Exercise vs Conventional Treatment for Treatment of Primary Osteoporosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: Physical exercise has obvious effects on bone loss, pain relief, and improvement of bone metabolism indexes in patients with osteoporosis, but currently lacks sufficient evidence. The aim of this systematic review and meta-analysis was to synthesize and present the best available evidence on the effectiveness and safety of exercises in the treatment of primary osteoporosis. METHODS: Publications pertaining to the effectiveness of exercise on bone mineral density (BMD), visual analog scores (VAS), and biochemical markers of bone metabolism in primary osteoporosis (POP) from PubMed, Cochrane Library, Embase, VIP, CNKI, and Wanfang Database were retrieved from their inception to April 2020. RESULTS: A total of 20 studies with 1824 participants were included. The results of the meta-analysis revealed that exercise therapy for lumbar spine and femoral neck BMD is statistically different from conventional therapy (lumbar spine BMD: SMD = 0.78, 95%CI: 0.46, 1.10, P < 0.00001, I2  = 85%; femoral neck BMD (SMD = 0.80, 95%CI: 0.34, 1.27, P = 0.0007, I2  = 88%), exercise therapy can significantly increase the lumbar spine BMD of patients with OP, especially in lumbar spine2-4 BMD (SMD = 0.47; 95%CI: 0.20, 0.75; P = 0.0008; I2  = 69%). Compared with conventional treatment, kinesitherapy also has significant differences in alleviating the pain of POP patients (SMD = -1.39, 95%CI: -2.47,-0.31, P = 0.01, I2  = 97%). Compared with conventional therapy, kinesitherapy has no significant difference in improving biochemical markers of bone metabolism such as bone glaprotein (BGP) (SMD = 2.59, 95%CI:0.90, 4.28, P = 0.003, I2  = 98%), N-terminal pro peptide of type I procollagen (PINP) (SMD = 0.77, 95%CI: -0.44 to 1.98, P = 0.21, I2  = 95%), serum phosphorus (SMD = 0.04, 95%CI: -0.13, 0.22, P = 0.61, I2  = 30%), alkaline phosphatase (ALP) (SMD = -0.08, 95%CI: -0.44, 0.27, P = 0.64, I2  = 76%), and serum calcium (SMD = 0.12, 95%CI: -0.18, 0.43, P = 0.42, I2  = 63%) in POP patients. CONCLUSIONS: Kinesitherapy significantly improved lumbar spine and femoral neck BMD, and relieve the pain of patients in the current low-quality evidence. Additional high-quality evidence is required to confirm the effect of exercise therapy on the biochemical markers of bone metabolism in POP patients.

Epidemiological Study Based on China Osteonecrosis of the Femoral Head Database.

OBJECTIVE: The aim of the present study was to reveal the case characteristics of osteonecrosis of the femoral head (ONFH) in Mainland China. METHODS: This cross-sectional epidemiological study derived data for ONFH patients from July 2016 to December 2018 from the China Osteonecrosis of the Femoral Head Database (CONFHD). The derived data included gender, age, body mass index (BMI), height, occupation, region, and etiology of femoral head necrosis. A descriptive analysis was performed to summarize the epidemiological characteristics of the case data in the CONFHD. RESULTS: A total of 1844 ONFH patients (2945 hips) were included in this study, comprising 1302 men and 542 women. The age of patients ranged from 18 to 95 years, with a median of 50 years, and the male to female ratio was 2.4. Male patients are younger than female patients (48.26 ± 12.56 years old and 55.56 ± 14.94 years old, respectively). Among the 1844 patients (2945 hips), there were 528 (17.92%) hips at ARCO stage I, 941 (31.99%) hips at ARCO stage II, 873 (29.63%) hips at ARCO stage III, and 603 (20.46%) hips at ARCO stage IV. In the subclassification of ARCO stages I and II, the majority of cases were type C; type A comprised the majority in the subclassification of ARCO stage III. According to the Kellgren-Lawrence classification system, among the 603 ARCO stage IV hips, there were 178 (29.52%) grade 1 hips, 201 (33.34%) grade 2 hips, 176 (29.18%) grade 3 hips, and 48 (7.96%) grade 4 hips. Most were from three provinces: Henan (27.3%), Shanxi (13.9%), and Shandong (11.9%). Regarding BMI, 982 patients (53.25%) were overweight or obese. Among all patients, the largest proportion of patients engaged in level IV manual work. Of all the patients, there were 495 (26.84%) with steroid-induced ONFH, 685 (37.15%) were alcoholics, and 290 (15.73%) had traumatic ONFH. The 495 patients with steroid-induced ONFH included 278 men (56.16%) and 217 women (43.84 %), had a complete history of hormone use. Among the primary diseases, there were 195 cases (39.39%) of immune system diseases, followed by dermatological diseases, respiratory diseases, nephropathy, and other diseases. There were a total of 685 patients with alcoholic ONFH, 589 of these patients (85.99%) were men. A total of 188 (27.45%) patients had drunk alcohol for 6-10 years (comprising the highest proportion), and 280 patients (40.88%) consumed 3001-3500 mL of alcohol each week (the highest proportion). CONCLUSION: Osteonecrosis of the femoral head most commonly occurs after the age of 40. Male patients have an earlier onset than female patients, and the number of male patients is approximately twice that of female patients. The BMI of patients was mainly in the overweight and obese range, and half of these patients engaged in level IV manual work. From the imaging findings, the numbers of hips at ARCO stages II and III were greatest, and the number at stage I was relatively small. Among all the causes of disease, alcohol, steroid use and trauma were the three most common reasons for ONFH.

