Osteoporotic Injuries Research Articles

Bu-Sui-Dan Enhances Osteoblast Differentiation by Upregulating VGLL4 to Counteract TEAD4-Mediated RUNX2 Transcription Suppression in Ovariectomized Rats

Ethnopharmacological relevancePostmenopausal osteoporosis (PMOP) has been considered as a major causative factor for bone-joint pain and inducing pathologic fractures. Bu-Sui-Dan (BSD), a classic ancient herbal formula, has been shown to exhibit osteoprotective effects by promoting bone marrow development and bone growth. However, the exact mechanism of BSD are still unexplored. Aim of studyThe study aimed to investigate the protective effect of BSD against osteoporotic injury, and to explore whether BSD regulated BMSCs’ osteogenic differentiation by targeting VGLL4, which in turn improved PMOP. Materials and methodsThe anti-osteoporotic effect of BSD was studied in ovariectomized (OVX) rats and bone marrow mesenchymal stem cells (BMSCs). Micro-CT imaging and HE staining were performed, and the levels of osteogenic protein RUNX2 and osteogenesis-related factor VGLL4 were determined. Co-immunoprecipitation (Co-IP) was further employed to delve into the effects of BSD on the interactions between TEAD4 and RUNX2. The key osteogenic factors 1ALP, COLl1A1, and Osterix expression were detected by RT-qPCR. Co-IP and proximity ligation assay (PLA) were employed to scrutinize the influence of BSD on TEAD4 and RUNX2 inter-binding. Moreover, VGLL4 knockdown in BMSCs was conducted to confirm the role of VGLL4 in the therapeutic mechanism of BSD. ResultsBSD showed a dose-dependent protective effect against osteoporotic injury, as evidenced by improvement in bone volume, bone microarchitecture, and histomorphometry. Additionally, BSD treatment increased the levels of RUNX2 and its downstream target genes including ALP, COL1A1, and Osterix. Moreover, BSD upregulated VGLL4 expression and lessened TEAD4-RUNX2 interactions. In BMSCs experiment, BSD-containing serum could promote osteogenic differentiation of BMSCs, boosted the expression of osteogenesis-related factors and VGLL4 level. The knockdown of VGLL4 in BMSCs diminished the promotion effect of BSD in osteoblast differentiation, suggesting that VGLL4 play a vital role in the therapeutic effects exerted by BSD. ConclusionBSD ameliorated osteoporosis injury and promoted osteoblast differentiation through upregulation of VGLL4 levels, which in turn antagonized TEAD4-mediated RUNX2 transcriptional repression. Our study implied that BSD may be an osteoporosis therapeutic agent.

ЛЕЧЕНИЕ ОСТЕОПОРОТИЧЕСКИХ ПОВРЕЖДЕНИЙ ЗАДНЕГО ПОЛУКОЛЬЦА ТАЗА БЕЗ СУЩЕСТВЕННОГО СМЕЩЕНИЯ

Relevance. The prevalence of osteoporosis and, as a result, the risk of life-threatening pathological fractures increases. At the same time, the optimal treatment tactic for low-energy injuries of the posterior half-ring of the pelvis without significant displacement has not been determined, which actualizes further studies of this type of damage. The aim of the study was to analyze the experience of diagnosing and treating osteoporotic injuries of the posterior pelvic half-ring without significant displacement. Materials and methods. The prospective controlled study included 63 patients aged 60-93 years who were treated in 2018-2020 for osteoporotic fractures of the posterior half-ring of the pelvis without significant displacement. Comprehensive examination of patients was carried out, including standard radiography and X-ray computed tomography (CT) of the pelvis, correction of comorbid conditions, analgesia, prevention of thromboembolism. In one outpatient observation based on standard radiography, pelvic ring injury was not detected in a timely manner. In 57 patients hospitalized up to 5 days after injury, early functional conservative treatment was used. In 33 of them, this treatment led to restoration of function, fusion. In 24 of 57 patients, in the conditions of early functional conservative treatment, a significant pain syndrome persisted and pelvic ring instability was determined, they underwent prompt minimally invasive pelvic stabilization followed by early activation. Intensive therapy for advanced heart and renal failure was performed in 2 patients 86 and 82 years hospitalized up to 5 days after the injury. In 4 patients hospitalized within more than 5 days after injury with significant pain syndrome and pelvic ring instability, its urgent operative minimally invasive stabilization was carried out with subsequent early activation. For minimally invasive stabilization of the rear half-ring, cannulated screws were used, the front half-ring - cannulated screws, lockable rods, in two - plate osteosynthesis. The outcome was assessed using the S.A. Majeed scale 6 months after hospitalization. Results. Three patients (4.8%) died due to decompensation of severe comorbid somatic pathology. There were no nonunions, thromboembolic and infectious complications. The terms of restoration of motor activity of patients with conservative treatment amounted to 8-24 weeks, with operative - 8-16 weeks. One patient had a screw migration from the anterior pelvic half-ring under the skin. The results were evaluated in 52 patients (82.5%): excellent - 26 (50%), good - 22 (42%), satisfactory - 1 (2%), bad - 3 (6%). Conclusions. 1. post-traumatic pelvic pain, impaired motor activity, and no detection of bone traumatic changes with standard pelvic radiography should be an indication for performing pelvic computed tomography. 2. The low mortality rate - 4.8% - and the high level of excellent and good results - 92% - in the group of elderly, senile and long-lived patients with osteoporotic fractures of the posterior half-ring of the pelvis without significant displacement indicate the adequacy of the applied protocol of multidisciplinary, early functional treatment of these injuries. 3. Minimally invasive osteosynthesis using blockable rods and cannulated screws of the front and rear half-rings of the pelvis in case of their instability allows early activation of elderly, senile and long-lived patients, accompanied by a low risk of complications.

