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.

Prevalence and risk factors of osteoporotic fracture among the elderly population in China: a multicenter cross-sectional study.

PURPOSE: Prevalence of osteoporotic fracture (OPF) is increasing with ageing, resulting in a significant financial burden for healthcare. However, research on the nationwide epidemiological data of OPF in Chinese elderly is still scarce. The aim of this study was to investigate the prevalence and risk factors of OPF in Chinese population aged 60 years or order. METHODS: A cross-sectional survey was conducted in an elderly Chinese population in five centres. Questionnaire investigation and imaging examination were taken in all participants to identify OPF prevalence and risk factors. Diagnosis of OPF was determined based on imaging of vertebral fractures or history of fall-related fractures. We then used multivariate logistic regression model to analyze the associations between the potential risk factors and OPF. RESULTS: The overall prevalence of OPF in population aged 60 years or older was 24.7% (1,071/4,331), showing an increasing trend with age (P < 0.001). The prevalence of OPF was geographically distinct (P < 0.001), but similar between men and women (P > 0.05). Up to 96.8% of OPFs consisted of vertebral fractures, especially involving T11, T12, and L1 segments. Advanced age (≥ 80), vision loss, severe hearing loss, multiple exercise forms, chronic kidney disease, osteoarthritis, and trauma-related vertebral fractures were significantly associated with risk factors, while education level and vitamin D supplementation were associated with protective factors of OPF. CONCLUSION: High prevalence of OPF is a serious threat to bone health among elderly people in China. There is an urgent need for effective strategies to diagnose, prevent, and treat OPF in elderly adults.

Efficacy of Oral Nefopam on Multimodal Analgesia in Total Knee Arthroplasty: A Prospective, Double-Blind, Placebo-Controlled, Randomized Trial.

BACKGROUND: Multimodal analgesia is central to pain management after total knee arthroplasty (TKA). This study aimed to evaluate the efficacy of adding oral nefopam to multimodal analgesia for post-TKA pain management. METHODS: In this prospective, double-blind, placebo-controlled, randomized trial, 100 patients who underwent TKA at our hospital were randomized to either the nefopam or the control group. After surgery, patients in the nefopam group received 200 mg of celecoxib, 150 mg of pregabalin, and 40 mg of nefopam twice daily to control postoperative pain. Patients in the control group received 200 mg of celecoxib, 150 mg of pregabalin, and a placebo. Oxycodone hydrochloride (10 mg) was used as the rescue analgesic. If the pain remained poorly controlled, 10 mg of morphine hydrochloride was injected subcutaneously as a secondary rescue analgesic. The primary outcome was the postoperative consumption of oxycodone and morphine as rescue analgesics. Secondary outcomes were postoperative pain assessed using the visual analogue scale (VAS), functional recovery assessed by the range of knee motion and ambulation distance, time until hospital discharge, indicators of liver function, and complication rates. RESULTS: Patients in the nefopam group had significantly lower postoperative oxycodone and morphine consumption within 24 hours after surgery and during hospitalization, lower VAS pain scores at rest and during motion within 24 h after surgery, better functional recovery on postoperative days 1 and 2, and a shorter hospital stay. However, the absolute reduction in 0 to 24 h opioid consumption, VAS pain scores, and knee range of motion did not exceed the reported minimal clinically important difference. Both groups had similar indicators of liver function and complication rates. CONCLUSIONS: Adding oral nefopam to multimodal analgesia resulted in statistically significant improvements in opioid consumption, VAS pain scores, and functional recovery. However, the amount of improvement may not be clinically important.

Immune regulation enhances osteogenesis and angiogenesis using an injectable thiolated hyaluronic acid hydrogel with lithium-doped nano-hydroxyapatite (Li-nHA) delivery for osteonecrosis.

Osteonecrosis is a devastating orthopedic disease in clinic that generally occurs in the femoral head associating with corticosteroid use up to 49 % in patients. In particular, glucocorticoids induced osteonecrosis of the femoral head is closely related to the local immune response that characterized by abnormal macrophage activation and inflammatory cell infiltration at the necrotic site, forming a pro-inflammatory microenvironment dominated by M1 macrophages, and thus leads to failure of bone repair and regeneration. Here, we report a bone regeneration strategy that constructs an immune regulatory biomaterial platform using an injectable thiolated hyaluronic acid hydrogel with lithium-doped nano-hydroxyapatite (Li-nHA@Gel) delivery for osteonecrosis treatment. Li-nHA@Gel achieved a sustain and longterm release of Li ions, which might enhance M2 macrophage polarization through the activation of the JAK1/STAT6/STAT3 signaling pathway, and the following induced pro-repair immune microenvironment mediated the enhancement of the osteogenic and angiogenic differentiation. Moreover, both in vitro and in vivo studies indicated that Li-nHA@Gel enhanced M2 macrophage polarization, osteogenesis, and angiogenesis, and thus promoted the bone and blood vessel formation. Taken together, this novel bone immunomodulatory biomaterial platform that promotes bone regeneration by enhancing M2 macrophage polarization, osteogenesis, and angiogenesis could be a promising strategy for osteonecrosis treatment.

