Would high-dose corticosteroid addition to multimodal cocktail periarticular injection contribute to prolonged pain control and better recovery following total knee arthroplasty?: study protocol for a randomized controlled trial.

BACKGROUND: Enhanced recovery following total knee arthroplasty (TKA) has been advocated to enhance postoperative recovery. Multimodal cocktail periarticular injection (MCPI) use for pain control in TKA has gained wide acceptance. MCPI-containing corticosteroids are believed to be an effective solution owing to their local anti-inflammatory effects and ability to reduce the local stress response postoperatively. However, there is conflicting evidence regarding its benefits. This trial aims to compare MCPI with a high dose of corticosteroid, normal dose of corticosteroid, and non-corticosteroid during TKA, to assess the effectiveness of MCPI containing corticosteroids in postoperative pain relief, functional improvement, rescue analgesia, and side effects and provide evidence that high-dose corticosteroids result in prolonged pain control and better recovery following TKA. METHODS: This is a double-blinded, randomized, placebo-controlled study. A total of 234 patients scheduled for TKA will be recruited. During surgery, before wound closure, 80 ml of the cocktail analgesic will be injected into the muscle and joint capsule for local infiltration analgesia; the participants will be randomly assigned to three groups to receive a high dose of betamethasone MCPI (group H), normal dose of betamethasone MCPI (group N), and non-betamethasone MCPI (group C). The following indices will be recorded and analyzed: the strongest knee pain experienced during 90° flexion at 6 h, 24 h, 48 h, 72 h, 5 days, 14 days, and 30 days after surgery; 1 min walking ability; and circumference around the patella at 2, 5, 14, and 30 days after surgery; Knee Society knee score at 14 days and 30 days after surgery; C-reactive protein and blood sedimentation; blood sugar 2, 5, 14, and 30 days following surgery; rescue analgesic consumption; and adverse events. If any participant withdraws from the trial, an intention-to-treat analysis will be performed. DISCUSSION: The results of this study will provide clinical evidence on the effectiveness of MCPI-containing corticosteroids in postoperative pain relief, functional improvement, rescue analgesia, and adverse events, as well as provide evidence on the efficacy of high-dose corticosteroids in prolonged pain control and better recovery following TKA. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000038671 . Registered on September 27, 2020.

Mechanics and Biology Interact in Intervertebral Disc Degeneration: A Novel Composite Mouse Model.

The aim of this study was to distinguish the characteristics of intervertebral disc degeneration (IVDD) originating from mechanics imbalance, biology disruption, and their communion, and to develop a composite IVDD model by ovariectomy combined with lumbar facetectomy for mimicking elderly IVDD with osteoporosis and lumbar spinal instability. Mice were randomly divided into four groups and subjected to sham surgery (CON), ovariectomy (OVX), facetectomy (mechanical instability, INS) or their combination (COM), respectively. Radiographical (n = 4) and histological changes (n = 8) of L4/5 spinal segments were analyzed. Tartrate-resistant acid phosphatase (TRAP) staining was conducted to detect osteoclasts, and expression of osterix (OSX), type I collagen (Col I), type II collagen (Col II) and vascular endothelial growth factor (VEGF) were evaluated by immunochemistry. OVX affected the body's metabolism but INS did not, as the body weight increased and uterus weight decreased in OVX and COM mice compared to CON and INS mice. OVX, INS, and COM caused IVDD in various degrees at 12 weeks after surgery. However, the major pathogeneses of OVX- and INS-induced IVDD were different, which focused on endplate (EP) remodeling and annulus fibrosus (AF) collapse, respectively. OVX induced osteopenia of vertebra. In contrast, INS promoted the stress-adaptive increase of subchondral bone trabeculae. The COM produced a reproducible severe IVDD model with characteristics of sparse vertebral trabeculae, cartilaginous EP ossification, subchondral bone sclerosis, fibrous matrix disorder, angiogenesis, disc stiffness, as well as space fusion. Additionally, all groups had elevated bone and cartilage turnover compared with CON group, as the quantity of trap + osteoclasts and the osteogenic OSX expression increased in these groups. Likewise, the VEGF expression levels were similar, accompanied by the altered matrix expression of disc, including the changed distribution and contents of Col II and Col I. The findings suggested that the composite mouse model to some extent could effectively mimic the interactions of biology and mechanics engaged in the onset and natural course of IVDD, which would be more compatible with the IVDD of elderly with vertebral osteoporosis and spinal instability and benefit to further clarify the complicated mechanobiological environment of elderly IVDD progression.

