Beneficial effects of paeoniflorin on osteoporosis induced by high-carbohydrate, high-fat diet-associated hyperlipidemia in vivo.

Osteoporosis is linked to reduced bone mineral density (BMD) as a major risk factor for fragility fractures. Recent studies indicated an association between BMD and abnormally elevated lipid levels in blood as common indicators for hyperlipidemia. In this study, we assessed the protective effect of paeoniflorin, a phytochemical compound with multiple pharmacological activities, against hyperlipidemia-induced osteoporosis in rats fed a high-carbohydrate, high-fat diet (HCHF). The special diet-fed rats were subjected to an 8-week treatment with either paeoniflorin (20 mg/kg, daily) or vehicle. The control group received a normal diet during the entire study. At study conclusion, serum markers of lipid metabolism and bone turnover were measured. Bone strength was assessed by biomechanical testing, and femurs were scanned using micro-computed tomography to analyze trabecular and cortical bone structure. Interestingly, paeoniflorin controlled the serum lipid profile by significantly decreasing HCHF-induced high levels of total cholesterol, triglyceride, and low-density lipoprotein cholesterol. Paeoniflorin significantly improved trabecular and cortical parameters as well as femur length and width that were negatively affected by HCHF diet. Biomechanical strength testing showed that femurs of HCHF diet-fed rats endured significantly lower force but higher displacement and strain than those of control rats, whereas paeoniflorin reversed the negative effects. Moreover, paeoniflorin rescued osteoblast differentiation and cell spreading activities along with bone turnover markers. In conclusion, HCHF-induced hyperlipidemia caused adverse effects on the bone that were rescued by paeoniflorin treatment.

Medial Plantar Venous Flap: Classic Donor Site Modification for Hand Defects.

BACKGROUND: Destruction of digits from trauma results in a much more significant influence on patients' mental state and quality of life than do injuries to other parts. The purpose of this study was to describe a novel modification of medial plantar venous flap for soft tissue defects in the hands and digits. METHODS: Nine patients received medial plantar venous flap to resurface soft tissue defects in the hands or digits between January 2015 and February 2017. This flap can be used either in a free-island pattern or in a flow-through pattern through the medial branch of the great saphenous vein. All patient data including preoperative statues and follow-up examinations (flap survival rates, complication rates, total active motion, static 2-point discrimination, and Semme-Weinstein test score) were analyzed. RESULTS: We included 6 men and 3 women, with a mean age of 34.2 years. The medial plantar venous flaps were used for vascularization in 5 patients because of segmental defects of bilateral digit arteries. Eight flaps survived uneventfully in this study. One flap partially failed (20% of the flap area) because of venous congestion. The functional outcomes and sensory restoration were satisfied for all 9 flaps. CONCLUSIONS: Compared with the traditional medial plantar flap, the medial plantar venous flap involves a simpler surgical procedure and allows for revascularization of distal areas using the flow-through technique. Furthermore, the medial plantar area presents a sensitive, glabrous skin with proper bulkiness and allows for movement of the underlying structure.

Association of gout with osteoporotic fractures.

PURPOSE: Previous studies have shown that serum uric acid levels and inflammation are associated with bone mineral density. Gout, a disease characterized by hyperuricemia and inflammation, contributes to the risk of osteoporotic fractures. However, this association is controversial. Therefore, this study investigated whether gout in older people (age > 55 years) is associated with osteoporotic fracture risk. METHODS: This population-based, cross-sectional study included 2674 participants (147 cases of gout and 388 fractures). Standardized and self-administered questionnaires were employed and physical examinations, blood tests, and bone mineral density examinations were performed; multivariate-adjusted logistic regression models were used to evaluate associations between gout and osteoporotic fracture risk. RESULTS: The data were adjusted for age; smoking status; alcohol status; physical activity; body mass index; waist circumference; hypertension; cardiovascular events; diabetes mellitus; rheumatoid arthritis; serum levels of total cholesterol (TC), triglycerides, and high- and low-density lipids; and T-scores. We found a significant association between gout and osteoporotic fracture risk in women (odds ratio [OR], 2.00; 95% confidence interval [CI], 1.12-3.56; P = 0.019), but no such association in men (OR, 1.30; 95% CI, 0.58-2.88; P = 0.525). Further stratified analyses showed a significant association between gout and osteoporotic fracture risk in women without rheumatic arthritis and in those with high TC levels or with osteoporosis (all, P < 0.05). CONCLUSIONS: In older Chinese adults, gout is significantly associated with the risk of osteoporotic fractures in women, especially those without rheumatic arthritis and in those with high TC levels or with osteoporosis.

