Hypobaric hypoxia aggravates osteoarthritis via the alteration of the oxygen environment and bone remodeling in the subchondral zone.

A high prevalence of osteoarthritis (OA) has been observed among individuals living at high altitudes, and hypobaric hypoxia (HH) can cause bone mass and strength deterioration. However, the effect of HH on OA remains unclear. In this study, we aimed to explore the impact of HH on OA and its potential mechanisms. A rat knee OA model was established by surgery, and the rats were bred in an HH chamber simulating a high-altitude environment. Micro-computed tomography (Micro-CT), histological analysis, and RNA sequencing were performed to evaluate the effects of HH on OA in vivo. A hypoxic co-culture model of osteoclasts and osteoblasts was also established to determine their effects on chondrogenesis in vitro. Cartilage degeneration significantly worsened in the HH-OA group compared to that in the normoxia-OA (N-OA) group, 4 weeks after surgery. Micro-CT analysis revealed more deteriorated bone mass in the HH-OA group than in the N-OA group. Decreased hypoxia levels in the cartilage and enhanced hypoxia levels in the subchondral bone were observed in the HH-OA group. Furthermore, chondrocytes cultured in a conditioned medium from the hypoxic co-culture model showed decreased anabolism and extracellular matrix compared to those in the normoxic model. RNA sequencing analysis of the subchondral bone indicated that the glycolytic signaling pathway was highly activated in the HH-OA group. HH-related OA progression was associated with alterations in the oxygen environment and bone remodeling in the subchondral zone, which provided new insights into the pathogenesis of OA.

Do Patients with Borderline Anemia Need Treatment before Total Hip Arthroplasty? A Propensity Score-Matched Cohort Study.

OBJECTIVE: Preoperative anemia has been identified as a modifiable risk factor for multiple adverse outcomes. In real clinical practice, considering treatment of anemia would increase costs and delay surgery. Patients undergoing total hip arthroplasty (THA) with mild anemia are usually neglected and still underdiagnosed or inadequately treated. This study investigated the effects of preoperative borderline anemia and anemia intervention before THA on perioperative outcomes. METHODS: We screened 706 patients from those receiving THA at our hospital from January 2020 to January 2022, with 112 in the borderline anemia group and 594 in the non-anemia group. The cohort for this retrospective study was created by using propensity score matching (PSM) and subgroup analysis. The primary outcome was perioperative blood loss, while secondary outcomes were the rate of allogeneic blood transfusion and human serum albumin transfusion, perioperative laboratory indicators, postoperative length of stay, and complications. The independent sample t-test and the Mann-Whitney U-test were used to analyze continuous data, and the Pearson χ2 -test or the Fisher exact test was used to analyze categorical variables. RESULTS: After PSM, there was no significant difference in perioperative blood loss between patients in the borderline anemia group and the non-anemia group. The primary outcomes of hidden (p = 0.004) and total (p = 0.005) blood loss were significantly lower in the intervention group than in the control group. No statistical differences were found in allogeneic blood transfusion, human serum albumin transfusion, postoperative length of stay, or complications (p > 0.05). CONCLUSIONS: Anemia treatments for patients with borderline anemia before THA significantly reduced hidden blood loss and total blood loss in the perioperative period and decreased the drop of hemoglobin and hematocrit without increasing postoperative complications.

Influencing factors of hidden blood loss after primary total hip arthroplasty through the posterior approach: a retrospective study.

BACKGROUND: Total hip arthroplasty (THA) is an excellent treatment for the end-stage hip disease, and perioperative blood management strategies have been effectively applied to this procedure. However, many patients still experience anemia after the operation, which is usually overlooked by orthopedic surgeons due to the hidden blood loss (HBL) in the perioperative period. Therefore, the objective of this study was to evaluate HBL in patients undergoing primary THA using the posterior approach and to explore its influencing factors. METHODS: A retrospective analysis of 707 patients who underwent primary THA through the posterior approach was conducted in our hospital from January 2020 to January 2022. By applying Gross's and Nadler's formula, the HBL was calculated. Six quantitative variables (age, body mass index, surgical duration, albumin loss, preoperative hemoglobin, and hemoglobin loss) as well as four qualitative variables (gender, American Society of Anesthesiologists class, major preoperative diagnosis, and hypertension) of patients were analyzed using multivariate linear regression. RESULTS: The HBL was recorded at 700.39 ± 368.59 mL. As a result of multivariate linear regression analysis, it was determined that body mass index, surgical duration, and hemoglobin loss were all significant risk factors for HBL, whereas preoperative hemoglobin was considered a protective factor. It has been demonstrated that HBL is not significantly correlated with age, albumin loss, gender, ASA class, or major preoperative diagnosis, but it also did not differ from HBL by hypertension. CONCLUSIONS: Hidden blood Loss (HBL) in patients after primary total hip arthroplasty (THA) using the posterior approach is large and significant. When optimizing the perioperative management of THA, orthopedic surgeons should keep in mind HBL and its influencing factors, especially for patients with high body mass indexes, long surgical durations, and low preoperative hemoglobin levels. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry (ChiCTR2100053888) in 02/12/2021, http://www.chictr.org.cn .