Dynamic evolution of osseous structure in osteonecrosis of the femoral head and dynamic collapse risks: a preliminary CT image study.

BACKGROUND: Collapse risk of osteonecrosis of the femoral head (ONFH) is estimated mainly based on static indicators, including lesion size and lesion location, but bone repairing is a dynamic process that lasts for years. The present study attempted to analyze the dynamic evolution of the osseous structure and its correlation with radiographic progression. METHODS: This retrospective study included 50 hips with ONFH from 50 patients. Participants were divided into the non-collapse group (n = 25) and the collapse group (n = 25). Original files of the initial computed tomography (CT) images were imported into imaging processing software for morphology analysis. The volume of sclerotic bone, the volume of soft tissue, and bone mineral density (BMD) were calculated. The linear correlations between the aforementioned indicators and the disease duration were estimated. The logistic regression analysis was conducted to evaluate the correlation of these indicators with the radiographic progression. Receiver operating characteristic (ROC) analysis was used to evaluate these indicators' prediction performance. RESULTS: The volume of sclerotic bone and the BMD grew with disease duration, but the volume of soft tissue decrease. The logistic regression analysis found that the volume of sclerotic bone and the BMD were statistically associated with radiographic progression. The ROC analysis found that the regression model, which integrated the volume of sclerotic bone and the BMD, had satisfactory performance in predicting radiographic progression. CONCLUSION: The present study suggested a dynamic evolution of the osseous structure and a dynamic variation trend of the collapse risk in ONFH. The volume of sclerotic bone and the BMD might serve as further prognostic indicators when estimating the collapse risk.

Current Treatment Modalities for Osteonecrosis of Femoral Head in Mainland China: A Cross-Sectional Study.

OBJECTIVE: To investigate the application of treatment modalities for patients with osteonecrosis of the femoral head (ONFH) in mainland China. METHODS: This cross-sectional study was based on the online application of China Osteonecrosis of the Femoral Head Database (CONFHD). Between July 2016 to December 2018, the CONFHD program planned to recruit ONFH patients from 12 administrative areas across mainland China. Real-world medical records of treatment regimens for these patients, including surgeries and prescriptions, were approved to upload to the CONFHD application for further analysis. The surgeries performed on these patients were classified into total hip arthroplasty and hip-preserving procedures, and the latter was further classified into core decompression, bone grafting, and tantalum rod implantation. Prescription medications were classified into chemical medicine and Chinese herbal medicine (CHM); chemical medicine was further classified according to their chemical compounds, and CHM was classified according to therapeutic functions based on traditional Chinese medicine theory. Descriptive analysis was performed to summarize the application of different treatment regimens on the overall sample. RESULTS: A total of 1491 patients (2381 hips) who fulfilled the protocol criteria were included. There were 1039 males and 452 females with a mean age of 47.29 ± 12.69 years. The causes of ONFH were alcoholism in 642 patients (43%), corticosteroid in 439 patients (29%), trauma in 239 patients (16%), and idiopathic ONFH in 171 patients (11%). Operative treatments (including total hip arthroplasty and hip-preserving procedures) were performed on 49% of patients (43% of hips), chemical medicine therapy (including bisphosphonate, statins, and prostacyclin) was given to 37% of patients (37% of hips), and CHM was administrated to 72% of patients (75% of hips). The aforementioned interventions were not always used alone, since 47% of patients (52% of hips) received combined regimens with multiple interventions. Among hips treated by surgery, all hips with ARCO stage IV ONFH received THA (305 hips), and THA was also performed on 63 hips with stage II ONFH. Over half of hips with stage I (81%), II (91%), and III (92%) ONFH had received pharmacological treatments. Prostacyclin and bisphosphonate were the top two most prescribed medicines used alone. CHM therapies with multiple CHM functions were more commonly prescribed. CONCLUSION: Current treatment modalities for ONFH patients in mainland China include operative treatment, chemical medicine, and CHM. Combined regimens with different treatment modalities are common in real-world clinical practices.

Mechanisms and Molecular Targets of the Tao-Hong-Si-Wu-Tang Formula for Treatment of Osteonecrosis of Femoral Head: A Network Pharmacology Study.