Geraniin inhibits migration and invasion of human osteosarcoma cancer cells through regulation of PI3K/Akt and ERK1/2 signaling pathways.

Geraniin, an active compound isolated from Geranium sibiricum, was found to inhibit proliferation and induce apoptosis of tumor cells. However, the antimetastatic effects of geraniin remain elusive. Our study found the potential antitumor mechanisms of geraniin through inhibiting the migration and invasion of human osteosarcoma U2OS cells. The western blot, gelatin zymography, and reversed transcription-PCR analysis showed that geraniin suppressed matrix metalloproteinase-9 (MMP-9) expression in a concentration-dependent manner. Geraniin potently suppressed the phosphorylation of extracellular signal regulating kinase (ERK)1/2, phosphatidylinositide-3-kinase (PI3K), and Akt, but did not affect phosphorylation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase. Furthermore, when transforming growth factor-ß1 (TGF-ß1) was used as an agonist, geraniin inhibited TGF-ß1-mediated cell invasion and upregulation of MMP-9. These results suggested that geraniin inhibited U2OS cell migration and invasion by reducing the expression of MMP-9 through the PI3K/Akt and ERK1/2 signaling pathways.

Baicalin inhibits human osteosarcoma cells invasion, metastasis, and anoikis resistance by suppressing the transforming growth factor-ß1-induced epithelial-to-mesenchymal transition.

The epithelial-mesenchymal transition (EMT) plays an important role in inducing cancer metastasis. Baicalin, a flavone derivative isolated from Scutellaria spp., shows a series of pharmacological and physiological activities. However, the possible role of baicalin in the EMT is unclear. In this study, we attempted to investigate the potential use of baicalin as an inhibitor of transforming growth factor-ß1 (TGF-ß1)-induced EMT in U2OS cells. We found that TGF-ß1 induced the EMT to promote U2OS cells migration, invasion, and anoikis resistance. Western blotting showed that baicalin inhibited U2OS cells' invasion and migration, increased the expression of the epithelial phenotype marker E-cadherin, repressed the expression of the mesenchymal phenotype marker vimentin, as well as decreased the level of EMT-inducing transcription factors Snail1 and Slug during the initiation of TGF-ß1-induced EMT. Baicalin also inhibited the TGF-ß1-induced increase in cell migration, invasion, and anoikis resistance in TGF-ß1-induced U2OS cells. In addition, the TGF-ß1-mediated phosphorylated levels of Smad2/3 were inhibited by baicalin pretreatment. Above all, we conclude that baicalin suppresses human osteosarcoma cells' migration, invasion, and anoikis resistance in vitro through suppression of TGF-ß1-induced EMT.

The Combined Use of a Neurocutaneous Flap and the Ilizarov Technique for Reconstruction of Large Soft Tissue Defects and Bone Loss in the Tibia.

BACKGROUND: Management of posttraumatic large soft tissue defects and bone loss remains a therapeutic and surgical challenge for orthopedic surgeons. We assessed the use of a neurocutaneous flap and the Ilizarov technique in the reconstruction of severe composite defects in the tibia. METHODS: We retrospectively reviewed 18 consecutive patients with trauma-related soft tissue defects and bone loss. The size of the soft tissue defect ranges from 8 × 9 cm to 14 × 18 cm. The mean size of bone loss was 4.5 cm. A great saphenous neurocutaneous flap or sural neurocutaneous flap was created to reconstruct the soft tissue defect. The Ilizarov external fixator was applied to reconstruct bony loss by means of distraction osteogenesis. RESULTS: The mean follow-up period was 38.8 months. All transferred flaps survived completely. The area covered ranged from 9 × 10 cm to 15 × 20 cm. The mean distraction length and duration of use of the external fixator were 6 cm and 11.4 months, respectively. All patients achieved final union. Complications of superficial pin-tract infections and mild Achilles tendon contracture were observed, but these were resolved over time. All patients were satisfied with the outcome of the surgery. CONCLUSIONS: A well-vascularized neurocutaneous flap is a safe and effective option in lower extremity reconstruction under a stable mechanical environment, which can be created using the Ilizarov technique. It is a good option for reconstructing severe complex defects in the lower limb.