Engineered Exosome-Functionalized Extracellular Matrix-Mimicking Hydrogel for Promoting Bone Repair in Glucocorticoid-Induced Osteonecrosis of the Femoral Head.

Glucocorticoid-induced osteonecrosis of the femoral head (GC-ONFH) is a serious bone disease that often affects young individuals. Bone grafting combined with core decompression is mainly used in the clinic to treat GC-ONFH. However, the outcome is usually not satisfactory, as expected. Here, we report an engineered exosome-functionalized extracellular matrix-mimicking hydrogel for promoting bone repair in GC-ONFH. Compared with Con-Exo, exosomes secreted by bone marrow stem cells (BMSCs) in conventional culture medium, the engineered Li-Exo, exosomes derived from bone marrow stem cells (BMSCs) stimulated by lithium ions, promoted macrophage M2 polarization while inhibiting macrophage M1 polarization. Furthermore, inspired by the fact that hydrogels can serve as desirable carriers of exosomes to facilitate their release in a sustained manner for improved therapeutic efficiency and in vivo application, an extracellular matrix (ECM)-mimicking hydrogel (Lightgel) composed of methacryloylated type I collagen was employed to incorporate Li-Exo/Con-Exo to construct the Lightgel-Li-Exo hydrogel/Lightgel-Con-Exo hydrogel. In vitro studies showed that the Lightgel-Li-Exo hydrogel had the most significant pro-osteogenic and pro-angiogenic activity. Finally, we evaluated the therapeutic effects of the hydrogel in rat models of GC-ONFH. As a result, the Lightgel-Li-Exo hydrogel had the most significant effect on enhancing macrophage M2 polarization, osteogenesis, and angiogenesis to promote bone repair in GC-ONFH. Taken together, this novel engineered exosome-functionalized ECM-mimicking hydrogel could be a promising strategy for osteonecrosis treatment.

Comparison of Perioperative Outcomes and Early Complications Between a Direct Anterior Approach or Posterolateral Approach in Simultaneous Bilateral Total Hip Arthroplasty: A Retrospective Study.

Background: Controversies remain on the best surgical approaches for unilateral total hip arthroplasty (THA). There are little data on simultaneous bilateral THA via direct anterior approach (SimBDAA-THA) or posterolateral approach (SimBPA-THA). Purpose: We sought to assess differences in perioperative outcomes and early medical and surgical complications between SimBDAA-THA and SimBPA-THA. Methods: This retrospective study involved patients who underwent either SimBDAA-THA in a supine position (n = 73) or SimBPA-THA in a lateral position (n = 162) at our institution from January 2015 to November 2021. The 2 groups were compared in terms of clinical and demographic characteristics, surgical parameters, and complications during 6-months of follow-up. Results: There were no differences in clinical and demographic characteristics between the 2 groups prior to surgery. Simultaneous bilateral THA via direct anterior approach significantly shortened the length of both the operation (117.50 ±19.42 vs 143.97 ± 32.20 min) and the hospitalization (140.64 ± 43.22 vs 156.24 ± 56.64 h) but increased perioperative loss of hemoglobin (3.28 ± 1.01 vs 3.21 ± 2.26 g/dL). There were no significant differences between the two groups in transfusion rate; levels of interleukin-6, C-reactive protein or creatine kinase; or complications. Conclusion: This retrospective study of patients at a single institution found minimal differences in perioperative outcomes or early medical and surgical complications between SimBDAA-THA and SimBPA-THA except operative time and length of hospitalization. Larger studies with longer follow-up should be conducted to identify whether a direct anterior approach is superior to a posterolateral one.

Effects of magnesium sulfate on periarticular infiltration analgesia in total knee arthroplasty: a prospective, double-blind, randomized controlled trial.

