A Bone-Penetrating Precise Controllable Drug Release System Enables Localized Treatment of Osteoporotic Fracture Prevention via Modulating Osteoblast-Osteoclast Communication.

Improving local bone mineral density (BMD) at fracture-prone sites of bone is a clinical concern for osteoporotic fracture prevention. In this study, a featured radial extracorporeal shock wave (rESW) responsive nano-drug delivery system (NDDS) is developed for local treatment. Based on a mechanic simulation, a sequence of hollow zoledronic acid (ZOL)-contained nanoparticles (HZNs) with controllable shell thickness that predicts various mechanical responsive properties is constructed by controlling the deposition time of ZOL and Ca2+ on liposome templates. Attributed to the controllable shell thickness, the fragmentation of HZNs and the release of ZOL and Ca2+ can be precisely controlled with the intervention of rESW. Furthermore, the distinct effect of HZNs with different shell thicknesses on bone metabolism after fragmentation is verified. In vitro co-culture experiments demonstrate that although HZN2 does not have the strongest osteoclasts inhibitory effect, the best pro-osteoblasts mineralization results are achieved via maintaining osteoblast-osteoclast (OB-OC) communication. In vivo, the HZN2 group also shows the strongest local BMD enhancement after rESW intervention and significantly improves bone-related parameters and mechanical properties in the ovariectomy (OVX)-induced osteoporosis (OP) rats. These findings suggest that an adjustable and precise rESW-responsive NDDS can effectively improve local BMD in OP therapy.

The changing trends of the knee function after anterior and posterior cruciate ligaments reconstruction with all-inside arthroscopy technique.

We aimed to summarize the effectiveness and changing trends of reconstruction for the anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) injuries using all-inside arthroscope technique. Between May 2013 and May 2019, 29 patients with ACL and PCL ligaments rupture were included. All the patients were male, with a mean age of 25.2±2.9 years. The mean follow-up period was 2.4±0.7 years (Range, 2-4 years). Reconstruction surgery of the ACL and PCL ligaments was performed by using autologous hamstring tendon with all-inside arthroscopy technique. The anterior and posterior drawer test, Lachman test, Pivot-shift test, stress test, IKDC score, Lysholm score, Tenger score were analyzed clinically. At the last follow-up, the symptoms were improved significantly, the anterior drawer test was normal and 1 degree in 96.6%, posterior drawer test in 89.7%, pivot shift test in 96.6%, Lachman test in 93.1%, and stress test in 93.3%, the stability was improved significant(P<0.05). The IKDC-2000 standard score was normal and near normal in 96.6%. The IKDC subjective score, Lysholm score, and Tenger scores results at the last follow-up were significantly improved when compared with those before operation ( P<0.05). The changing trends of function evaluation score in the first six months were most obviously better, especially in the third month. All-inside arthroscopy technique is an effective procedure for the ACL and PCL ligaments injuries, and the first six months (especially the third month) after the reconstruction is the key period for a successful recovery. However, there was still a significant improvement at the later stage of rehabilitation.

Au Nanoparticles Attenuate RANKL-Induced Osteoclastogenesis by Suppressing Pre-Osteoclast Fusion.

Osteoclasts are multinucleated terminal cells that originate from a hematopoietic monocyte/macrophage lineage. Excessive osteoclast formation in vivo can lead to bone metabolic diseases such as postmenopausal osteoporosis, multiple myeloma, rheumatoid arthritis, and lytic bone metastases of cancer cells. Au nanoparticles (AuNPs) are inorganic nanoparticles with outstanding biocompatibility. We assessed their effect on osteoclastogenesis and found that pre-osteoclast fusion induced by receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colonystimulating factor (M-CSF) was suppressed by AuNPs. Cell migration and actin ring formation were also significantly inhibited. Finally, AuNPs reduced osteoclast bone absorption function. Interestingly, we observed altered fusogenic gene expression in treated pre-osteoclasts. Our results suggest that AuNPs have potential as a therapeutic agent for osteoclast-related bone metabolism diseases.