Amputation Stump Revision Using a Free Sural Neurocutaneous Perforator Flap.

BACKGROUND: The development of microsurgery and the concept of the surgical flap have enabled orthopedic surgeons to deal with various soft tissue defects and compositions during limb salvage procedures. However, severely damaged bony structures with accompanying soft tissue deficiencies often result in amputation. When performing amputations, surgeons must preserve the stump length to maximize functional ambulation, even during the posttraumatic phase and chronic period when a fillet flap is not an option. PATIENTS AND METHODS: Eleven patients with previous below-knee amputation were enrolled in our study from January 2006 to December 2011. Each patient underwent stump revision using a free sural neurocutaneous perforator flap. Preoperative and postoperative data were reviewed to evaluate the functional and aesthetic results. RESULTS: The 11 patients comprised 7 men and 4 women with an average age of 35.6 years (range, 26.0-49.0 years). The mean follow-up period was 15.3 months (range, 10.0 months-2.0 years). All free flap reconstructions of the amputation stump ultimately survived. All patients achieved both superficial and deep sensory recovery and are comfortable with their prostheses, and none have required further surgical intervention. CONCLUSIONS: The sural neurocutaneous perforator flap provided stable coverage and improved patients' quality of life by aiding in early rehabilitation and prosthetic fitting, function, and comfort.

Distally Based Saphenous Neurocutaneous Perforator Flap: A Versatile Donor Site for Reconstruction of Soft Tissue Defects of the Medial Malleolar Region.

Repair of both simple and complex defects in the medial malleolar region continues to be a challenging task for surgeons because of the local paucity of soft tissue available for transfer. The popular neurocutaneous flap has provided a reliable and less technically demanding method for resurfacing defects of the lower extremities. We present our experience with the versatile design of the distally based saphenous neurocutaneous perforator flap to provide coverage of complex post-traumatic medial malleolar defects by harvesting multiple tissue components in various combinations. Our series included 11 patients (8 males [72.7%] and 3 females [27.3%]); mean age 39.2 (range 22 to 58) years, who were followed for a mean duration of 13.3 (range 9 to 18) months. Three flaps (27.3%) were harvested with massive subcutaneous tissue to obliterate dead space. The procedure was uneventful in 10 patients (90.9%). Venous congestion was noted in 1 patient (9.1%), in whom secondary healing was achieved with conservative treatment.

One-stage reconstruction of complex lower extremity deformity combining Ilizarov external fixation and sural neurocutaneous flap.

BACKGROUND: Complex lower extremity deformities include multidirectional foot and ankle deformities, which are complicated therapeutic and surgical challenges. Correction often requires several stages, which is time consuming and costly. The need to restore the physical, mechanical, and cosmetic aspects of the lower extremity results in a difficult balancing act between these concerns and the deformity correction and soft tissue reconstruction. METHODS: Between January 2009 and September 2011, we treated 5 patients with multidirectional foot and ankle deformities. Significant mobility limitation was caused by abnormal scarring, which led to abnormal gait and weight-bearing regions. We used a sural neurocutaneous flap to repair the soft tissue defects after scar-tissue removal in all patients and placed a circular hinged Ilizarov external fixator for gradual correction. RESULTS: All the flaps survived and resulted in good texture match and contour. The follow-up period was 19 to 26 months. The correction lasted 3 to 5 months, and all of the patients were able to walk with satisfactory gaits and without assistance. We encountered no complications, such as pin-track infection or drop foot in our series. CONCLUSION: Our approach, combining a sural neurocutaneous flap and Ilizarov external fixation, was a reliable and effective tool for one-stage reconstruction of complex lower extremity deformities.

Bacterial Contamination of Open Fractures: Pathogens and Antibiotic Resistance Patterns in East China.