BACKGROUND: To investigate whether adding magnesium sulfate to a periarticular infiltration analgesia (PIA) cocktail could improve pain control and functional outcomes in patients undergoing total knee arthroplasty (TKA). METHODS: Ninety patients were randomly assigned to the magnesium sulfate and control groups, with 45 patients in each group. In the magnesium sulfate group, patients were given a periarticular infusion of a cocktail of analgesics consisting of epinephrine, ropivacaine, magnesium sulfate, and dexamethasone. The control group received no magnesium sulfate. The primary outcomes consisted of visual analogue scale (VAS) pain scores, postoperative morphine hydrochloride consumption for rescue analgesia, and time to first rescue analgesia. Secondary outcomes were postoperative inflammatory biomarkers (IL-6 and CRP), postoperative length of stay, and knee functional recovery (assessed by knee range of motion, quadriceps strength, daily mobilization distance, and time to first straight-leg raising). Tertiary outcomes included the postoperative swelling ratio and complication rates. RESULTS: Within 24 h of surgery, patients in the magnesium sulfate group had markedly lower VAS pain scores during motion and at rest. After the addition of magnesium sulfate, the analgesic effect was dramatically prolonged, leading to a reduction in morphine dosage within 24 h and the total morphine dosage postoperatively. Postoperative inflammatory biomarker levels were significantly reduced in the magnesium sulfate group compared with the control. There were no considerable differences between the groups in terms of the postoperative length of stay and knee functional recovery. Both groups had similar postoperative swelling ratios and incidences of complications. CONCLUSIONS: The addition of magnesium sulfate to the analgesic cocktail for PIA can prolong postoperative analgesia, decrease the consumption of opioids, and effectively alleviate early postoperative pain after TKA. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200056549. Registered on 7 February 2022, https://www.chictr.org.cn/showproj.aspx?proj=151489 .

Activated intestinal microbiome-associated tryptophan metabolism upregulates aryl hydrocarbon receptor to promote osteoarthritis in a rat model.

OBJECTIVE: To evaluate the role of aryl hydrocarbon receptor in the pathogenesis of osteoarthritis (OA) and its association with intestinal microbiome-related tryptophan metabolism. METHODS: Cartilage was isolated from OA patients undergoing total knee arthroplasty and analyzed for expression of aryl hydrocarbon receptor (AhR) and cytochrome P450 of family 1, subfamily A, and polypeptide 1 (CyP1A1). To gain mechanistic insights, OA model was induced in Sprague Dawley rats after antibiotic pretreatment combined with a tryptophan-rich diet (or not). The severity of OA was assessed eight weeks after surgery according to the Osteoarthritis Research Society International grading system. Expression of AhR, CyP1A1 as well as markers of bone and cartilage metabolism, inflammation, and intestinal microbiome-related tryptophan metabolism was assessed. RESULTS: Severity of OA in cartilage from patients positively correlated with expression of AhR and CyP1A1 in chondrocytes. In the rat model of OA, antibiotic pretreatment led to lower expression of AhR and CyP1A1 and lower serum levels of lipopolysaccharide (LPS). Conversely, antibiotics upregulated Col2A1 and SOX9 in cartilage, which mitigated the cartilage damage and synovitis, reduced the relative abundance of Lactobacillus. Additional tryptophan supplementation activated intestinal microbiome-related tryptophan metabolism, antagonizing the effects of antibiotics, exacerbating OA synovitis. CONCLUSION: Our study established an underlying intestinal microbiome associated tryptophan metabolism-OA connection which sets a new target for exploring OA pathogenesis. The alteration of tryptophan metabolism might prompt the activation and synthesis of AhR, accelerating the development of OA.

Different Doses of Intravenous Tranexamic Acid in Revision Total Knee Arthroplasty: A Retrospective Study.