The Tao-Hong-Si-Wu-Tang (THSWT) formula, a classic prescription of traditional Chinese medicine, has long been used for the treatment of osteonecrosis of femoral head (ONFH). However, its mechanisms of action and molecular targets are not comprehensively clear. In the present study, the Traditional Chinese Medicine System Pharmacology (TCMSP) database was employed to retrieve the active compounds of each herb included in the THSWT formula. After identifying the drug targets of active compounds and disease targets of ONFH, intersection analysis was conducted to screen out the shared targets. The protein-protein network of the shared targets was built for further topological analysis. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis were then carried out. A gene pathway network was constructed to screen the core target genes. We identified 61 active compounds, 155 drug targets, and 5443 disease targets. However, intersection analysis only screened out 37 shared targets. Kaempferol, luteolin, and baicalein regulated the greatest number of targets associated with ONFH. The THSWT formula may regulate osteocyte function through specific biological processes, including responses to toxic substances and oxidative stress. The regulated pathways included the relaxin, focal adhesion, nuclear factor-κB, toll-like receptor, and AGE/RAGE signaling pathways. RELA, VEGFA, and STAT1 were the important target genes in the gene network associated with the THSWT formula for the treatment of ONFH. Therefore, the present study suggested that the THSWT formula has an action mechanism involving multiple compounds and network targets for the treatment of ONFH.

Chinese herbal Huo-Gu formula for the treatment of steroid-associated osteonecrosis of femoral head: A 14-year follow-up of convalescent SARS patients.

PURPOSE: The coronavirus disease 2019 (COVID-19) reminds us of the severe acute respiratory syndrome (SARS) outbreak in 2003, and up to date, corticosteroid is commonly administrated to severe patients with COVID-19. Osteonecrosis of the femoral head (ONFH) is a common disabling complication among convalescent SARS patients who received corticosteroid therapy. In China, a considerable number of convalescent SARS patients with steroid-associated ONFH had undergone conservative treatment by traditional Chinese medicine, and this study aims to evaluate the long-term results of a spleen-invigorating Huo-Gu formula (HGF) therapy in these patients. PARTICIPANTS AND METHODS: A total of 33 convalescent SARS patients (9 males and 24 females) with bilateral steroid-associated ONFH (66 hips) were enrolled in this study. All patients received oral HGF therapy for 6 months when they were confirmed the diagnosis of steroid-associated ONFH. They had been regularly followed up at an interval of 1 year. Harris hip score and medical imaging modalities, including plain radiography, computed tomography and magnetic resonance imaging, were performed to evaluate the outcomes. RESULTS: Based on average 14 years of follow-up of HGF therapy (ranging from 6 to 16 years), 38 hips (57%) among the 66 hips developed definite osteoarthritis, and 14 hips (26%) in 53 precollapse hips (Association Research Circulation Osseous [ARCO] Stage I or II) progressed to femoral head collapse (ARCO Stage III or IV). Only five patients (also 5 hips) underwent total hip arthroplasty, and the mean hip survival time was over 15 years by the Kaplan-Meier analysis. We observed a mean Harris hip score of 63 points, which represented the reserve of 55% in pain score and 70% in physical function score. The severity of groin pain was not correlated to the severity of osteoarthritis. CONCLUSION: Chinese herbal HGF therapy demonstrates beneficial effects on preventing femoral head collapse, delaying total hip arthroplasty, and maintaining physical function in the treatment of steroid-associated ONFH. HGF therapy might be therefore a good alternative for the treatment of steroid-associated ONFH secondary to rheumatologic and infection diseases. TRANSLATIONAL POTENTIAL OF THE ARTICLE: HGF therapy might be a good alternative for the treatment of steroid-associated ONFH secondary to rheumatologic and infectious diseases.

Influence of passive smoking on the onset of Legg-Calvè-Perthes disease: a systematic review and meta-analysis.

The relationship between passive smoking and the onset of Legg-Calvè-Perthes disease is still controversial. Therefore, we conducted the study to systematically evaluate and analyze the relationship. A comprehensive search was conducted. Meta-analysis was performed with RevMan 5.3 software, with the odds ratio as the effect size. Eight English articles with a total of 1379 Legg-Calvè-Perthes disease patients were eventually included. Passive smoking type of family members smoking in indoor (odds ratio = 2.53), paternal smoking (odds ratio = 2.76), maternal smoking (odds ratio = 2.02), maternal smoking during pregnancy (odds ratio = 1.68), using stove indoor (odds ratio = 2.56) are statistically significant (P < 0.05). For the family members smoking indoor, region may be a confounding factor (European group I = 92%, odds ratio = 2.51; USA group I = 5%, odds ratio = 3.26; and Asian group I = 0%, odds ratio = 2.25). In addition, the type of maternal smoking (odds ratio = 0.80, for 1-10 per day; odds ratio = 2.73, for 10-20 per day; odds ratio = 2.78, for >20 per day) and the type of maternal smoking during pregnancy (odds ratio = 1.36, for 1-9 per day; odds ratio = 2.02, for ≥10 per day) may show a dose-effect relationship. Passive smoking is a risk factor for the onset of Legg-Calvè-Perthes disease, but the specific types of passive smoking (haze, etc.), dose, dose-effect relationship, regional confounding, pathological mechanisms, etc. also require clinicians and researchers to continue exploring.