Bacterial contamination of soft tissue in open fractures leads to high infection rates. Pathogens and their resistance against therapeutic agents change with time and vary in different regions. The purpose of this study was to characterize the bacterial spectrum present in open fractures and analyze the bacterial resistance to antibiotic agents based on five trauma centers in East China. A retrospective multicenter cohort study was conducted in six major trauma centers in East China from January 2015 to December 2017. Patients who sustained open fractures of the lower extremities were included. The data collected included the mechanism of injury, the Gustilo-Anderson classification, the isolated pathogens and their resistance against therapeutic agents, as well as the prophylactic antibiotics administered. In total, 1348 patients were included in our study, all of whom received antibiotic prophylaxis (cefotiam or cefuroxime) during the first debridement at the emergency room. Wound cultures were taken in 1187 patients (85.8%); the results showed that the positive rate of open fracture was 54.8% (651/1187), and 59% of the bacterial detections occurred in grade III fractures. Most pathogens (72.7%) were sensitive to prophylactic antibiotics, according to the EAST guideline. Quinolones and cotrimoxazole showed the lowest rates of resistance. The updated EAST guidelines for antibiotic prophylaxis in open fracture (2011) have been proven to be adequate for a large portion of patients, and we would like to suggest additional Gram-negative coverage for patients with grade II open fractures based on the results obtained in this setting in East China.

Effectiveness of blood flow restriction versus traditional weight-bearing training in rehabilitation of knee osteoarthritis patients with MASLD: a multicenter randomized controlled trial.

To compare the reliability and effectiveness of blood blow restriction resistance training (BFR) versus traditional weight-bearing training (WB) in knee osteoarthritis (KOA) patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: This multicenter randomized controlled trial was conducted from January 2021 to June 2022 at Shanghai Jiao Tong University affiliated Sixth People's Hospital and The People's Hospital of Mengla County. A total of 120 outpatients were recruited and randomized to perform WB (n=60) or BFR (n=60) resistance training protocols in accordance with standard recommended protocols for 12 weeks. Demographic data and Kellgren and Lawrence grading system scores were collected. Pain, range of motion (ROM), scaled maximal isotonic strength (10RM), self-reported function (KOOS), and 30-s chair sit-to-stand test results were assessed at weeks 1, 4, and 12. Results: 112 patients (57 in the WB group, 55 in the BFR group) completed the training programs and assessments. No significant intergroup demographic differences were noted. ROM and scaled 10RM significantly increased at the 4- and 12-week assessments and differed significantly between groups. The pain, ability of daily living and quality of life subscale in KOOS increased significantly at the 12-week assessment and differed significantly between groups, adjusted for baseline value. Significant and comparable increases in 30-s chair sit-to-stand test results were observed within and between study groups. Conclusion: BFR training enhanced muscle strength, reduced pain, and improved daily living and sports activities in patients with KOA, compared to WB training alone. BFR should be recommended for rehabilitation in KOA individuals with MASLD. Clinical trial registration number: ChiCTR2100042872.

Relative efficacy of three different tendon repairs in complete flexor digitorum profundus laceration in Zone I: A randomized controlled study.

Hand flexor tendon injuries are common and biomechanically challenging to achieve good functional outcomes. Several approaches using the Pennington-modified Kessler repair technique have been attempted, but high-level evidence is still lacking. Here, we evaluated the relative efficacy of three versions of the Pennington-modified Kessler technique in repairing complete flexor digitorum profundus (FDP) laceration in Zone 1. We conducted a 2-year, single-center, double-blind, randomized clinical trial involving 85 patients with 105 digits enrolled between June 1, 2017 and January 1, 2019. Eligible participants were 20-60 years of age and underwent tendon repair in the acute phase for complete FDP laceration distal to the insertion of the superficial flexor tendon. The digits were randomized 1:1:1 to three treatment groups: (1) Pennington-modified Kessler repair; (2) Pennington-modified Kessler repair followed by circumferential tendon suture; or (3) Pennington-modified Kessler repair followed by circumferential epitenon suture. The primary endpoint was total active range of motion (TAROM) at 2 years after the initial surgery. The secondary endpoint was the reoperation rate. Compared with group 1, both techniques for peripheral suture were associated with a decrease in TAROM at 2 years after surgery. The total reoperation rates of the three groups were 11.4%, 18.2%, and 17.6%, and we found no significant differences among the three groups possibly due to the limited sample size. Unexpectedly, among participants with complete FDP laceration in Zone I, both circumferential-tendon and circumferential-epitenon sutures caused worsening of TAROM after 2 years. No conclusions can be drawn regarding reoperation rates among the groups. Level of evidence: Therapeutic level I.

