Controversies in spine research: organ culture versus in vivo models for studies of the intervertebral disc

Intervertebral disc degeneration is a common cause of low back pain, the leading cause of disability worldwide. Appropriate preclinical models for intervertebral disc research are essential to achieving a better understanding of underlying pathophysiology and for the development, evaluation, and translation of more effective treatments. To this end, in vivo animal and ex vivo organ culture models are both widely used by spine researchers; however, the relative strengths and weaknesses of these two approaches are a source of ongoing controversy. In this article, members from the Spine and Preclinical Models Sections of the Orthopedic Research Society, including experts in both basic and translational spine research, present contrasting arguments in support of in vivo animal models versus ex vivo organ culture models for studies of the disc, supported by a comprehensive review of the relevant literature. The objective is to provide a deeper understanding of the respective advantages and limitations of these approaches, and advance the field toward a consensus with respect to appropriate model selection and implementation. We conclude that complementary use of several model types and leveraging the unique advantages of each is likely to result in the highest impact research in most instances

Is the Use of Bisphosphonates Putting Horses at Risk? An Osteoclast Perspective

Osteoclasts are unique and vital bone cells involved in bone turnover. These cells are active throughout the individual’s life and play an intricate role in growth and remodeling. However, extra-label bisphosphonate use may impair osteoclast function, which could result in skeletal microdamage and impaired healing without commonly associated pain, affecting bone remodeling, fracture healing, and growth. These effects could be heightened when administered to growing and exercising animals. Bisphosphonates (BPs) are unevenly distributed in the skeleton; blood supply and bone turnover rate determine BPs uptake in bone. Currently, there is a critical gap in scientific knowledge surrounding the biological impacts of BP use in exercising animals under two years old. This may have significant welfare ramifications for growing and exercising equids. Therefore, future research should investigate the effects of these drugs on skeletally immature horses

Induction of Synovitis Using Interleukin-1 Beta: Are There Differences in the Response of Middle Carpal Joint Compared to the Tibiotarsal Joint?

Background: The effects of recombinant interleukin-1β (rIL-1β) have been described for the middle carpal joint (MCJ). However, we are unaware of any studies that have described the cytological response of the tibiotarsal joint (TTJ) to rIL-1β or compared the clinical and cytological responses of the MCJ to the TTJ following the administration of intra-articular rIL-1β. Such information is critical for researchers planning to use rIL-1β to create acute synovitis models in horses.Objectives: To compare the clinical and cytological responses of the MCJ to the TTJ following administration of intra-articular rIL-1β.Methods: Twelve horses were used for the study. Eight horses received 75 ng of rIL-1β into the MCJ and four horses received 75 ng of rIL-1β into the TTJ. Clinical and cytological outcome parameters including lameness, joint circumference, joint effusion score, total nucleated cell count, cellular differentials, C-reactive protein, and prostaglandin-E2 concentrations were determined at baseline and multiple post-treatment time points over a 336 h period (2 weeks).Results: Recombinant IL-1β administered into the TTJ resulted in a significantly greater respiratory rate at 24 h and heart rate at 12 h when compared to rIL-1β administered into the MCJ. In addition, the TTJ had a significantly greater increase in joint circumference at 24 post-injection hour (PIH) and subjective effusion grade at 24 PIH and 336 PIH. The MCJ had significantly higher total protein concentration at 6 PIH, and a significantly higher NCC at 24 and 72 PIH when compared to the TTJ. Conversely, the TTJ had significantly higher neutrophilic infiltration than the MCJ at 6 PIH and 168 PIH.Conclusions: This study establishes that the same intra-articular dose of rIL-1 β elicits significantly different clinical and cytological responses in the MCJ compared to the TTJ in the equine model of intra-articular synovitis. In addition, clinical and cytological evidence of synovitis may persist up to or >1 week following intra-articular administration of rIL-1 β