Fracture Healing on Bone Turnover Markers in Cats

Vasileva,

Chaprazov,

Milanova

2024

JFB

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In orthopaedics, erythropoietin (EPO) is applied in the preoperative management of anaemic patients, but also as a stimulating factor to assist bone regeneration due to its angiogenic and osteoinductive potential. Since orthopaedists mainly rely on their clinical experience to assess bone healing, additional and more objective methods such as studying the dynamics of bone markers are needed. Therefore, the aim of this study was to investigate the plasma activity of bone-specific alkaline phosphatase (BALP), the N-terminal propeptide of type I collagen (PINP), the C-terminal telopeptide of type I collagen (CTX), and deoxypyridinoline (DPD) during the first 2 months of healing of comminuted fractures in cats, either non-stimulated or locally stimulated with recombinant human erythropoietin (rhEPO). The study included twelve cats of mixed breeds, aged 7.2 ± 4 months, weighing 2.11 ± 1.1 kg, with comminuted diaphyseal fractures of the femur. Surgical treatment with plate osteosynthesis was performed in all animals. The cats were randomly divided into two groups—a control (n = 6) and an EPO group (n = 6). The locally applied EPO leads to the increased activity of bone formation markers (BALP and PINP) during the second week after the osteosynthesis, preceding the peaks in the control group by two weeks. The studied bone resorption markers (DPD, CTX) varied insignificantly during the studied period. In conclusion, erythropoietin could serve as a promoter of bone healing in comminuted fractures in cats.

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Section: Discussionmentioning

confidence: 99%

Effects of Erythropoietin-Promoted Fracture Healing on Bone Turnover Markers in Cats

Vasileva,

Chaprazov,

Milanova

2024

JFB

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“…Oikonomidou et al reported that chronically elevated circulating EPO can cause polycythemia and bone loss [ 143 ]. However, EPO has little effect on bone healing for the elderly, and this may be because of the gradual weakening of microcirculation [ 144 ]. Naamit et al observed that high EPO-level treatment induces bone loss.…”

Section: Hif/epo Pathwaymentioning

confidence: 99%

Hypoxia-Inducible Factors Signaling in Osteogenesis and Skeletal Repair

Qin

Liu²,

Yang³

et al. 2022

IJMS

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Sufficient oxygen is required to maintain normal cellular and physiological function, such as a creature’s development, breeding, and homeostasis. Lately, some researchers have reported that both pathological hypoxia and environmental hypoxia might affect bone health. Adaptation to hypoxia is a pivotal cellular event in normal cell development and differentiation and in pathological settings such as ischemia. As central mediators of homeostasis, hypoxia-inducible transcription factors (HIFs) can allow cells to survive in a low-oxygen environment and are essential for the regulation of osteogenesis and skeletal repair. From this perspective, we summarized the role of HIF-1 and HIF-2 in signaling pathways implicated in bone development and skeletal repair and outlined the molecular mechanism of regulation of downstream growth factors and protein molecules such as VEGF, EPO, and so on. All of these present an opportunity for developing therapies for bone regeneration.

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“…In spite of its relatively invasive nature and complex surgical technique, this model has the advantage of no medullary cavity damage and allows for a closer replication of the clinical scenario of a hip fixator. 49 The model with internal fixation was however not employed to study fracture pain.…”

Section: Animal Models Mostly Used To Study Fracture Painmentioning

confidence: 99%

What Did We Learn About Fracture Pain from Animal Models?

Radulescu¹,

White²,

Chenu³

2022

JPR

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Progress in bone fracture repair research has been made possible due to the development of reproducible models of fracture in rodents with more clinically relevant fracture fixation, where there is considerably better assessment of the factors that affect fracture healing and/or novel therapeutics. However, chronic or persistent pain is one of the worst, longest-lasting and most difficult symptoms to manage after fracture repair, and an ongoing challenge remains for animal welfare as limited information exists regarding pain scoring and management in these rodent fracture models. This failure of adequate pre-clinical pain assessment following osteotomy in the rodent population may not only subject the animal to severe pain states but may also affect the outcome of the bone healing study. Animal models to study pain were also mainly developed in rodents, and there is increasing validation of fracture and pain models to quantitatively evaluate fracture pain and to study the factors that generate and maintain fracture pain and develop new therapies for treating fracture pain. This review aims to discuss the different animal models for fracture pain research and characterize what can be learned from using animal models of fracture regarding behavioral pain states and new molecular targets for future management of these behaviors.

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Erythropoietin does not improve fracture healing in aged mice

Cited by 10 publications

References 22 publications

Effects of Erythropoietin-Promoted Fracture Healing on Bone Turnover Markers in Cats

Effects of Erythropoietin-Promoted Fracture Healing on Bone Turnover Markers in Cats

Hypoxia-Inducible Factors Signaling in Osteogenesis and Skeletal Repair

What Did We Learn About Fracture Pain from Animal Models?

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