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.

Efficacy of Diosmin in Reducing Lower-Extremity Swelling and Pain After Total Knee Arthroplasty: A Randomized, Controlled Multicenter Trial.

BACKGROUND: Many patients experience lower-extremity swelling following total knee arthroplasty (TKA), which impedes recovery. Diosmin is a semisynthetic flavonoid that is often utilized to treat swelling and pain caused by chronic venous insufficiency. We aimed to evaluate the efficacy and safety of diosmin in reducing lower-extremity swelling and pain as well as in improving functional outcomes following TKA. METHODS: This study was designed as a randomized, controlled multicenter trial and conducted in 13 university-affiliated tertiary hospitals. A total of 330 patients undergoing TKA were randomized to either receive or not receive diosmin postoperatively. The diosmin group received 0.9 g of diosmin twice per day for 14 consecutive days starting on the day after surgery, whereas the control group received neither diosmin nor a placebo postoperatively. The primary outcome was lower-extremity swelling 1, 2, 3, and 14 days postoperatively. The secondary outcomes were postoperative pain assessed with use of a visual analogue scale, Hospital for Special Surgery score, range of knee motion, levels of the inflammatory biomarkers C-reactive protein and interleukin-6, and complications. RESULTS: At all postoperative time points, diosmin was associated with significantly less swelling of the calf, thigh, and upper pole of the patella as well as with significantly lower pain scores during motion. However, no significant differences in postoperative pain scores at rest, Hospital for Special Surgery scores, range of motion, levels of inflammatory biomarkers, or complication rates were found between the diosmin and control groups. CONCLUSIONS: The use of diosmin after TKA reduced lower-extremity swelling and pain during motion and was not associated with an increased incidence of short-term complications involving the outcomes studied. However, further studies are needed to continue exploring the efficacy and safety of diosmin use in TKA. LEVEL OF EVIDENCE: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Lithium prevents glucocorticoid­induced chondrocyte autophagy: An in vitro study.

Glucocorticoids can induce chondrocyte autophagy. Lithium is a classical regulator of autophagy. The present study aimed to determine whether lithium can prevent glucocorticoid­induced chondrocyte autophagy by regulating the PI3K/AKT/mTOR signaling pathway. For this purpose, rat and human chondrocytes were treated with dexamethasone (200 µM) or dexamethasone (200 µM) combined with lithium chloride at various concentrations (0.01, 0.1, 1 and 10 mM). CYTO­ID® autophagy fluorescence staining and transmission electron microscopy were used to detect the levels of autophagy in the chondrocytes. Reverse transcription­quantitative PCR and western blot analysis were used to measure the expression levels of the autophagy marker, LC3B and the autophagy regulatory signaling pathway (PI3K/AKT/mTOR signaling pathways) markers, AKT and mTOR. The viability of chondrocytes was measured using the Cell Counting Kit­8 assay. It was found that compared with that in the control group, dexamethasone induced the autophagy of chondrocytes, decreased the expression levels of AKT and mTOR, and reduced cell viability. Compared with the treatment with dexamethasone alone, lithium chloride (10 mM) + dexamethasone reduced the autophagy levels, increased the expression level of AKT and mTOR, and increased cell viability. In conclusion, the present study demonstrated that lithium can prevent glucocorticoid­induced autophagy by activating the PI3K/AKT/mTOR signaling pathway and preventing the glucocorticoid­induced decrease in chondrocyte viability.

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 .

Efficacy of Adding Acetaminophen to Preemptive Multimodal Analgesia in Total Knee Arthroplasty: A Double-blinded Randomized Study.