Clinical efficacy of individual extracorporeal shockwave treatment.

BACKGROUND: This retrospective study investigated the clinical efficacy of individual extracorporeal shockwave treatment (IESWT) for early stage osteonecrosis of the femoral head (ONFH). MATERIAL AND METHODS: The study included 56 patients (89 hips) with 28 patients (46 hips) in the IESWT group and 28 patients (43 hips) in the conventional ESWT (CESWT) group. The ONFH was caused by the use of steroids, trauma and alcohol consumption. The IESWT focal point was from the front of the femoral head and the exposed necrotic tissue in 3D environment was guided by simulation software. The CESWT focal point was the side of the femoral head and guided by MRI and X­ray imaging. The evaluation standards included VAS score, Harris hip score (HHS), necrosis volume and healing rate. RESULTS: For the healing rate the results were 66.67% were improved, 21.43% unimproved and 11.90% aggravated in the CESWT group and 77.78% improved, 17.78% unimproved and 4.45% aggravated in the IESWT group. Statistically significant differences were observed in the healing rate between the two groups (P < 0.05). This retrospective study demonstrated that the healing rate for IEWST was higher than for CEWST. There were no statistically significant differences in the VAS score and the HHS between the two groups (P > 0.05). The effects of pain relief and functional recovery were not obvious and according to our clinical experience this may be due to a short clinical observation time where a longer time might result in better clinical results. Statistically significant differences were observed in the necrosis volume after 18 months between the 2 groups (P < 0.05) and implied that IESWT can significantly reduce the volume of necrosis. The volume after 18 months in the IESWT group was significantly improved compared with baseline (P < 0.05). CONCLUSION: The use of IESWT can significantly reduce the necrosis volume. No complications were found.

Highly Dispersed Fullerenols Hamper Osteoclast Ruffled Border Formation by Perturbing Ca2+ Bundles.

Osteoporosis, a common and serious bone disorder affecting aged people and postmenopausal women, is characterized by osteoclast overactivity. One therapeutic strategy is suppressing the bone resorption function of hyperactive osteoclasts, but there is no effective drug in clinical practice so far. Herein, it is demonstrated that fullerenols suppress the bone resorption of osteoclasts by inhibiting ruffled borders (RBs) formation. The RBs formation, which is supported by well-aligned actin bundles (B-actins), is a critical event for osteoclast bone resorption. To facilitate this function, osteoclast RBs dynamics is regulated by variable microenvironments to bundle F-actins, protrude cell membrane, and so on. B-actin perturbation by fullerenols is determined here, offering an opportunity to regulate osteoclast function by destroying RBs. In vivo, the therapeutic effect of fullerenols on overactive osteoclasts is confirmed in a mouse model of lipopolysaccharide-induced bone erosion. Collectively, the findings suggest that fullerenols adhere to F-actin surfaces and inhibit RBs formation in osteoclasts, mainly through hampering Ca2+ from bundling F-actins, and this is likely due to the stereo-hindrance effect caused by adherent fullerenols.

Small size fullerenol nanoparticles inhibit thrombosis and blood coagulation through inhibiting activities of thrombin and FXa.

Thrombus is one of main causes of death in the world and also a vital trouble of biomaterials application in vivo. Recently, effect of fullerenol nanomaterials on anticoagulation was found in our research through extension of bleeding times in treated Sprague-Dawley rats via intravenous injection. Inhibiting of fullerenols on thrombosis was ascertained further by thromboembolism model. Effects of fullerenols on intrinsic and extrinsic pathway were distinct in prolonging activated partial thromboplastin time and prothrombin time, which supported that fullerenols induced defects in both pathways. Inhibited activities of activated coagulation factor X (FXa) and thrombin were verified by experiments in vitro and AutoDock Vina. The results suggest that fullerenols depending on small size and certainly surface property occupied the active domain of FXa and thrombin to block their activity; further, thrombosis was inhibited. This putative mechanism offers an insight into how fullerenol NPs were utilized further in biomedical applications.