Cartilage degradation in osteoarthritis: A process of osteochondral remodeling resembles the endochondral ossification in growth plate?

Osteoarthritis (OA) is one of the most common degenerative disease which causes pain and disability of joint and brings heavy socioeconomic burden in the world. However, the pathogenesis of OA has not been fully understood. Articular cartilage degradation or loss was often regarded as the characteristic of osteoarthritis. But we believe that there may had a illusion that OA was simply considered to be a process of wear and tear because evidences have supported all joint tissues remodeling including cartilage, subchondral bone, synovium, ligament, fat pad, and etc, were engaged in OA, in particular the cartilage and subchondral bone. Many factors such as mechanics, inflammation and immunological abnormality could drive the joint tissues metabolic and disturb the steady state of cartilage and bone, which further devoted to a serial pathological manifestations, consisting of hypertrophy and apoptosis of articular chondrocytes, degradation of cartilage matrix, angiogenesis and calcification of hyaline cartilage, replication of tidemark, formation of osteophytes, degeneration of ligaments and, in the knee, the menisci, hypertrophy of the joint capsule and remodeling of subchondral bone along with increased permeability of the osteochondral interface. The thickening of calcified cartilage, the thinning of superficial hyaline cartilage and the remodeling of subchondral bone indicated that the cartilage degradation could be a procedure of enchondral ossification similar to the growth plate, of driven by a host of cytokines within the affected joint. Articular cartilage loses stable state from normal resting to a high turnover in the stimulation of abnormal mechanical stresses and cytokines would subsequently contributed to slowly sustained remodeling and calcification, which might be the key features of the initiation and development of OA. In this article, the development and structural comparison of articular cartilage and growth plate as well as the major pathologic features of OA will be discussed to explain that cartilage degeneration in OA might be a process of enchondral ossification similar to growth plate. This would provide a new perspective for understanding OA's pathogenesis and the treatment in the future.

Clinical Characteristics and Treatment of Spontaneous Osteonecrosis of Medial Tibial Plateau: A Retrospective Case Study.

BACKGROUND: In a small proportion of cases, spontaneous osteonecrosis of the knee (SONK) involves the medial tibial plateau (MT). Here, we introduced the clinical characteristics of spontaneous osteonecrosis of the MT and unicompartmental knee arthroplasty (UKA) as the favorable treatment for this situation based on a retrospective case study. METHODS: Patients with spontaneous osteonecrosis of the MT, confirmed by magnetic resonance imaging (MRI) at Guangdong Provincial Hospital of Chinese Medicine (China) from March 2015 to June 2016, were included as a case serial and analyzed retrospectively. All patients underwent Oxford Medial UKA. The characteristics of their lesions, corresponding treatment, and results of follow-up were presented. The lesion scores and grade were determined according to the criteria of Ficat and Arlet. RESULTS: In total, 22 patients (5 men, 17 women; mean age, 64.1 years) with spontaneous osteonecrosis of the MT were analyzed. The lesion stages assessment showed that 3 (14%) were Stage II, 10 (45%) were Stage III, 7 (32%) were Stage IV, and 2 (9%) were Stage V. In the sagittal plane, 7 (32%) were in the anterior region (MTa) and 15 (68%) were central (MTc). The lesion volume averaged 2.24 ± 0.79 cm3 (range: 1.57-3.08 cm3). Seventeen patients (77%) had Level III posterior medial meniscus root tears (MMRTs). All the patients underwent UKA. Average follow-up was 30.0 ± 6.4 months with a range of 23.0-38.0 months. The visual analog scale score was 7.78 ± 0.67 before surgery while decreased to 2.22 ± 1.09 at the final follow-up (P < 0.001). The Hospital for Special Surgery scores of pre-/post-surgery were 65.67 ± 5.45 and 84.10 ± 4.20, respectively (P < 0.001). CONCLUSIONS: SONK often occurs in the anterior and central tibial plateau due to abnormal stresses. Most of the patients had Level III posterior medial meniscus root tears. MRI is recommended for suspected cases to identify SONK at an early stage. The use of the Oxford Medial UKA for SONK of the MT is reliable both immediately and at follow-up.

