A missed opportunity: A scoping review of the effect of sex and age on osteoarthritis using large animal models.

OBJECTIVE: The objective was to critically analyze the published literature accounting for sex differences and skeletal age (open vs. closed physis) in preclinical animal models of OA, including the disaggregation of data by sex and skeletal maturity when data is generated from combined sex and/or multi-aged cohorts without proper confounding. METHOD: A scoping literature review of PubMed, Web of Science, EMBASE, and SCOPUS was performed for studies evaluating the effect of sex and age in experimental studies and clinical trials utilizing preclinical large animal models of OA. RESULTS: A total of 9727 papers were identified in large animal (dog, pig, sheep, goat, horse) models for preclinical OA research, of which 238 ex vivo and/or in vivo studies disclosed model type, animal species, sex, and skeletal age sufficient to analyze their effect on outcomes. Dogs, followed by pigs, sheep, and horses, were the most commonly used models. A paucity of preclinical studies evaluated the effect of sex and age in large animal models of naturally occurring or experimentally induced OA: 26 total studies reported some kind of analysis of the effects of sex or age, with 4 studies discussing the effects of sex only, 11 studies discussing the effects of age only, and 11 studies analyzing both the effects of age and sex. CONCLUSION: Fundamental to translational research, OARSI is uniquely positioned to develop recommendations for conducting preclinical studies using large animal models of OA that consider biological mechanisms linked to sex chromosomes, skeletal age, castration, and gonadal hormones affecting OA pathophysiology and treatment response.

Sub-hourly water temperature data collected across the Nechako Watershed, 2019-2021.

Water temperature is actively being monitored along the regulated Nechako River and some of its unregulated tributaries in northern British Columbia (BC) to determine how climate variability, climate change and flow regulation influence water temperatures. The Nechako Watershed, located mainly in the sub-boreal spruce biogeoclimatic zone, spans 47,200 km2 in area [1]. The regional climate experiences a prominent seasonal cycle in air temperature and precipitation, with subfreezing temperatures and snow accumulating during winter. Waterways therefore experience extended near 0°C water/ice temperatures during the winter season. The accumulation of snow yields snowmelt-generated peaks in discharge during the spring freshet period in unregulated tributaries [2]. Regional studies on climate reveal recent warming trends that are anticipated to persist through the 21st century, with a projected mean air temperature increase of ∼2°C by the 2050's [3]. In response to warming air temperatures, regional water temperatures are also on the rise, with an average warming trend of 0.7°C from 1950 to 2015 [4]. Changing water temperatures are important in understanding ecological and environmental impacts on riverine systems, including aquatic species such as fish (e.g., sockeye salmon (Oncorhynchus nerka), rainbow trout (Oncorhynchus mykiss) and white sturgeon (Acipenser transmontanus), all endemic species to the Nechako Watershed), invertebrates, and micro-organisms. Managing water temperatures during the fish spawning season is crucial as elevated temperatures induce stress and affect reproduction success [5]. Starting with a pilot project in summer of 2019, we expanded in situ monitoring of water temperature to 29 sites; however, for the purposes of this paper, only data from 24 sites are included (some sites have limited data samples or loggers could not be retrieved in the field). Currently, 25 sites are fully operational and collecting data, all deployed to sample and record data at 15-minute intervals starting at the top of the hour. Site data collection occurs at minimum once annually (typically during summer/early fall), along with site and logger maintenance. Field notes are taken to identify any potential issues with data collection, such as loggers dewatering during low flows, duration of logger removal for data collection, and any other environmental concerns that should later be considered during data analysis. The assembled data are useful to build long-term time series of observed water temperatures within the Nechako Watershed and as a baseline for future projects. The data are also used to determine the effectiveness of the Summer Temperature Management Program at the Nechako Reservoir and Skins Lake Spillway [1]. Therefore, these data can be used in the future to better identify the optimal discharge from the reservoir to minimize ecological effects on the watershed.