Epidemiological updates of post-traumatic related limb osteomyelitis in china: a 10 years multicentre cohort study.

BACKGROUND: Post-traumatic related limb osteomyelitis (PTRLO) is a complex bone infection. Currently, there are no available microbial data on a national scale that can guide appropriate antibiotic selection, and explore the dynamic changes in dominant pathogens over time. This study aimed to conduct a comprehensive epidemiological analysis of PTRLO in China. METHODS: The study was approved by the Institutional Research Board (IRB), and 3526 PTRLO patients were identified from 212 394 traumatic limb fracture patients at 21 hospitals between 1 January 2008 and 31 December 2017. A retrospective analysis was conducted to investigate the epidemiology of PTRLO, including changes in infection rate (IR), pathogens, infection risk factors and antibiotic resistance and sensitivity. RESULTS: The IR of PTRLO increased gradually from 0.93 to 2.16% (Z=14.392, P <0.001). Monomicrobial infection (82.6%) was significantly higher than polymicrobial infection (17.4%) ( P <0.001). The IR of Gram-positive (GP) and Gram-negative (GN) pathogens showed a significant increase from the lowest 0.41% to the highest 1.15% (GP) or 1.62% (GN), respectively. However, the longitudinal trend of GP vs. GN's composition did not show any significance (Z=±1.1918, P >0.05). The most prevalent GP strains were Methicillin-sensitive Staphylococcus aureus (MSSA) (17.03%), Methicillin-resistant Staphylococcus aureus (MRSA) (10.46%), E. faecalis (5.19%) and S. epidermidis (4.87%). In contrast, the dominant strains GN strains were Pseudomonas Aeruginosa (10.92%), E. cloacae (10.34%), E. coli (9.47%), Acinetobacter Baumannii (7.92%) and Klebsiella Pneumoniae (3.33%). In general, the high-risk factors for polymicrobial infection include opened-fracture (odds ratio, 2.223), hypoproteinemia (odds ratio, 2.328), and multiple fractures (odds ratio, 1.465). It is important to note that the antibiotics resistance and sensitivity analysis of the pathogens may be influenced by complications or comorbidities. CONCLUSIONS: This study provides the latest data of PTRLO in China and offers trustworthy guidelines for clinical practice. (China Clinical Trials.gov number, ChiCTR1800017597).

Chiral Supramolecular Hydrogel Loaded with Dimethyloxalyglycine to Accelerate Chronic Diabetic Wound Healing by Promoting Cell Proliferation and Angiogenesis.

Chronic refractory wounds are one of the most serious complications of diabetes, and the effects of common treatments are limited. Chiral hydrogel combined with dimethyloxalyglycine (DMOG) as a dressing is a promising strategy for the treatment of chronic wounds. In this research, we have developed a DMOG-loaded supramolecular chiral amino-acid-derivative hydrogel for wound dressings for full-thickness skin regeneration of chronic wounds. The properties of the materials, the ability of sustained release drugs, and the ability to promote angiogenesis were tested in vitro, and the regeneration rate and repair ability of full-thickness skin were tested in vivo. The chiral hydrogel had the ability to release drugs slowly. It can effectively promote cell migration and angiogenesis in vitro, and promote full-thickness skin regeneration and angiogenesis in vivo. This work offers a new approach for repairing chronic wounds completely through a supramolecular chiral hydrogel loaded with DMOG.

[Clinical application of free peroneal artery perforator flap in soft tissue defect of foot and ankle].