Osteoporosis of the vertebra and osteochondral remodeling of the endplate causes intervertebral disc degeneration in ovariectomized mice.

BACKGROUND: Studies on the relationship between osteoporosis and intervertebral disc degeneration (IVDD) are inconsistent. Therefore, we assessed whether IVDD is affected by vertebral osteoporosis in ovariectomized mice and investigated the underlying pathogenesis of IVDD related to osteoporosis. METHODS: Thirty healthy female C57BL/6 J mice aged 8 weeks were randomly divided into two groups: a control group (sham operation, n = 15) and an ovariectomy group (OVX; bilateral ovariectomy, n = 15). At 12 weeks after surgery, the bone quantity and microstructure in the lumbar vertebra and endplate as well as the volume of the L4/5 disc space were evaluated by microcomputed tomography (micro-CT). The occurrence and characteristic alterations of IVDD were identified via histopathological staining. The osteoclasts were detected using tartrate-resistant acid phosphatase (TRAP) staining. Type II collagen (Col II), osterix (OSX), osteopontin (OPN), and vascular endothelial growth factor (VEGF) expression in the intervertebral disc were detected by immunohistochemical analysis. RESULTS: OVX significantly increased the body weight and decreased the uterus weight. Micro-CT analysis showed that osteoporosis of the vertebra and osteochondral remodeling of the endplate were accompanied by an increase in the endplate porosity and a decrease in the disc volume in the OVX group. Likewise, histological evaluation revealed that IVDD occurred at 12 weeks after ovariectomy, with features of endochondral ossification of the endplate, loose and broken annulus fibrosus, and degeneration of nucleus pulposus. TRAP staining showed that numerous active osteoclasts appeared in the subchondral bone and cartilaginous endplate of OVX mice, whereas osteoclasts were rarely detected in control mice. Immunohistochemical analysis demonstrated that the expression of osterix was significantly increased, notably in the endplate of OVX mice. In addition, Col II was decreased in the ossification endplate and the degenerative annulus fibrosus, where OPN and VEGF expressions were elevated in OVX mice. CONCLUSIONS: OVX induced vertebral osteoporosis and osteochondral remodeling of the cartilaginous endplate contributing to the angiogenesis and an increase in porosity of the bone-cartilage surface, and also affected the matrix metabolism which consequently had detrimental effects on the intervertebral disc. Our study suggests that preserving the structural integrity and the function of the adjacent structures, including the vertebrae and endplates, may protect the disc against degeneration.

New insights into the tonifying kidney-yin herbs and formulas for the treatment of osteoporosis.

Osteoporosis is characterized by an increasing osseous fragility and fracture resulting from the low mass and deteriorated microarchitecture in the bone tissue. The hormone replacement therapy and alendronate were frequently used to treat osteoporosis as the primary therapeutic strategy, but their adverse effects have severely limited their extensive clinical application, therefore, it is urgent to develop alternative or complementary therapeutic agents for anti-osteoporosis. Interestingly, with more people focusing on the complementary and alternative medicine, traditional Chinese herbs and formulas are being gradually recognized as safe and effective agents in the treatment of osteoporosis. In particular, a notable trend is that increasing studies are making efforts to clarify the anti-osteoporotic effects and mechanism of the tonifying kidney-yin herbs and formulas, a category of agents identified as effective therapy. Therefore, the purpose of this study is to comprehensively review the tonifying kidney-yin herbs and formulas that have been reported in the treatment of osteoporosis as well as how the agents play their roles in detail. This current study not only will advance our understanding of the actions of tonifying kidney-yin herbs and formulas, but also provide new evidence for the clinic use of the tonifying kidney-yin herbs and formulas in the treatment of osteoporosis.