Paravertebral Muscular Neurophysiological Function as an Independent Outcome Predictor of Recurring Herniation/Low Back Pain after Radiofrequency Ablation: A Prospective Follow-Up and Case-Control Study Based on Surface Electromyography.

OBJECTIVE: Spinal endoscopy radiofrequency is a minimally invasive technique for lumbar disc herniation (LDH) and low back pain (LBP). However, recurring LDH/LBP following spinal endoscopy radiofrequency is a significant problem. Paravertebral musculature plays a crucial role in spine stability and motor function, and the purpose of the present study was to identify whether patients' baseline lumbar muscular electrophysiological function could be a predictor of recurring LDH/LBP. METHODS: This was a prospective follow-up and case-control study focusing on elderly patients with LDH who were treated in our department between January 1, 2018, and October 31, 2021. The end of follow-up was recurring LBP, recurring LDH, death, missing to follow-up or 2 years postoperation. The surface electromyography test was performed before the endoscopy C-arm radiofrequency (ECRF) operation to detect the flexion-relaxation ratio (FRR) of the lumbar multifidus (FRRLM ) and the longissimus erector spinae (FRRES ), and the other baseline parameters included the general characteristics, the visual analogue scale, the Japanese Orthopaedic Association score, and the Oswestry Disability Index. Intergroup comparisons were performed by independent t-test and χ2 -test, and further binary logistic regression analysis was performed. RESULTS: Fifty-four patients completed the 2-year follow-up and were retrospectively divided into a recurring LDH/LBP group (Group R) (n = 21) and a no recurring group (Group N) (n = 33) according to their clinical outcomes. FRRLM and FRRES in Group N were much higher than those in Group R (p < 0.001, p = 0.009). Logistic regression analysis showed that only the FRRLM (odds ratio [OR] = 0.123, p = 0.011) and FRRES (OR = 0.115, p = 0.036) were independent factors associated with the ECRF outcome. CONCLUSIONS: Lumbar disc herniation patients' baseline FRRLM and FRRES are independent outcome predictors of recurring LDH/LBP after ECRF. For every unit increase in baseline FRRLM , the risk of recurring LDH/LBP is decreased by 87.7%, and for every unit increase in baseline FRRES , the risk of recurring LDH/LBP is decreased by 88.5%.

Efficacy of extracorporeal shockwave therapy for knee osteoarthritis: a randomized controlled trial.

BACKGROUND: Extracorporeal shockwave therapy (ESWT) has been widely used for pain relief and treatment of musculoskeletal disorders. We aimed to assess ESWT for knee osteoarthritis (OA) over 12 wk by comparison with placebo treatment. MATERIALS AND METHODS: We randomized 70 patients to receive placebo (n = 36) or ESWT (n = 34). For ESWT, patients received 4000 pulses of shockwave at 0.25 mJ/mm(2) weekly for 4 wk. In the placebo group, patients received shockwave at 0 mJ/mm(2) in the same area. The effect on OA was assessed by pain on a visual analog scale and disability on the Lequesne index, Western Ontario and McMaster University Osteoarthritis Index, and patient perception of the clinical severity of OA. Evaluation was performed at baseline and after 1, 4, and 12 wk. RESULTS: We found no adverse events during and after ESWT. ESWT was more effective than placebo in reducing pain on movement at each period (P < 0.01). The mean visual analog scale score with ESWT was 3.83 at 12 wk versus 7.56 at baseline (P < 0.01). The Lequesne index and the Western Ontario and McMaster University Osteoarthritis Index score were reduced with ESWT. Moreover, patient perception of clinical severity of OA was significantly greater with ESWT than that with placebo (P < 0.01). CONCLUSIONS: ESWT is effective in reducing pain and improving knee function, with better results than placebo during the 12-wk treatment. However, further pilot studies are needed to determine whether ESWT should be recommended at an early or later stage of OA or combined with conventional therapies.

The Efficacy of Microfracture Combined with Extracorporeal Shock Wave Therapy for Treating Osteochondral Lesion of the Talus and the Quality of Regenerated Cartilage: A Retrospective Cohort Study and MRI Assessment.

