Effect of Stem Cell Injections on Osteoarthritis-related Structural Outcomes: A Systematic Review.

OBJECTIVE: To systematically review the evidence for the efficacy of mesenchymal stem cell (MSC) injections in improving osteoarthritis (OA)-related structural outcomes. METHODS: Ovid Medline and EMBASE were searched from their inceptions to April 2020 using MeSH terms and key words. Independent reviewers extracted data and assessed methodological quality. Qualitative evidence synthesis was performed due to the heterogeneity of interventions and outcome measures. RESULTS: Thirteen randomized controlled trials (phase I or II) were identified: 10 in OA populations and 3 in populations at risk of OA, with low (n = 9), moderate (n = 3), or high (n = 1) risk of bias. Seven studies used allogeneic MSCs (4 bone marrow, 1 umbilical cord, 1 placenta, 1 adipose tissue), 6 studies used autologous MSCs (3 adipose tissue, 2 bone marrow, 1 peripheral blood). Among the 11 studies examining cartilage outcomes, 10 found a benefit of MSCs on cartilage volume, morphology, quality, regeneration, and repair, assessed by magnetic resonance imaging, arthroscopy, or histology. The evidence for subchondral bone was consistent in all 3 studies in populations at risk of OA, showing beneficial effects. Sixteen unpublished, eligible trials were identified by searching trial registries, including 8 with actual or estimated completion dates before 2016. CONCLUSION: Our systematic review of early-phase clinical trials demonstrated consistent evidence of a beneficial effect of intraarticular MSC injections on articular cartilage and subchondral bone. Due to the heterogeneity of MSCs, modest sample sizes, methodological limitations, and potential for publication bias, further work is needed before this therapy is recommended in the management of OA.

Twelve month mortality rates and independent living in people aged 65 years or older after isolated hip fracture: A prospective registry-based study.

INTRODUCTION: This study investigated which patient and injury characteristics are associated with 12-month mortality rates and living independently after isolated hip fracture. METHODS: Older adults aged ≥65 years were included if they had an isolated hip fracture, were admitted to hospital between July 2009 and June 2016, inclusive, and were registered to the Victorian Orthopaedic Trauma Outcomes Registry. Mortality up to 12 months (365 days) post-injury, and functional outcomes (Glasgow Outcome Scale-Extended; GOS-E) at 12 months post-injury were examined. Multivariable Cox proportional hazards regression was used to estimate adjusted hazard ratios (aHRs), and multivariable logistic regression was used to identify predictors of living independently compared with severe disability or death on the GOS-E. RESULTS: 4,912 patients were included, of whom 28% died, 46% had moderate-severe disability, and 26% were living independently 12 months post-injury. Mortality rates were lower in women (aHR=0.56, 95%CI: 0.50, 0.63), and in people injured in a high fall vs low fall (aHR=0.47, 95%CI: 0.31, 0.72). Mortality rates were higher in people in the older age groups (75-84 years: aHR=1.53, 95%CI: 1.21, 1.93; 95+ years: aHR=3.58, 95%CI: 2.68, 4.77), living in areas with the highest level of socioeconomic disadvantage (aHR=1.25, 95%CI: 1.01, 1.55), with a Charlson Comorbidity Index weighting of one (aHR=1.60, 95%CI: 1.36, 1.88) or more than one (aHR=2.21, 95%CI: 1.94, 2.53), whose injury occurred in a residential institution versus at home (aHR=2.63, 95%CI: 1.97, 3.52), that resulted in intensive care unit admission (aHR=1.68, 95%CI: 1.21, 2.32), and in people who did not have surgery versus people who had internal fixation (aHR=1.65, 95%CI: 1.33, 2.04). Independent living was inversely associated with most of the same characteristics; however, people also had lower odds of living independently if they were from metropolitan residential areas versus rural areas (aOR=0.77, 95%CI: 0.62, 0.96), or had mild to moderate (aOR=0.33, 95%CI: 0.27, 0.39) or marked to severe (aOR=0.13, 95%CI: 0.09, 0.20) preinjury disability vs no preinjury disability. CONCLUSIONS: Characteristics that are associated with social disadvantage, frailty, poor health and reduced independence before injury were associated with increased rates of death and reduced odds of living independently 12 months after isolated hip fracture.