OBJECTIVE: To investigate clinical application of the free peroneal artery perforator flap in soft tissue defect of foot and ankle. METHODS: The clinical data of 18 patients with soft tissue defects of foot and ankle who were repaired with free peroneal artery perforator flaps between March 2019 and March 2020 were retrospectively analyzed. Among them, there were 11 males and 7 females; the age ranged from 21 to 58 years, with an average age of 45 years. The defect was located in the ankle in 2 cases, in the hindfoot in 4 cases, in the midfoot in 5 cases, and in the forefoot in 7 cases. The causes of injury included 11 cases of traffic accident, 4 cases of machine injuries, 3 cases of infection and necrosis after internal fixation. The time from injury to flap repair was 12-48 days, with an average of 24 days. The range of wound was 3 cm×3 cm to 15 cm×8 cm, and the range of skin flap was 4 cm×3 cm to 16 cm×9 cm. The flap harvesting time, operation time, intraoperative blood loss, and complications were recorded; the flap survival and patient satisfaction were observed during follow-up; and the American Orthopaedic Foot and Ankle Society (AOFAS) foot function score was used to evaluate the foot function. RESULTS: The flap harvesting time was 15-33 minutes (mean, 22 minutes); the operation time was 120-160 minutes (mean, 150 minutes); the intraoperative blood loss was 90-180 mL (mean, 120 mL). There were 3 cases of vascular crisis after operation, including 2 cases of arterial crisis, which survived after vascular exploration and vein graft repair; 1 case of venous crisis, partial necrosis of the skin flap, and skin grafting to cover the wound after repeated debridement. The remaining 15 skin flaps survived completely. All patients were followed up 6 months. The skin flaps were in good shape without obvious bloat. According to the AOFAS foot function score, 5 cases were excellent, 10 cases were good, and 3 cases were fair. The excellent and good rate was 83.3%. CONCLUSION: The free peroneal artery perforator flap is easy to harvest, the shape and size of the flap are easy to design, and it does not damage the main blood vessels of the limb. The appearance and function of the limbs are satisfactory after operation. It can be widely used in the repair of soft tissue defects of the foot and ankle.

Platelet-Rich Plasma with Endothelial Progenitor Cells Accelerates Diabetic Wound Healing in Rats by Upregulating the Notch1 Signaling Pathway.

Diabetic wounds, as a kind of refractory wound, are very difficult to heal. Both endothelial progenitor cell (EPC) transplantation and platelet-rich plasma (PRP) can improve diabetic wound healing to some extent. However, PRP application cannot provide reparative cells, while EPC transplantation cannot replenish the required growth factors for wound healing. Thus, when applied alone, neither of these factors is sufficient for effective wound healing. Furthermore, the proliferation, differentiation, and fate of the transplanted EPCs are not well known. Therefore, in this study, we examined the efficacy of combined PRP application with EPC transplantation in diabetic wound healing. Our results indicated that PRP application improved EPC proliferation and migration. The Notch signaling pathway plays a key role in the regulation of the proliferation and differentiation of stem cells and angiogenesis in wound healing. The application of PRP upregulated the Notch pathway-related gene and protein expression in EPCs. Furthermore, experiments with shNotch1-transfected EPCs indicated that PRP enhanced the function of EPCs by upregulating the Notch1 signaling pathway. In vivo studies further indicated that the combination of PRP and EPC transplantation increased neovascularization, reduced wound size, and improved healing in rat wound models. Thus, PRP application can provide the necessary growth factors for wound healing, while EPC transplantation offers the required cells, indicating that the combination of both is a potent novel approach for treating diabetic wounds.

Establishing an Evaluation System and Limb-Salvage Protocol for Mangled Lower Extremities in China.

Road traffic accident-related severely injured extremities account for the majority of disabilities in young people in China. Limb-salvage concepts and techniques vary greatly from physician to physician and from district to district in China. Current severity-scoring systems for lower-extremity injuries lack sensitivity and cannot be used as the sole criterion by which amputation decisions are made. China lacks a national database of mangled lower extremities, which is a priority for both limb-salvage protocols and scoring system development.

Association between Serum Cholesterol Level and Osteoporotic Fractures.