BACKGROUND: osteochondral lesion of the talus (OLT) is a common disease in the physically active population, and extracorporeal shock wave therapy (ESWT) is a noninvasive treatment. We hypothesized that microfracture (MF) combined with ESWT may have great potential to become a novel combination treatment of OLT. METHODS: the OLT patients who received MF + ESWT or MF + platelet-rich plasma (PRP) injection were retrospectively included, with a minimal follow up of 2y. The daily activating VAS, exercising VAS, and American Orthopedic Foot and Ankle Society Ankle-Hindfoot Score (AOFAS) were used to assess the efficacy and functional outcome, and ankle MRI T2 mapping was used to evaluate the quality of regenerated cartilage in the OLT patients. RESULTS: only transient synovium-stimulated complications were found during the treatment sessions; the complication rate and daily activating VAS did not have differences between groups. MF + ESWT had a higher AOFAS and a lower T2 mapping value than MF + PRP at the 2y follow up. CONCLUSIONS: the MF + ESWT had superior efficacy for treating OLT, which resulted in better ankle function and more hyaline-like regenerated cartilage, superior to the traditional MF + PRP.

Effects of individual shock wave therapy vs celecoxib on hip pain caused by femoral head necrosis.

BACKGROUND: Celecoxib has been used to treat hip discomfort and functional difficulties associated with osteonecrosis of the femoral head (ONFH), although significant adverse reactions often follow long-term use. Extracorporeal shock wave therapy (ESWT) can delay the progression of ONFH, alleviate the pain and functional limitations it causes, and avoid the adverse effects of celecoxib. AIM: To investigate the effects of individual ESWT, a treatment alternative to the use of celecoxib, in alleviating pain and dysfunction caused by ONFH. METHODS: This was a randomized, controlled, double-blinded, non-inferiority trial. We examined 80 patients for eligibility in this study; 8 patients were excluded based on inclusion and exclusion criteria. A total of 72 subjects with ONFH were randomly assigned to group A (n = 36; celecoxib + alendronate + sham-placebo shock wave) or group B (n = 36; individual focused shock wave [ESWT based on magnetic resonance imaging three-dimensional (MRI-3D) reconstruction] + alendronate). The outcomes were assessed at baseline, at the end of treatment, and at an 8-wk follow-up. The primary outcome measure was treatment efficiency after 2 wk of intervention using the Harris hip score (HHS) (improvement of 10 points or more from the baseline was deemed sufficient). Secondary outcome measures were post-treatment HHS, visual analog scale (VAS), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores. RESULTS: After treatment, the pain treatment efficiency of group B was greater than that of group A (69% vs 51%; 95%CI: 4.56% to 40.56%), with non-inferiority thresholds of -4.56% and -10%, respectively. Furthermore, the HHS, WOMAC, and VAS scores in group B dramatically improved during the follow-up period as compared to those in group A (P < 0.001). After therapy, the VAS and WOMAC in group A were significantly improved from the 2nd to 8th wk (P < 0.001), although HHS was only significantly altered at the 2 wk point (P < 0.001). On the 1st d and 2nd wk after treatment, HHS and VAS scores were different between groups, with the difference in HHS lasting until week 4. Neither group had severe complications such as skin ulcer infection or lower limb motor-sensory disturbance. CONCLUSION: Individual shock wave therapy (ESWT) based on MRI-3D reconstruction was not inferior to celecoxib in managing hip pain and restrictions associated with ONFH.

Comparative study of the clinical efficacy of all-inside and traditional techniques in anterior cruciate ligament reconstruction.