PURPOSE: This article assessed the efficacy and safety of different doses of intravenous tranexamic acid (TXA) in revision total knee arthroplasty (TKA). METHODS: We retrospectively identified 122 patients in our institution who underwent revision TKA with a history of perioperative intravenous TXA utilization. According to the sum of intravenous TXA documented, all patients were divided into three groups: 1 g intravenous TXA, 2 g intravenous TXA, and equal or greater than 3 g intravenous TXA. The primary outcomes included total blood loss (TBL), hidden blood loss (HBL), transfusion rate, and the incidence of symptomatic venous thromboembolism among the three groups. A correlation analysis was conducted to analyze the correlation between the dose of TXA and the blood loss. RESULTS: In total, there was no significance difference in TBL and revised HBL (rHBL) between the first two groups (1 g/dL for intravenous TXA, 2 g/dL for intravenous TXA; p = 0.486; p = 0.525). Equal or greater than 3 g intravenous TXA (≥3 g/dL for intravenous TXA) reached a significant reduction in TBL, rHBL, and length of stay compared with the first two groups (p = 0.01; p = 0.01; p = 0.01). The rate of transfusion between the three groups did not differ significantly (p = 0.21). Due to the limitations in sample size, only one symptomatic venous thromboembolism was reported in the 1 g intravenous TXA group. CONCLUSION: Applying the dose of intravenous TXA equal or greater than 3 g in revision TKA might further reduce the blood loss and shorten the length of stay.

Does living at high altitude increase the risk of bleeding events after total knee arthroplasty? A retrospective cohort study.

OBJECTIVE: Post-operative bleeding after total knee arthroplasty (TKA) is a frequent cause of post-operative complications. This study compared blood loss and indicators of coagulation and fibrinolysis between TKA patients living at low or high altitudes. METHODS: We retrospectively analyzed 120 patients at our institution who underwent primary TKA from May 2019 to March 2020, and we divided them into those living in areas about 500 m or > 3000 m above sea level. We compared the primary outcome of total blood loss between them. We also compared them in terms of several secondary outcomes: coagulation and fibrinolysis parameters, platelet count, reduction in hemoglobin, hidden blood loss, intra-operative blood loss, transfusion rate, and incidence of thromboembolic events and other complications. RESULTS: Total blood loss was significantly higher in the high-altitude group than in the low-altitude group (mean, 748.2 mL [95% CI, 658.5-837.9] vs 556.6 mL [95% CI, 496.0-617.1]; p = 0.001). The high-altitude group also showed significantly longer activated partial thromboplastin time, prothrombin time, and thrombin time before surgery and on post-operative day one, as well as increased levels of fibrinogen/fibrin degradation product on post-operative days one and three. Ecchymosis was significantly more frequent in the high-altitude group (41.7 vs 21.7%; relative risk (RR) = 1.923 [95% CI, 1.091-3.389]; p = 0.019). The two groups showed similar transfusion rates, and none of the patients experienced venous thromboembolism, pulmonary embolism, or infection. CONCLUSION: High altitude may alter coagulation and fibrinolysis parameters in a way that increases risk of blood loss after TKA. Such patients may benefit from special management to avoid bleeding events.

The effects of body mass index on insulin resistance in patients undergoing total hip arthroplasty: a pilot study.

PURPOSE: We aimed to examine the effects of body mass index (BMI) on insulin resistance (IR), glycaemic control and adverse events in patients undergoing total hip arthroplasty (THA). METHODS: A total of 118 patients undergoing THA were enrolled in this prospective cohort study and divided into two groups based on their BMI: Group A (n = 50, 18.5 ≤ BMI < 24 kg/m2) and Group B (n = 68, BMI ≥ 24 kg/m2). IR was calculated using Homeostasis Model Assessment 2 (HOMA2). Insulin resistance indicators, fasting plasma glucose (FPG), inflammatory markers, blood loss, length of stay and complications were compared between the two groups. RESULTS: Multivariate analysis using generalized estimating equations revealed that BMI and surgery stress were risk factors for IR (P < 0.001). These two factors exhibited significant interactions for HOMA2-IR on post-operative day one (Exp (B) = 1.880, P = 0.003), accompanied by a higher level of FPG (Group B versus Group A, P = 0.004). Furthermore, subgroup analysis based on the IR value demonstrated that patients in Group B with a HOMA2-IR greater than 2.25 after surgery were at increased risk of wound complications (P = 0.045). Similarly, our results showed that the rate of post-operative hyperglycaemia was notably higher in Group B than in Group A (P = 0.013). CONCLUSION: Patients with high BMI may experience significantly elevated IR and increased risk of hyperglycaemia and wound complications after THA. Therefore, routine glycaemia monitoring should be suggested for those patients during peri-operative period to optimize surgical stress management.

Meta-analysis of retrospective studies suggests that the pre-operative opioid use is associated with an increased risk of adverse outcomes in total hip and or knee arthroplasty.