OBJECTIVE: Preemptive multimodal analgesia is a frequently utilized method for controlling pain after total knee arthroplasty (TKA). So far, no studies have specifically examined the efficacy of adding acetaminophen to preemptive multimodal analgesia in TKA. The current work aimed to assess the efficacy of adding acetaminophen to preemptive multimodal analgesia for clinical pain management after TKA. METHODS: This was a double-blinded randomized study including 80 cases randomized to the acetaminophen and control groups, respectively. The acetaminophen group was administered celecoxib at 400 mg, pregabalin at 150 mg, and acetaminophen at 300 mg 2 h before TKA. Control patients were administered celecoxib, pregabalin, and placebo. The primary outcome was postsurgical use of morphine hydrochloride for rescue analgesia. Secondary outcomes included the time to the initial rescue analgesia, postsurgical pain as determined by a visual analogue scale (VAS), functional recovery as reflected by the range of knee motion and ambulation distance, hospitalization duration, and complication rates. Continuous data with normal and skewed distributions were compared by the Student's t test and the Mann-Whitney U test, respectively. Categorical variables were compared by the Pearson's chi-squared test. RESULTS: The control and acetaminophen groups were comparable in postoperative 0-24 h morphine consumption (11.3 ± 6.5 mg vs 12.3 ± 7.7 mg, P = 0.445) and total morphine consumption (17.3 ± 10.1 mg vs 19.3 ± 9.4 mg, P = 0.242). Additionally, time to the initial rescue analgesia, postoperative VAS score at any time point, postoperative functional recovery of the knee, and hospitalization duration were similar in both groups. Both groups also had similar occurrence rates of postoperative complications. CONCLUSIONS: In this study, adding acetaminophen to preoperative preemptive multimodal analgesia did not decrease postoperative morphine use or ameliorate pain relief. The efficacy of adding acetaminophen to preemptive multimodal analgesia in TKA need to be further explored in future studies.

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 between Ultrasound-Guided Pericapsular Nerve Group Block and Local Infiltration Analgesia for Postoperative Analgesia after Total Hip Arthroplasty: A Prospective Randomized Controlled Trial.

OBJECTIVES: Pericapsular nerve group (PENG) blocking is a novel nerve block modality for analgesia after total hip arthroplasty (THA); however, its analgesic efficacy is unclear. We aimed to compare the analgesic effect of ultrasound-guided PENG blocking and periarticular local infiltration analgesia after THA. METHODS: This study involved patients undergoing unilateral primary THA at our institution between October 2022 and December 2022. Based on a prospective double-blind, randomized approach, patients were randomly divided into two groups: the PENG and infiltration groups. The former received ultrasound-guided pericapsular nerve block before surgery while the latter received local anesthesia and local infiltration analgesia during surgery. The primary outcome was the amount of morphine used for rescue analgesia within 48 h after surgery and the visual analog scale (VAS) pain score at 3, 6, 12, 24, and 48 h after surgery. Secondary outcomes consisted of postoperative hip function on the first and second postoperative days, including hip extension angle and flexion, as well as distance traveled by the patient. Tertiary outcomes included length of hospital stay and postoperative adverse reactions. The data were analyzed using SPSS 26.0. Using the appropriate statistical methodology, continuous and categorical data were analyzed, and p < 0.05 was considered statistically significant. RESULTS: There was no clear difference in morphine requirements during the first 24 hours postoperatively (5.8 ± 5.9 vs. 6.0 ± 6.3, p = 0.910), in the total postoperative morphine consumption (7.5 ± 6.3 vs. 7.8 ± 6.6, p = 0.889), and in the postoperative resting VAS pain scores (p > 0.05). However, the exercise VAS score in the PENG group was significantly higher than that in the infiltration group within 12 hours after surgery (6.1 + 1.2 vs. 5.4 + 1.0, p = 0.008). There was no significant difference in hip function, length of hospital stay, or incidence of complications between the two groups. CONCLUSION: The analgesic effect and functional recovery of ultrasound-guided pericapsular nerve block for THA was not superior to that of periarticular local infiltration analgesia.

Comparative study of carbazochrome sodium sulfonate and tranexamic acid in reducing blood loss and inflammatory response following direct anterior total hip arthroplasty: a prospective randomized controlled trial.

PURPOSE: Carbazochrome sodium sulfonate (CSS) is a haemostatic agent. However, its hemostatic and anti-inflammatory effects in patients undergoing total hip arthroplasty (THA) via a direct anterior approach (DAA) are unknown. We investigated the efficacy and safety of CSS combined with tranexamic acid (TXA) in THA using DAA. METHODS: This study enrolled 100 patients who underwent primary, unilateral THA through a direct anterior approach. Patients were randomly divided into two groups: Group A used a combination of TXA and CSS, while Group B used TXA only. The primary outcome was total perioperative blood loss. The secondary outcomes were hidden blood loss, postoperative blood transfusion rate, inflammatory reactant levels, hip function, pain score, venous thromboembolism (VTE), and incidence of associated adverse reactions. RESULTS: The total blood loss (TBL) in group A was significantly lower than in group B. The levels of inflammatory reactants and the rate of blood transfusion were also significantly lower. However, the two groups had no significant differences in intraoperative blood loss, postoperative pain score, or joint function. There were no significant differences in VTE or postoperative complications between the groups. CONCLUSION: As a haemostatic agent, CSS combined with TXA can reduce postoperative blood loss in patients undergoing THA via DAA and seems to have an anti-inflammatory effect. Moreover, it did not increase the incidence of VTE or its related complications.