BACKGROUND: Many studies have focused on the femoral tunnel technique and fixation method, but few studies have involved the tibial tunnel technique and fixation method. The all-inside technique is one of the new techniques that has been described in recent years. All-inside anterior cruciate ligament (ACL) reconstruction is based on a tibial socket instead of a full tunnel. This method has many potential advantages. AIM: To compare clinical outcomes of knee ACL autograft reconstruction using all-inside quadrupled semitendinosus (AIST) and traditional hamstring tendon (TBT) techniques. METHODS: From January 2017 to October 2019, the clinical data of 80 patients with ACL reconstruction were retrospectively analyzed, including 67 males and 13 females. The patients had an average age of 24.3 ± 3.1 years (age range: 18-33 years). The AIST technique was used in 42 patients and the TBT technique was used in 38 patients. The time between operation and injury, operative duration, postoperative visual analogue scale (VAS) score and knee functional recovery were recorded and compared between the two groups. The International Knee Documentation Committee (IKDC) and Lysholm scoring system were used to comprehensively evaluate clinical efficacy. RESULTS: Eighty patients were followed for 24-36 mo, with an average follow-up duration of 27.5 ± 1.8 mo. There were no significant differences in the time between surgery and injury, operative duration, IKDC and Lysholm scores of the affected knee at the last follow-up evaluation between the two groups. There were significant differences in VAS scores 1 d, 3 d, 7 d, 2 wk and 1 mo after surgery (P < 0.05). There was no significant difference in VAS score at 3 mo, 6 mo and 1 year after operation. CONCLUSION: The efficacy of the AIST ACL reconstruction technique was comparable to the TBT technique, but the postoperative pain was less with the AIST technique. Thus, the AIST technique is an ideal treatment choice for ACL reconstruction.

Extracorporeal shock-wave therapy reduces progression of knee osteoarthritis in rabbits by reducing nitric oxide level and chondrocyte apoptosis.

INTRODUCTION: The goal for treating osteoarthritis (OA) is finding ways to decrease joint pain and dysfunction and prevent and slow the cartilage degeneration. Extracorporeal shock-wave therapy (ESWT) has been found to improve motor dysfunction and ameliorate pain with OA in animals. However, few studies have found that it can prevent and slow joint degeneration in vivo. The aim of study was to investigate the effect of ESWT on OA in rabbit. MATERIALS AND METHODS: A total of 30 male New Zealand white rabbits were divided into 3 groups: control, OA induced by anterior cruciate ligament transaction (ACLT), and ALCT plus ESWT. The animals were killed at 4 and 8 weeks. Nitric oxide (NO) level was measured in the synovial cavity of knee joints, and cartilage sections were graded macroscopically by a Mankin scoring system. Chondrocyte apoptosis was investigated by flow cytometry and the expression of active caspase 3 by indirect immunohistochemistry. RESULTS: ESWT significantly reduced the NO level in the synovial cavity of knee joints (P < 0.05) and chondrocyte apoptosis (P < 0.05) of rabbits with OA. ESWT treatment significantly decreased the severity of cartilage lesions at both times as compared to rabbits with OA alone (P < 0.05). CONCLUSION: ESWT reduced the progression of OA in rabbits. This effect may be related to decreased level of NO and is likely mediated by reduced chondrocyte apoptosis. ESWT may be a useful treatment for knee OA.

[Arthroscopic Pushlock anchor fixation with iliac creast bone autograft in the treatment of recurrent anterior shoulder instability with critical bone defect].

OBJECTIVE: To evaluate the effectiveness of arthroscopic Pushlock anchor fixation with iliac creast bone autograft in the treatment of recurrent anterior shoulder instability with critical bone defect. METHODS: The clinical data of 80 patients with recurrent anterior shoulder instability with critical bone defect treated by arthroscopic Pushlock anchor fixation with iliac creast bone autograft between January 2016 and January 2019 were retrospectively analyzed. The patients were all male; they were 18-45 years old at the surgery, with an average of 25 years old. The disease duration ranged from 3 months to 5 years, with an average of 2 years. The shoulder joint dislocated 3-50 times, with an average of 8 times. X-ray films, MRI, CT scans and three-dimensional reconstruction of the shoulder were performed before operation. The area of the anterior glenoid defect was 25%-45%, with an average of 27.3%. The shoulder mobility (forward flexion and external rotation in abduction at 90°), the Constant-Murley score, and the Rowe score were used to evaluate the shoulder function before operation and at last follow-up. RESULTS: Patients were followed up 1-3 years, with an average of 2 years. No shoulder dislocation occurred again during follow-up. All partial graft absorption occurred after operation, CT scan showed that the graft absorption ratio was less than 30% at 1 week and 3 months after operation. CT three-dimensional reconstruction at 1 year after operation showed that all grafts had healed to the glenoid. The anterior glenoid bone defect was less than 5% (from 0 to 5%, with an average of 3.2%). At last follow-up, the shoulder mobility (forward flexion and external rotation in abduction at 90°), the Constant-Murley score, and the Rowe score significantly improved when compared with preoperative ones ( P<0.05). The shoulder mobility of external rotation in abduction at 90° of the affected side limited when compared with the healthy side [(6.7±5.1)°]. CONCLUSION: Arthroscopic Pushlock anchor fixation with iliac creast bone autograft has a good effectiveness in the treatment of recurrent anterior shoulder instability with critical bone defect. The method is relatively simple and the learning curve is short.

