Stem cell therapy for the treatment of early stage avascular necrosis of the femoral head: a systematic review

BACKGROUND: Avascular necrosis (AVN) of the femoral head (FH) is believed to be caused by a multitude of etiologic factors and is associated with significant morbidity in younger populations. Eventually, the disease progresses and results in FH collapse. Thus, a focus on early disease management aimed at joint preservation by preventing or delaying progression is key. The use of stem cells (SC) for the treatment of AVN of the FH has been proposed. We undertook a systematic review of the medical literature examining the use of SC for the treatment of early stage (precollapse) AVN of the FH, in both pre-clinical and clinical studies. METHODS: Data collected included: Pre-clinical studies – model of AVN, variety and dosage of SC, histologic and imaging analyses. Clinical studies – study design, classification and etiology of AVN, SC dosage and treatment protocol, incidence of disease progression, patient reported outcomes, volume of necrotic lesion and hip survivorship. RESULTS: In pre-clinical studies, the use of SC uniformly demonstrated improvements in osteogenesis and angiogenesis, yet source of implanted SC was variable. In clinical studies, groups treated with SC showed significant improvements in patient reported outcomes; however hip survivorship was not affected. Discrepancies regarding dose of SC, AVN etiology and disease severity were present. CONCLUSIONS: Routine use of this treatment method will first require further research into dose and quality optimization as well as confirmed improvements in hip survivorship

Racial Differences in Serum Adipokine and Insulin Levels in a Matched Osteoarthritis Sample: A Pilot Study

Background. In an attempt to correlate biomarkers with disease, serum-based biomarkers often are compared between individuals with osteoarthritis (OA) and control subjects. However, variable results have been reported. Some studies have suggested an association between certain adipokines and insulin and OA. We know that there are racial differences in OA prevalence and incidence, and from general population-based studies, those of Asian race consistently demonstrate a unique adipokine/insulin serum concentration profile as compared to Caucasians. Whether similar racial differences exist within OA samples is unknown and may have implications for selecting appropriate controls in comparative studies. Methods. Serum levels of adipokines, leptin, and adiponectin, along with insulin, were determined by ELISA in patients scheduled for total hip or knee replacement surgery for OA. Fifteen Asian patients were matched 1 : 1 on age (±2 years), gender, body mass index (±1.5 kg/m2), and surgical joint with Caucasian patients. Differences in serum concentrations were tested using paired t-tests. Results. Serum leptin and insulin levels were significantly higher in Asians compared to Caucasians (p<0.05). While serum adiponectin levels were lower among Asians, the difference did not reach statistical significance (p=0.12). Conclusion. Findings from this work suggest that when studying serum biomarker concentrations in OA versus controls, race may be an important factor to consider. Our findings warrant confirmation in larger studies

Factors Influencing Pain Response Following Patient Education and Supervised Exercise in Male and Female Subjects With Hip Osteoarthritis

Objective: To understand factors associated with pain intensity responder status following nonsurgical hip osteoarthritis (OA) intervention, according to sex. Methods: Data were from individuals with hip OA participating in the Danish Good Life With Osteoarthritis in Denmark 8-week education and exercise program. The following factors were recorded at program entry: age; education; mental well-being; comorbidities; body mass index; symptoms in hip, knee, and low back; and program-specific factors including education sessions, former participant lectures, and supervised exercise sessions. Pain intensity was recorded at baseline and at month 3 (post-program) on a 0–100-mm visual analog scale. Response was defined as pain intensity improvement of ≥30% from baseline to post-program. Logistic regression was used and conducted separately in male and female subjects. Results: The sample included 791 men and 2,253 women. Female subjects had a mean baseline pain score of 47.2 of 100 (95% confidence interval [95% CI] 46.4–48.1) and male subjects had a score of 41.7 (95% CI 40.3–43.1). By post-program, the proportion of pain responders was 50.4% among women and 45.8% among men (difference P = 0.025). Among women, program-specific factors (attending former participant lectures and more supervised exercise sessions) were positively associated with pain response, as were better mental well-being and fewer comorbidities, while symptoms in other joints/sites were associated with a decreased likelihood of response. Among men, program-specific factors were not associated with response, while better mental well-being and fewer comorbidities were associated with being a responder. Conclusion: Findings suggest that the influence of some factors on pain response differ for male and female subjects and point to a potential need for targeted approaches for men and women who may require different key messages/approaches from health care providers.</p

