Age related effects of selective and non-selective COX-2 inhibitors on bone healing

Kigera, James; Gichangi, Peter; Abdelmalek, Adel K.M.; Ogeng’o, Julius A

doi:10.1016/j.jcot.2022.101763

Cited by 2 publications

(1 citation statement)

References 29 publications

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“…Obviously, the use of some medications to treat co-morbidities could also influence outcomes depending on the type and dosages being used. Treatment with anti-inflammatory medications, such as NSAIDS [ 67 , 68 , 69 ] or high or continuous doses of glucocorticoids [ 70 , 71 ], could potentially adversely affect outcomes after interventions with cell therapy approaches. Therefore, the presence of co-morbidities and their treatment, as well age and sex, should be recognized and addressed before initiating interventions to enhance the repair/regeneration of injured connective tissues of the MSK system.…”

Section: Factors That Can Complicate Post-injury Processes and Inflam...mentioning

confidence: 99%

Creating an Optimal In Vivo Environment to Enhance Outcomes Using Cell Therapy to Repair/Regenerate Injured Tissues of the Musculoskeletal System

Hart

Nakamura

2022

Biomedicines

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Following most injuries to a musculoskeletal tissue which function in unique mechanical environments, an inflammatory response occurs to facilitate endogenous repair. This is a process that usually yields functionally inferior scar tissue. In the case of such injuries occurring in adults, the injury environment no longer expresses the anabolic processes that contributed to growth and maturation. An injury can also contribute to the development of a degenerative process, such as osteoarthritis. Over the past several years, researchers have attempted to use cellular therapies to enhance the repair and regeneration of injured tissues, including Platelet-rich Plasma and mesenchymal stem/medicinal signaling cells (MSC) from a variety of tissue sources, either as free MSC or incorporated into tissue engineered constructs, to facilitate regeneration of such damaged tissues. The use of free MSC can sometimes affect pain symptoms associated with conditions such as OA, but regeneration of damaged tissues has been challenging, particularly as some of these tissues have very complex structures. Therefore, implanting MSC or engineered constructs into an inflammatory environment in an adult may compromise the potential of the cells to facilitate regeneration, and neutralizing the inflammatory environment and enhancing the anabolic environment may be required for MSC-based interventions to fulfill their potential. Thus, success may depend on first eliminating negative influences (e.g., inflammation) in an environment, and secondly, implanting optimally cultured MSC or tissue engineered constructs into an anabolic environment to achieve the best outcomes. Furthermore, such interventions should be considered early rather than later on in a disease process, at a time when sufficient endogenous cells remain to serve as a template for repair and regeneration. This review discusses how the interface between inflammation and cell-based regeneration of damaged tissues may be at odds, and outlines approaches to improve outcomes. In addition, other variables that could contribute to the success of cell therapies are discussed. Thus, there may be a need to adopt a Precision Medicine approach to optimize tissue repair and regeneration following injury to these important tissues.

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Section: Factors That Can Complicate Post-injury Processes and Inflam...mentioning

confidence: 99%

Creating an Optimal In Vivo Environment to Enhance Outcomes Using Cell Therapy to Repair/Regenerate Injured Tissues of the Musculoskeletal System

Hart

Nakamura

2022

Biomedicines

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Effect of Timing of Cox-2-Selective Nsaids Use on Fracture Healing in an Adult Rat Model

Kigera

Gichangi

Abdelmalek

et al. 2022

J. Musculoskelet. Res.

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Introduction: Fractures are common in the old and are associated with increased morbidity. The pain of fractures and surgery can be managed using NSAIDs, but this may result in impaired healing. The inflammatory stage of bone healing is responsible for laying the foundation for subsequent proliferative stages. This may be the stage when NSAIDs may have their greatest impact and it is unclear if avoiding NSAIDs in this stage would result in differences in healing or whether different molecules have varied responses. This study sought to determine the differences in the histomorphometry of fracture callus in older rats when diclofenac and celecoxib were avoided in the first week after a fracture. Methods: Fractures of the tibia were induced in 43 15-month-old (equivalent to 50 human years) rats which were then allocated to receive either diclofenac or celecoxib. Each group was further subdivided into early or late subgroups of 10 animals each receiving the study medication from the day after the fracture or eight days later, respectively. Histological and stereological examination of the callus on days 21 and 42 enabled comparison of histological grades, tissue proportions and cellular densities. Results: The histological grade and amount of bone increased and the amount of cartilage reduced in all groups. The group that received celecoxib early had the least proportion of bone. The osteocyte and chondrocyte cellular densities increased in all groups across both time points. Conclusion: Administration of celecoxib in the early fracture period in the old is associated with poorer histological grades, lower proportions of bone and increased cellularity which may result in delayed union of the fracture. Use of selective COX-2 inhibitors is discouraged for the management of pain in older patients with fractures especially in the first seven days.

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Age related effects of selective and non-selective COX-2 inhibitors on bone healing

Cited by 2 publications

References 29 publications

Creating an Optimal In Vivo Environment to Enhance Outcomes Using Cell Therapy to Repair/Regenerate Injured Tissues of the Musculoskeletal System

Creating an Optimal In Vivo Environment to Enhance Outcomes Using Cell Therapy to Repair/Regenerate Injured Tissues of the Musculoskeletal System

Effect of Timing of Cox-2-Selective Nsaids Use on Fracture Healing in an Adult Rat Model

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