Arthroscopy with subscapularis upper one-third tenodesis for treatment of recurrent anterior shoulder instability independent of glenoid bone loss.

BACKGROUND: Recurrent anterior shoulder instability is a common traumatic injury, the main clinical manifestation of which is recurrent anteroinferior dislocation of the humeral head. The current follow-up study showed that the effect of arthroscopic Bankart repair is unreliable. AIM: To evaluate the clinical efficacy of arthroscopy with subscapularis upper one-third tenodesis for treatment of anterior shoulder instability, and to develop a method to further improve anterior stability and reduce the recurrence rate. METHODS: Between January 2015 and December 2018, male patients with recurrent anterior shoulder instability were selected. One hundred and twenty patients had a glenoid defect < 20% and 80 patients had a glenoid defect > 20%. The average age was 25 years (range, 18-45 years). Patients with a glenoid defect < 20% underwent arthroscopic Bankart repair with a subscapularis upper one-third tenodesis. The patients with a glenoid defect > 20% underwent an arthroscopic iliac crest bone autograft with a subscapularis upper one-third tenodesis. All patients were assessed with Rowe and Constant scores. RESULTS: The average shoulder forward flexion angle was 163.6° ± 8.3° and 171.8° ± 3.6° preoperatively and at the last follow-up evaluation, respectively. The average external rotation angle when abduction was 90° was 68.4° ± 13.6° and 88.5° ± 6.2° preoperatively and at the last follow-up evaluation, respectively. The mean Rowe scores preoperatively and at the last follow-up evaluation were 32.6 ± 3.2 and 95.2 ± 2.2, respectively (P < 0.05). The mean Constant scores preoperatively and at the last follow-up evaluation were 75.4 ± 3.5 and 95.8 ± 3.3, respectively (P < 0.05). No postoperative dislocations were recorded by the end of the follow-up period. CONCLUSION: Arthroscopy with subscapularis upper one-third tenodesis was effective for treatment of recurrent anterior shoulder instability independent of the size of the glenoid bone defect, enhanced anterior stability of the shoulder, and did not affect postoperative range of motion of the affected limb.

Impact of soft tissue around the knee on the efficacy of extracorporeal shockwave therapy in knee osteoarthritis.