Retraction: Enhanced bone defect repairing effects in glucocorticoid-induced osteonecrosis of the femoral head using a porous nano-lithium-hydroxyapatite/gelatin microsphere/erythropoietin composite scaffold.

Retraction of 'Enhanced bone defect repairing effects in glucocorticoid-induced osteonecrosis of the femoral head using a porous nano-lithium-hydroxyapatite/gelatin microsphere/erythropoietin composite scaffold' by Donghai Li et al., Biomater. Sci., 2018, 6, 519-537, https://doi.org/10.1039/C7BM00975E.

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.

Outcomes of total hip arthroplasty with a standard prosthesis for the affected hip in patients with poliomyelitis sequelae: a mid-term retrospective follow-up study.

INTRODUCTION: Total hip arthroplasty for poliomyelitis sequelae could be a technical challenge due to the higher risk for prosthetic dislocation and degenerative changes in the affected limbs. This study aimed to analyse the mid-term outcomes of primary total hip arthroplasty on the affected hip with standard prosthesis. MATERIALS AND METHODS: From January 2008 to January 2018, 32 patients with poliomyelitis sequelae underwent total hip arthroplasty on the affected hip with standard prosthesis. Clinical and radiographical outcomes, complications, and prosthesis survival rates were evaluated. RESULTS: After a mean follow-up of 7.9 (4.4-13.1) years, the Harris Hip Score, University of California Los Angeles activity level rating, and 12-item Short Form Health Survey Questionnaire scale score significantly improved. The abduction and flexion motions of the hip joint improved dramatically, and the visual analogue scale pain score decreased significantly. The leg length discrepancy was effectively corrected. During the follow-up, one patient experienced prosthetic dislocation, one underwent revision surgery due to acetabular component loosening, two had osteolysis, four had heterotopic ossification, two experienced transient sciatic nerve palsy, and one had intermuscular vein thrombosis. The prosthesis survival rate was 96.9% at 5 years postoperatively. No periprosthetic infection occurred. CONCLUSION: Total hip arthroplasty with standard prosthesis could be an effective treatment for hip arthropathy on the affected hip of patients with poliomyelitis sequelae, resulting in good clinical outcomes and few complications. Constrained liner and dual mobility articulation are not recommended unless the hip muscle strength of the abductor is < III.

Efficacy of Modified Lightbulb Technique by Percutaneous Femoral Neck-Head Fenestration Combined With Compacted Artificial Bone Graft for Treating Precollapse Osteonecrosis of the Femoral Head.

BACKGROUND: Whether artificial bone provides comparable outcomes to autogenous bone has not been determined for osteonecrosis of the femoral head (ONFH). This study was conducted to compare the clinical outcomes of autogenous and artificial bone grafting (demineralized bone matrix/calcium sulfate [DBM/CaS]) through a modified lightbulb technique by percutaneous femoral neck-head fenestration for treating precollapse ONFH. METHODS: A total of 73 Association Research Circulation Osseous Stage Ⅱ ONFH patients (81 hips) who had a mean follow-up of 61 months (range, 52 to 74) were included in this retrospective study. Among them were 40 hips treated with autogenous bone and 41 hips treated with DBM/CaS grafting through the percutaneous femoral neck-head fenestration. The Harris scores, radiographic progressions, clinical success rates, and survival analyses were analyzed. RESULTS: At final follow-up, the mean Harris score was 80 points (range, 63 to 92) in the DBM/CaS group and 76 points (range, 69 to 91) in the autogenous bone group (P = .751). The radiographic progression rate was 29.9% in the DBM/CaS group, without significant difference from the autogenous bone group, which was 37.5% (P = .43). About 73.2% of patients in the DBM/CaS group and 75% in the autologous bone group avoided a total hip arthroplasty (P = .85). Survival analysis for femoral head protection revealed similar outcomes between the 2 groups (P > .05). CONCLUSION: Percutaneous femoral neck-head fenestration combined with artificial bone (DBM/CaS) grafting had comparable clinical outcomes to autologous bone grafting on preventing femoral head collapse and rescuing THA at a mean of 61-month follow-up for treating early ONFH.