OBJECTIVE: Previous epidemiological studies have found an association between serum cholesterol level and bone mineral density. However, epidemiological studies evaluating the association between serum cholesterol level and the incidence of osteoporotic fracture are scant. Therefore, the objective of this study was to investigate whether serum cholesterol levels in Chinese participants aged 55 years or older was associated with an increased risk of osteoporotic fracture. MATERIALS AND METHODS: We performed a cross-sectional study, including 1,791 participants (62.1% postmenopausal women and 213 fractures). Standardized self-administered questionnaires, physical examination, laboratory tests, and dual-energy X-ray absorptiometry examination were performed. Multivariate-adjusted logistic regression models were used to evaluate associations between serum cholesterol [total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C)] levels and the osteoporotic fracture risk. RESULTS: After adjusting for potential confounding factors, there were no associations between per SD increase in TC and LDL level and an increased risk of osteoporotic fracture in total participants, and in men and women as individual groups. There was a significant association between per SD increase in HDL-C level and an increased risk of osteoporotic fracture in total participants [odds ratios (OR) 1.20, 95% confidence interval (CI) 1.03, 1.40, P = 0.023] and in women (OR 1.37, 95% CI 1.12, 1.68, P = 0.003), whereas no association was observed in men (OR 1.01, 95% CI 0.73, 1.40, P = 0.951). Additionally, we found a significant association between per SD increase in TG level and an increased risk of osteoporotic fracture in total participants (OR 1.20, 95% CI 1.04, 1.38, P = 0.015). In women, a nonlinear relationship was observed between per SD increase in TG level and an increased risk of osteoporotic fracture. The risk of osteoporotic fracture in women increased with TG level >1.64 mmol/L (OR 1.93, 95% CI 1.24, 3.00, P = 0.004). CONCLUSION: Among Chinese older adults, serum HDL-C level is significantly associated with a risk of osteoporotic fractures in women, and serum TG level is significantly associated with a risk of osteoporotic fractures in total participants and in women with TG >1.64 mmol/L.

Association of Nonalcoholic Fatty Liver Disease With Osteoporotic Fractures: A Cross-Sectional Retrospective Study of Chinese Individuals.

Objective: Nonalcoholic fatty liver disease (NAFLD) is related to several inflammatory or metabolic diseases. However, findings of previous studies investigating the association between NAFLD and BMD are inconsistent. Only one study reported a potential association between NAFLD and osteoporotic fracture. This study investigated whether NAFLD in older participants (>55 years) was associated with osteoporotic fracture risk. Materials and Methods: This cross-sectional, observational study included 2,695 participants (35.7% men, 614 cases of NAFLD, and 383 fractures). Standardized questionnaires, laboratory tests, and physical and ultrasonic examinations were completed. Results: After adjusting for various factors including serum triglycerides (TG), high-density cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), multivariate logistic regression models revealed a marginal association between NAFLD and osteoporotic fracture risk in men (odds ratio [OR], 1.86; 95% confidence interval [CI], 1.06-3.27; P = 0.030) but no association in women (OR, 1.05; 95% CI, 0.74-1.48; P = 0.800). Further stratified analyses showed a significant association between NAFLD and osteoporotic fracture risk in men without high TG, low HDL-C, and high LDL-C. Conclusions: There was a significant association between NAFLD and osteoporotic fracture risk in older Chinese men, particularly men without dyslipidemia.

Paeoniflorin regulates osteoclastogenesis and osteoblastogenesis via manipulating NF-κB signaling pathway both in vitro and in vivo.

The metabolic balance between synthesis and resorption of the bone is maintained by osteoblasts and osteoclasts, respectively. Identification of agents that stimulate bone formation and suppress excessive osteoclast formation, may aid in preventing and treating conditions like osteoporosis and periprosthetic loosening. Paeoniflorin is a natural product derived from Paeonia lactiflora Pall with anti-inflammatory, analgesic, and diuretic properties. However, the effect of paeoniflorin on osteoclastogenesis and osteoblastogenesis is unknown. Herein, we demonstrated that paeoniflorin has a dose-dependent suppressive action on RANKL-evoked osteoclast differentiation and bone resorption, achieved by inhibiting the NF-κB pathway and subunit p65 nuclear translocation. Simultaneously, paeoniflorin was also found to stimulate osteoblast differentiation and bone mineralization, in addition to rescuing TNFα-impaired osteoblastogenesis. At the molecular level, paeoniflorin was found to inhibit NF-κB transcriptional activity and stimulate osteoblastogenesis-related marker gene expression (ALP, osteocalcin, OPN and Runx2), a trend that was inhibited by p65 overexpression. In ovariectomized mice, paeoniflorin was found to improve osteoblast activity, inhibit osteoclast activity, and thus, reduce ovariectomy-induced osteoporosis. Our study demonstrated that paeoniflorin simultaneously suppressed osteoclastogenesis and facilitated osteoblastogenesis by manipulating the actions of NF-κB. Therefore, paeoniflorin may serve as an ideal therapeutic antidote for osteoporosis.