Knee osteoarthritis (KOA) is the leading cause of knee pain in middle-aged and older individuals. Extracorporeal shockwave therapy (ESWT) has been applied to treat patients with KOA to reduce pain and improve function. Patients (n = 123) diagnosed with KOA who received ESWT were selected to participate in this study, and were grouped according to their body mass index (BMI). The treatment parameters were as follows: 8000 pulses, 2.0 bar, 0.25 mJ/mm2, and 6 Hz/s once per week for 8 weeks. The visual analog scale (VAS), Lequesne index, and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) were measured to assess knee pain and functional recovery according to BMI groups. Radiographs were used to measure the richness of the soft tissue around the knee joint. The correlation between the distribution of tissue, pain, and functional improvement was analyzed using the receiver operator characteristic curve. All the patients showed a reduction in pain after treatment compared to that before treatment (P < .01). As measured by the VAS, the Lequesne and WOMAC indexes, after the intervention, the pain and functional index of the overweight and above BMI group improved to a greater extent than that of the normal or below normal BMI group (P < .01). The area under the curve showed, with VAS as the demarcation criterion, when the tibial plateau soft tissue ratio, femoral intercondylar apex soft tissue ratio, and medial tibial soft tissue ratio exceeded 1.538, 1.534, and 1.296, respectively, the patient's pain relief was more pronounced the ESWT treatment was better. With pain in WOMAC as the demarcation criterion, the tibial plateau soft tissue ratio, femoral intercondylar apex soft tissue ratio, and medial tibial soft tissue ratio also are positively correlated with pain relief in patients. When the Lequesne and WOMAC scores were the demarcation criteria, the patients' function improved significantly when the patella apical soft tissue ratio exceeded 2.401 and 2.635, respectively. ESWT can effectively alleviate pain and improve knee function in patients with KOA, and the soft tissue around the knee joint should also be an important reference factor in KOA treatment.

Modulated podosome patterning in osteoclasts by fullerenol nanoparticles disturbs the bone resorption for osteoporosis treatment.

Overactivation and excessive differentiation of osteoclasts (OCs) has been implicated in the course of bone metabolism-related diseases. Although fullerenol nanoparticles (fNPs) have been suggested to inhibit OC differentiation and OC function in our previous work, systemic studies on the effect of fNPs on bone diseases, e.g., osteoporosis (OP), in vivo remain elusive. Herein, it is demonstrated that fNPs significantly suppress the differentiation of OCs that derived from the murine bone marrow monocytes and inhibit the formation of the sealing zone by blocking the formation and patterning of podosomes in OCs spatiotemporally. In vivo, fNPs are supposed to be an efficient inhibitor of the overactivation of OCs in a LPS-induced bone erosion mouse model. The therapeutic effect of fNPs on osteoporosis is also investigated in an ovariectomy-induced osteoporosis rat model. The well-organized trabecular bone, the reduction in the number of TRAP positive cells, the improvement of bone-associated parameters, and the mechanical properties all demonstrate that fNPs, similar to diphosphonates, can be a promising candidate for the effective treatment of osteoporosis.

Correction: Modulated podosome patterning in osteoclasts by fullerenol nanoparticles disturbs the bone resorption for osteoporosis treatment.

Correction for 'Modulated podosome patterning in osteoclasts by fullerenol nanoparticles disturbs the bone resorption for osteoporosis treatment' by Kui Chen et al., Nanoscale, 2020, 12, 9359-9365, DOI: 10.1039/D0NR01625J.

Carboxylated gold nanoparticles inhibit bone erosion by disturbing the acidification of an osteoclast absorption microenvironment.

Hyperactive osteoclasts (OCs) are a fundamental reason for excessive bone resorption and consequent osteoporosis that lead to one-third of the patients sustaining a fracture. OCs, with the help of acidifying vesicles containing vacuolar-type H+-ATPase (V-ATPase), transport cytoplasmic protons into a resorptive pit and create an acidic microenvironment where proteolytic enzymes degrade the bone matrix. Here, we report a previously undescribed application of gold nanoparticles (AuNPs) to inhibit excessive bone resorption by regulating the acidic microenvironment in which OCs resorb bone. Internalized AuNPs, with relatively abundant carboxyl groups, eventually accumulate in the membrane of the intracellular vesicles and interact with the V0 domain of V-ATPase, which prevents it from recruiting the V1 domain. This destroys the acid-secretion function of OCs. The therapeutic effect of AuNPs on bone resorption was assessed in an established lipopolysaccharide-induced bone erosion mouse model. Micro-computed tomography, histology, and tartrate-resistant acid phosphatase staining showed that AuNPs significantly reduced bone erosion. In summary, AuNPs are promising nano-functional materials for repairing bone defects by regulating OC acid secretion.

The BMP signaling pathway enhances the osteoblastic differentiation of bone marrow mesenchymal stem cells in rats with osteoporosis.