The efficacy and safety of the Shaoyao Shujin tablet for knee osteoarthritis: study protocol for a randomized controlled trial.

BACKGROUND: Knee osteoarthritis (KOA) is a major public health issue causing chronic disability as well as a burden on healthcare resources. In China, a herbal drug tablet has been used as an effective and conventional therapy to alleviate clinical symptoms caused by KOA. However, evidence gathered from systematic reviews or randomized controlled trials that validated herbal drugs for the management of osteoarthritic pain is weak. The purpose of this study is to explore the efficacy and safety of the Shaoyao Shujin tablet for the management of KOA in a short-term study. METHODS/DESIGN: This trial is a multicenter randomized, double-blind, placebo-controlled study. A total of 276 patients will be randomized into 3 groups: (1) the high-dose Shaoyao Shujin tablet group (HD group), (2) the low-dose Shaoyao Shujin tablet group (LD group), and (3) the placebo tablet group (control group). In the three groups, four tablets will be administered three times per day for 6 weeks. Follow-up will be at regular intervals during a 10-week period with the Western Ontario and McMaster Universities Index (WOMAC) score, visual analog scale (VAS) score, and rescue medication use assessed as outcome measures. DISCUSSION: This study will provide clinical evidence on the efficacy and safety of the Shaoyao Shujin tablet in treating KOA. TRIAL REGISTRATION: Chinese Cochrane Center ChiCTR-IPR- 15006194 , registered 4 April 2015.

Clinical effectiveness and micro-perfusion alteration of Jingui external lotion in patients with knee osteoarthritis: study protocol for a randomized controlled trial.

BACKGROUND: Knee osteoarthritis is a major cause of disability in the aging population. Based on pathological, magnetic resonance imaging (MRI) and arthroscopy studies, progressive osteoarthritis involves all tissues of the joint and includes bone marrow lesions, synovial proliferation, fat pad inflammation, and high subchondral bone turnover. Recent research suggests that abnormal perfusion in bone marrow lesions, fat pads, and subchondral bone is associated with pain in knee osteoarthritis, and that dynamic contrast-enhanced MRI is a promising method for studying micro-perfusion alteration in knee osteoarthritis. Traditional Chinese Medicine approaches have been employed for thousands of years to relieve knee osteoarthritis pain. Among herbal medicines, the Jingui external lotion is the preferred and most commonly used method in China to reduce pain in patients with knee osteoarthritis; however, there is a lack of validated evidence for its effectiveness. The purpose of this study is to explore the effectiveness of Jingui external lotion for the management of painful knee osteoarthritis in a short-term study. In addition, we will assess micro-perfusion alteration in the patellar fat pad as well as the femur and tibia subchondral bone via dynamic contrast-enhanced MRI. METHODS/DESIGN: This trial is a randomized, controlled study. A total of 168 patients will be randomized into the following two groups: 1) the Jingui external lotion group (treatment group); and 2) the placebo lotion group (control group). In both groups, lotion fumigation and external washing of the patients' knees will be administered twice a day for 14 consecutive days. Follow-up will be at regular intervals during a 4-week period with a visual analog scale to assess pain, and additional characterization with the Western Ontario and McMaster Universities Index score; rescue medication will be recorded as the extent and time pattern. In addition, micro-perfusion alteration in the patellar fat pad, femur and tibia subchondral bone will be assessed via dynamic contrast-enhanced MRI. DISCUSSION: This study will provide clinical evidence of the efficacy of Jingui external lotion in treating knee osteoarthritis, and it will be the first randomized controlled trial to investigate micro-perfusion alteration of knee osteoarthritis with Traditional Chinese Medicine external lotion via dynamic contrast-enhanced MRI. TRIAL REGISTRATION: ClinicalTrials.gov identifier: ChiCTR-TRC-14004727 ; 31 May 2014.