The GLA:D® Canada program for knee and hip osteoarthritis:A comprehensive profile of program participants from 2017 to 2022

BACKGROUND: The Good Life with osteoArthritis in Denmark (GLA:D®) program was implemented in Canada in 2017 with the aim of making treatment guideline-recommended care available to the 4 million Canadians with knee and hip osteoarthritis (OA). This report describes the GLA:D® Canada program, registry and data collection procedures, and summarizes the sociodemographic and clinical profile of participants with knee and hip OA to inform the scientific research community of the availability of these data for future investigations and collaborations. METHODS: The GLA:D® program consists of three standardized components: a training course for health care providers, a group-based patient education and exercise therapy program, and a participant data registry. Patients seeking care for knee or hip OA symptoms and enrolling in GLA:D® are given the option to provide data to the GLA:D® Canada registry. Participants agreeing to provide data complete a pre-program survey and are followed up after 3-, and 12-months. Data collected on the pre-program and follow-up surveys include sociodemographic factors, clinical characteristics, health status measures, and objective physical function tests. These variables were selected to capture information across relevant health constructs and for future research investigations. RESULTS: At 2022 year-end, a total of 15,193 (11,228 knee; 3,965 hip) participants were included in the GLA:D® Canada registry with 7,527 (knee; 67.0%) and 2,798 (hip; 70.6%) providing pre-program data. Participants were 66 years of age on average, predominately female, and overweight or obese. Typically, participants had knee or hip problems for multiple years prior to initiating GLA:D®, multiple symptomatic knee and hip joints, and at least one medical comorbidity. Before starting the program, the average pain intensity was 5 out of 10, with approximately 2 out of 3 participants using pain medication and 1 in 3 participants reporting a desire to have joint surgery. Likewise, 9 out 10 participants report having previously been given a diagnosis of OA, with 9 out 10 also reporting having had a radiograph, of which approximately 87% reported the radiograph showed signs of OA. CONCLUSION: We have described the GLA:D® Canada program, registry and data collection procedures, and provided a detailed summary to date of the profiles of participants with knee and hip OA. These individual participant data have the potential to be linked with local health administrative data registries and comparatively assessed with other international GLA:D® registries. Researchers are invited to make use of these rich datasets and participate in collaborative endeavours to tackle questions of Canadian and global importance for a large and growing clinical population of individuals with hip and knee OA.</p

Does the person’s context influence engagement in life activities following primary knee replacement? Results from a Canadian prospective cohort study

Peer reviewe

Total knee arthroplasty versus education and exercise for knee osteoarthritis: a propensity‐matched analysis

Objective: We estimate the treatment effect of total knee arthroplasty (TKA) versus an education and exercise (Edu+Ex) program on pain, function, and quality of life outcomes 3 and 12 months after treatment initiation for knee osteoarthritis (OA). Methods: Patients with knee OA who had undergone TKA were matched on a 1:1 ratio with participants in an Edu+Ex program based on a propensity score fitted to a range of pretreatment covariates. After matching, between-group differences in improvement (the treatment effect) in Knee Injury and Osteoarthritis Outcome Score 12-item version (0, worst to 100, best) pain, function, and quality of life from baseline to 3 and 12 months were estimated using linear mixed models, adjusting for unbalanced covariates, if any, after matching. Results: The matched sample consisted of 522 patients (Edu+Ex, n = 261; TKA, n = 261) who were balanced on all pretreatment characteristics. At 12-month follow-up, TKA resulted in significantly greater improvements in pain (mean difference [MD] 22.8; 95% confidence interval [95% CI] 19.7–25.8), function (MD 21.2; 95% CI 17.7–24.4), and quality of life (MD 18.3; 15.0–21.6). Even so, at least one-third of patients receiving Edu+Ex had a clinically meaningful improvement in outcomes at 12 months compared with 75% of patients with TKA. Conclusion: TKA is associated with greater improvements in pain, function, and quality of life, but these findings also suggest that Edu+Ex may be a viable alternative to TKA in a meaningful proportion of patients, which may reduce overall TKA need. Confirmatory trials are needed.</p