BACKGROUND: This study was conducted with the aim of exploring the effect of the BMP signaling pathway on osteoblastic differentiation in rat bone marrow mesenchymal stem cells (rBMSCs) in rats with osteoporosis (OP). METHODS: The bilateral ovaries of female SD rats were resected for the establishment of a rat OP model. The osteoblastic differentiation of isolated rBMSCs was identified through osteogenic induction. Adipogenetic induction and flow cytometry (FCM) were used to detect adipogenic differentiation and the expression of rBMSC surface markers. The rBMSCs were grouped into the blank group, NC group, si-BMP2 group, and oe-BMP2 group. The expression levels of key factors and osteogenesis-related factors were determined by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR). The formation of calcified nodules was observed by alizarin red staining. ALP activity was measured by alkaline phosphatase staining. RESULTS: The rats with OP had greater weight but decreased bone mineral density (BMD) than normal rats (all P < 0.01). The rBMSCs from rats with OP were capable of osteoblastic differentiation and adipogenic differentiation and showed high expression of CD44 (91.3 ± 2.9%) and CD105 (94.8 ± 2.1%). Compared with the blank group, the oe-BMP2 group had elevated BMP-2 and Smad1 levels and an increase in calcified nodules and ALP-positive staining areas (all P < 0.05). Moreover, the expression levels of Runx2, OC, and OPN in the oe-BMP2 group were relatively higher than those in the blank group (all P < 0.05). The findings in the si-BMP2 group were opposite to those in the oe-BMP2 group. CONCLUSION: BMP signaling pathways activated by BMP-2 can promote the osteoblastic differentiation of rBMSCs from rats with OP.

The effect of extracorporeal shock wave therapy on the treatment of moderate to severe knee osteoarthritis and cartilage lesion.

BACKGROUND: Knee osteoarthritis (KOA) is a major cause leading to chronic bone and muscle pain. Extracorporeal shock wave therapy (ESWT) has been applied in treating KOA in recent years. METHODS: From April 2016 to April 2017, 82 patients were diagnosed with KOA that received ESWT were selected as the ESWT group. The treatment parameters were as follows, 2.0 bar, 0.25 mJ/mm, and 8 Hz/s for twice a week for 4 weeks continuously. In addition, 104 patients receiving oral administration of nonsteroidal anti-inflammatory drugs (NSAIDs) from April 2015 to April 2016 were also selected as the NSAIDs group. At 4, 8, 12, and 16 weeks upon the completion of treatment, the Visual Analogue Scale (VAS) and Western Ontario and McMaster Universities Arthritis Index (WOMAC) were adopted to evaluate the changes in pain and function of patients in both groups. For the ESWT group, the 50-m quick walk time and gait analysis were applied to observe the functional recovery at 4, 8, 12, and 16 weeks upon the completion of treatment; meanwhile, patients were followed up by magnetic resonance imaging (MRI) at 24 weeks upon the completion of treatment, so as to observe the cartilage changes. RESULTS: Differences in VAS, 4, 8, and 12 weeks after treatment were statistically significant compared with that before treatment (4.59 ±â€Š0.5, P < .05; 2.55 ±â€Š0.5, P < .05; 4.39 ±â€Š0.49, P < .05). Differences in 4, 8, and 12 weeks after treatment were statistically significant compared with that before treatment (90.41 ±â€Š6.64, P < .05; 59.94 ±â€Š3.19, P < .05; 90.49 ±â€Š6.87, P < .05). Gait analysis suggested differences in 50 m walk time, walking speed, swing phase, and stance phase 8 weeks after treatment were statistically significant compared with that before treatment (36.23 ±â€Š4.08, P < .05; 1.25 ±â€Š0.09, P < .05; 58.56 ±â€Š0.87, P < .05; 41.44 ±â€Š0.87, P < .05). Differences in the VAS and WOMAC at 4 and 8 weeks after treatment between ESWT group and NASIDs group were not statistically significant. CONCLUSIONS: The ESWT has potential in reducing pain and improving knee function, and the therapeutic effects may peak at 8 weeks after the completion of treatment. Further research is needed to arrive at a definitive conclusion.