[Observation of clinical curative effect of "oblique-pulling" maneuver in the treatment of lumbar intervertebral disc herniation].

OBJECTIVE: To evaluate the clinical curative effect of "oblique-pulling" maneuver in patients with lumbar intervertebral disc herniation (LIDH). METHODS: Sixty-five LIDH cases were randomly divided into experimental group and control group. In the experimental group 32 patients were treated by "oblique-pulling" maneuver, and 32 patients in the control group were treated by lumbar traction therapy. One case were excluded from the study and another one case were dropped from the study. After one course of treatment, the therapeutic effects of the two groups were compared quantitatively by using the JOA and VAS scores, including the improvement of signs, symptoms, living ability, and low back and leg pain. RESULTS: After one course of treatment, in the experimental group, 7 cases were controlled well, 16 cases were marked effect, 8 cases were effect, 1 case was no effect. In the control group, 4 cases were controlled well, 10 cases were marked effect, 13 cases were effect, 4 cases was no effect in control group. The clinical effective rate of the experimental group was 96.86%, which was higher than 87.10% of the control group (P < 0.05). In the experimental group the scores of JOA and VAS were obviously improved after treatment (P < 0.001) and the improvement was better than that of control group (P < 0.01). CONCLUSION: The "oblique-pulling" maneuver has the characteristics of simple operation, repeatability, good efficiency, high safety.

[A 10-year-review (1998 - 2007) on 3449 cases of osteoporotic hip fractures: trend of hospitalization and inpatient costs].

OBJECTIVE: The purpose of this retrospective research was to analyze the trend of hospitalized prevalence in the past 10 years (1998 - 2007) and to estimate resource utilization associated with osteoporotic hip fractures, including hospital length of stay and inpatient costs in Guangzhou, China. METHODS: 3449 patients aged 50 years and older, hospitalized for primary diagnose of hip fractures in both hospitals in the past ten years were included in our study. Completed data was obtained retrospectively from the hospital medical records. Clinical parameters such as sex-specifics, hospital length of stay, inpatient costs, and the constitutions of the inpatient costs were analyzed with multiple statistics methods and regressions. RESULTS: Over the 10-year study period, the number of hospitalizations for hip fractures increased with a curve model. Male and female ratio was 1:1.95 with an average age of the patients as 76.32 +/- 9.52 years old. Average hospital length of stay was 23.59 +/- 13.48 days with no significant difference between males and females, years of admission and the different diagnoses. The number of hospitalization went to the top at the age of 70 to 79 years old (38.45%), followed by 80-89 years old (33.08%). Femoral neck fractures was significantly more than that of inter-trochanteric fractures in those patients aged 50 to 79 years (P < 0.01) but less than those intertrochanteric fractures aged 90 years and older (P < 0.05). Average inpatient costs is about 23.52 +/- 17.00 thousand Yuan (RMB) (femoral neck fractures is about 25.09 +/- 17.62 thousand Yuan and intertrochanteric fracture is 21.44 +/- 15.92 thousand Yuan) of which treatment costs (included implants, materials used in the theatre and routinely care of the wound) contributed 52%, pharmacy intervention 25%, operation 6%, ward expenditure 5%, radiology and physical investigation 5%, and chemistry test 4%. The inpatient cost went to a peak at the age of 60 - 69 years old and were significantly correlated with the hospital length of stay. The cost increased every year in the past 10 years by 6.18%. CONCLUSION: These results emphasized that the growing economic impact arising from the inpatient treatment of osteoporotic hip fractures and most of which related to treatment cost (include implants, materials used in the theatre and routinely care of the wound), and drugs and always correlated to length of hospital stay. Cost control should be paid more attention to the implants and drugs.