Fractures of humerus and their treatment modalities

Introduction: The majority of humerus fractures are low energy osteoporotic injuries in the elderly and their incidence is increasing in the light of an ageing population. Non-operative management has been associated with good functional outcomes in stable, minimally displaced and certain types of displaced fractures. Absolute indications for surgery are infrequent and comprise compound, pathological, multi-fragmentary head-splitting fractures and fracture dislocations, as well as those associated with neurovascular injury. Aim of the study: The aim of study is to understand current concepts with regards to treatment options for fractures of the humerus. Materials and Methods: This is a retrospective study involving 181 cases of fracture humerus which occurred due to fall or trauma. Results: In this study, 84 cases (46.40) were proximal humerus fractures, 58 cases (32.04) were shaft of the humerus fractures and 39 cases (21.56) were distal humerus fractures and which were treated conservatively, open reduction and internal fixation or other surgical methods. Conclusion: Patients presenting with fractures of the humerus were more commonly elderly women and occur due to low energy fall or minor trauma. Early restoration of function is the main aim of the treating orthopedician depending on the age and other comorbidities and surrounding structures involvement.

Hip fracture care and national systems: Australia and Asia.

The Asia-Pacific region includes countries with diverse cultural, demographic, and socio-political backgrounds. Countries such as Japan have very high life expectancy and an aged population. China and India, with a combined population over 2.7 billion, will experience a huge wave of ageing population with subsequent osteoporotic injuries. Australia will experience a similar increase in the osteoporotic fracture burden, and is leading the region by establishing a national hip fracture registry with governmental guidelines and outcome monitoring. While it is impossible to compare fragility hip fracture care in every Asia-Pacific country, this review of 4 major nations gives insight into the challenges facing diverse systems. They are united by the pursuit of internationally accepted standards of timely surgery, combined orthogeriatric care, and secondary fracture prevention strategies.

TIMP-1 suppressed by miR-138 participates in endoplasmic reticulum stress-induced osteoblast apoptosis in osteoporosis

The aim of this study was to investigate the role of miR-138 in osteoporosis and its underlying mechanism. Hydrogen peroxide (H2O2) was used to induce osteoporotic injury of osteoblasts. The cell viability and apoptosis of MC3T3-E1 cells was assessed using MTT assay and flow cytometry, respectively. The cell transfection was carried out to modulate the expression levels of miR-138 and TIMP-1 in MC3T3-E1 cells. Luciferase reporter gene assay was performed to determine the interaction between miR-138 and TIMP-1 3′UTR. In the present study, H2O2 inhibited osteoblasts growth and induced intracellular endoplasmic reticulum (ER) stress accompanied by high expression of miR-138. We also confirmed that miR-138 promoted osteoblasts apoptosis in vitro and in vivo. MiR-138 was further indicated to inhibit osteoblast survival via negative regulating TIMP-1 expression. Moreover, the downregulated TIMP-1 also mediated the ER stress-induced apoptosis of osteoblasts. We confirmed that miR-138 and ER stress were induced in osteoporosis and then promoted the apoptosis of osteoblasts, at least in part, through TIMP-1.

A missense single nucleotide polymorphism in the ALDH2 gene, rs671, is associated with hip fracture

Hip fracture is the most severe bone fragility fracture among osteoporotic injuries. Family history is a known risk factor for fracture and now included among criteria for osteoporosis diagnosis and treatment; however, genetic factors underlying family history favoring fracture remain to be elucidated. Here we demonstrate that a missense SNP in the ALDH2 gene, rs671 (ALDH2*2), is significantly associated with hip fracture (odds ratio = 2.48, 95% confidence interval: 1.20–5.10, p = 0.021). The rs671 SNP was also significantly associated with osteoporosis development (odds ratio = 2.04, 95% confidence interval: 1.07–3.88, p = 0.040). For analysis we enrolled 92 hip fracture patients plus 48 control subjects without bone fragility fractures with higher than −2.5 SD bone mineral density. We also recruited 156 osteoporosis patients diagnosed as below −2.5 SD in terms of bone mineral density but without hip fracture. Association of rs671 with hip fracture and osteoporosis was significant even after adjustment for age and body mass index. Our results provide new insight into the pathogenesis of hip fracture.

Management of proximal humerus fractures in adults.

The majority of proximal humerus fractures are low-energy osteoporotic injuries in the elderly and their incidence is increasing in the light of an ageing population. The diversity of fracture patterns encountered renders objective classification of prognostic value challenging. Non-operative management has been associated with good functional outcomes in stable, minimally displaced and certain types of displaced fractures. Absolute indications for surgery are infrequent and comprise compound, pathological, multi-fragmentary head-splitting fractures and fracture dislocations, as well as those associated with neurovascular injury. A constantly expanding range of reconstructive and replacement options however has been extending the indications for surgical management of complex proximal humerus fractures. As a result, management decisions are becoming increasingly complicated, in an attempt to provide the best possible treatment for each individual patient, that will successfully address their specific fracture configuration, comorbidities and functional expectations. Our aim was to review the management options available for the full range of proximal humerus fractures in adults, along with their specific advantages, disadvantages and outcomes.