BACKGROUND: Opioid use is prevalent in the general population. This systematic review and meta-analysis sought to evaluate whether it affects patient-reported outcomes (PROs) following total hip or knee arthroplasty. METHODS: The following databases were systematically searched on February 5, 2020: Medline, Embase (Ovid), Cochrane Library, and Web of Science. Studies were included if they compared patients who received opioids or not before total hip or knee arthroplasty. Outcomes of interest were rates of post-operative revision, peri-prosthetic infection, and readmission. RESULTS: Ten retrospective studies were included for review. Pre-operative opioid use was identified as a risk factor for post-operative revision [odds ratio (OR) 1.58, 95% confidence interval (CI) 1.15-1.73, p<0.01], peri-prosthetic infection (OR 1.36, 95% CI 1.08-1.71, p=0.01), and readmission (OR 1.41, 95% CI 1.20-1.75, p<0.01). CONCLUSION: The available evidence indicates that pre-operative opioid use increases the risk of adverse outcomes following total hip or knee arthroplasty. Orthopedic physicians should consider these risks when treating their patients.

Adding corticosteroids to periarticular infiltration analgesia improves the short-term analgesic effects after total knee arthroplasty: a prospective, double-blind, randomized controlled trial.

PURPOSE: Periarticular infiltration analgesia (PIA) is widely used to control postoperative pain in patients who underwent total knee arthroplasty (TKA). This study aimed to evaluate the efficacy of adding corticosteroids to the PIA cocktail for pain management in patients who underwent TKA. METHODS: The patients were randomized to the corticosteroid or control group (double-blind). The patients in the corticosteroid group received a periarticular infiltration of an analgesic cocktail of ropivacaine, epinephrine, and dexamethasone. Dexamethasone was omitted from the cocktail in the control group. The primary outcomes were postoperative pain [assessed using a visual analog scale (VAS)], time until the administration of first rescue analgesia, morphine consumption, and postoperative inflammatory biomarkers [C-reactive protein (CRP) and interleukin-6 (IL-6)]. The secondary outcomes were functional recovery, assessed by the range of knee motion, quadriceps strength, and daily ambulation distance. The tertiary outcomes included postoperative adverse effects. RESULTS: The patients in the corticosteroid group had significantly lower resting VAS scores at 6 and 12 h after surgery, lower VAS scores during motion up to 24 h after surgery, and lower levels of inflammatory biomarkers. All the differences in the VAS scores between the two groups did not reach the point to be considered clinically significant. The additional use of corticosteroid significantly prolonged analgesic effects and led to lower rescue morphine consumption. The patients in the corticosteroid group had significantly better functional recovery on the first day after surgery. The two groups had a similar occurrence of adverse effects. CONCLUSIONS: Adding corticosteroids to an analgesic cocktail for PIA could lightly improve early pain relief and accelerate recovery in the first 24 h after TKA. LEVEL OF EVIDENCE: Randomized controlled trial, Level I.

Comparison of Postoperative Outcomes Between Traditional Longitudinal Incision and Bikini Incision in Total Hip Arthroplasty via Direct Anterior Approach: A Randomized Controlled Trial.

BACKGROUND: The purpose of this study is to compare a traditional longitudinal incision to an oblique "bikini" incision during total hip arthroplasty (THA) via direct anterior approach (DAA), in terms of the aesthetic appearance of the scar, postoperative functional recovery, and complications. METHODS: This study is a single-surgeon experience in the Chinese population. Patients who came to our institute needing a THA via DAA were enrolled in our randomized controlled trial and randomly allocated to undergo traditional longitudinal incision (control) or bikini incision. Primary outcomes were measured using the scar cosmesis assessment and rating scale, the visual analog scale for pain, Oxford hip score, and University of California Los Angeles activity-level rating. Secondary outcomes were postoperative serum markers of muscle damage, inflammation, hemoglobin drop, and implant stability. The occurrence of postoperative complications, such as nerve and wound healing, was also recorded. RESULTS: There were no differences in demographic or clinical characteristics before surgery. A greater proportion of patients in the bikini group were satisfied with the appearance of their scar, giving significantly better scar cosmesis assessment and rating scores. There was no difference in postoperative functional recovery, levels of serum markers, or positioning of the implant components. Incision type had no effect on duration of hospitalization. The incidence of complications did not differ significantly between groups. CONCLUSION: The bikini incision can improve patients' subjective satisfaction with scar aesthetics after THA via DAA and does not detract from a quick functional recovery. Studies with larger sample sizes should be conducted to further investigate associated complications. THE CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR1900022870.