The Contribution of Physical, Mental and Social Dimensions of Health to Predicting Self-rated Health Over the Course of Recovery Following Total Joint Replacement Surgery

Background: Self-rated health (SRH) is among the most frequently assessed health perceptions in epidemiological research. While the predominant focus has been the predictive relevance of SRH, there is increasing interest in understanding the nature of SRH. Recently a conceptual interpretation of SRH was proposed. Purpose: To assess the tenability of the recently proposed distinctions of self-rated health, as a spontaneous assessment of overall health, or as an enduring self-concept, or both, and to determine the significance of mental well-being, physical and social health for SRH. Methods: A cohort of individuals undergoing total joint replacement (TJR) for hip or knee osteoarthritis (OA) was followed over 6 months of recovery. Participants (n=449) completed (pre-surgery, 3 and 6 months post-surgery) measures associated with physical health: pain, physical function, sports/recreation, fatigue; mental well-being: anxiety, depression; and social health: social participation, passive/active recreation, community access. Using structural equation modeling, confirmatory factor analyses (CFA) investigated 3 latent health variables, and the responsiveness of SRH to current and changing health status, as well as its predictive significance for future health status was investigated. Results: CFA analyses confirmed relationships between observed health measures and hypothesized latent health dimensions. SRH was responsive to current and changing mental well-being. The effects of physical and social health were mediated through mental well-being. SRH was a strong predictor of future SRH and future health status. Conclusion: SRH displayed features of both an enduring self-concept and spontaneous assessment of health status; evidence is provided that both operate simultaneously. While aspects of physical health have always been perceived as the major determinants of SRH, these findings indicate that mental and social health explain much of the relationship between physical health and SRH. These results are particularly unexpected since this is a sample of individuals undergoing TJR surgery, for which pain and restricted physical function are primary indicators. Since SRH is a significant predictor of health status, TJR outcomes, health care utilization and mortality, this study suggests that health research and care, treatment and management modalities should consider a broad range of health dimensions, not only physical aspects of health, and SRH.Ph

The Contribution of Physical, Mental and Social Dimensions of Health to Predicting Self-rated Health Over the Course of Recovery Following Total Joint Replacement Surgery

Background: Self-rated health (SRH) is among the most frequently assessed health perceptions in epidemiological research. While the predominant focus has been the predictive relevance of SRH, there is increasing interest in understanding the nature of SRH. Recently a conceptual interpretation of SRH was proposed. Purpose: To assess the tenability of the recently proposed distinctions of self-rated health, as a spontaneous assessment of overall health, or as an enduring self-concept, or both, and to determine the significance of mental well-being, physical and social health for SRH. Methods: A cohort of individuals undergoing total joint replacement (TJR) for hip or knee osteoarthritis (OA) was followed over 6 months of recovery. Participants (n=449) completed (pre-surgery, 3 and 6 months post-surgery) measures associated with physical health: pain, physical function, sports/recreation, fatigue; mental well-being: anxiety, depression; and social health: social participation, passive/active recreation, community access. Using structural equation modeling, confirmatory factor analyses (CFA) investigated 3 latent health variables, and the responsiveness of SRH to current and changing health status, as well as its predictive significance for future health status was investigated. Results: CFA analyses confirmed relationships between observed health measures and hypothesized latent health dimensions. SRH was responsive to current and changing mental well-being. The effects of physical and social health were mediated through mental well-being. SRH was a strong predictor of future SRH and future health status. Conclusion: SRH displayed features of both an enduring self-concept and spontaneous assessment of health status; evidence is provided that both operate simultaneously. While aspects of physical health have always been perceived as the major determinants of SRH, these findings indicate that mental and social health explain much of the relationship between physical health and SRH. These results are particularly unexpected since this is a sample of individuals undergoing TJR surgery, for which pain and restricted physical function are primary indicators. Since SRH is a significant predictor of health status, TJR outcomes, health care utilization and mortality, this study suggests that health research and care, treatment and management modalities should consider a broad range of health dimensions, not only physical aspects of health, and SRH.Ph